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Sample records for residual recipient cells

  1. Residual amoebic liver abscess in a prospective renal transplant recipient

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    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.

  2. Characterizing Electrocochleography in Cochlear Implant Recipients with Residual Low-Frequency Hearing

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    Bester, Christofer W.; Campbell, Luke; Dragovic, Adrian; Collins, Aaron; O'Leary, Stephen J.

    2017-01-01

    Objective: Lay the groundwork for using electrocochleography (ECochG) as a measure of cochlear health, by characterizing typical patterns of the ECochG response observed across the electrode array in cochlear implant recipients with residual hearing. Methods: ECochG was measured immediately after electrode insertion in 45 cochlear implant recipients with residual hearing. The Cochlear Response Telemetry system was used to record ECochG across the electrode array, in response to 100- or 110-dB...

  3. Expression of assayable residual stem cell damage in erythroid differentiation

    International Nuclear Information System (INIS)

    Huebner, G.E.; Miller, M.E.; Cronkite, E.P.

    1985-01-01

    In rodents, residual damage is inducible in hematopoietic stem cells by exposure to ionizing radiation or alkylating agents. This damage can b e assayed in mice by transferring bone marrow into lethally irradiated syngeneic recipients and subsequently measuring the incremental increase of-( 125 I)iodo-2'-deoxyuridine incorporation in spleens. In this study, bone marrow from mice treated 3 weeks previously with Methylnitrosourea (50 mg/kg) or 450 rad was injected into recipients in order to determine possible residual effects of treatment of erythroid cell differentiation following stem cell seeding. Such effects were detected by a reduced amount of 59 Fe incorporation into spleens, thus indicatin g transfer of residual stem cell damage to differentiating cells. (orig.)

  4. Automated detection of residual cells after sex-mismatched stem-cell transplantation – evidence for presence of disease-marker negative residual cells

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    Johannes Tilman

    2009-05-01

    Full Text Available Abstract Background A new chimerism analysis based on automated interphase fluorescence in situ hybridization (FISH evaluation was established to detect residual cells after allogene sex-mismatched bone marrow or blood stem-cell transplantation. Cells of 58 patients were characterized as disease-associated due to presence of a bcr/abl-gene-fusion or a trisomy 8 and/or a simultaneous hybridization of gonosome-specific centromeric probes. The automatic slide scanning platform Metafer with its module MetaCyte was used to analyse 3,000 cells per sample. Results Overall 454 assays of 58 patients were analyzed. 13 of 58 patients showed residual recipient cells at one stage of more than 4% and 12 of 58 showed residual recipient cells less than 4%, respectively. As to be expected, patients of the latter group were associated with a higher survival rate (48 vs. 34 month. In only two of seven patients with disease-marker positive residual cells between 0.1–1.3% a relapse was observed. Besides, disease-marker negative residual cells were found in two patients without relapse at a rate of 2.8% and 3.3%, respectively. Conclusion The definite origin and meaning of disease-marker negative residual cells is still unclear. Overall, with the presented automatic chimerism analysis of interphase FISH slides, a sensitive method for detection of disease-marker positive residual cells is on hand.

  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. 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...... autologous) from 1999 through 2014, 4789 RTRs from 1976 through 2014, and 10 age- and sex-matched nontransplanted individuals for each of the groups from the background population. Person-years at risk were calculated from the time of study inclusion until first cutaneous cancer. To compare the risk of skin...... 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...

  7. The sound sensation of apical electric stimulation in cochlear implant recipients with contralateral residual hearing.

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    Diane S Lazard

    Full Text Available BACKGROUND: Studies using vocoders as acoustic simulators of cochlear implants have generally focused on simulation of speech understanding, gender recognition, or music appreciation. The aim of the present experiment was to study the auditory sensation perceived by cochlear implant (CI recipients with steady electrical stimulation on the most-apical electrode. METHODOLOGY/PRINCIPAL FINDINGS: Five unilateral CI users with contralateral residual hearing were asked to vary the parameters of an acoustic signal played to the non-implanted ear, in order to match its sensation to that of the electric stimulus. They also provided a rating of similarity between each acoustic sound they selected and the electric stimulus. On average across subjects, the sound rated as most similar was a complex signal with a concentration of energy around 523 Hz. This sound was inharmonic in 3 out of 5 subjects with a moderate, progressive increase in the spacing between the frequency components. CONCLUSIONS/SIGNIFICANCE: For these subjects, the sound sensation created by steady electric stimulation on the most-apical electrode was neither a white noise nor a pure tone, but a complex signal with a progressive increase in the spacing between the frequency components in 3 out of 5 subjects. Knowing whether the inharmonic nature of the sound was related to the fact that the non-implanted ear was impaired has to be explored in single-sided deafened patients with a contralateral CI. These results may be used in the future to better understand peripheral and central auditory processing in relation to cochlear implants.

  8. Difficulties in the revaccination program of hematopoietic stem cell transplantation recipients

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    da Silva, Paula Moreira; da Silva, Élen Monteiro; Simioni, Anderson João; de Souza, Mair Pedro; Colturato, Vergílio Antonio Rensi; Machado, Clarisse Martins

    2017-01-01

    ABSTRACT Hematopoietic stem cell transplant (HSCT) recipients should be routinely revaccinated after transplantation. We evaluated the difficulties met in the revaccination program and how a prospective and tailored follow-up could help to overcome these obstacles. HSCT recipients (n=122) were prospectively followed up and categorized into Group 1 (n=72), recipients who had already started the revaccination program, and Group 2 (n=50), recipients starting their vaccines. Whenever a difficulty...

  9. Disseminated Fusarium infection in autologous stem cell transplant recipient

    OpenAIRE

    Avelino-Silva, Vivian Iida; Ramos, Jessica Fernandes; Leal, Fabio Eudes; Testagrossa, Leonardo; Novis, Yana Sarkis

    2015-01-01

    Disseminated infection by Fusarium is a rare, frequently lethal condition in severely immunocompromised patients, including bone marrow transplant recipients. However, autologous bone marrow transplant recipients are not expected to be at high risk to develop fusariosis. We report a rare case of lethal disseminated Fusarium infection in an autologous bone marrow transplant recipient during pre-engraftment phase.

  10. Disseminated Fusarium infection in autologous stem cell transplant recipient

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    Vivian Iida Avelino-Silva

    2015-01-01

    Full Text Available Disseminated infection by Fusarium is a rare, frequently lethal condition in severely immunocompromised patients, including bone marrow transplant recipients. However, autologous bone marrow transplant recipients are not expected to be at high risk to develop fusariosis. We report a rare case of lethal disseminated Fusarium infection in an autologous bone marrow transplant recipient during pre-engraftment phase.

  11. Cutaneous Squamous Cell Carcinomas in Organ Transplant Recipients

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    Ramya Chockalingam

    2015-06-01

    Full Text Available Non-melanoma skin cancers represent a major cause of morbidity after organ transplantation. Squamous cell carcinomas (SCC are the most common cutaneous malignancies seen in this population, with a 65–100 fold greater incidence in organ transplant recipients compared to the general population. In recent years, human papillomaviruses (HPV of the beta genus have been implicated in the pathogenesis of post-transplant SCCs. The underlying mechanism of carcinogenesis has been attributed to the E6 and E7 proteins of HPV. Specific immunosuppressive medications, such as the calcineurin inhibitors and azathioprine, are associated with a higher incidence of post-transplant SCCs compared to other immunosuppressive agents. Compared to other immunosuppressives, mTOR inhibitors and mycophenolate mofetil have been associated with a decreased risk of developing post-transplant non-melanoma skin cancers. As a result, they may represent ideal immunosuppressive medications in organ transplant recipients. Treatment options for post-transplant SCCs include surgical excision, Mohs micrographic surgery, systemic retinoid therapy, adjunct topical therapy, electrodessication and curettage, and radiation therapy. This review will discuss the epidemiology, risk factors, and management options of post-transplant SCCs. In addition, the underlying mechanisms of beta-HPV mediated carcinogenesis will be discussed.

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

    International Nuclear Information System (INIS)

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

    1986-01-01

    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

  13. Measuring Immune Response to Commonly Used Vaccinations in Adult Recipients of Allogeneic Hematopoietic Cell Transplantation.

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    Kennedy, Lucy Boyce; Li, Zhuoyan; Savani, Bipin N; Ljungman, Per

    2017-10-01

    Recipients of hematopoietic cell transplantation (HCT) are at risk for potentially preventable infectious complications because of defects in humoral and cell-mediated immunity. Studies of vaccine immunogenicity in HCT recipients have shown that antibody response rates depend on age, type of vaccine, and presence or absence of graft-versus-host disease. However, few large-scale studies have assessed the immune response to vaccination in HCT recipients. Additionally, HCT recipients have much higher rates of potentially preventable infections compared with the general population even after vaccination. This review evaluates the available studies and our view on the measurement of specific antibody titers, definition of an immune response, and durability of response in HCT recipients in both inactivated and live attenuated vaccines. Published by Elsevier Inc.

  14. Opioid tapering in hematopoietic progenitor cell transplant recipients.

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    Pederson, C; Parran, L

    2000-10-01

    To describe current opioid-tapering practice, patient pain levels and withdrawal symptoms, and nurse documentation during opioid tapers. Descriptive, exploratory, prospective, quantitative, and qualitative. A 32-bed blood and marrow transplant unit in a large, tertiary U.S. care center. 45 blood and marrow transplant recipients between the ages of 7-64. Types of transplant were autologous, allogeneic, and unrelated donor marrow; peripheral blood stem cell; and umbilical cord blood. In daily interviews, patients reported pain levels and withdrawal symptoms during opioid tapers. Demographic, medication, and nurse documentation data were obtained from patient hospital records. Taper length, daily opioid dosage, pain, withdrawal symptoms, and nurse documentation. Length of taper ranged from 1-17 days (X = 6.53, SD = 4.26). Analysis of variance indicated no difference by disease or transplant type in length of taper, cumulative opioids given pretaper or during taper, or number of self-reports of withdrawal symptoms. Daily changes in nurse-administered opioid dosage during tapers ranged from a decrease of 67% to an increase of 14%. Children received significantly more opioids/kg during taper than adults. Means of adults' and children's self-reports of pain were low. The means of patient-reported withdrawal symptoms were highest on taper days two through six. Nurse documentation was sparse. Daily taper rates vary widely, pain is well managed, and most patients experience several withdrawal symptoms. Use of an opioid-taper guideline may promote consistency of tapering while not increasing levels of pain or withdrawal symptoms.

  15. Financial burden in recipients of allogeneic hematopoietic cell transplantation.

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    Khera, Nandita; Chang, Yu-hui; Hashmi, Shahrukh; Slack, James; Beebe, Timothy; Roy, Vivek; Noel, Pierre; Fauble, Veena; Sproat, Lisa; Tilburt, Jon; Leis, Jose F; Mikhael, Joseph

    2014-09-01

    Although allogeneic hematopoietic cell transplantation (HCT) is an expensive treatment for hematological disorders, little is known about the financial consequences for the patients who undergo this procedure. We analyzed factors associated with its financial burden and its impact on health behaviors of allogeneic HCT recipients. A questionnaire was retrospectively mailed to 482 patients who underwent allogeneic HCT from January 2006 to June 2012 at the Mayo Clinic, to collect information regarding current financial concerns, household income, employment, insurance, out-of-pocket expenses, and health and functional status. A multivariable logistic regression analysis identified factors associated with financial burden and treatment nonadherence. Of the 268 respondents (56% response rate), 73% reported that their sickness had hurt them financially. All patients for whom the insurance information was available (missing, n = 13) were insured. Forty-seven percent of respondents experienced financial burden, such as household income decreased by >50%, selling/mortgaging home, or withdrawing money from retirement accounts. Three percent declared bankruptcy. Younger age and poor current mental and physical functioning increased the likelihood of financial burden. Thirty-five percent of patients reported deleterious health behaviors because of financial constraints. These patients were likely to be younger, have lower education, and with a longer time since HCT. Being employed decreased the likelihood of experiencing financial burden and treatment nonadherence due to concern about costs. A significant proportion of allogeneic HCT survivors experience financial hardship despite insurance coverage. Future research should investigate potential interventions to help at-risk patients and prevent adverse financial outcomes after this life-saving procedure. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  16. Persistent rhinovirus infection in pediatric hematopoietic stem cell transplant recipients with impaired cellular immunity.

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    Piralla, Antonio; Zecca, Marco; Comoli, Patrizia; Girello, Alessia; Maccario, Rita; Baldanti, Fausto

    2015-06-01

    HRV infections are generally self-limiting in healthy subjects, whereas in immunocompromised hosts HRV infections can lead to severe complications and persistent infections. The persistence of HRV shedding could be due to the inefficient immunological control of a single infectious episode. To investigate the clinical, virologic and immunologic characteristics of pediatric HSCT recipients with HRV-PI infection. During the period 2006-2012, eight hematopoietic stem cell transplant (HSCT) recipients presented with persistent rhinovirus infection (HRV-PI, ≥30 days). Viral load and T-CD4(+), T-CD8(+), B and NK lymphocyte counts at the onset of infection were compared with those of fourteen HSCT recipients with acute HRV infection (HRV-AI, ≤15 days). The median duration of HRV positivity in patients with HRV-PI was 61 days (range 30-174 days) and phylogenetic analysis showed the persistence of a single HRV type in all patients (100%). In HSCT recipients with HRV-PI, T-CD4(+), T-CD8(+) and NK cell counts at the onset of infection were significantly lower than those observed in recipients with HRV-AI (pimmunity in HRV clearance and highlights the importance of its recovery for the control of HRV infection in HSCT recipients. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. A Comprehensive Review of Immunization Practices in Solid Organ Transplant and Hematopoietic Stem Cell Transplant Recipients.

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    Chong, Pearlie P; Avery, Robin K

    2017-08-01

    Vaccine-preventable diseases, especially influenza, varicella, herpes zoster, and invasive pneumococcal infections, continue to lead to significant morbidity and mortality in solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients. We highlight guideline recommendations for the use of key vaccines in SOT and HSCT recipients and to review the latest evidence and developments in the field. Physicians should vaccinate individuals with end-stage organ disease, as vaccine seroresponse rates are higher pretransplantation. Most live attenuated vaccines continue to be contraindicated post-transplantation, but there are emerging safety profile and efficacy data to support the use of specific live attenuated vaccines, such as measles, mumps, and rubella in pediatric liver or kidney transplant recipients who are on low-level maintenance immunosuppression and without recent history of allograft rejection. An inactivated subunit varicella zoster virus vaccine is currently awaiting US Food and Drug Administration approval. While we await the safety profile and efficacy data of this subunit vaccine in transplant recipients, it will likely benefit immunocompromised individuals, including transplant recipients, because the live attenuated herpes zoster vaccine is currently contraindicated in transplant recipients and transplantation candidates receiving immunosuppression. There is currently no evidence that vaccines lead to allograft rejection in SOT recipients. Household contacts of SOT and HSCT recipients should be vaccinated per the Advisory Committee on Immunization Practices schedule and recommendations. Immunizations remain underutilized in transplantation patients. Although efficacy of vaccines in SOT and HSCT may be suboptimal, partial protection is preferred over no protection. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  18. Direct visualization of Agrobacterium-delivered VirE2 in recipient cells

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    Li, Xiaoyang; Yang, Qinghua; Tu, Haitao; Lim, Zijie; Pan, Shen Q

    2014-01-01

    Agrobacterium tumefaciens is a natural genetic engineer widely used to deliver DNA into various recipients, including plant, yeast and fungal cells. The bacterium can transfer single-stranded DNA molecules (T–DNAs) and bacterial virulence proteins, including VirE2. However, neither the DNA nor the protein molecules have ever been directly visualized after the delivery. In this report, we adopted a split-GFP approach: the small GFP fragment (GFP11) was inserted into VirE2 at a permissive site to create the VirE2-GFP11 fusion, which was expressed in A. tumefaciens; and the large fragment (GFP1–10) was expressed in recipient cells. Upon delivery of VirE2-GFP11 into the recipient cells, GFP fluorescence signals were visualized. VirE2-GFP11 was functional like VirE2; the GFP fusion movement could indicate the trafficking of Agrobacterium-delivered VirE2. As the natural host, all plant cells seen under a microscope received the VirE2 protein in a leaf-infiltration assay; most of VirE2 moved at a speed of 1.3–3.1 μm sec−1 in a nearly linear direction, suggesting an active trafficking process. Inside plant cells, VirE2-GFP formed filamentous structures of different lengths, even in the absence of T-DNA. As a non-natural host recipient, 51% of yeast cells received VirE2, which did not move inside yeast. All plant cells seen under a microscope transiently expressed the Agrobacterium-delivered transgene, but only 0.2% yeast cells expressed the transgene. This indicates that Agrobacterium is a more efficient vector for protein delivery than T-DNA transformation for a non-natural host recipient: VirE2 trafficking is a limiting factor for the genetic transformation of a non-natural host recipient. The split-GFP approach could enable the real-time visualization of VirE2 trafficking inside recipient cells. PMID:24299048

  19. Recipient dendritic cells, but not B cells, are required antigen-presenting cells for peripheral alloreactive CD8+ T-cell tolerance.

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    Mollov, J L; Lucas, C L; Haspot, F; Gaspar, J Kurtz C; Guzman, A; Sykes, M

    2010-03-01

    Induction of mixed allogeneic chimerism is a promising approach for achieving donor-specific tolerance, thereby obviating the need for life-long immunosuppression for solid organ allograft acceptance. In mice receiving a low dose (3Gy) of total body irradiation, allogeneic bone marrow transplantation combined with anti-CD154 tolerizes peripheral CD4 and CD8 T cells, allowing achievement of mixed chimerism with specific tolerance to donor. With this approach, peripheral CD8 T-cell tolerance requires recipient MHC class II, CD4 T cells, B cells and DCs. Recipient-type B cells from chimeras that were tolerant to donor still promoted CD8 T-cell tolerance, but their role could not be replaced by donor-type B cells. Using recipients whose B cells or DCs specifically lack MHC class I and/or class II or lack CD80 and CD86, we demonstrate that dendritic cells (DCs) must express CD80/86 and either MHC class I or class II to promote CD8 tolerance. In contrast, B cells, though required, did not need to express MHC class I or class II or CD80/86 to promote CD8 tolerance. Moreover, recipient IDO and IL-10 were not required. Thus, antigen presentation by recipient DCs and not by B cells is critical for peripheral alloreactive CD8 T cell tolerance.

  20. Analysis of the results of allogeneic hematopoietic stem cell transplantation depending on HLA matching of the unrelated donor / recipient pair

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    Ye. V. Kuzmich

    2015-01-01

    Full Text Available HLA matching of the donor / recipient pair is a major factor associated with the outcome of allogeneic stem cell transplantation. In the presentstudy we analyzed the risk of severe acute graft-versus-host disease, graft failure, 2.year overall survival of the patients after allogeneic stem cell transplantation depending on HLA matching of the unrelated donor / recipient pair.

  1. Inflammatory response to mucosal barrier injury after myeloablative therapy in allogeneic stem cell transplant recipients.

    NARCIS (Netherlands)

    Blijlevens, N.M.A.; Donnelly, J.P.; Pauw, B.E. de

    2005-01-01

    We noted a significant increase of interleukin-8 (IL-8), LBP and CRP mirroring the pattern of mucosal barrier injury as measured by gut integrity (lactulose/rhamnose ratio), daily mucositis score (DMS) and serum citrulline concentrations of 32 haematopoietic stem cell transplant (HSCT) recipients

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

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    Hua Shen

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

  3. Plasma markers of B-cell activation and clonality in pediatric liver and hematopoietic stem cell transplant recipients

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    Engels, Eric A.; Savoldo, Barbara; Pfeiffer, Ruth M.; Costello, Rene; Zingone, Adriana; Heslop, Helen E.; Landgren, Ola

    2012-01-01

    Introduction Transplant recipients are at risk of post-transplant lymphoproliferative disease (PTLD). Methods: Thirty-six pediatric transplant recipients were evaluated (18 hematopoietic stem cell and 18 liver recipients; 12 had PTLD). We studied 207 longitudinal plasma samples from these recipients for three markers of B-cell activation or clonality: immunoglobulin free light chains (FLCs), soluble CD30 (sCD30), and monoclonal immunoglobulins (M-proteins). Results Kappa FLCs, lambda FLCs, and sCD30 were elevated in 20.8%, 28.0%, and 94.2% of plasma specimens, respectively. FLC and sCD30 levels increased significantly 1.18–1.82 fold per log10 Epstein Barr virus (EBV) load in peripheral blood. Five PTLD cases manifested elevated FLCs with an abnormal kappa/lambda ratio, suggesting monoclonal FLC production. M-proteins were present in 91% of PTLD cases, vs. 50–67% of other recipients with high or low EBV loads (p=0.13). Concordance of FLCs, M-proteins, and PTLD tumor light chain restriction was imperfect. For example, one PTLD case with an IgG lambda M-protein had a tumor that was kappa restricted, and another case with an M-protein had a T-cell PTLD. In an additional case, an IgM kappa M-protein and excess kappa FLCs were both detected in plasma at PTLD diagnosis; while the tumor was not restricted at diagnosis, kappa restriction was present 5 years later when the PTLD relapsed. Discussion Plasma markers of B-cell dysfunction are frequent following transplantation and associated with poor EBV control. These abnormal markers may be produced by oligoclonal B-cell populations or PTLD tumor cells, and could potentially help identify recipients at high risk of PTLD. PMID:23222884

  4. The incidence of autoimmune hemolytic anemia in pediatric hematopoietic stem cell recipients post first and second hematopoietic stem cell transplant

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    Ahmed, Ibrahim; Teruya, Jun; Murray-Krezan, Cristina; Krance, Robert

    2015-01-01

    The reported incidence of post allogeneic hematopoietic stem cell transplant (HSCT) auto-immune hemolytic anemia (AIHA) was between 4.4% and 6% following a single transplant. Cord blood transplantation, T-cell depletion and chronic GvHD are significantly associated with post-transplant AIHA. During an 11 year period, data for 500 pediatric HSCT recipients were eligible for evaluation of the incidence of AIHA post first and second transplants. Demographic, transplant, and post-transplant related variables were analyzed. Twelve/500 (2.4%) recipients at a median of 273 days and 7/72 (9.7%) recipients at a median of 157 days developed AIHA post first and second HSCT respectively. Post first HSCT, none of the matched related donor recipients developed AIHA (0/175 MRD vs. 12/325 other donors, p=0.04). Four/12 required a second HSCT to control the AIHA. Post the second HSCT, matched unrelated donor was significantly associated with the development of AIHA. No other variables were associated with the post-second transplant AIHA. The incidence of AIHA post first and second HSCT was less than reported. The increased incidence of AIHA among recipients of second HSCT is most likely due to the profound immune dysregulation. A much larger, prospective study would be needed to evaluate the incidence, complications and management of post-transplant AIHA. PMID:25809012

  5. Microbiologic yield of bronchoalveolar lavage specimens from stem cell transplant recipients.

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    Sakata, Kenneth K; Klassen, Christine L; Bollin, Kathryn B; Grys, Thomas E; Slack, James L; Wesselius, Lewis J; Vikram, Holenarasipur R

    2017-06-01

    Stem cell transplant (SCT) recipients commonly undergo bronchoalveolar lavage (BAL) collection as an infectious pulmonary work-up. Previous studies report the utility and overall diagnostic yield of fiberoptic bronchoscopy with BAL in this vulnerable population, though none focused purely on microbiologic yield or made comparisons with less invasive means of pathogen detection. We sought to determine and elaborate on the microbiologic yield of BAL in SCT recipients, assess a correlation between BAL studies and less invasive means of pathogen detection, and assess the utility of repeating a BAL within 30 days. Between January 1, 2009, and July 31, 2013, we reviewed medical records of 125 SCT recipients who underwent 179 BALs. In addition to demographic information and details pertaining to their SCT, a comprehensive review of their microbiologic data was performed and recorded. Our study showed an overall BAL microbiologic yield of 40%, despite 92% of patients receiving broad-spectrum antimicrobial therapy at the time of the BAL procedure. Although an initial BAL sample in this population provides crucial microbiologic information, repeating the procedure within 30 days may have minimal additional microbiologic yield. BAL continues to be an essential diagnostic tool in SCT recipients undergoing an infectious pulmonary work-up. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. A transplant recipient with a mixed germ-cell ovarian tumor

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    Ketata Hafed

    2008-01-01

    Full Text Available Immunosuppressed renal transplant recipients seem to be at significantly increased risk of developing neoplasms comparatively to nonimmunosuppressed individuals. A history of malignancy exposes the patient to a high risk for relapse after transplantation. We present a trans-plant recipient with a history of an ovarian mixed germ-cell tumor, with choriocarcinoma com-ponent, which was treated seven years prior to transplantation. After three years of follow-up, there was no evidence of tumor relapse. To our knowledge, there is no report of such case in the English literature. Regarding our case report and patients with a history of ovarian germ-cell neoplasm, waiting time before transplantation must take into consideration the stage of the tumor, its prognosis, the proportion of different tumor components, and the overall prognosis of the patient if transplantation is withheld.

  7. Invasive Pulmonary Aspergillosis in a Sickle Cell Patient Transplant Recipient: A Successful Treatment

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    Katia Paciaroni

    2015-08-01

    Full Text Available Sickle Cell Anaemia (SCA is the most common inherited blood disorder and is associated with severe morbidity and decreased survival. Allogeneic Haematopoietic Stem Cell Transplantation (HSCT is the only curative approach. Nevertheless the decision to perform a marrow transplant includes the risk of major complications  and mortality transplant related. The infections represent the main cause of mortality for SCA patients undergoing transplant. Invasive Pulmonary Aspergillosis (IPA is a devastating opportunistic infection and remains a significant cause of morbidity and mortality in HSCT recipients. Data regarding IPA in the setting of SCA are lacking. In the present report,  we describe a patient with SCA who developed IPA after allogeneic bone marrow transplant. The fungal infection was treated by systemic antifungal therapy in addition to the surgery, despite  mild chronic GVHD and with continuing immunosuppression therapy. This case shows that IPA occurring in bone marrow recipient with SCA can be successful treated

  8. Systematic Nutritional Support in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

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    Fuji, Shigeo; Einsele, Hermann; Savani, Bipin N; Kapp, Markus

    2015-10-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) has become an established treatment modality for various hematological diseases. However, in allogeneic HSCT, patients often suffer from severe gastrointestinal complications caused by the conditioning regimen and acute/chronic graft-versus-host disease, which requires support by multidisciplinary nutritional support teams (NST). In addition, pretransplantation nutritional status can affect the clinical outcome after allogeneic HSCT. Therefore, it is important to refer the patient to a NST when becoming aware of nutritional problems before allogeneic HSCT. It is also important to follow nutritional status over the long term, as patients often suffer from various nutritional problems, such as malnutrition and metabolic syndrome, even late after allogeneic HSCT. In summary, NST can contribute to the improvement of nutritional status and possibly prognosis at every stage before and after allogeneic HSCT. Here, we aim to give a comprehensive overview of current understanding about nutritional support in allogeneic HSCT and try to provoke a constructive discussion to stimulate further investigation. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  9. Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation.

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    Galleu, Antonio; Riffo-Vasquez, Yanira; Trento, Cristina; Lomas, Cara; Dolcetti, Luigi; Cheung, Tik Shing; von Bonin, Malte; Barbieri, Laura; Halai, Krishma; Ward, Sophie; Weng, Ling; Chakraverty, Ronjon; Lombardi, Giovanna; Watt, Fiona M; Orchard, Kim; Marks, David I; Apperley, Jane; Bornhauser, Martin; Walczak, Henning; Bennett, Clare; Dazzi, Francesco

    2017-11-15

    The immunosuppressive activity of mesenchymal stromal cells (MSCs) is well documented. However, the therapeutic benefit is completely unpredictable, thus raising concerns about MSC efficacy. One of the affecting factors is the unresolved conundrum that, despite being immunosuppressive, MSCs are undetectable after administration. Therefore, understanding the fate of infused MSCs could help predict clinical responses. Using a murine model of graft-versus-host disease (GvHD), we demonstrate that MSCs are actively induced to undergo perforin-dependent apoptosis by recipient cytotoxic cells and that this process is essential to initiate MSC-induced immunosuppression. When examining patients with GvHD who received MSCs, we found a striking parallel, whereby only those with high cytotoxic activity against MSCs responded to MSC infusion, whereas those with low activity did not. The need for recipient cytotoxic cell activity could be replaced by the infusion of apoptotic MSCs generated ex vivo. After infusion, recipient phagocytes engulf apoptotic MSCs and produce indoleamine 2,3-dioxygenase, which is ultimately necessary for effecting immunosuppression. Therefore, we propose the innovative concept that patients should be stratified for MSC treatment according to their ability to kill MSCs or that all patients could be treated with ex vivo apoptotic MSCs. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  10. Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients.

    Science.gov (United States)

    Chilton, Paula M; Rezzoug, Francine; Ratajczak, Mariusz Z; Fugier-Vivier, Isabelle; Ratajczak, Janina; Kucia, Magda; Huang, Yiming; Tanner, Michael K; Ildstad, Suzanne T

    2005-03-01

    Type 1 diabetes is a systemic autoimmune disease that can be cured by transplantation of hematopoietic stem cells (HSCs) from disease-resistant donors. Nonobese diabetic (NOD) mice have a number of features that distinguish them as bone marrow transplant recipients that must be understood prior to the clinical application of chimerism to induce tolerance. In the present studies, we characterized NOD HSCs, comparing their engraftment characteristics to HSCs from disease-resistant strains. Strikingly, NOD HSCs are significantly enhanced in engraftment potential compared with HSCs from disease-resistant donors. Unlike HSCs from disease-resistant strains, they do not require graft-facilitating cells to engraft in allogeneic recipients. Additionally, they exhibit a competitive advantage when coadministered with increasing numbers of syngeneic HSCs, produce significantly more spleen colony-forming units (CFU-Ss) in vivo in allogeneic recipients, and more granulocyte macrophage-colony-forming units (CFU-GMs) in vitro compared with HSCs from disease-resistant controls. NOD HSCs also exhibit significantly enhanced chemotaxis to a stromal cell-derived factor 1 (SDF-1) gradient and adhere significantly better on primary stroma. This enhanced engraftment potential maps to the insulin-dependent diabetes locus 9 (Idd9) locus, and as such the tumor necrosis factor (TNF) receptor family as well as ski/sno genes may be involved in the mechanism underlying the autonomy of NOD HSCs. These findings may have important implications to understand the evolution of autoimmune disease and impact on potential strategies for cure.

  11. An Algorithm Measuring Donor Cell-Free DNA in Plasma of Cellular and Solid Organ Transplant Recipients That Does Not Require Donor or Recipient Genotyping

    Directory of Open Access Journals (Sweden)

    Paul MK Gordon

    2016-09-01

    Full Text Available Cell-free DNA (cfDNA has significant potential in the diagnosis and monitoring of clinical conditions but accurately and easily distinguishing the relative proportion of DNA molecules in a mixture derived from two different sources (i.e. donor and recipient tissues after transplantation is challenging. In human cellular transplantation there is currently no useable method to detect in vivo engraftment and blood-based non-invasive tests for allograft rejection in solid organ transplantation are either non-specific (e.g. creatinine in kidney transplantation, liver enzymes in hepatic transplantation or absent (i.e. heart transplantation. Elevated levels of donor cfDNA have been shown to correlate with solid organ rejection but complex methodology limits implementation of this promising biomarker. We describe a cost-effective method to quantify donor cfDNA in recipient plasma using a panel of high-frequency single nucleotide polymorphisms, next-generation (semiconductor sequencing and a novel mixture model algorithm. In vitro, our method accurately and rapidly determined donor/recipient DNA admixture. For in vivo testing, donor cfDNA was serially quantified in an infant with a urea cycle disorder after receiving six daily infusions of donor liver cells. Donor cfDNA isolated from 1-2 ml of recipient plasma was detected as late as 24 weeks after infusion suggesting engraftment. The percentage of circulating donor cfDNA was also assessed in pediatric and adult heart transplant recipients undergoing routine endomyocardial biopsy with levels observed to be stable over time and generally measuring <1% in cases without moderate or severe cellular rejection. Unlike existing non-invasive methods used to define the proportion of donor cfDNA in solid organ transplant patients, our assay does not require sex mismatch, donor genotyping or whole-genome sequencing and potentially has broad application to detect cellular engraftment or allograft injury after

  12. Differential antibody production by adherent and nonadherent spleen cells transferred to irradiated and cyclophosphamide-treated recipient mice

    International Nuclear Information System (INIS)

    Albright, J.F.; Deitchman, J.W.; Hassell, S.A.; Ozato, K.

    1975-01-01

    Mouse spleen cells were separated into adherent (Ad) and nonadherent (Nad) populations by incubation in plastic petri dishes. Adherent, Nad and unfractionated cell preparations (UCP) were transferred into syngeneic recipient mice that had been either irradiated or cyclophosphamide (CY) treated and the adoptive humoral Ab responses were studied by assessment of hemolytic Ab-forming cells (PFC) or humoral serum Ab production. Adherent cells failed to produce PFC in irradiated recipients, but functioned vigorously in CY-treated recipients. Nonadherent cells generated PFC in either type of host, as did UCP. Studies of comparative responses in CY-treated recipients revealed that: (a) Ad-cells generated 2 / 3 the number of PFC given by equivalent numbers of transferred Nad cells and UCP; (b) per equivalent numbers of transferred cells the Ad fraction generated 5 times more and 16 times more Ab than did the Nad cells and UCP, respectively. Spleen cells taken from mice 6 hr after CY treatment failed to respond to the mitogens phytohemagglutinin and bacterial lipopolysaccharide, showing that all cells were temporarily incapable of proliferation. Transfer of spleen cells from donor mice 16 hr after CY treatment, into thymectomized, irradiated, bone marrow-reconstituted recipients revealed substantial T-helper cell activity. We conclude that: (a) Ad preparations lacked T cells that were supplied by CY-treated recipients although T cell proliferation was temporarily inhibited in the latter; (b) B cells present in the Ad fraction were removed from some type of inhibitor of Ab synthesis and/or secretion, the production of which may be associated with T cells present in Nad preparations and UCP; (c) T-helper cells were only transiently affected by CY

  13. Frequency of tuberculosis in haematological malignancies and stem cell transplant recipients

    International Nuclear Information System (INIS)

    Khan, Badsha; Raza, S.; Ahmed, P.; Ullah, K.; Hussain, C.A.; Hussain, I.

    2005-01-01

    Objective: To assess magnitude of tuberculosis (TB) in patients suffering from various haematological malignancies and stem cell transplant (SCT) recipients. Patients and Methods: Patients suffering from various haematological malignancies treated between July 2001 and December 2002 were included in the study. The hospital records and out-patient follow-up charts were reviewed for demographic information, diagnosis, clinical presentation, laboratory investigations, radiological and pathological examinations, sites involved in TB, methods of diagnosis, number and type of anti-tuberculosis drugs given and response to treatment. Results: During the study period a total of 213 (including 25 allogeneic stem cell transplant (SCT) recipients) patients with different haematological disorders were treated. Out of these, 34, including 4 SCT recipients developed tuberculosis. Overall frequency of TB was 16 %. Median age of TB patients was 33.5 years (range 8-80 years). Median time between diagnosis of haematological disorders and tuberculosis was 21 weeks. Sites of involvement by TB were lung (18), disseminated (6), lymph node (5), pleura (2), spine (2) and pericardium (1). Three of the patients died of TB; one undiagnosed, second with multi-drug resistant TB and the third soon after the start of anti-tuberculosis treatment while remaining 31 cases responded to anti-tuberculosis treatment. Conclusion: Tuberculosis is a major problem in immunocompromised patients and there is need to establish guidelines for TB chemoprophylaxis in our setup. (author)

  14. Outcome of pandemic H1N1 infections in hematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Ljungman, Per; de la Camara, Rafael; Perez-Bercoff, Lena; Abecasis, Manuel; Nieto Campuzano, Jose Bartolo; Cannata-Ortiz, M Jimena; Cordonnier, Catherine; Einsele, Hermann; Gonzalez-Vicent, Marta; Espigado, Ildefonso; Halter, Jörg; Martino, Rodrigo; Mohty, Bilal; Sucak, Gülsan; Ullmann, Andrew J; Vázquez, Lourdes; Ward, Katherine N; Engelhard, Dan

    2011-08-01

    During 2009, a new strain of A/H1N1 influenza appeared and became pandemic. A prospective study was performed to collect data regarding risk factors and outcome of A/H1N1 in hematopoietic stem cell transplant recipients. Only verified pandemic A/H1N1 influenza strains were included: 286 patients were reported, 222 allogeneic and 64 autologous recipients. The median age was 38.3 years and the median time from transplant was 19.4 months. Oseltamivir was administered to 267 patients and 15 patients received zanamivir. One hundred and twenty-five patients (43.7%) were hospitalized. Ninety-three patients (32.5%) developed lower respiratory tract disease. In multivariate analysis, risk factors were age (OR 1.025; 1.01-1.04; P=0.002) and lymphopenia (OR 2.49; 1.33-4.67; P<0.001). Thirty-three patients (11.5%) required mechanical ventilation. Eighteen patients (6.3%) died from A/H1N1 infection or its complications. Neutropenia (P=0.03) and patient age (P=0.04) were significant risk factors for death. The 2009 A/H1N1 influenza pandemic caused severe complications in stem cell transplant recipients.

  15. Oral Complications in Hematopoietic Stem Cell Recipients: The Role of Inflammation

    Directory of Open Access Journals (Sweden)

    T. M. Haverman

    2014-01-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is widely used as a potentially curative treatment for patients with various hematological malignancies, bone marrow failure syndromes, and congenital immune deficiencies. The prevalence of oral complications in both autologous and allogeneic HSCT recipients remains high, despite advances in transplant medicine and in supportive care. Frequently encountered oral complications include mucositis, infections, oral dryness, taste changes, and graft versus host disease in allogeneic HSCT. Oral complications are associated with substantial morbidity and in some cases with increased mortality and may significantly affect quality of life, even many years after HSCT. Inflammatory processes are key in the pathobiology of most oral complications in HSCT recipients. This review article will discuss frequently encountered oral complications associated with HSCT focusing on the inflammatory pathways and inflammatory mediators involved in their pathogenesis.

  16. Prolonged Shedding of Human Coronavirus in Hematopoietic Cell Transplant Recipients: Risk Factors and Viral Genome Evolution.

    Science.gov (United States)

    Ogimi, Chikara; Greninger, Alexander L; Waghmare, Alpana A; Kuypers, Jane M; Shean, Ryan C; Xie, Hu; Leisenring, Wendy M; Stevens-Ayers, Terry L; Jerome, Keith R; Englund, Janet A; Boeckh, Michael

    2017-07-15

    Recent data suggest that human coronavirus (HCoV) pneumonia is associated with significant mortality in hematopoietic cell transplant (HCT) recipients. Investigation of risk factors for prolonged shedding and intrahost genome evolution may provide critical information for development of novel therapeutics. We retrospectively reviewed HCT recipients with HCoV detected in nasal samples by polymerase chain reaction (PCR). HCoV strains were identified using strain-specific PCR. Shedding duration was defined as time between first positive and first negative sample. Logistic regression analyses were performed to evaluate factors for prolonged shedding (≥21 days). Metagenomic next-generation sequencing (mNGS) was conducted when ≥4 samples with cycle threshold values of Genome changes were consistent with the expected molecular clock of HCoV. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  17. Sleep disruption in hematopoietic cell transplantation recipients: prevalence, severity, and clinical management.

    Science.gov (United States)

    Jim, Heather S L; Evans, Bryan; Jeong, Jiyeon M; Gonzalez, Brian D; Johnston, Laura; Nelson, Ashley M; Kesler, Shelli; Phillips, Kristin M; Barata, Anna; Pidala, Joseph; Palesh, Oxana

    2014-10-01

    Sleep disruption is common among hematopoietic cell transplant (HCT) recipients, with over 50% of recipients experiencing sleep disruption pre-transplant, with up to 82% of patients experiencing moderate to severe sleep disruption during hospitalization for transplant and up to 43% after transplant. These rates of sleep disruption are substantially higher than what we see in the general population. Although sleep disruption can be distressing to patients and contribute to diminished quality of life, it is rarely discussed during clinical visits. The goal of the current review is to draw attention to sleep disruption and disorders (ie, insomnia, obstructive sleep apnea, restless legs syndrome) as a clinical problem in HCT in order to facilitate patient education, intervention, and research. We identified 35 observational studies published in the past decade that examined sleep disruption or disorders in HCT. Most studies utilized a single item measure of sleep, had small sample size, and included heterogeneous samples of patients. Six studies of the effects of psychosocial and exercise interventions on sleep in HCT have reported no significant improvements. These results highlight the need for rigorous observational and interventional studies of sleep disruption and disorders in HCT recipients.. Copyright © 2014 American Society for Blood and Marrow Transplantation. All rights reserved.

  18. Source, pattern and antibiotic resistance of blood stream infections in hematopoietic stem cell transplant recipients

    International Nuclear Information System (INIS)

    El-Mahallawy, H.; Samir, I.; Kadry, D.; Abdel Fattah, R.; El-Kholy, A.

    2014-01-01

    Mucositis developing as a result of myelo-ablative high dose therapy administered prior to hematopoietic stem cell transplantation (HSCT) is associated with the risk of bacteremia. The aim of the present study was to detect the pattern of bacteremia coinciding with the present practice of HSCT, to study the contribution of health-care associated infection (HAI) to the pattern of infection, in the context of the problem of antibiotic resistance in HSCT recipients. Patients and methods: This is a retrospective, single center study including patients who developed febrile neutropenia (FN) among HSCT recipients in one year duration. Results: Ninety FN episodes were recorded in 50 patients. Out of 39 positive blood cultures, Gram negative rods (GNR) were the predominant pathogens, constituting 67% (n =26) of isolated organisms, while 33% of infections were caused by gram positive cocci (GPC) (n= 13). Bacteremia was significantly associated with central venous line (CVL) infections and gastroenteritis (diarrhea and vomiting) with a p-value 0.024, 0.20 and 0.0001, respectively. Multi-drug resistant organisms (MDROs) were identified in 27 (69%) of the 39 positive blood cultures. Conclusion: In one year duration, gram negative pathogens were the predominant causes of infection in HSCT recipients with high rates of MDROs in our institution. Gastroenteritis and central venous line infections are the main sources of bacteremia

  19. Inspiratory muscle training in allogeneic hematopoietic stem cell transplantation recipients: a randomized controlled trial.

    Science.gov (United States)

    Barğı, Gülşah; Güçlü, Meral Boşnak; Arıbaş, Zeynep; Akı, Şahika Zeynep; Sucak, Gülsan Türköz

    2016-02-01

    Respiratory muscles are known to be weakened and are a cause of reduced exercise capacity in both recipients and candidates of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Effects of inspiratory muscle training (IMT) in this patient population have not been comprehensively investigated so far. The current study was planned to investigate the effects of IMT during allo-HSCT on early transplantation-related outcomes. This is a prospective, randomized controlled, double-blinded study. Thirty-eight allo-HSCT recipients, 20 of whom were allocated to the treatment group (40 % of maximal inspiratory pressure (MIP)) and 18 to the control group (5 % of MIP), received IMT for 6 weeks. Pulmonary functions, dyspnea, respiratory (MIP, maximal expiratory pressure (MEP)) and peripheral muscle strength, maximal exercise capacity using modified incremental shuttle walking test (MISWT) and submaximal exercise capacity using 6-min walking test (6-MWT), fatigue, depression, and quality of life were evaluated before and after IMT. The distance covered during MISWT (61.94 m) and 6-MWT (29.30 m), respiratory muscle strength (MIP 34.99 cmH2O, MEP 12.69 cmH2O), depression (-0.95), and modified Borg dyspnea scores (-0.11) showed a significant improvement in the treatment group compared to controls (p ≤ 0.05). Inspiratory muscle training is a safe and effective intervention which improves respiratory muscle strength and exercise capacity and decreases depression and dyspnea in allo-HSCT recipients. These positive changes might be further enhanced by prolonging the duration of training or inclusion of more recipients with inspiratory muscle weakness. NCT02270346.

  20. Recipient-donor KIR ligand matching prevents CMV reactivation post-haploidentical T cell-replete transplantation.

    Science.gov (United States)

    Zhao, Xiang-Yu; Luo, Xue-Yi; Yu, Xing-Xing; Zhao, Xiao-Su; Han, Ting-Ting; Chang, Ying-Jun; Huo, Ming-Rui; Xu, Lan-Ping; Zhang, Xiao-Hui; Liu, Kai-Yan; Li, Dan; Jiang, Zheng-Fan; Huang, Xiao-Jun

    2017-06-01

    Licensed natural killer (NK) cells have been demonstrated to have anti-cytomegalovirus (CMV) activity. We prospectively analysed the human leucocyte antigen typing of donor-recipient pairs and the killer cell immunoglobulin-like receptor (KIR) typing of donors for 180 leukaemia patients to assess the predictive roles of licensed NK cells on CMV reactivation post-T-cell-replete haploidentical stem cell transplantation. Multivariate analysis showed that donor-recipient KIR ligand graft-versus-host or host-versus-graft direction mismatch was associated with increased refractory CMV infection (Hazard ratio = 2·556, 95% confidence interval, 1·377-4·744, P = 0·003) post-transplantation. Donor-recipient KIR ligand matching decreased CMV reactivation [51·65% (46·67, 56·62%) vs. 75·28% (70·87, 79·69%), P = 0·012], refractory CMV infection [17·58% (13·77, 21·40%) vs. 35·96% (31·09, 40·82%), P = 0·004] and CMV disease [3·30% (1·51, 5·08%) vs. 11·24% (8·04, 14·43%), P = 0·024] by day 100 post-transplantation. In addition, the percentage of γ-interferon expression on donor-derived NK cells was significantly higher in the recipients among the recipient-donor pairs with a KIR ligand match compared with that in the recipients among the pairs with a KIR ligand graft-versus-host or host-versus-graft direction mismatch on days 30 and 100 post-transplantation (P = 0·036 and 0·047, respectively). These findings have suggested that donor-recipient KIR ligand matching might promote the NK cell licensing process, thereby increasing NK cell-mediated protection against CMV reactivation. © 2017 John Wiley & Sons Ltd.

  1. Basic oral care for hematology–oncology patients and hematopoietic stem cell transplantation recipients

    DEFF Research Database (Denmark)

    Elad, Sharon; Raber-Durlacher, Judith E; Brennan, Michael T

    2015-01-01

    PURPOSE: Hematology-oncology patients undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT) recipients are at risk for oral complications which may cause significant morbidity and a potential risk of mortality. This emphasizes the importance of basic oral care prior to, during...... and following chemotherapy/HSCT. While scientific evidence is available to support some of the clinical practices used to manage the oral complications, expert opinion is needed to shape the current optimal protocols. METHODS: This position paper was developed by members of the Oral Care Study Group...

  2. A non-fatal case of invasive zygomycete (Lichtheimia corymbifera) infection in an allogeneic haematopoietic cell transplant recipient

    DEFF Research Database (Denmark)

    Eickhardt, Steffen; Braendstrup, Peter; Clasen-Linde, Erik

    2013-01-01

    Post-transplant infections in allogeneic haematopoietic cell transplant (allo-HCT) recipients often have severe consequences. This is especially the case when dealing with zygomycete infections where the result is often fatal. A major problem when dealing with zygomycete infections is the need...... for an accurate and fast diagnosis as the phylum is highly resistant towards the conventional antifungals. We herein describe a non-fatal case of Lichtheimia corymbifera infection in an allo-HCT recipient....

  3. Recipient bone marrow-derived stromal cells prolong graft survival in a rat hind limb allotransplantation model.

    Science.gov (United States)

    Ikeguchi, Ryosuke; Kakinoki, Ryosuke; Ohta, Souichi; Oda, Hiroki; Yurie, Hirofumi; Kaizawa, Yukitoshi; Mitsui, Hiroto; Aoyama, Tomoki; Toguchida, Junya; Matsuda, Shuichi

    2017-09-01

    Recent studies have indicated that bone marrow-derived stromal cells (BMSCs) have immunomodulatory properties that suppress the T cell responses that cause graft rejection. The purpose of this study is to evaluate the effect of recipient BMSCs intravenous infusion for immunomodulation in a rat vascularized composite allotransplantation model. A total of nine Wistar (WIS) rats and thirty Lewis (LEW) rats were used. BMSCs were harvested from three LEW rats. Twenty-four LEW rats were used as recipients and divided randomly into four groups: BMSC group, FK group, UT group, and Iso group. In the BMSC group, orthotopic rat hind limb transplantation was performed between WIS donor and LEW recipient rats. Recipient rats were injected intravenously with 2 × 10 6 recipient BMSCs on day 6, and with 0.2 mg/kg/day tacrolimus administered over 7 days (n = 6). In the FK group, recipient rats were treated with tacrolimus alone (n = 6). Rats in the UT group received no immunosuppressive treatment (n = 6). In the Iso group, transplantation was performed from three LEW donor rats to six LEW recipient rats without any immunosuppressive treatment (n = 6). Graft survival was assessed by daily inspection and histology. The immunological reactions of recipients were also evaluated. The graft survival of recipient rats in the BMSC group (24.5 days) was significantly prolonged in comparison with that of the FK group (18 days) (P Recipient rats in the BMSC group had significantly reduced serum IFN-γ cytokine levels (1.571 ± 0.779 pg/ml) in comparison with that of the FK group (7.059 ± 1.522 pg/ml) (P = .001). In in vitro study, BMSCs induce T cell hyporesponsiveness in a mixed lymphocyte reaction. BMSCs induce T cell hyporesponsiveness and prolong graft survival in the rat vascularized composite allotransplantation model. BMSCs exhibit immunomodulatory properties against acute rejection that can be realized without the need for significant recipient

  4. Primary mediastinal large B-cell lymphoma arising from thyroid in a renal recipient with Hashimoto’s thyroiditis

    OpenAIRE

    Wu, Fang; Qu, Lu; Li, Dai-Qiang; Hu, Chun-Hong

    2015-01-01

    Primary mediastinal large B-cell lymphoma is a subtype of diffuse large B-cell lymphoma, arising in the mediastinum from putative thymic B-cell origin with distinctive clinical and genetic features. Generally, primary mediastinal large B-cell lymphoma is believed as only deriving in the mediastinum. The current study presents a rare case of primary mediastinal large B-cell lymphoma which arising from thyroid in a renal recipient with Hashimoto’s thyroiditis. Moreover, we devoted a discussion ...

  5. Eliminating Hairy Cell Leukemia Minimal Residual Disease

    Science.gov (United States)

    In this trial, patients with hairy cell leukemia who have disease-related symptoms that require treatment will be randomly assigned to receive cladribine with either concurrent rituximab or rituximab at least 6 months after completing cladribine therapy.

  6. T cell repertoire expression in murine recipients of bone marrow transplant after LF 08-0299 (Tresperimus) administration.

    Science.gov (United States)

    Annat, J; Dutartre, P

    1998-12-01

    LF 08-0299 (Tresperimus), a novel immunosuppressive compound, has been previously shown to prevent graft-versus-host disease in murine models. In this study, we investigated the influence of LF 08-0299 on the TCR Vbeta repertoire of irradiated F1 recipient mice reconstituted with either syngeneic or parental bone marrow cells. We showed that a partial blockade of thymic differentiation occurred in normal mice under treatment at the transition CD4-/CD8- to CD4+/CD8+, and that this blockade was fully reversible. Despite the effect on the thymus, normal T cell repertoire negative selection was preserved following syngeneic bone marrow transplantation. We further assessed whether LF 08-0299 administration could modify Vbeta T cell expression in irradiated recipients reconstituted with parental bone marrow cells. In our murine parental to F1 transplant model, abnormal TCR Vbeta3, Vbeta5, Vbeta6 and Vbeta11 expression was demonstrated in peripheral lymph nodes of irradiated recipients. Moreover, Vbeta6 and Vbeta3 T cell populations were overexpressed. Administration of LF 08-0299 modified the pattern of Vbeta T cell expression. The expansion of Vbeta6 T cells was selectively inhibited under LF 08-0299 therapy and, in contrast, Vbeta5 T cells were overexpressed. Lymph node histological analysis showed that LF 08-0299 administration fully prevented the graft-versus-host reaction occurring in untreated recipient mice.

  7. Quantitative proteomics reveals differential regulation of protein expression in recipient myocardium after trilineage cardiovascular cell transplantation

    Science.gov (United States)

    Chang, Ying-Hua; Ye, Lei; Cai, Wenxuan; Lee, Yoonkyu; Guner, Huseyin; Lee, Youngsook; Kamp, Timothy J.; Zhang, Jianyi; Ge, Ying

    2015-01-01

    Intramyocardial transplantation of cardiomyocytes (CMs), endothelial cells (ECs), and smooth muscle cells (SMCs) derived from human induced pluripotent stem cells (hiPSCs) has beneficial effects on the post-infarction heart. However, the mechanisms underlying the functional improvements remain undefined. We employed large-scale label-free quantitative proteomics to identify proteins that were differentially regulated following cellular transplantation in a swine model of myocardial infarction (MI). We identified 22 proteins that were significantly up-regulated after trilineage cell transplantation compared to both MI and Sham groups. Among them, 12 proteins, including adenylyl cyclase-associated protein 1 and tropomodulin-1, are associated with positive regulation of muscular contraction whereas 11 proteins, such as desmoplakin and zyxin, are involved in embryonic and muscular development and regeneration. Moreover, we identified 21 proteins up-regulated and another 21 down-regulated in MI, but reversed after trilineage cell transplantation. Proteins up-regulated after MI but reversed by transplantation are related to fibrosis and apoptosis. Conversely, proteins down-regulated in MI but restored after cell therapy are regulators of protein nitrosylation. Our results show that the functionally beneficial effects of trilineage cell therapy are accompanied by differential regulation of protein expression in the recipient myocardium, which may contribute to the improved cardiac function. PMID:26033914

  8. Diagnosis and treatment of fungal infections in allogeneic stem cell and solid organ transplant recipients.

    Science.gov (United States)

    Vehreschild, Jörg J; Rüping, Maria J G T; Steinbach, Angela; Cornely, Oliver A

    2010-01-01

    Invasive fungal diseases (IFD) are severe complications in patients receiving immunosuppression after solid organ or allogeneic stem cell transplantation. Extensive study has been conducted on therapeutic strategies for IFD in neutropenic patients, mostly those with hematological malignancy. There is an ongoing discussion on whether these studies may be applied to transplant patients as well. We have reviewed relevant literature on transplantation and clinical mycology of the last 20 years and selected articles relevant for today's treatment decisions. This article reports on the epidemiology of IFD in transplant recipients and current antifungal drugs in the context of tansplantation medicine. For invasive aspergillosis and invasive candidiasis, we give a detailed report of current clinical evidence. This review is intended as a quick-start for clinicians and other care providers new to transplant care and as an update for experienced transplant physicians. In a field in which evidence is scarce and conflicting, we provide evidence-based strategies for diagnosing and treating the most relevant IFD in transplant recipients. Physicians treating transplant patients should maintain a high level of awareness towards IFD. They should know the local epidemiology of IFD to make the optimal decision between current diagnostic and therapeutic strategies. Prophylaxis or early treatment should be considered given the high mortality of IFD.

  9. Correlation and Agreement of Handheld Spirometry with Laboratory Spirometry in Allogeneic Hematopoietic Cell Transplant Recipients.

    Science.gov (United States)

    Cheng, Guang-Shing; Campbell, Angela P; Xie, Hu; Stednick, Zach; Callais, Cheryl; Leisenring, Wendy M; Englund, Janet A; Chien, Jason W; Boeckh, Michael

    2016-05-01

    Early detection of subclinical lung function decline may help identify allogeneic hematopoietic cell transplant (HCT) recipients who are at increased risk for late noninfectious pulmonary complications, including bronchiolitis obliterans syndrome. We evaluated the use of handheld spirometry in this population. Allogeneic HCT recipients enrolled in a single-center observational trial performed weekly spirometry with a handheld spirometer for 1 year after transplantation. Participants performed pulmonary function tests in an outpatient laboratory setting at 3 time points: before transplantation, at day 80 after transplantation, and at 1 year after transplantation. Correlation between the 2 methods was assessed by Pearson and Spearman correlations; agreement was assessed using Bland-Altman plots. A total of 437 subjects had evaluable pulmonary function tests. Correlation for forced expiratory volume in 1 second (FEV1) was r = .954 (P spirometry correlated well with laboratory spirometry after allogeneic HCT and may be useful for self-monitoring of patients for early identification of airflow obstruction. Copyright © 2016 American Society for Blood and Marrow Transplantation. All rights reserved.

  10. How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients

    Science.gov (United States)

    El Chaer, Firas; Shah, Dimpy P.

    2016-01-01

    Cytomegalovirus (CMV) infection is a significant complication in hematopoietic cell transplantation (HCT) recipients. Four antiviral drugs are used for preventing or treating CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. With prolonged and repeated use of these drugs, CMV can become resistant to standard therapy, resulting in increased morbidity and mortality, especially in HCT recipients. Antiviral drug resistance should be suspected when CMV viremia (DNAemia or antigenemia) fails to improve or continue to increase after 2 weeks of appropriately dosed and delivered antiviral therapy. CMV resistance is diagnosed by detecting specific genetic mutations. UL97 mutations confer resistance to ganciclovir and valganciclovir, and a UL54 mutation confers multidrug resistance. Risk factors for resistance include prolonged or previous anti-CMV drug exposure or inadequate dosing, absorption, or bioavailability. Host risk factors include type of HCT and degree of immunosuppression. Depending on the genotyping results, multiple strategies can be adopted to treat resistant CMV infections, albeit no randomized clinical trials exist so far, after reducing immunosuppression (if possible): ganciclovir dose escalation, ganciclovir and foscarnet combination, and adjunct therapy such as CMV-specific cytotoxic T-lymphocyte infusions. Novel therapies such as maribavir, brincidofovir, and letermovir should be further studied for treatment of resistant CMV. PMID:27760756

  11. Bacterial meningitis in hematopoietic stem cell transplant recipients: a population-based prospective study.

    Science.gov (United States)

    van Veen, K E B; Brouwer, M C; van der Ende, A; van de Beek, D

    2016-11-01

    We performed a nationwide prospective cohort study on the epidemiology and clinical features of community-acquired bacterial meningitis. Patients with a medical history of autologous or allogeneic hematopoietic stem cell transplantation (HSCT) were identified from the cohort performed from March 2006 to October 2014. Fourteen of 1449 episodes (1.0%) of bacterial meningitis occurred in patients with a history of HSCT. The incidence of bacterial meningitis in HSCT recipients was 40.4 per 100 000 patients per year (95% confidence interval (CI) 23.9-62.2), which is 30-fold (95% CI 18-51; Pmeningitis were infected with a serotype included in the 23-valent pneumococcal polysaccharide vaccine, of whom four developed meningitis despite vaccination. In conclusion, HSCT recipients have a substantially increased risk compared with the general population of acquiring bacterial meningitis, which is mostly due to S. pneumoniae, and disease is associated with high mortality and morbidity. Vaccination is important to prevent disease although vaccine failures did occur.

  12. Feasibility of Using Electrocochleography for Objective Estimation of Electro-Acoustic Interactions in Cochlear Implant Recipients with Residual Hearing.

    Science.gov (United States)

    Koka, Kanthaiah; Litvak, Leonid M

    2017-01-01

    Although cochlear implants (CI) traditionally have been used to treat individuals with bilateral profound sensorineural hearing loss, a recent trend is to implant individuals with residual low-frequency hearing. Patients who retain some residual acoustic hearing after surgery often can benefit from electro-acoustic stimulation (EAS) technologies, which combine conventional acoustic amplification with electrical stimulation. However, interactions between acoustic and electrical stimulation may affect outcomes adversely and are time-consuming and difficult to assess behaviorally. This study demonstrated the feasibility of using the Advanced Bionics HiRes90K Advantage implant electronics and HiFocus Mid Scala/1j electrode to measure electrocochleography (ECochG) responses in the presence of electrical stimulation to provide an objective estimate of peripheral physiologic EAS interactions. In general, electrical stimulation reduced ECochG response amplitudes to acoustic stimulation. The degree of peripheral EAS interaction varied as a function of acoustic pure tone frequency and the intra-cochlear location of the electrically stimulated electrode. Further development of this technique may serve to guide and optimize clinical EAS system fittings in the future.

  13. Coinfection with Human Cytomegalovirus Genetic Variants in Transplant Recipients and Its Impact on Antiviral T Cell Immune Reconstitution.

    Science.gov (United States)

    Smith, Corey; Brennan, Rebekah M; Tey, Siok-Keen; Smyth, Mark J; Burrows, Scott R; Miles, John J; Hill, Geoffrey R; Khanna, Rajiv

    2016-08-15

    Reconstitution of T cell immunity is absolutely critical for the effective control of virus-associated infectious complications in hematopoietic stem cell transplant (HSCT) recipients. Coinfection with genetic variants of human cytomegalovirus (CMV) in transplant recipients has been linked to clinical disease manifestation; however, how these genetic variants impact T cell immune reconstitution remains poorly understood. In this study, we have evaluated dynamic changes in the emergence of genetic variants of CMV in HSCT recipients and correlated these changes with reconstitution of antiviral T cell responses. In an analysis of single nucleotide polymorphisms within sequences encoding HLA class I-restricted CMV epitopes from the immediate early 1 gene of CMV, coinfection with genetically distinct variants of CMV was detected in 52% of patients. However, in spite of exposure to multiple viral variants, the T cell responses in these patients were preferentially directed to a limited repertoire of HLA class I-restricted CMV epitopes, either conserved, variant, or cross-reactive. More importantly, we also demonstrate that long-term control of CMV infection after HSCT is primarily mediated through the efficient induction of stable antiviral T cell immunity irrespective of the nature of the antigenic target. These observations provide important insights for the future design of antiviral T cell-based immunotherapeutic strategies for transplant recipients, emphasizing the critical impact of robust immune reconstitution on efficient control of viral infection. Infection and disease caused by human cytomegalovirus (CMV) remain a significant burden in patients undergoing hematopoietic stem cell transplantation (HSCT). The establishment of efficient immunological control, primarily mediated by cytotoxic T cells, plays a critical role in preventing CMV-associated disease in transplant recipients. Recent studies have also begun to investigate the impact genetic variation in CMV

  14. Microbiology and epidemiology of oral yeast colonization in hemopoietic progenitor cell transplant recipients.

    Science.gov (United States)

    Westbrook, Steven D; Kirkpatrick, William R; Wiederhold, Nathan P; Freytes, Cesar O; Toro, Juan J; Patterson, Thomas F; Redding, Spencer W

    2013-03-01

    We monitored the epidemiology and microbiology of oral yeast colonization in patients undergoing hemopoietic progenitor cell transplantation (HPCT) to examine associations between yeast colonization and oral mucositis. One hundred twenty-one consecutive HPCT patients were sampled for oral yeasts prior to fluconazole (FLC) prophylaxis, at transplantation, and weekly until discharge. Clinical oral mucositis screenings were performed triweekly. Yeast colonization was evident at 216 of 510 total visits. Candida albicans and Candida glabrata were the predominant organisms. Eight patients showed elevated minimal inhibitory concentrations to FLC. One patient developed fungal septicemia. Patients with oral mucositis assessment scale scores oral yeasts in HPCT recipients. FLC-resistant yeasts do emerge and can be the source of fungal sepsis. A positive association was not shown between yeast colonization and the presence or severity of oral mucositis. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Prognosis of Allogeneic Haematopoietic Stem Cell Recipients Admitted to the Intensive Care Unit

    DEFF Research Database (Denmark)

    Lindgaard, Sidsel Christy; Nielsen, Jonas; Lindmark, Anders

    2016-01-01

    BACKGROUND: Allogeneic haematopoietic stem cell transplantation (HSCT) is a procedure with inherent complications and intensive care may be necessary. We evaluated the short- and long-term outcomes of the HSCT recipients requiring admission to the intensive care unit (ICU). METHODS: We...... ventilation had a statistically significant effect on in-ICU (p = 0.02), 6-month (p = 0.049) and 1-year (p = 0.014) mortality. Renal replacement therapy also had a statistically significant effect on in-hospital (p = 0.038) and 6-month (p = 0.026) mortality. Short ICU admissions, i.e. ... to the ICU was confirmed in our study. Mechanical ventilation, renal replacement therapy and an ICU admission of ≥10 days were each risk factors for mortality in the first year after ICU admission....

  16. A non-fatal case of invasive zygomycete (Lichtheimia corymbifera) infection in an allogeneic haematopoietic cell transplant recipient.

    Science.gov (United States)

    Eickhardt, Steffen; Braendstrup, Peter; Clasen-Linde, Erik; Jensen, Karl E; Alhede, Morten; Bjarnsholt, Thomas; Høiby, Niels; Vindeløv, Lars; Moser, Claus

    2013-05-01

    Post-transplant infections in allogeneic haematopoietic cell transplant (allo-HCT) recipients often have severe consequences. This is especially the case when dealing with zygomycete infections where the result is often fatal. A major problem when dealing with zygomycete infections is the need for an accurate and fast diagnosis as the phylum is highly resistant towards the conventional antifungals. We herein describe a non-fatal case of Lichtheimia corymbifera infection in an allo-HCT recipient. © 2012 The Authors APMIS © 2012 APMIS.

  17. Renal pathology in hematopoietic cell transplant recipients: a contemporary biopsy, nephrectomy, and autopsy series.

    Science.gov (United States)

    Brinkerhoff, Brian T; Houghton, Donald C; Troxell, Megan L

    2016-06-01

    Renal injury in hematopoietic cell transplant recipients may be related to a combination of factors including chemotherapy, radiation, infection, immunosuppressive agents, ischemia, and graft-versus-host disease, and can involve glomerular, tubulointerstitial, and vascular structures. We reviewed renal pathology from 67 patients at a single institution (2009-2014), including 14 patients with biopsy for clinical dysfunction, 6 patients with surgical kidney resection for other causes, and 47 autopsy patients. Kidney specimens frequently contained multiple histopathologic abnormalities. Thrombotic microangiopathy, membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis were the most common glomerular findings. Pathologies not previously reported in the hematopoietic cell transplant setting included collapsing glomerulopathy, antiglomerular basement membrane disease, fibrillary glomerulonephritis, and in the case of two surgical resections distinctive cellular segmental glomerular lesions that defied classification. Kidney specimens frequently demonstrated acute tubular injury, interstitial fibrosis, arteriolar hyaline, and arteriosclerosis. Other kidney findings at autopsy included leukemia and amyloid (both recurrent), diabetic nephropathy, bacterial infection, fungal invasion, and silver deposition along glomerular and tubular basement membranes. Also in the autopsy cohort, C4d immunohistochemistry demonstrated unexpected membranous nephropathy in two patients, yet C4d also colocalized with arteriolar hyaline. This retrospective hematopoietic cell transplant cohort illustrates multifaceted renal injury in patients with renal dysfunction, as well as in patients without clinically recognized kidney injury.

  18. Sequence typing of adenovirus from samples from hematological stem cell transplant recipients.

    Science.gov (United States)

    Al Qurashi, Yasir Mohammed A; Guiver, Malcolm; Cooper, Robert J

    2011-11-01

    Adenovirus infections are usually mild or even asymptomatic, but infections with the virus are being recognized increasingly as a major cause of mortality and morbidity in the immunocompromised, particularly hematological stem cell transplant patients where infections can be life threatening and mortality may reach 60%. Typing by sequencing the HVR7 region of the hexon was established and validated using 60 isolates of different serotypes from the six of the seven species which had been typed previously by serum neutralization. Analysis of nucleotide sequences was used to type 227 samples from 41 hematological stem cell transplant recipients. Types from six species were detected but species C types were detected in 51.4% and species A in 34.3% of patients. Seven patients were infected with different adenovirus types sequentially and a further six patients had evidence of simultaneous multiple infections. Many of the sequences had several differences from the prototype strains which will allow tracing of outbreaks and provide evidence for cross-infection in a hospital setting. In this study, the phylogenetic analysis of adenovirus sequences from hematological stem cell transplant patients' samples showed evidence of two possible cross-infection incidents involving three and five patients, respectively. Copyright © 2011 Wiley-Liss, Inc.

  19. Y-chromosome status identification suggests a recipient origin of posttransplant non-small cell lung carcinomas: chromogenic in situ hybridization analysis.

    Science.gov (United States)

    Chen, Wei; Brodsky, Sergey V; Zhao, Weiqiang; Otterson, Gregory A; Villalona-Calero, Miguel; Satoskar, Anjali A; Hasan, Ayesha; Pelletier, Ronald; Ivanov, Iouri; Ross, Patrick; Nadasdy, Tibor; Shilo, Konstantin

    2014-05-01

    Owing to the need of lifelong immunosuppression, solid-organ transplant recipients are known to have an increased risk of posttransplant malignancies including lung cancer. Posttransplant neoplastic transformation of donor-derived cells giving rise to hematopoietic malignancies, Kaposi sarcoma, and basal cell carcinoma in nongraft tissues has been reported. The goal of this study was to assess the cell origin (donor versus recipient derived) of posttransplant non-small cell lung carcinomas (NSCLCs) in kidney and heart transplant recipients. An institutional database search identified 2557 kidney and heart transplant recipients in 8 consecutive years. Among this cohort, 20 (0.8%) renal and 18 (0.7%) heart transplant recipients developed NSCLC. The study cohort comprised 6 of 38 NSCLCs arising in donor-recipient sex-mismatched transplant patients. The tumor cell origin was evaluated by chromogenic in situ hybridization with Y-chromosome probe on formalin-fixed, paraffin-embedded tissues. Y-chromosome was identified in 97% ± 1% (range from 92% to 99%) of all types of nucleated cells in male control tissues. In all 5 NSCLCs from male recipients of female donor organ, Y-chromosome was identified in 97% ± 2% (range from 92% to 100%) of tumor cells, statistically equivalent to normal control (P recipient of male kidney. These findings suggest a recipient derivation of NSCLC arising in kidney and heart transplant recipients. A combination of histologic evaluation and chromogenic in situ hybridization with Y-chromosome analysis allows reliable determination of tissue origin in sex-mismatched solid-organ transplant recipients and may aid in management of posttransplant malignancy in such cases. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Reactivation of Hepatitis B Virus in Hematopoietic Stem Cell Transplant Recipients in Japan: Efficacy of Nucleos(tide Analogues for Prevention and Treatment

    Directory of Open Access Journals (Sweden)

    Shingo Nakamoto

    2014-11-01

    Full Text Available We retrospectively reviewed 413 recipients with hematologic malignancies who underwent hematopoietic stem cell transplantation (HSCT between June 1986 and March 2013. Recipients with antibody to hepatitis B core antigen (anti-HBc and/or to hepatitis B surface antigen (anti-HBs were regarded as experiencing previous hepatitis B virus (HBV infection. Clinical data of these recipients were reviewed from medical records. We defined ≥1 log IU/mL increase in serum HBV DNA from nadir as HBV reactivation in hepatitis B surface antigen (HBsAg-positive recipients, and also defined ≥1 log IU/mL increase or re-appearance of HBV DNA and/or HBsAg as HBV reactivation in HBsAg-negative recipients. In 5 HBsAg-positive recipients, 2 recipients initially not administered with nucleos(tide analogues (NUCs experienced HBV reactivation, but finally all 5 were successfully controlled with NUCs. HBV reactivation was observed in 11 (2.7% of 408 HBsAg-negative recipients; 8 of these were treated with NUCs, and fortunately none developed acute liver failure. In 5 (6.0% of 83 anti-HBc and/or anti-HBs-positive recipients, HBV reactivation occurred. None of 157 (0% recipients without HBsAg, anti-HBs or anti-HBc experienced HBV reactivation. In HSCT recipients, HBV reactivation is a common event in HBsAg-positive recipients, or in HBsAg-negative recipients with anti-HBc and/or anti-HBs. Further attention should be paid to HSCT recipients with previous exposure to HBV.

  1. Effect of adrenalectomy on recipients of allogeneic lymphocytes on inactivation of endogenous colony-forming cells in mice

    International Nuclear Information System (INIS)

    Semenkov, V.F.

    1985-01-01

    This paper presents a study of the killer functions of lymph node cells directed against endogenous colony-forming cells in adrenalectomized recipients in a genetic system with one-way incompatibility: parental line - F 1 hybrid. Mice were irradiated with Co 60 gamma rays on the EGO-2 apparatus with dose rate from 200 to 250 R/min. The results were subjected to statistical analysis by Student's test. It can be tentatively suggested that the killer action of T lymphocytes on endogenous colonies was intensified in adrenal-ectomized recipients with endogenous hypocorticism, as a result of cooperation with the cortisol-sensitive subpopulation of T helper cells, of a change in the properties of the antigen-recognizing receptors, or an increase in the sensitivity of target cells to the killer action of T lymphocytes

  2. In vivo effects of high-dose steroids on nucleic acid content of immunocompetent cells of renal allograft recipients

    International Nuclear Information System (INIS)

    Walle, A.J.; Wong, G.Y.; Suthanthiran, M.; Rubin, A.L.; Stenzel, K.H.

    1988-01-01

    High-dose steroids administered to renal allograft recipients for treatment of acute graft rejection episodes may affect cell cycle progression of peripheral blood mononuclear (PBM) cells. DNA synthesis and cellular DNA and RNA contents of PBM cells were measured in 8 patients during clinically stable periods, and in another 10 patients both during acute rejection episodes and during 7 days of administration of high-dose steroids. Improved renal function documented successful reversal of the rejection episodes in the 10 patients. Compared with the stable patients, the rejecting patients had higher numbers of cells undergoing clonal expansion--namely, higher proportions of G1-cells and of proliferating, or S, G2, and M (SG2M) cells. Steroid treatment had no acute effects on proportions of G1 or SG2M cells in vivo or on incorporation of 3 H thymidine by PBM cells in vitro. However, cells in the prereplicative compartment of the cell cycle (G0/1 cells) had significantly lower RNA content within 7 days of treatment with high doses of steroids. The results suggest that steroids do not acutely influence the posttranscriptional synthesis and the contents of nucleic acids of cells undergoing clonal expansion in vivo. The prereplicative phase of allogeneically stimulated PBM cells of renal allograft recipients may therefore be the cell cycle phase most sensitive to steroids in vivo

  3. Effectiveness of Visual Methods in Information Procedures for Stem Cell Recipients and Donors

    Directory of Open Access Journals (Sweden)

    Çağla Sarıtürk

    2017-12-01

    Full Text Available Objective: Obtaining informed consent from hematopoietic stem cell recipients and donors is a critical step in the transplantation process. Anxiety may affect their understanding of the provided information. However, use of audiovisual methods may facilitate understanding. In this prospective randomized study, we investigated the effectiveness of using an audiovisual method of providing information to patients and donors in combination with the standard model. Materials and Methods: A 10-min informational animation was prepared for this purpose. In total, 82 participants were randomly assigned to two groups: group 1 received the additional audiovisual information and group 2 received standard information. A 20-item questionnaire was administered to participants at the end of the informational session. Results: A reliability test and factor analysis showed that the questionnaire was reliable and valid. For all participants, the mean overall satisfaction score was 184.8±19.8 (maximum possible score of 200. However, for satisfaction with information about written informed consent, group 1 scored significantly higher than group 2 (p=0.039. Satisfaction level was not affected by age, education level, or differences between the physicians conducting the informative session. Conclusion: This study shows that using audiovisual tools may contribute to a better understanding of the informed consent procedure and potential risks of stem cell transplantation.

  4. Effectiveness of Visual Methods in Information Procedures for Stem Cell Recipients and Donors.

    Science.gov (United States)

    Sarıtürk, Çağla; Gereklioğlu, Çiğdem; Korur, Aslı; Asma, Süheyl; Yeral, Mahmut; Solmaz, Soner; Büyükkurt, Nurhilal; Tepebaşı, Songül; Kozanoğlu, İlknur; Boğa, Can; Özdoğu, Hakan

    2017-12-01

    Obtaining informed consent from hematopoietic stem cell recipients and donors is a critical step in the transplantation process. Anxiety may affect their understanding of the provided information. However, use of audiovisual methods may facilitate understanding. In this prospective randomized study, we investigated the effectiveness of using an audiovisual method of providing information to patients and donors in combination with the standard model. A 10-min informational animation was prepared for this purpose. In total, 82 participants were randomly assigned to two groups: group 1 received the additional audiovisual information and group 2 received standard information. A 20-item questionnaire was administered to participants at the end of the informational session. A reliability test and factor analysis showed that the questionnaire was reliable and valid. For all participants, the mean overall satisfaction score was 184.8±19.8 (maximum possible score of 200). However, for satisfaction with information about written informed consent, group 1 scored significantly higher than group 2 (p=0.039). Satisfaction level was not affected by age, education level, or differences between the physicians conducting the informative session. This study shows that using audiovisual tools may contribute to a better understanding of the informed consent procedure and potential risks of stem cell transplantation.

  5. Depletion of host CCR7(+) dendritic cells prevented donor T cell tissue tropism in anti-CD3-conditioned recipients.

    Science.gov (United States)

    He, Wei; Racine, Jeremy J; Johnston, Heather F; Li, Xiaofan; Li, Nainong; Cassady, Kaniel; Liu, Can; Deng, Ruishu; Martin, Paul; Forman, Stephen; Zeng, Defu

    2014-07-01

    We reported previously that anti-CD3 mAb treatment before hematopoietic cell transplantation (HCT) prevented graft-versus-host disease (GVHD) and preserved graft-versus-leukemia (GVL) effects in mice. These effects were associated with downregulated donor T cell expression of tissue-specific homing and chemokine receptors, marked reduction of donor T cell migration into GVHD target tissues, and deletion of CD103(+) dendritic cells (DCs) in mesenteric lymph nodes (MLN). MLN CD103(+) DCs and peripheral lymph node (PLN) DCs include CCR7(+) and CCR7(-) subsets, but the role of these DC subsets in regulating donor T cell expression of homing and chemokine receptors remain unclear. Here, we show that recipient CCR7(+), but not CCR7(-), DCs in MLN induced donor T cell expression of gut-specific homing and chemokine receptors in a retinoid acid-dependent manner. CCR7 regulated activated DC migration from tissue to draining lymph node, but it was not required for the ability of DCs to induce donor T cell expression of tissue-specific homing and chemokine receptors. Finally, anti-CD3 treatment depleted CCR7(+) but not CCR7(-) DCs by inducing sequential expansion and apoptosis of CCR7(+) DCs in MLN and PLN. Apoptosis of CCR7(+) DCs was associated with DC upregulation of Fas expression and natural killer cell but not T, B, or dendritic cell upregulation of FasL expression in the lymph nodes. These results suggest that depletion of CCR7(+) host-type DCs, with subsequent inhibition of donor T cell migration into GVHD target tissues, can be an effective approach in prevention of acute GVHD and preservation of GVL effects. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  6. Sleep Disruption in Hematopoietic Cell Transplant Recipients: Prevalence, Severity, and Clinical Management

    Science.gov (United States)

    Jim, Heather S.L.; Evans, Bryan; Jeong, Jiyeon M.; Gonzalez, Brian D.; Johnston, Laura; Nelson, Ashley M.; Kesler, Shelli; Phillips, Kristin M.; Barata, Anna; Pidala, Joseph; Palesh, Oxana

    2014-01-01

    Sleep disruption is common among hematopoietic cell transplant (HCT) recipients, with over 50% of patients experiencing sleep disruption pre-transplant, up to 82% experiencing moderate to severe sleep disruption during hospitalization for transplant, and up to 43% in the post-transplant period. These rates of sleep disruption are substantially higher than the general population. Although sleep disruption can be distressing to patients and contribute to diminished quality of life, it is rarely discussed during clinical visits. The goal of the current review is to draw attention to sleep disruption as a clinical problem in HCT in order to facilitate patient education, intervention, and research. The review opens with a discussion of sleep disruption measurement and clinical diagnosis of sleep disorders. An overview of the prevalence, severity, and chronicity of sleep disruption and disorders in patients receiving HCT follows. Current evidence regarding sociodemographic and clinical predictors of sleep disruption and disorders is summarized. The review concludes with suggestions for behavioral and pharmacologic management of sleep disruption and disorders as well as directions for future research. PMID:24747335

  7. Radiobiological studies on target cell populations in murine bone marrow transplantation recipients.

    NARCIS (Netherlands)

    van Os, Ronald Peter

    1994-01-01

    The experiments presented in this thesis were designed to investigate the role of total body irradiation (TBI) in conditioning murine recipients of syngeneic and allogeneic bone marrow transplantation (BMT). ... Zie: Summary

  8. Outcome of Hematopoietic Stem Cell Recipients Who Were Mechanically Ventilated and Admitted to Intensive Care Units

    Directory of Open Access Journals (Sweden)

    Tsung-Ming Yang

    2007-01-01

    Conclusion: The ICU mortality rate of mechanically ventilated HSCT recipients was high. Factors associated with ICU mortality were older age, high APACHE II score, presence of shock, and higher respiratory or heart rate at the time of ICU admission. SLB might provide specific diagnosis in HSCT recipients with unexplained pulmonary infiltrates and aid modification of treatment. [J Formos Med Assoc 2007;106(4:295-301

  9. Bone marrow cells from allogeneic bone marrow chimeras inhibit the generation of cytotoxic lymphocyte responses against both donor and recipient cells

    International Nuclear Information System (INIS)

    Ogasawara, M.; Iwabuchi, K.; Good, R.A.; Onoe, K.

    1988-01-01

    When added to a mixed lymphocyte culture, bone marrow cells suppress the generation of CTL activity against H-2 Ag shared by the BM cells and the stimulator cells. These cells have been referred to as veto cells and are thought to play a role in maintaining self-tolerance. We analyzed the H-2 specificity of the suppression expressed by the veto cells from H-2 incompatible bone marrow chimeras, because lymphocytes of such chimeras had been shown to be tolerant to both donor and recipient Ag when tested by CTL responses. We found that the bone marrow cells of such chimeras which were featured by non-T and non-B cell characteristics inhibited the generation of CTL directed against either donor or recipient Ag, but not against third-party Ag. These observations suggest that in allogeneic chimeras the veto or veto-like cells alter the inhibitory specificity exhibited in the recipient microenvironment and indicate that these cells are directly involved in the induction and maintenance of self-tolerance

  10. Infections caused by Acinetobacter baumannii in recipients of hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Khalid Ahmed Al-Anazi

    2014-07-01

    Full Text Available Acinetobacter baumannii (A. baumannii is a Gram-negative, strictly aerobic, non-fermentative coccobacillus which is widely distributed in nature. Recently, it has emerged as a major cause of health care-associated infections in addition to its capacity to cause community acquired infections. Risk factors for A. baumannii infections and bacteremia in recipients of hematopoietic stem cell transplantation include: severe underlying illness such as hematological malignancy, prolonged use of broad-spectrum antibiotics, invasive instrumentation such as central venous catheters or endotracheal intubation, colonization of respiratory, gastrointestinal or urinary tracts in addition to severe immunosuppression caused by using corticosteroids for treating graft versus host disease. The organism causes a wide spectrum of clinical manifestations, but serious complications such as bacteremia, septic shock, ventilator-associated pneumonia, extensive soft tissue necrosis and rapidly progressive systemic infections that ultimately lead to multiorgan failure and death are prone to occur in severely immunocompromised hosts. The organism is usually resistant to many antimicrobials including penicillins, cephalosporins, trimethoprim-sulfamethoxazole, almost all flouroquinolones and most of the aminoglycosides. The recently increasing resistance to carbapenems, colistin and polymyxins is alarming. Additionally, there are geographic variations in the resistance patterns and several globally and regionally resistant strains have already been described. Successful management of A.baumannii infections depends upon appropriate utilization of antibiotics and strict application of preventive and infection control measures. In uncomplicated infections, the use of a single active beta-lactam may be justified, while definitive treatment of complicated infections in critically ill individuals may require drug combinations such as colistin and rifampicin or colistin and

  11. Prolonged outbreak of adenovirus A31 in allogeneic stem cell transplant recipients.

    Science.gov (United States)

    Swartling, L; Allard, A; Törlen, J; Ljungman, P; Mattsson, J; Sparrelid, E

    2015-12-01

    An outbreak of human adenovirus (HAdV) A31 occurred from December 2011 to March 2012 at the Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital in Sweden. We analyzed the outbreak, the routes of transmission, and report the medical consequences. The medical records of all patients admitted to CAST during the outbreak period were studied. Phylogenetic analysis of the patient HAdV strains was performed by sequencing the hexon gene and the more variable E3 gene. We identified 9 cases of HAdV A31. Hygiene measures were implemented, but transmission continued for 2 months. All 9 patients had been admitted to the ward, but 2 had no connection in time to other known HAdV A31 cases. DNA sequencing of the patient strains strongly suggested nosocomial transmission. Transplantation was postponed and then cancelled in 1 patient, and 5 patients were treated with cidofovir because of high levels of viremia. In 7 patients, concomitant graft-versus-host disease (GVHD) grade II-V complicated the clinical picture, as it was difficult to distinguish symptoms of GVHD from those of HAdV infection. An outbreak of HAdV in HSCT recipients can be difficult to control. Although none of the patients had severe disease, the medical consequences were significant. It is possible that unidentified cases with mild symptoms may have caused continuous transmission at the unit. Regular testing of all patients several weeks beyond the last case identified may be an important measure to control transmission. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Two-year randomized controlled prospective trial converting treatment of stable renal transplant recipients with cutaneous invasive squamous cell carcinomas to sirolimus

    NARCIS (Netherlands)

    Hoogendijk-van den Akker, J.M.; Harden, P.N.; Hoitsma, A.J.; Proby, C.M.; Wolterbeek, R..; Bavinck, J.N.; Fijter, J.W. de

    2013-01-01

    PURPOSE In light of the significant morbidity and mortality of cutaneous invasive squamous cell carcinomas (SCCs) in renal transplant recipients, we investigated whether conversion to sirolimus-based immunosuppression from standard immunosuppression could diminish the recurrence rate of these skin

  13. Application of allogeneic bone marrow cells in view of residual alloreactivity: sirolimus but not cyclosporine evolves tolerogenic properties.

    Directory of Open Access Journals (Sweden)

    Kai Timrott

    Full Text Available Application of bone marrow cells (BMC is a promising strategy for tolerance induction, but usually requires strong depletion of the host immune system. This study evaluates the ability of immunosuppressants to evolve tolerogenic properties of BMC in view of residual alloreactivity.The rat model used a major histocompatibility complex (MHC class II disparate bone marrow transplantation (BMT setting (LEW.1AR1 (RT1auu → LEW.1AR2 (RT1aau. Heart grafts (LEW.1WR1 (RT1uua were disparate for the complete MHC to recipients and for MHC class I to BMC donors. Limited conditioning was performed by total body irradiation of 6 Gy. Cyclosporine (CsA or Sirolimus (Srl were administered for 14 or 28 days. Transplantation of heart grafts (HTx was performed at day 16 or at day 100 after BMT. Chimerism and changes in the T cell pool were detected by flow cytometry.Mixed chimeras accepted HTx indefinitely, although the composition of the regenerated T cell pool was not changed to a basically donor MHC class II haplotype. Non-chimeric animals rejected HTx spontaneously. BMC recipients, who received HTx during T cell recovery at day 16, accepted HTx only after pre-treatment with Srl, although chimerism was lost. CsA pre-treatment led to accelerated HTx rejection as did isolated application of BMC.Srl evolves tolerogenic properties of allogeneic BMC to achieve indefinite acceptance of partly MHC disparate HTx despite residual alloreactivity and in particular loss of chimerism.

  14. Mechanisms of immunological eradication of a syngeneic guinea pig tumor. II. Effect of methotrexate treatment and T cell depletion of the recipient on adoptive immunity

    Energy Technology Data Exchange (ETDEWEB)

    Shu, S.; Fonseca, L.S.; Hunter, J.T.; Rapp, H.J.

    1983-01-01

    The influence of methotrexate on the development of immunity to the line 10 hepatoma was studied in guinea pigs. Chronic methotrexate treatment had no apparent effect on the ability of immune guinea pigs to suppress the growth of inoculated tumor cells. In contrast, the same methotrexate regimen inhibited the development of tumor immunity if started before the 8th day after immunization with a vaccine containing viable line 10 cells admixed with Bacillus Calmette-Guerin (BCG) cell walls. Thus, methotrexate selectively inhibited the afferent limb of the immune response. In adoptive transfer experiments, methotrexate-treated recipient guinea pigs were capable of being passively sensitized with immune spleen cells, indicating that the primary cell-mediated immune response of the recipient was not required for adoptive immunity. The contribution of recipient T cells in adoptive immunity was further investigated in guinea pigs deleted of T cells by thymectomy, irradiation, and bone marrow reconstitution. Despite demonstrable deficiency in T lymphocyte reactions, B animals were fully capable of rejecting tumors after transfer of immune cells. These results suggest that the expression of adoptive immunity was independent of recipient T cell participation. In addition, sublethal irradiation of immune spleen cells prior to adoptive transfer abolished their efficacy. Proliferation of transferred immune cells in the recipient may be essential for expression of adoptive immunity.

  15. Mechanisms of immunological eradication of a syngeneic guinea pig tumor. II. Effect of methotrexate treatment and T cell depletion of the recipient on adoptive immunity

    International Nuclear Information System (INIS)

    Shu, S.; Fonseca, L.S.; Hunter, J.T.; Rapp, H.J.

    1983-01-01

    The influence of methotrexate on the development of immunity to the line 10 hepatoma was studied in guinea pigs. Chronic methotrexate treatment had no apparent effect on the ability of immune guinea pigs to suppress the growth of inoculated tumor cells. In contrast, the same methotrexate regimen inhibited the development of tumor immunity if started before the 8th day after immunization with a vaccine containing viable line 10 cells admixed with Bacillus Calmette-Guerin (BCG) cell walls. Thus, methotrexate selectively inhibited the afferent limb of the immune response. In adoptive transfer experiments, methotrexate-treated recipient guinea pigs were capable of being passively sensitized with immune spleen cells, indicating that the primary cell-mediated immune response of the recipient was not required for adoptive immunity. The contribution of recipient T cells in adoptive immunity was further investigated in guinea pigs deleted of T cells by thymectomy, irradiation, and bone marrow reconstitution. Despite demonstrable deficiency in T lymphocyte reactions, B animals were fully capable of rejecting tumors after transfer of immune cells. These results suggest that the expression of adoptive immunity was independent of recipient T cell participation. In addition, sublethal irradiation of immune spleen cells prior to adoptive transfer abolished their efficacy. Proliferation of transferred immune cells in the recipient may be essential for expression of adoptive immunity

  16. Relationship between Mixed Donor-Recipient Chimerism and Disease Recurrence after Hematopoietic Cell Transplantation for Sickle Cell Disease.

    Science.gov (United States)

    Abraham, Allistair; Hsieh, Matthew; Eapen, Mary; Fitzhugh, Courtney; Carreras, Jeanette; Keesler, Daniel; Guilcher, Gregory; Kamani, Naynesh; Walters, Mark C; Boelens, Jaap J; Tisdale, John; Shenoy, Shalini

    2017-12-01

    Mixed donor chimerism after hematopoietic cell transplantation for sickle cell disease (SCD) can result in resolution of disease symptoms, but symptoms recur when donor chimerism is critically low. The relationship between chimerism, hemoglobin S (HbS) level, and symptomatic disease was correlated retrospectively in 95 patients who had chimerism reports available at day 100 and at 1 and 2 years after transplantation. Recurrent disease was defined as recurrence of vaso-occlusive crises, acute chest syndrome, stroke, and/or HbS levels > 50%. Thirty-five patients maintained full donor chimerism (myeloid or whole blood) through 2 years. Donor chimerism was less than 10% (defined as graft failure) in 13 patients during this period. Mixed chimerism was reported in the remaining 47 patients (range, 10% to 94%). The lowest documented donor chimerism without symptomatic disease was 26%. Of 12 surviving patients with recurrent disease, 2 had recurrence of symptoms before documented graft failure (donor chimerism of 11% and 17%, respectively). Three patients underwent second transplantation for graft failure. None received donor leukocyte infusion to maintain mixed chimerism or prevent graft failure. We conclude stable donor chimerism greater than 25% is associated with resolution of SCD-related symptoms, and HbS levels in transplant recipients should be interpreted in context of the sickle trait status of the donors. Copyright © 2017 The American Society for Blood and Marrow Transplantation. All rights reserved.

  17. Primary mediastinal large B-cell lymphoma arising from thyroid in a renal recipient with Hashimoto's thyroiditis.

    Science.gov (United States)

    Wu, Fang; Qu, Lu; Li, Dai-Qiang; Hu, Chun-Hong

    2015-01-01

    Primary mediastinal large B-cell lymphoma is a subtype of diffuse large B-cell lymphoma, arising in the mediastinum from putative thymic B-cell origin with distinctive clinical and genetic features. Generally, primary mediastinal large B-cell lymphoma is believed as only deriving in the mediastinum. The current study presents a rare case of primary mediastinal large B-cell lymphoma which arising from thyroid in a renal recipient with Hashimoto's thyroiditis. Moreover, we devoted a discussion to the relationship among primary mediastinal large B-cell lymphoma, immunomodulatory therapy and autoimmune diseases. The immunologic derangement induced by long-term immunomodulatory therapy and Hashimoto's thyroiditis may be the possible cause for the ectopic lymphoma.

  18. Clinical Significance of Human Coronavirus in Bronchoalveolar Lavage Samples From Hematopoietic Cell Transplant Recipients and Patients With Hematologic Malignancies.

    Science.gov (United States)

    Ogimi, Chikara; Waghmare, Alpana A; Kuypers, Jane M; Xie, Hu; Yeung, Cecilia C; Leisenring, Wendy M; Seo, Sachiko; Choi, Su-Mi; Jerome, Keith R; Englund, Janet A; Boeckh, Michael

    2017-06-01

    The possible role of human coronavirus (HCoV) in lower respiratory tract disease (LRTD) in hematopoietic cell transplant (HCT) recipients and patients with hematologic malignancies (HM) has not been well studied. We conducted a retrospective review of HCT/HM patients with HCoV detected in bronchoalveolar lavage (BAL). HCoV strains were identified in BAL samples using strain-specific polymerase chain reaction. Mortality rates were compared among HCT recipients with LRTD caused by HCoV, respiratory syncytial virus (RSV), influenza virus, or parainfluenza virus (PIV) by multivariable Cox regression analysis. We identified 35 patients (37 episodes) with HCoV LRTD. Among 23 available BAL samples, 48% were strain OC43, 22% were NL63, 17% were 229E, and 13% were HKU1. Overall, 21 patients (60%) required oxygen therapy at diagnosis and 19 (54%) died within 90 days of diagnosis. Respiratory copathogens were detected in 21 episodes (57%), including viruses (n = 12), fungi (n = 10), and bacteria (n = 8). Mortality rates were not different between patients with and without copathogens (P = .65). In multivariable models, mortality associated with HCoV LRTD was similar to that seen with RSV, influenza, and PIV LRTD in HCT recipients (adjusted hazard ratio, 1.34 [95% confidence interval, .66-2.71], P = .41 vs RSV, adjusted for cell source, cytopenia, copathogens, oxygen use, and steroid use). HCoV LRTD in patients with HCT or HM is associated with high rates of oxygen use and mortality. Mortality associated with HCoV LRTD in HCT recipients appears to be similar to that seen with RSV, influenza virus, and PIV. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com

  19. International travel patterns and travel risks for stem cell transplant recipients.

    Science.gov (United States)

    Mikati, Tarek; Griffin, Kenneth; Lane, Dakotah; Matasar, Matthew; Shah, Monika K

    2015-01-01

    Stem cell transplantation (SCT) is being increasingly utilized for multiple medical illnesses. However, there is limited knowledge about international travel patterns and travel-related illnesses of stem cell transplant recipients (SCTRs). An observational cross-sectional study was conducted among 979 SCTRs at Memorial Sloan Kettering Cancer Center using a previously standardized and validated questionnaire. International travel post SCT, pre-travel health advice, exposure risks, and travel-related illnesses were queried. A total of 516 SCTRs completed the survey (55% response rate); of these, 40% were allogeneic SCTRs. A total of 229 (44.3%) respondents reported international travel outside the United States and Canada post SCT. The international travel incidence was 32% [95% confidence interval CI 28-36] within 2 years after SCT. Using multivariable Cox regression analysis, variables significantly associated with international travel within first 2 years after SCT were history of international travel prior to SCT [hazard ratio (HR) = 5.3, 95% CI 2.3-12.0], autologous SCT (HR = 2.6, 95% CI 1.6-2.8), foreign birth (HR = 2.3, 95% CI 1.5-3.3), and high income (HR = 2.0, 95% CI 1.8-3.7). During their first trip, 64 travelers (28%) had traveled to destinations that may have required vaccination or malaria chemoprophylaxis. Only 56% reported seeking pre-travel health advice. Of those who traveled, 16 travelers (7%) became ill enough to require medical attention during their first trip after SCT. Ill travelers were more likely to have visited high-risk areas (60 vs 26%, p = 0.005), to have had a longer mean trip duration (24 vs 12 days, p = 0.0002), and to have visited friends and relatives (69 vs 21%, p travel was common among SCTRs within 2 years after SCT and was mainly to low-risk destinations. Although the overall incidence of travel-related illnesses was low, certain subgroups of travelers were at a significantly higher risk. Pre

  20. Residual stresses in a co-sintered SOC half-cell during post-sintering cooling

    DEFF Research Database (Denmark)

    Charlas, Benoit; Chatzichristodoulou, Christodoulos; Brodersen, Karen

    2014-01-01

    Due to the thermal expansion mismatch between the layers of a Solid Oxide Cell, residual stresses (thermal stresses) develop during the cooling after sintering. Residual stresses can induce cell curvature for asymmetric cells but more importantly they also result in more fragile cells. Depending...

  1. Quantification of residual host cell DNA in adenoviral vectors produced on PER.C6 cells

    NARCIS (Netherlands)

    Gijsbers, Linda; Koel, Björn; Weggeman, Miranda; Goudsmit, Jaap; Havenga, Menzo; Marzio, Giuseppe

    2005-01-01

    Recombinant adenoviral vectors for gene therapy and vaccination are routinely prepared on cultures of immortalized cells, allowing the production of vector batches of high titer and consistent quality. Quantification of residual DNA from the producing cell line is part of the purity tests for

  2. Predominant or complete recipient T-cell chimerism following alemtuzumab-based allogeneic transplantation is reversed by donor lymphocytes and not associated with graft failure.

    Science.gov (United States)

    Mohamedbhai, Sajir G; Edwards, Noha; Morris, Emma C; Mackinnon, Stephen; Thomson, Kirsty J; Peggs, Karl S

    2012-02-01

    The clinical significance of mixed chimerism following allogeneic haematopoietic stem cell transplantation (HSCT) remains controversial. Its relevance and incidence are probably influenced by the conditioning regimen and incorporation of T-cell depletion. The presence of recipient chimerism levels >40-50% following T-cell replete reduced intensity transplantation correlates with a high risk of graft rejection, regardless of donor-lymphocyte infusions, but it is unclear whether this finding translates to T-cell depleted transplants. We conducted a retrospective single-institution analysis of patients receiving alemtuzumab-based HSCT. 27/152 (18%) evaluable cases had predominantly recipient T-cell chimerism at 3 months or beyond. By contrast, coincident chimerism in the granulocyte lineage was predominantly of donor origin (median 100%) in all but one patient. Donor lymphocyte infusion effectively converted predominantly recipient T-cell chimerism to ful donor chimerism in all evaluable cases including three cases with no detectable donor T cells. The only graft failure occurred in the patient with predominantly recipient myeloid chimerism in whom rejection occurred rapidly before donor lymphocytes could be administered. We conclude that predominant or complete recipient T-cell chimerism following alemtuzumab-based regimens does not have the same clinical implications as that following T-cell replete transplants and can be effectively converted with donor lymphocytes without the need for lympho-depleting agents or re-conditioning. © 2011 Blackwell Publishing Ltd.

  3. Correlation of Pain and Fluoride Concentration in Allogeneic Hematopoietic Stem Cell Transplant Recipients on Voriconazole.

    Science.gov (United States)

    Barajas, Megan R; McCullough, Kristen B; Merten, Julianna A; Dierkhising, Ross A; Bartoo, Gabriel T; Hashmi, Shahrukh K; Hogan, William J; Litzow, Mark R; Patnaik, Mrinal M; Wilson, John W; Wolf, Robert C; Wermers, Robert A

    2016-03-01

    Supportive care guidelines recommend antimold prophylaxis in hematopoietic stem cell transplant (HSCT) recipients deemed to have high risk for invasive fungal infection, leading to long-term use of voriconazole after allogeneic HSCT in patients who remain immunocompromised. Voriconazole has been associated with periostitis, exostoses, and fluoride excess in patients after solid organ transplantation, HSCT, and leukemia therapy. The aims of this study were to describe the frequency and clinical presentation of patients presenting with pain and fluoride excess among allogeneic HSCT patients taking voriconazole, to identify when a plasma fluoride concentration was measured with respect to voriconazole initiation and onset of pain, and to describe the outcomes of patients with fluoride excess in the setting of HSCT. A retrospective review was conducted of all adult allogeneic HSCT patients receiving voriconazole at Mayo Clinic in Rochester, Minnesota, between January 1, 2009 and July 31, 2012. Of 242 patients included, 32 had plasma fluoride measured to explore the etiology of musculoskeletal pain. In 31 patients with fluoride measurement while on voriconazole, 29 (93.5%) had elevated levels. The median plasma fluoride was 11.1 μmol/L (range, 2.4 to 24.7). The median duration of voriconazole was 163 days (range, 2 to 1327). The median time to fluoride measurement was 128 days after voriconazole initiation (range, 28 to 692). At 1 year after the start of voriconazole after HSCT, 15.3% of patients had developed pain associated with voriconazole use and 35.7% developed pain while on voriconazole after 2 years. Of the patients with an elevated fluoride level, 22 discontinued voriconazole; pain resolved or improved in 15, stabilized in 3, and worsened in 4 patients. Ten patients continued voriconazole; pain resolved or improved in 7, was attributable to alternative causes in 2, and undefined in 1. Serum creatinine, estimated glomerular filtration rate, alkaline phosphatase

  4. Molecular profiling of cutaneous squamous cell carcinomas and actinic keratoses from organ transplant recipients

    Directory of Open Access Journals (Sweden)

    Hameetman Liesbeth

    2013-02-01

    Full Text Available Abstract Background The risk of developing cutaneous squamous cell carcinoma (SCC is markedly increased in organ transplant recipients (OTRs compared to the normal population. Next to sun exposure, the immunosuppressive regimen is an important risk factor for the development of SCC in OTRs. Various gene mutations (e.g. TP53 and genetic alterations (e.g. loss of CDKN2A, amplification of RAS have been found in SCCs. The aim of this genome-wide study was to identify pathways and genomic alterations that are consistently involved in the formation of SCCs and their precursor lesions, actinic keratoses (AKs. Methods To perform the analysis in an isogenic background, RNA and DNA were isolated from SCC, AK and normal (unexposed epidermis (NS from each of 13 OTRs. Samples were subjected to genome-wide expression analysis and genome SNP analysis using Illumina’s HumanWG-6 BeadChips and Infinium II HumanHap550 Genotyping BeadChips, respectively. mRNA expression results were verified by quantitative PCR. Results Hierarchical cluster analysis of mRNA expression profiles showed SCC, AK and NS samples to separate into three distinct groups. Several thousand genes were differentially expressed between epidermis, AK and SCC; most upregulated in SCCs were hyperproliferation related genes and stress markers, such as keratin 6 (KRT6, KRT16 and KRT17. Matching to oncogenic pathways revealed activation of downstream targets of RAS and cMYC in SCCs and of NFκB and TNF already in AKs. In contrast to what has been reported previously, genome-wide SNP analysis showed very few copy number variations in AKs and SCCs, and these variations had no apparent relationship with observed changes in mRNA expression profiles. Conclusion Vast differences in gene expression profiles exist between SCC, AK and NS from immunosuppressed OTRs. Moreover, several pathways activated in SCCs were already activated in AKs, confirming the assumption that AKs are the precursor lesions of SCCs

  5. Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T cells and down-regulates cardiac allograft rejection

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, De-Hua [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China); Dou, Li-Ping [Department of Hematology, Chinese PLA General Hospital, No. 28 Fu-Xing Road, Beijing 100853 (China); Wei, Yu-Xiang; Du, Guo-Sheng; Zou, Yi-Ping; Song, Ji-Yong; Zhu, Zhi-Dong; Cai, Ming; Qian, Ye-Yong [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China); Shi, Bing-Yi, E-mail: shibingyi@medmail.com.cn [Organ Transplant Center, Chinese PLA 309th Hospital, No. 17A Hei-Shan-Hu Road, Beijing 100091 (China)

    2010-05-14

    Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-{gamma} by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4{sup +}CD25{sup high}Foxp3{sup +} regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

  6. Uptake of donor lymphocytes treated with 8-methoxypsoralen and ultraviolet A light by recipient dendritic cells induces CD4+CD25+Foxp3+ regulatory T cells and down-regulates cardiac allograft rejection

    International Nuclear Information System (INIS)

    Zheng, De-Hua; Dou, Li-Ping; Wei, Yu-Xiang; Du, Guo-Sheng; Zou, Yi-Ping; Song, Ji-Yong; Zhu, Zhi-Dong; Cai, Ming; Qian, Ye-Yong; Shi, Bing-Yi

    2010-01-01

    Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy and has been demonstrated to be beneficial for graft-vs-host disease and solid-organ allograft rejection. ECP involves reinfusion of a patient's autologous peripheral blood leukocytes treated ex vivo with 8-methoxypsoralen and UVA light radiation (PUVA). Previous studies focused only on ECP treatment of recipient immune cells. Our study is the first to extend the target of ECP treatment to donor immune cells. The results of in vitro co-culture experiments demonstrate uptake of donor PUVA-treated splenic lymphocytes (PUVA-SPs) by recipient immature dendritic cells (DCs). Phagocytosis of donor PUVA-SPs does not stimulate phenotype maturation of recipient DCs. In the same co-culture system, donor PUVA-SPs enhanced production of interleukin-10 and interferon-γ by recipient DCs and impaired the subsequent capability of recipient DCs to stimulate recipient naive T cells. Phagocytosis of donor PUVA-SP (PUVA-SP DCs) by recipient DCs shifted T-cell responses in favor of T helper 2 cells. Infusion of PUVA-SP DCs inhibited cardiac allograft rejection in an antigen-specific manner and induced CD4 + CD25 high Foxp3 + regulatory T cells. In conclusion, PUVA-SP DCs simultaneously deliver the donor antigen and the regulatory signal to the transplant recipient, and thus can be used to develop a novel DC vaccine for negative immune regulation and immune tolerance induction.

  7. Interspecies nuclear transfer using fibroblasts from leopard, tiger, and lion ear piece collected postmortem as donor cells and rabbit oocytes as recipients.

    Science.gov (United States)

    Yelisetti, Uma Mahesh; Komjeti, Suman; Katari, Venu Charan; Sisinthy, Shivaji; Brahmasani, Sambasiva Rao

    2016-06-01

    Skin fibroblast cells were obtained from a small piece of an ear of leopard, lion, and tiger collected postmortem and attempts were made to synchronize the skin fibroblasts at G0/G1 of cell cycle using three different approaches. Efficiency of the approaches was tested following interspecies nuclear transfer with rabbit oocytes as recipient cytoplasm. Fluorescence-activated cell sorting revealed that the proportion of G0/G1 cells increased significantly (P lion, and tiger were successfully synchronized and used for the development of blastocysts using rabbit oocytes as recipient cytoplasm.

  8. NUP98-HOXA10hd-expanded hematopoietic stem cells efficiently reconstitute bone marrow of mismatched recipients and induce tolerance.

    Science.gov (United States)

    Even, Y; Bennett, J L; Sekulovic, S; So, L; Yi, L; McNagny, K; Humphries, R K; Rossi, F M V

    2011-01-01

    Gene therapy as well as methods capable of returning cells to a pluripotent state (iPS) have enabled the correction of genetic deficiencies in syngenic adult progenitors, reducing the need for immunosuppression in cell therapy approaches. However, in diseases involving mutations that lead to the complete lack of a protein, such as Duchenne muscular dystrophy, the main immunogens leading to rejection of transplanted cells are the therapeutic proteins themselves. In these cases even iPS cells would not circumvent the need for immunosuppression, and alternative strategies must be developed. One such potential strategy seeks to induce immune tolerance using hematopoietic stem cells originated from the same donor or iPS line from which the therapeutic progenitors are derived. However, donor hematopoietic stem cells (HSCs) are available in limiting numbers and embryonic stem (ES) cell-derived HSCs engraft poorly in adults. While these limitations have been circumvented by ectopic expression of HOXB4, overexpression of this protein is associated with inefficient lymphoid reconstitution. Here we show that adult HSCs expanded with a NUP98- HOXA10hd fusion protein sustain long-term engraftment in immunologically mismatched recipients and generate normal numbers of lymphoid cells. In addition, NUP98-HOXA10hd-expanded cells induce functional immune tolerance to a subsequent transplant of myogenic progenitors immunologically matched with the transplanted HSCs.

  9. Trans-epithelial immune cell transfer during suckling modulates delayed-type hypersensitivity in recipients as a function of gender.

    Directory of Open Access Journals (Sweden)

    Lisa J Ma

    Full Text Available INTRODUCTION: Breast feeding has long term effects on the developing immune system which outlive passive immunization of the neonate. We have investigated the transfer of milk immune cells and examined the result of transfer once the recipients were adult. METHODS: Non-transgenic mouse pups were foster-nursed by green fluorescent protein (GFP transgenic dams for 3 weeks and the fate of GFP+ cells was followed by FACS analysis, immunohistochemistry and RT-PCR for GFP and appropriate immune cell markers. Pups suckled by non-transgenic dams served as controls. RESULTS: Despite a preponderance of B cells and macrophages in the stomach contents of the pups, most cells undergoing trans-epithelial migration derived from the 3-4% of milk cells positive for T lymphocyte markers. These cells homed to the spleen and thymus, with maximal accumulation at 3-4 weeks. By sensitizing dams with an antigen which elicits a T cell-mediated delayed-type-hypersensitivity (DTH response, we determined that nursing by a sensitized dam (compared to a non-sensitized dam amplified a subsequent DTH response in females and yet suppressed one in males. DISCUSSION: These results suggest that clinical evaluation weighing the pros and cons of nursing male versus female children by mothers with genetically-linked hypersensitivity diseases, such as celiac disease and eczema, or those in regions of the world with endemic DTH-eliciting diseases, such as tuberculosis, may be warranted.

  10. Recipient-derived HPA-1a antibodies: a cause of prolonged thrombocytopenia after unrelated donor stem cell transplantation.

    Science.gov (United States)

    Lucas, Geoff; Culliford, Steven; Green, Frances; Sidra, Gamal; Calvert, Anthony; Green, Ann; Harrison, Penny; Harvey, John; Allen, Dave; Smillie, David; Masurekar, Ashish; Marks, David; Russell, Nigel; Massey, Edwin

    2010-02-01

    Patients with human platelet antigen (HPA) specific antibodies in cases of neonatal alloimmune thrombocytopenia and platelet (PLT) refractoriness derive clinical benefit from the use of HPA-selected PLTs. This study describes three patients with underlying diagnoses of acute myeloid leukemia, chronic lymphocytic leukemia, and myelodysplasia, respectively, who underwent allogeneic bone marrow transplantation (BMT) with unrelated donors matched at the HLA-A, B, C, Dr, and DQ loci but who failed to achieve an adequate PLT count. Investigation using PLT immunofluorescence test, monoclonal antibody immobilization of PLT antigens assay, and genotyping revealed the presence of recipient-derived HPA-1a antibodies. In two patients, anti-HPA-1a was detected post-BMT and in the third patient, anti-HPA-1a was detected during pre-BMT chemotherapy. Despite apparent 100% engraftment of donor cells, the patients' PLT counts failed to recover 9-10 months posttransplant. The patients remained PLT-transfusion dependent and failed to achieve satisfactory increments following random donor or HLA-matched PLT transfusions. After the identification of HPA-1a antibodies, the patients were supported by HPA-1a(-) PLTs and satisfactory posttransfusion PLT increments were obtained. These cases illustrate that HPA-1a antibodies may remain detectable for 10 months following apparently successful donor engraftment and the disappearance of recipient-derived HLA antibodies. The prolonged persistence of recipient-derived PLT-specific antibodies following BMT has to our knowledge not been described previously. HPA-1a antibodies were associated with protracted PLT-transfusion dependence and significant hemorrhagic complications. Appropriate and timely laboratory investigation for HPA-specific antibodies followed by transfusion support with HPA-selected PLTs provided the cornerstone of the hemostatic management in these cases.

  11. Clinical significance of human cytomegalovirus viruria and the effect of antiviral therapy in hematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Wei-Lu; Chen, Su-Jung; Huang, Shiang-Fen; Chan, Yu-Jiun; Wang, Fu-Der; Chen, Hsin-Pai

    2017-09-23

    Cytomegalovirus (CMV) causes life-threatening infections in immunocompromised host. The clinical significance of asymptomatic CMV viruria in patients receiving hematopoietic stem cell transplantation (HSCT) remains unclear. This study aims to clarify whether antiviral therapy is associated with a favorable clinical outcome. HSCT recipients whose urine was culture-positive for CMV were retrospectively reviewed and followed. Viruria episodes were divided according to whether or not antiviral therapy was used. Mortality and the estimated glomerular filtration rate (eGFR) in 2 years following CMV viruria were compared between patients with and without antiviral therapy. Sixty-two episodes of culture-proven asymptomatic CMV viruria were identified in 28 HSCT recipients. Antiviral therapy was used in 35 (56.5%) and spared in 27 (43.5%) viruric episodes. Compared with the baselines, there were no significant difference in the decrements of eGFR between the two groups at the end the 1st year (4.78 vs 5.02 mL/min/1.73 m 2 , p = 0.968) and the 2nd year (1.13 vs 7.66 mL/min/1.73 m 2 , p = 0.276). Antiviral therapy for asymptomatic CMV viruria was also not associated with a favorable survival (p = 0.288). On the other hand, presence of CMV viremia correlated with a poorer survival (2-year mortality rate 60% vs 13.33%, p Antiviral therapy for asymptomatic CMV viruria is not associated with a clear clinical benefit in HSCT recipients. Further studies may be needed to identify if specific patient populations may benefit from antiviral therapy in CMV viruria. Copyright © 2017. Published by Elsevier B.V.

  12. The impact of virus population diversity on the dynamics of cytomegalovirus DNAemia in allogeneic stem cell transplant recipients.

    Science.gov (United States)

    Vinuesa, Víctor; Bracho, María Alma; Albert, Eliseo; Solano, Carlos; Torres-Puente, Manuela; Giménez, Estela; González-Candelas, Fernando; Navarro, David

    2017-10-01

    Mixed cytomegalovirus (CMV) infections are associated with delayed viral clearance in solid organ transplant recipients. We investigated whether this could be extrapolated to allogeneic stem cell transplant (allo-SCT) recipients. A total of 48 plasma specimens, obtained during 29 episodes of active CMV infection in 25 non-consecutive allo-SCT patients, were analysed. Baseline blood specimens, drawn shortly prior to the inception of pre-emptive antiviral therapy (pre-treatment specimen; n=29), as well as follow-up samples obtained either after the initiation of antiviral therapy (post-treatment specimen; n=15) or during recurrent episodes (n=4) were analysed. Plasma CMV DNA loads were quantified by real-time PCR and the CMV genotyping was performed by ultra-deep sequencing of hypervariable regions in the genes coding for glycoproteins N (gN) and O (gO). A trend towards higher CMV DNA peak loads, longer CMV DNAemia episode durations and slower CMV DNAemia decay rates was observed for episodes with mixed CMV genotype populations compared to those caused by single CMV variants, although the differences did not reach statistical significance. The length of the treatment course required to clear DNAemia was significantly longer in these mixed episodes (P=0.002). Significant changes in the number or frequency of CMV gN or gO genetic variants were documented following the initiation of antiviral therapy or in recurrent episodes. CMV diversity may have a major impact on the kinetics of CMV DNAemia clearance during the treatment of active CMV infection episodes in allo-SCT recipients.

  13. Clinical and Microbiological Characteristics of Breakthrough Candidemia in Allogeneic Hematopoietic Stem Cell Transplant Recipients in a Japanese Hospital.

    Science.gov (United States)

    Kimura, Muneyoshi; Araoka, Hideki; Yamamoto, Hisashi; Asano-Mori, Yuki; Nakamura, Shigeki; Yamagoe, Satoshi; Ohno, Hideaki; Miyazaki, Yoshitsugu; Abe, Masahiro; Yuasa, Mitsuhiro; Kaji, Daisuke; Kageyama, Kosei; Nishida, Aya; Ishiwata, Kazuya; Takagi, Shinsuke; Yamamoto, Go; Uchida, Naoyuki; Izutsu, Koji; Wake, Atsushi; Taniguchi, Shuichi; Yoneyama, Akiko

    2017-04-01

    Few data on breakthrough candidemia (BC), defined as candidemia that develops on administration of antifungal agents (AFAs), in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are available. The medical and microbiological records of recipients of an allo-HSCT obtained between December 2008 and December 2014 were reviewed. Of 768 allo-HSCT cases, 26 developed BC. Among the 26 causative strains, 22 strains were stored and identified by sequencing. The following species were isolated: Candida parapsilosis (9 strains), C. glabrata (4 strains), C. guilliermondii (3 strains), and other Candida species (6 strains). The AFAs being used when BC developed were micafungin (17 cases), liposomal amphotericin B (5 cases), itraconazole (2 cases), and voriconazole (2 cases). All 17 cases who developed BC during micafungin administration were administered 150 mg/day of micafungin. The susceptibilities of the causative Candida species to the administered AFAs when breakthrough occurred ranged from susceptible to resistant. Especially, 85% of the Candida species that caused BC during micafungin administration were susceptible to micafungin. Additionally, 75% of the strains were wild type for susceptibility to the administered AFAs when breakthrough occurred. Systemic steroid administration and a longer severe neutropenic phase (≥5 days) were independent risk factors for BC ( P = 0.016 and P = 0.015, respectively). BC developed in allo-HSCT recipients even when they received a sufficient dose of AFA, including micafungin, to which the causative Candida species were susceptible and/or had wild-type susceptibility in vitro Systemic steroid administration and a longer severe neutropenic phase were host-based factors associated with BC. Copyright © 2017 American Society for Microbiology.

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

    Science.gov (United States)

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

    2009-04-30

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

  15. Breakthrough viridans streptococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients receiving levofloxacin prophylaxis in a Japanese hospital.

    Science.gov (United States)

    Kimura, Muneyoshi; Araoka, Hideki; Yoshida, Atsushi; Yamamoto, Hisashi; Abe, Masahiro; Okamoto, Yuki; Yuasa, Mitsuhiro; Kaji, Daisuke; Kageyama, Kosei; Nishida, Aya; Ishiwata, Kazuya; Takagi, Shinsuke; Yamamoto, Go; Asano-Mori, Yuki; Uchida, Naoyuki; Hishinuma, Akira; Izutsu, Koji; Wake, Atsushi; Taniguchi, Shuichi; Yoneyama, Akiko

    2016-08-05

    Breakthrough viridans streptococcal bacteremia (VSB) in patients with hematological malignancy receiving levofloxacin prophylaxis is a major blood stream infection (BSI) occurring during febrile neutropenia. However, clinical data focused on VSB in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are lacking. The medical records of allo-HSCT recipients who received oral levofloxacin prophylaxis between January 2011 and August 2013 at Toranomon Hospital were reviewed to evaluate breakthrough VSB. Stored viridans streptococcal (VGS) species were identified by using sodA gene sequencing, and were assessed for drug susceptibility. Among the 184 allo-HSCT recipients on levofloxacin prophylaxis, 28 (15.2 %) experienced breakthrough VSB. All of the 28 recipients with VSB were treated with a cefepime-based or piperacillin/tazobactam-based regimen. The susceptibility rates of the VGS strains for levofloxacin, cefepime, piperacillin/tazobactam, meropenem, and vancomycin were 0 %, 95 %, 100 %, 100 %, and 100 %, respectively. Both the MIC50 (minimum inhibitory concentration) and the MIC90 of ceftazidim (0.5 μg/mL and 2 μg/mL, respectively) were higher than the MIC90 of all the other anti-pseudomonal beta-lactams (APBLs). Only 1 VGS strain had a penicillin MIC ≥ 2 μg/mL by the Etest (3.6 %). There were no cases with acute respiratory distress syndrome (ARDS) that was associated with VSB, although the rate of viridans group streptococcal shock syndrome was high (26 %). The crude 30-day mortality rate in the VSB group (10.7 %) did not differ significantly from that in the BSI without VSB group (9.3 %) or non-BSI group (7.0 %) (P = 0.77). Also, VSB was not a risk factor for all-cause mortality up to 60 days following allo-HSCT (P = 0.43). APBL with increased anti-VGS activity (APBL-VA) monotherapy would typically be optimal for treating the VGS strains in this setting. Indication of adding an empiric anti-gram-positive agent to

  16. Different effects of lansoprazole and rabeprazole on the plasma voriconazole trough levels in allogeneic hematopoietic cell transplant recipients.

    Science.gov (United States)

    Yasu, Takeo; Konuma, Takaaki; Kato, Seiko; Kurokawa, Yosuke; Takahashi, Satoshi; Tojo, Arinobu

    2016-10-01

    Voriconazole (VRC) is widely used as prophylaxis and in the treatment of invasive fungal disease (IFD) after allogeneic hematopoietic cell transplantation (HCT). We retrospectively examined the results of VRC therapeutic drug monitoring (TDM) in allogeneic HCT recipients. A total of 474 samples were obtained from 59 adult patients who received VRC during the first 100 days following HCT between 2009 and 2014 in our institute. Seventeen patients received VRC for prophylaxis of IFD, and 42 received VRC for the empirical or preemptive therapy for IFD. A total of 299 samples (63 %) were obtained during the administration of the intravenous form of VRC. The median VRC daily dose based on the actual body weight was 6.68 mg/kg/day (range, 1.92-10.41 mg/kg/day). The median VRC trough level was 0.99 mg/l (range, lansoprazole as compared to rabeprazole (P lansoprazole and rabeprazole have different effects on the plasma VRC trough levels in the allogeneic HCT recipients.

  17. Expression of BMP-2 in Vascular Endothelial Cells of Recipient May Predict Delayed Graft Function After Renal Transplantation

    Directory of Open Access Journals (Sweden)

    Nikolina Basic-Jukic

    2016-11-01

    Full Text Available Background/Aims: Delayed graft function (DGF is associated with adverse outcomes after renal transplantation. Bone morphogenetic protein-2 (BMP-2 is involved in both endothelial function and immunological events. We compared expression of BMP-2 in epigastric artery of renal transplant recipients with immediate graft function (IGF and DGF. Methods: 79 patients were included in this prospective study. Patients were divided in IGF group (64 patients and DGF group (15 patients. BMP-2 expression in intima media (BMP2m and endothelium (BMP2e of epigastric artery was assessed by immunohistochemistry. Results: Lower intensity of BMP2e staining was recorded in DGF compared to IGF. In DGF patients, 93% had no expression of BMP2e and 7% had 1st grade expression, compared to 45% and 41% in IGF group, respectively (P=0.001 (Pst grade expression. Patients who had BMP2e staining positive had lower odds for DGF (OR 0.059 [0.007, 0.477] and this remained significant even after adjustment for donor and recipient variables, cold ischemia time, and immunological matching (OR 0.038 [0.003, 0.492]. Conclusions: Our results demonstrate that BMP-2 expression in endothelial cells of epigastric arteries may predict development of DGF.

  18. Expression of BMP-2 in Vascular Endothelial Cells of Recipient May Predict Delayed Graft Function After Renal Transplantation.

    Science.gov (United States)

    Basic-Jukic, Nikolina; Gulin, Marijana; Hudolin, Tvrtko; Kastelan, Zeljko; Katalinic, Lea; Coric, Marijana; Veda, Marija Varnai; Ivkovic, Vanja; Kes, Petar; Jelakovic, Bojan

    2016-01-01

    Delayed graft function (DGF) is associated with adverse outcomes after renal transplantation. Bone morphogenetic protein-2 (BMP-2) is involved in both endothelial function and immunological events. We compared expression of BMP-2 in epigastric artery of renal transplant recipients with immediate graft function (IGF) and DGF. 79 patients were included in this prospective study. Patients were divided in IGF group (64 patients) and DGF group (15 patients). BMP-2 expression in intima media (BMP2m) and endothelium (BMP2e) of epigastric artery was assessed by immunohistochemistry. Lower intensity of BMP2e staining was recorded in DGF compared to IGF. In DGF patients, 93% had no expression of BMP2e and 7% had 1st grade expression, compared to 45% and 41% in IGF group, respectively (P=0.001) (P<0.001 for no expression and P = 0.015 for 1st grade expression). Patients who had BMP2e staining positive had lower odds for DGF (OR 0.059 [0.007, 0.477]) and this remained significant even after adjustment for donor and recipient variables, cold ischemia time, and immunological matching (OR 0.038 [0.003, 0.492]). Our results demonstrate that BMP-2 expression in endothelial cells of epigastric arteries may predict development of DGF. © 2016 The Author(s) Published by S. Karger AG, Basel.

  19. PREVENTION AND TREATMENT OF HEPATITIS VIRUS INFECTION IN HEMATOPOIETIC STEM CELL TRANSPLANTATION RECIPIENTS

    Directory of Open Access Journals (Sweden)

    Suparno Chakrabarti

    2009-12-01

    Full Text Available Abstract: Infections with Hepatitis viruses B and C pose major problems both short and long term respectively after HSCT. The key to prevention for Hepatitis B disease remains vaccination for HBV-naïve patients and judicial use of anti-viral therapy in both pre- and post-transplant settings for HBV-infected patients. HBsAg positive grafts to HBV-naïve recipients result in transmission of the virus in about 50%. The newer anti-viral agents have enabled effective treatment of post-transplant patients who might be lamivudine-resistant or might develop so. Selecting a previously infected donor who has high titres of surface antibody for HBsAg positive patients gives the best chance for immunological clearance. The most challenging aspect of preventing HBV reactivation remains the duration of anti-viral therapy and timing of its withdrawal as most reactivations and often fatal ones occur after this period. Hepatitis C, on the other hand affects long-term survival with early onset of fibrosis and cirrhosis. Early effect of Hepatitis C virus on the immune system remains conjectural. The standard combination therapy seems to be effective, but data on this front remains sparse, as in the case of the use of newer antiviral agents. HSCT from HCV infected grafts result in more consistent transmission of the virus and pre-donation treatment of donors should be undertaken to render them non-viremic, if possible.  The current understanding and recommendations regarding prevention and management of these infections in HSCT recipients are discussed.

  20. Adenovirus Viremia in Adult CD34(+) Selected Hematopoietic Cell Transplant Recipients: Low Incidence and High Clinical Impact.

    Science.gov (United States)

    Lee, Yeon Joo; Huang, Yao-Ting; Kim, Seong Jin; Maloy, Molly; Tamari, Roni; Giralt, Sergio A; Papadopoulos, Esperanza B; Jakubowski, Ann A; Papanicolaou, Genovefa A

    2016-01-01

    Adenovirus (ADV) infections after hematopoietic cell transplantation (HCT) range in severity from self-limited to fatal. We have previously reported high mortality rates in CD34(+) selected T cell-depleted (TCD) HCT recipients using symptomatic testing and culture methods for ADV detection. We report rates and outcomes of ADV viremia in 215 adult recipients of TCD HCT using the CliniMACS CD34(+) selection system. This was a prospective observational study of adults transplanted from March 21, 2012 through November 30, 2014 at Memorial Sloan-Kettering Cancer Center. TCD was performed using CliniMACS CD34(+) cell selection. Patients were monitored for ADV by whole blood PCR assay from +14 to +100 days post-transplant. ADV viremia was defined as ≥1 PCR above the lower limit of quantitation. ADV disease was defined per European Group for Blood and Marrow Transplantation guidelines. Treatment for ADV was at the clinician's discretion. Competing risk regression analyses were used to identify predictors for ADV viremia and overall survival. The median age was 55 years (range, 22 to 72); 215 patients underwent TCD. All patients received myeloablative conditioning. Eighteen patients (8% of cohort) had ADV viremia at a median onset of 57 days (interquartile range [IQR], 23 to 79) and with a median viral load at first detection of 2.6 log10 copies/mL (IQR, 2.5 to 4.0). The median maximal viral load was 4.5 log10 copies/mL (IQR, 3.5 to 5.9). No significant risk factor was identified for ADV viremia by univariate analysis. Six patients (3% of total cohort, 33% of viremic patients) developed ADV disease (3 colitis, 2 nephritis/cystitis, 1 pneumonitis). ADV viremia preceded onset of ADV disease a median of 11 days from the first positive quantitative PCR (range, +3 to +37) except in 1 patient with nephritis. Overall, 12 of 18 viremic patients (67%) received antiviral treatment (5 cidofovir only, 7 brincidofovir ± cidofovir). All patients with ADV disease were treated, and 6

  1. PREVENTION AND TREATMENT OF HEPATITIS VIRUS INFECTION IN HEMATOPOIETIC STEM CELL TRANSPLANTATION RECIPIENTS

    Directory of Open Access Journals (Sweden)

    Somnath Mukherjee

    2009-11-01

    Full Text Available

    Abstract: Infections with Hepatitis viruses B and C pose major problems both short and long term respectively after HSCT. The key to prevention for Hepatitis B disease remains vaccination for HBV-naïve patients and judicial use of anti-viral therapy in both pre- and post-transplant settings for HBV-infected patients. HBsAg positive grafts to HBV-naïve recipients result in transmission of the virus in about 50%. The newer anti-viral agents have enabled effective treatment of post-transplant patients who might be lamivudine-resistant or might develop so. Selecting a previously infected donor who has high titres of surface antibody for HBsAg positive patients gives the best chance for immunological clearance. The most challenging aspect of preventing HBV reactivation remains the duration of anti-viral therapy and timing of its withdrawal as most reactivations and often fatal ones occur after this period. Hepatitis C, on the other hand affects long-term survival with early onset of fibrosis and cirrhosis. Early effect of Hepatitis C virus on the immune system remains conjectural. The standard combination therapy seems to be effective, but data on this front remains sparse, as in the case of the use of newer antiviral agents. HSCT from HCV infected grafts result in more consistent transmission of the virus and pre-donation treatment of donors should be undertaken to render them non-viremic, if possible.  The current understanding and recommendations regarding prevention and management of these infections in HSCT recipients are discussed.

  2. Sirolimus Increases T-Cell Abundance in the Sun Exposed Skin of Kidney Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Michael Thomas Burke, MBBS

    2017-07-01

    Conclusions. This study demonstrated that immunosuppressive drug class and sun exposure modify the abundance of multiple T-cell subsets in the skin of KTRs. Correlation analysis revealed that the prevalence of Treg cells in KTR blood does not accurately reflect the prevalence of Treg cells in KTR skin.

  3. Bone marrow transplantation across major histocompatibility barriers in mice: II. T cell requirement for engraftment in total lymphoid irradiation-conditioned recipients

    Energy Technology Data Exchange (ETDEWEB)

    Vallera, D.A.; Soderling, C.C.B.; Carlson, G.J.; Kersey, J.H.

    1982-03-01

    Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatability barriers.Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then given to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 100-rad TLI. In TLI plus CY-conditioned recipients, it was also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for these findings are discussed. (JMT)

  4. Bone marrow transplantation across major histocompatibility barriers in mice: II. T cell requirement for engraftment in total lymphoid irradiation-conditioned recipients

    International Nuclear Information System (INIS)

    Vallera, D.A.; Soderling, C.C.B.; Carlson, G.J.; Kersey, J.H.

    1982-01-01

    Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatability barriers.Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then given to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 100-rad TLI. In TLI plus CY-conditioned recipients, it was also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for these findings are discussed

  5. Prospective analysis of human cytomegalovirus DNAemia and specific CD8+ T cell responses in lung transplant recipients.

    Science.gov (United States)

    Weseslindtner, L; Kerschner, H; Steinacher, D; Nachbagauer, R; Kundi, M; Jaksch, P; Simon, B; Hatos-Agyi, L; Scheed, A; Klepetko, W; Puchhammer-Stöckl, E

    2012-08-01

    In lung transplant recipients (LuTRs), human cytomegalovirus (HCMV) DNAemia may be associated with HCMV disease and reduced survival of the allograft. Because T cells are essential for controlling HCMV replication, we investigated in this prospective study whether the kinetics of plasma HCMV DNA loads in LuTRs are associated with HCMV-specific CD8+ T cell responses, which were longitudinally assessed using a standardized assay. Sixty-seven LuTRs were monitored during the first year posttransplantation, with a mean of 17 HCMV DNA PCR quantifications and 11.5 CD8+ T cell tests performed per patient. HCMV-specific CD8+ T cell responses displayed variable kinetics in different patients, differed significantly before the onset of HCMV DNAemia in LuTRs who subsequently experienced episodes of DNAemia with high (>1000 copies/mL) and low plasma DNA levels (p = 0.0046, Fisher's exact test), and were absent before HCMV disease. In HCMV-seropositive LuTRs, high-level DNAemia requiring preemptive therapy occurred more frequently when HCMV-specific CD8+ T cell responses fluctuated, were detected only after HCMV DNA detection, or remained undetectable (p = 0.0392, Fisher's exact test). Thus, our data indicate that HCMV-specific CD8+ T cells influence the magnitude of HCMV DNAemia episodes, and we propose that a standardized measurement of CD8+ T cell immunity might contribute to monitoring the immune status of LuTRs posttransplantation. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

  6. Economic evaluation of targeted treatments of invasive aspergillosis in adult haematopoietic stem cell transplant recipients in the Netherlands: a modelling approach.

    NARCIS (Netherlands)

    Ament, A.J.; Hubben, M.W.; Verweij, P.E.; Groot, R. de; Warris, A.; Donnelly, J.P.; Wout, J. van 't; Severens, J.L.

    2007-01-01

    OBJECTIVES: The aim of this study was to assess the cost-effectiveness of a targeted treatment model of antifungal treatment strategies for adult haematopoietic stem cell transplant (HSCT) recipients in the Netherlands from a hospital perspective, using a decision analytic modelling approach.

  7. Body Mass Index and creatinine clearance are associated with steady-state serum concentrations of the cell damage marker S100B in renal transplant recipients

    NARCIS (Netherlands)

    Gross, Sascha; van der Heide, Jaap J. Homan; van Son, Willem J.; Gans, Reinold O. B.; Foell, Dirk; Navis, Gerjan; Bakker, Stephan J. L.

    2010-01-01

    Background: S100B is a prominent cell damage marker which can lead to sustained pro-inflammatory signaling. The aim was to investigate cross-sectional associations of steady-state S100B concentrations, particularly with C-reactive protein (CRP), in renal transplant recipients (RTRs) and also to

  8. Body mass index and creatinine clearance are associated with steady-state serum concentrations of the cell damage marker S100B in renal transplant recipients

    NARCIS (Netherlands)

    Gross, Sascha; Homan van der Heide, Jaap J. J.; van Son, Willem J.; Gans, Reinold O. B.; Foell, Dirk; Navis, Gerjan; Bakker, Stephan J. L.

    2010-01-01

    S100B is a prominent cell damage marker which can lead to sustained pro-inflammatory signaling. The aim was to investigate cross-sectional associations of steady-state S100B concentrations, particularly with C-reactive protein (CRP), in renal transplant recipients (RTRs) and also to investigate

  9. Use of indium 111-labeled white blood cell scan in the diagnosis of cytomegalovirus pneumonia in a renal transplant recipient with a normal chest roentgenogram

    International Nuclear Information System (INIS)

    Chinsky, K.; Goodenberger, D.M.

    1991-01-01

    Opportunistic infections are common in patients after renal transplantation. This report describes a case of cytomegalovirus pneumonia in a renal transplant recipient with a normal chest roentgenogram and normal arterial oxygenation. An abnormal 111In-white blood cell scan led to the discovery of a pulmonary source of his recurrent fevers

  10. Bone marrow transplantation across major histocompatibility barriers in mice. II. T cell requirement for engraftment in total lymphoid irradiation-conditioned recipients

    International Nuclear Information System (INIS)

    Vallera, D.A.; Soderling, C.C.; Carlson, G.J.; Kersey, J.H.

    1982-01-01

    Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatibility barriers. Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then give to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 200-rad TLI. In TLI plus CY-conditional recipients, we have also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. Furthermore, graft failure in mice receiving normal dosages of anti-Thy-1.2 plus C-treated donor cells was not a strain-restricted phenomenon. Moreover, removal of bone marrow T cells with monoclonal anti-Lyt-1 plus complement also resulted in graft failure in TLI-conditioned recipients. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for there findings are discussed

  11. Bone marrow transplantation across major histocompatibility barriers in mice. II. T cell requirement for engraftment in total lymphoid irradiation-conditioned recipients

    Energy Technology Data Exchange (ETDEWEB)

    Vallera, D.A.; Soderling, C.C.; Carlson, G.J.; Kersey, J.H.

    1982-03-01

    Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatibility barriers. Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then give to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 200-rad TLI. In TLI plus CY-conditional recipients, we have also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. Furthermore, graft failure in mice receiving normal dosages of anti-Thy-1.2 plus C-treated donor cells was not a strain-restricted phenomenon. Moreover, removal of bone marrow T cells with monoclonal anti-Lyt-1 plus complement also resulted in graft failure in TLI-conditioned recipients. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for there findings are discussed.

  12. HLA Genotypes in Turkish Hematopoietic Cell Recipients and Likelihood of Finding a Matched Donor Through Family Searches.

    Science.gov (United States)

    Kaya, Zühre; Gönen, Sevim; Çalışkan, Burcu; Kemer, Zeynep; Ünal, Ayşe Betül; Değirmenci, Enes

    2017-03-28

    Allogeneic hematopoietic stem cell transplant is a life-saving treatment, but donor numbers in Turkey do not meet the increasing demand for this procedure. Here, our objectives were (1) to assess the frequency of HLA-matched related donors in the Turkish population and (2) to identify the HLA antigens and haplotypes that are most frequent in Turkey. The HLA genotypes of 841 consecutive recipients and 3071 family members were retrospectively reviewed. Matched related donors were identified for 368/841 recipients (44%). Extended family donor searches were performed for 111/181 pediatric recipients (61%), with nonsibling matched related donors found for 23 patients (21%). Matched related donors were found for a significantly higher proportion of pediatric patients (52%) than adult patients (41%) (odds ratio of 2.5; 95% confidence interval, 1.9-4.1; P = .02). The percentage of pediatric versus adult patients with 3 or more siblings was 13% versus 46% (odds ratio of 5.6; 95% confidence interval, 3.6-8.5; P = .001). The most frequent HLA class I antigens at each locus were HLA-A*02 (20.2%), HLA-B*35 (19.5%), and HLA-C*07 (19.8%). The most frequent HLA class II antigens at each locus were HLA-DRB1*11 (21.6%) and HLA-DQB1*03 (40.2%). The most common 3-locus haplotypes were HLA-A*24 B*35 DRB1*11 (F:0.020) and HLA-A*01 B*08 DRB1*03 (F:0.015). When adult and pediatric groups were combined, the most common locus haplotypes were found in 43/345 sibling donors (12%) and in 7/23 nonsibling pediatric donors (30%) (odds ratio of 2.7; 95% confidence interval, 1.2-6.4; P = .02). The results indicate that, in Turkey, it can be beneficial to revise donor search algorithms to include an extended family donor search before an unrelated donor search. This type of search can be effective because of the HLA haplotype diversity in Turkey, the frequency of consanguinity, and the country's limited donor pool.

  13. Rhodococcus globerulus bacteremia in an allogeneic hematopoietic stem cell transplant recipient: report of the first transplant case and review of the literature.

    Science.gov (United States)

    Ramanan, P; Deziel, P J; Razonable, R R

    2014-06-01

    Rhodococcus species are environmental organisms that predominantly cause opportunistic infections in immunocompromised hosts. Rhodococcus equi is the most common species associated with human infections, but there are uncommon but increasing number of cases of infections caused by non-equi Rhodococcus species. We report a case of Rhodococcus globerulus bacteremia in an allogeneic hematopoietic stem cell transplant recipient, who presented with subacute systemic illness accompanied by severe hepatitis. In the context of this case, we review the literature on Rhodococcus species infections in transplant recipients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma, Aspergillus Colonization, Invasive Aspergillosis and Death in Lung Transplant Recipients.

    Science.gov (United States)

    Mansh, M; Binstock, M; Williams, K; Hafeez, F; Kim, J; Glidden, D; Boettger, R; Hays, S; Kukreja, J; Golden, J; Asgari, M M; Chin-Hong, P; Singer, J P; Arron, S T

    2016-01-01

    Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n = 455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all-cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04-2.88; p = 0.03), with each additional 30-day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02-1.04; p Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR 0.50; 95% CI: 0.34-0.72; p Voriconazole exposure significantly reduced all-cause mortality among subjects who developed Aspergillus colonization (HR 0.34; 95% CI: 0.13-0.91; p = 0.03) but had no significant impact on those without colonization. Physicians should consider patient-specific factors that modify the potential risks and benefits of voriconazole for the care of lung transplant recipients. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  15. Analysis of Residual DSBs in Ataxia-Telangiectasia Lymphoblast Cells Initiating Apoptosis

    Directory of Open Access Journals (Sweden)

    Teresa Anglada

    2016-01-01

    Full Text Available In order to examine the relationship between accumulation of residual DNA double-strand breaks (DSBs and cell death, we have used a control and an ATM (Ataxia-Telangiectasia Mutated defective cell line, as Ataxia-Telangiectasia (AT cells tend to accumulate residual DSBs at long times after damage infliction. After irradiation, AT cells showed checkpoint impairment and a fraction of cells displayed an abnormal centrosome number and tetraploid DNA content, and this fraction increased along with apoptosis rates. At all times analyzed, AT cells displayed a significantly higher rate of radiation-induced apoptosis than normal cells. Besides apoptosis, 70–85% of the AT viable cells (TUNEL-negative carried ≥10 γH2AX foci/cell, while only 12–27% of normal cells did. The fraction of AT and normal cells undergoing early and late apoptosis were isolated by flow cytometry and residual DSBs were concretely scored in these populations. Half of the γH2AX-positive AT cells undergoing early apoptosis carried ≥10 γH2AX foci/cell and this fraction increased to 75% in late apoptosis. The results suggest that retention of DNA damage-induced γH2AX foci is an indicative of lethal DNA damage, as cells undergoing apoptosis are those accumulating more DSBs. Scoring of residual γH2AX foci might function as a predictive tool to assess radiation-induced apoptosis.

  16. Persistent risk of HBV reactivation despite extensive lamivudine prophylaxis in haematopoietic stem cell transplant recipients who are anti-HBc-positive or HBV-negative recipients with an anti-HBc-positive donor.

    Science.gov (United States)

    Cerva, C; Colagrossi, L; Maffongelli, G; Salpini, R; Di Carlo, D; Malagnino, V; Battisti, A; Ricciardi, A; Pollicita, M; Bianchi, A; Picardi, A; Cudillo, L; Cerretti, R; De Angelis, G; Cantonetti, M; Andreoni, M; Perno, C F; Arcese, W; Svicher, V; Sarmati, L

    2016-11-01

    The overall rate of hepatitis B virus (HBV) reactivation was evaluated in a population of 373 haematological stem cell transplant (HSCT) patients treated with lamivudine (LMV) if they were anti-HBc-positive/HBV-DNA-negative recipients or if they were HBV-negative recipients with an anti-HBc-positive donor. The incidence of HBV reactivation was calculated in two groups of autologous (auto) or allogeneic (allo) HSCT patients who were stratified according to their HBV serostatus. The former group included 57 cases: 10 auto-HSCT and 27 allo-HSCT anti-HBc-positive recipients, two auto-HSCT and three allo-HSCT inactive carriers, and 15 allo-HSCT recipients with an anti-HBc-positive donor. Forty-seven (82.4%) patients in this group received LMV prophylaxis (the median (interquartile range, IQR) of LMV treatment was 30 (20-38) months). The second group consisted of 320 anti-HBc-negative auto-HSCT and allo-HSCT recipients with anti-HBc-negative donors. None of these patients received any prophylaxis. Two patients in the first group and two in the second group experienced reactivation of HBV infection, with an incidence of 3.5% (95% CI 0.4-12.1%) and 0.6% (95% CI 0.1-2.2%), respectively. Only one out of four reactivated patients was LMV-treated. The cumulative probability of HBV reactivation at 6 years from HSCT was 15.8% (95% CI 15.2-16.4%). Three of four viral isolates obtained from the HBV-reactivated patients harboured mutations in the immune-active HBsAg-region. In a HSCT population carefully evaluated for HBV prophylaxis, a risk of HBV reactivation persisted in the group of patients who were not LMV-treated. Only one LMV-treated patient experienced reactivation of HBV with a resistant HBV isolate. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  17. [Patient with B-CLL with a history of unrelated hematopoietic cells donation--retrospective analysis of CLL development and implication for the recipient].

    Science.gov (United States)

    Jindra, P; Žejšková, L; Peková, S; Navrátilová, J; Schutzová, M; Vokurka, S; Koza, V

    2012-01-01

    Donor cell leukemia (DCL) is a relatively rare but well documented complication of hematopoietic stem cell transplantation. So far, publications described only DCL arising de novo in the recipient. In this study, we describe a case of chronic lymphocytic leukemia (B-CLL) developing in a volunteer unrelated donor from the Czech National Marrow Donors Registry (CNMDR) several years after donation. From archival DNA sample, we have retrospectively found that subclinical CLL clone was already present at the time of donation but early death of recipient prevented eventual development of DCL. This case documents well the long period between detection of B-CLL clone and full development of clinical-laboratory symptomatology. The medical and ethical questions posed by an isolated case of detection of hematological malignancy present either only in the donor or only in the recipient are discussed. The case demonstrates the increasing risk of development of various forms of DCL and thus highlights the need for long-term monitoring of stem cell donor, not only in terms of health of donor but also in terms of potential risks for the recipient.

  18. Circulating endothelial progenitor cell numbers are not associated with donor organ age or allograft vasculopathy in cardiac transplant recipients.

    Science.gov (United States)

    Thomas, H E; Parry, G; Dark, J H; Arthur, H M; Keavney, B D

    2009-02-01

    Increasing age is associated with reduced numbers of circulating endothelial progenitor cells (EPCs). It is unclear whether this relates to depletion or impairment of bone marrow progenitors, or to deficient mobilization signals from aging tissues. In cardiac transplant patients, one previous study has reported an association between circulating EPCs and the risk of cardiac allograft vasculopathy (CAV). We investigated whether increased donor heart age, a strong risk factor for CAV, was associated with reduced circulating EPC numbers in a group of cardiac transplant recipients matched for factors which influence EPC numbers, but with maximally discordant donor heart ages. We identified 32 patient pairs, matched for factors known to influence EPC numbers, but who had discordant donor heart ages by at least 20 years. EPCs were quantified using flow cytometry for absolute counts of cells expressing all the combinations of CD45, CD34, CD133 and the kinase domain receptor (KDR). There were no significant differences in the numbers of circulating EPCs between patients with old or young donor heart age. There was no association between the presence of CAV and circulating EPC numbers. We suggest that the increased susceptibility to CAV of older donor hearts is not mediated via circulating EPCs. Our results are consistent with the theory that the normal age-related decline in EPC numbers relates to bone marrow aging rather than failure of target tissues to induce EPC mobilization.

  19. Mesenchymal stem cell therapy for immune-modulation: the donor, the recipient, and the drugs in-between.

    Science.gov (United States)

    Nemeth, Krisztian

    2014-09-01

    Adoptive transfer of cultured bone marrow stromal cells (mesenchymal stem cells also known as MSCs) is a promising new way to aid tissue regeneration and treat a wide variety of diseases where regulation of inflammatory responses is derailed. Although significant advances have been made in the field, pinpointing important mechanistic details about how MSCs function in vitro and in vivo, there are still many unanswered questions that need to be addressed before welcoming MSCs in the therapeutic arsenal of immune mediated diseases. In this viewpoint, we highlight and discuss a few factors that we believe are critical in terms of therapeutic success employing cultured MSCs. Selecting the right donor population, choosing the best culture conditions and picking the patient population that is most likely to give a favourable therapeutic response is just as important as considering interactions between MSCs and the combination of drugs in the recipient's body. Given the complexity of MSC-host interactions, it is also imperative to develop screening tools that account for as many variables as possible and predict precisely the in vivo response rates before MSCs enter the body. To achieve this, a multidisciplinary approach is required with comprehensive knowledge of basic MSC biology, immunology, pharmacology and good clinical practice. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Oral complications in hematopoietic stem cell recipients: the role of inflammation

    NARCIS (Netherlands)

    Haverman, T. M.; Raber-Durlacher, J. E.; Rademacher, W. M. H.; Vokurka, S.; Epstein, J. B.; Huisman, C.; Hazenberg, M. D.; de Soet, J. J.; de Lange, J.; Rozema, F. R.

    2014-01-01

    Hematopoietic stem cell transplantation (HSCT) is widely used as a potentially curative treatment for patients with various hematological malignancies, bone marrow failure syndromes, and congenital immune deficiencies. The prevalence of oral complications in both autologous and allogeneic HSCT

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

    OpenAIRE

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

    2009-01-01

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

  2. Persistent seropositivity for yellow fever in a previously vaccinated autologous hematopoietic stem cell transplantation recipient.

    Science.gov (United States)

    Hayakawa, Kayoko; Takasaki, Tomohiko; Tsunemine, Hiroko; Kanagawa, Shuzo; Kutsuna, Satoshi; Takeshita, Nozomi; Mawatari, Momoko; Fujiya, Yoshihiro; Yamamoto, Kei; Ohmagari, Norio; Kato, Yasuyuki

    2015-08-01

    The duration of a protective level of yellow fever antibodies after autologous hematopoietic stem cell transplantation in a previously vaccinated person is unclear. The case of a patient who had previously been vaccinated for yellow fever and who remained seropositive for 22 months after autologous peripheral blood stem cell transplantation for malignant lymphoma is described herein. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Abundance of a restricted fetal B cell repertoire in marrow transplant recipients.

    Science.gov (United States)

    Storek, J; King, L; Ferrara, S; Marcelo, D; Saxon, A; Braun, J

    1994-11-01

    Patients undergoing bone marrow transplantation are humorally immunodeficient for one or more years post-transplant. This immunodeficiency could be partially caused by B cell repertoire restriction similar to that observed in ontogeny. To test this idea, the abundance of rearranged genomic segments bearing five variable heavy chain (VH) genes was compared in patients at several timepoints post-transplant and in immunologically normal neonates, infants and adults. The genes evaluated in the study (VH6, VH4-58p2, VH3-56p1, VH3-20p1 and VH3-13-2) were selected from those commonly utilized by fetal B cells. The assay employed quantitative PCR and oligonucleotide hybridization detection under conditions designed to detect relatively unmutated forms of these genes. In blood B cells from early post-transplant (2-5 months) patients, these VH genes were markedly overutilized compared with normal adults. B cells from late post-transplant (6-21 months) patients and from normal neonates and infants also overutilized these genes; however, to a lesser degree than early post-transplant B cells. The data suggest that, as in ontogeny, the B cell repertoire is strikingly restricted to fetal-type VH genes early post-transplant, and may become normal only very late (years) post-transplant.

  4. Retrospective Analysis of T and B Cells Flow-Cross Matches in Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Lakshmi Kiran C

    2008-01-01

    Full Text Available Complement-mediated cytotoxic antibodies in conventional cross match, often result in misappropriation of true positives and borderline positives which are detrimental to allograft survival. Flow cross matches (FCXM are sensitive to capture even non comple-ment fixing cytotoxic antibodies. This retrospective study evaluates the utility of FCXM in effectively predicting acute allograft rejection. A total of 17 cases were processed for FCXM (T and B cell of whom seven had no rejection episodes, while the remaining 11 had acute rejection despite negative cross match and panel reacting antibodies being ne-gative (less than 20%. The sensitivity and specificity of the FCXM outcome demons-trated that positive B-cell FCXM has potential to be a good tool in pre-transplant scree-ning. The current analysis proposes the possible utility of B-cell positive FCXM as a more sensitive parameter in predicting acute allograft rejection prior to transplantation.

  5. Bacterial meningitis in hematopoietic stem cell transplant recipients: a population-based prospective study

    NARCIS (Netherlands)

    van Veen, K. E. B.; Brouwer, M. C.; van der Ende, A.; van de Beek, D.

    2016-01-01

    We performed a nationwide prospective cohort study on the epidemiology and clinical features of community-acquired bacterial meningitis. Patients with a medical history of autologous or allogeneic hematopoietic stem cell transplantation (HSCT) were identified from the cohort performed from March

  6. Oral bacteria and yeasts in relationship to oral ulcerations in hematopoietic stem cell transplant recipients

    NARCIS (Netherlands)

    Laheij, A.M.G.A.; de Soet, J.J.; von dem Borne, P.A.; Kuijper, E.J.; Kraneveld, E.A.; van Loveren, C.; Raber-Durlacher, J.E.

    2012-01-01

    BACKGROUND: Oral mucositis is a serious and debilitating side effect of conditioning regimens for hematopoietic stem cell transplant (HSCT). Through HSCT, the homeostasis in the oral cavity is disrupted. The contribution of the oral microflora to mucositis remains to be clarified. The aim of our

  7. Oral bacteria and yeasts in relationship to oral ulcerations in hematopoietic stem cell transplant recipients

    NARCIS (Netherlands)

    Laheij, Alexa M. G. A.; de Soet, Johannes J.; von dem Borne, Peter A.; Kuijper, Ed J.; Kraneveld, Eefje A.; van Loveren, Cor; Raber-Durlacher, Judith E.

    2012-01-01

    Oral mucositis is a serious and debilitating side effect of conditioning regimens for hematopoietic stem cell transplant (HSCT). Through HSCT, the homeostasis in the oral cavity is disrupted. The contribution of the oral microflora to mucositis remains to be clarified. The aim of our study was to

  8. Fatal adenovirus encephalomyeloradiculitis in an umbilical cord stem cell transplant recipient

    OpenAIRE

    Awosika, Oluwole O.; Lyons, Jennifer L.; Ciarlini, Pedro; Phillips, Richard E.; Alfson, Elizabeth D.; Johnson, Emily L.; Koo, Sophia; Marty, Francisco; Drew, Clifton; Zaki, Sherif; Folkerth, Rebecca D.; Klein, Joshua P.

    2013-01-01

    Adenovirus infections frequently complicate allogeneic stem cell transplants but nervous system involvement, usually presenting as encephalitis, is atypical. Progression from encephalitis to myeloradiculitis has not been described previously.1 We present a unique case of fatal adenoviral encephalomyeloradiculitis with imaging and pathologic correlates.

  9. Human induced pluripotent stem cells improve stroke outcome and reduce secondary degeneration in the recipient brain

    Czech Academy of Sciences Publication Activity Database

    Polentes, J.; Jendelová, Pavla; Cailleret, M.; Braun, H.; Romanyuk, Nataliya; Tropel, P.; Brenot, M.; Itier, V.; Seminatore, CH.; Baldauf, K.; Turnovcová, Karolína; Jirák, D.; Teletin, M.; Côme, J.; Tournois, J.; Reymann, K.; Syková, Eva; Viville, S.; Onteniente, B.

    2012-01-01

    Roč. 21, č. 12 (2012), s. 2587-2602 ISSN 0963-6897 Grant - others:GA MŠk(CZ) 1M0538 Program:1M Institutional research plan: CEZ:AV0Z50390703 Keywords : cell replacement therapy * cerebral ischemia * reprogramming Subject RIV: FH - Neurology Impact factor: 4.422, year: 2012

  10. Donor-recipient killer immunoglobulin like receptor (KIR) genotype matching has a protective effect on chronic graft versus host disease and relapse incidence following HLA-identical sibling hematopoietic stem cell transplantation.

    Science.gov (United States)

    Sahin, Ugur; Dalva, Klara; Gungor, Funda; Ustun, Celalettin; Beksac, Meral

    2018-03-16

    .02) and increased in the presence of haplotype-AB and -BB donors (OR: 7.9; p = 0.02; OR: 5.1; p = 0.03, respectively). In an attempt to investigate the pathogenesis underlying KIR-matching, we searched for residual NK/T cells on day 0 peripheral blood samples of six additional recipients and noted the presence of CD3 + (7.0-91.4 × 10 6 /L) and CD56 + 57 + (0.8-12.7 × 10 6 /L) cells. In conclusion, conditioning regimen surviving recipient NK/T cells potentially influenced by KIR-matching may contribute to GvL/GvH reactions.

  11. Distinctive in vitro effects of T-cell growth cytokines on cytomegalovirus-stimulated T-cell responses of HIV-infected HAART recipients

    International Nuclear Information System (INIS)

    Patterson, Julie; Jesser, Renee; Weinberg, Adriana

    2008-01-01

    Functional immune reconstitution is limited after HAART, maintaining the interest in adjunctive immune-modulators. We compared in vitro the effects of the γ-chain T-cell growth cytokines IL-2, IL-4, IL-7 and IL-15 on cytomegalovirus-stimulated cell-mediated immunity. IL-2 and IL-15 increased cytomegalovirus-specific lymphocyte proliferation in HAART recipients, whereas IL-4 and IL-7 did not. The boosting effect of IL-2 and IL-15 on proliferation correlated with their ability to prevent late apoptosis. However, IL-2 increased the frequency of cells in early apoptosis, whereas IL-15 increased the frequency of fully viable cells. Both IL-2 and IL-15 increased cytomegalovirus-induced CD4 + and CD8 + T-cell proliferation and the synthesis of Th1 and pro-inflammatory cytokines and chemokines. However, only IL-2 increased the frequency of regulatory T cells and Th2 cytokine production, both of which have the potential to attenuate antiviral immune responses. Overall, compared to other γ-chain cytokines, IL-15 had the most favorable profile for boosting antiviral cell-mediated immunity

  12. Voriconazole for secondary prophylaxis of invasive fungal infections in allogeneic stem cell transplant recipients: results of the VOSIFI study.

    Science.gov (United States)

    Cordonnier, Catherine; Rovira, Montserrat; Maertens, Johan; Olavarria, Eduardo; Faucher, Catherine; Bilger, Karin; Pigneux, Arnaud; Cornely, Oliver A; Ullmann, Andrew J; Bofarull, Rodrigo Martino; de la Cámara, Rafael; Weisser, Maja; Liakopoulou, Effie; Abecasis, Manuel; Heussel, Claus Peter; Pineau, Marc; Ljungman, Per; Einsele, Hermann

    2010-10-01

    Recurrence of prior invasive fungal infection (relapse rate of 30-50%) limits the success of stem cell transplantation. Secondary prophylaxis could reduce disease burden and improve survival. A prospective, open-label, multicenter trial was conducted evaluating voriconazole (4 mg/kg/12 h intravenously or 200 mg/12 h orally) as secondary antifungal prophylaxis in allogeneic stem cell transplant recipients with previous proven or probable invasive fungal infection. Voriconazole was started 48 h or more after completion of conditioning chemotherapy and was planned to be continued for 100-150 days. Patients were followed for 12 months. The primary end-point of the study was the incidence of proven or probable invasive fungal infection. Forty-five patients were enrolled, 41 of whom had acute leukemia. Previous invasive fungal infections were proven or probable aspergillosis (n=31), proven candidiasis (n=5) and other proven or probable infections (n=6); prior infection could not be confirmed in three patients. The median duration of voriconazole prophylaxis was 94 days. Eleven patients (24%) died within 12 months of transplantation, but only one due to systemic fungal disease. Three invasive fungal infections occurred post-transplant: two relapses (one candidemia and one fatal scedosporiosis) and one new zygomycosis in a patient with previous aspergillosis. The 1-year cumulative incidence of invasive fungal disease was 6.7±3.6%. Two patients were withdrawn from the study due to treatment-related adverse events (i.e. liver toxicity). Voriconazole appears to be safe and effective for secondary prophylaxis of systemic fungal infection after allogeneic stem cell transplantation. The observed incidence of 6.7% (with one attributable death) is considerably lower than the relapse rate reported in historical controls, thus suggesting that voriconazole is a promising prophylactic agent in this population.

  13. Rifampin-sirolimus-voriconazole interaction in a hematopoietic cell transplant recipient.

    Science.gov (United States)

    Wasko, Justin A; Westholder, James S; Jacobson, Pamala A

    2017-01-01

    Purpose Patients undergoing hematopoietic cell transplantation are treated with multiple medications, potentially complicated by drug-drug interactions. Drug interactions with sirolimus, voriconazole, and rifampin are particularly difficult because of the complex and simultaneous enzyme inhibition and induction mechanisms. We report a hematopoietic cell transplantation patient receiving sirolimus and voriconazole who was given rifampin while being treated for presumed methicillin-resistant Staphylococcus aureus meningitis. Summary A 31 year-old female received a nonmyeloablative allogeneic umbilical cord hematopoietic cell transplantation for myelodysplastic syndrome transformed to acute myeloid leukemia (AML). Her graft versus host disease and antifungal prophylaxis included sirolimus and voriconazole, respectively. Therapeutic drug monitoring prior to admission revealed a stable outpatient sirolimus regimen of 0.4 mg orally daily (trough goal 3-12 mcg/L). She was admitted to the inpatient hematopoietic cell transplantation service and diagnosed with methicillin-resistant Staphylococcus aureus bacteremia and presumed bacterial meningitis 217 days after transplant. Intravenous rifampin and vancomycin were initiated and voriconazole was changed to micafungin. Sirolimus trough concentrations were undetectable two days after starting rifampin. Therapeutic sirolimus concentrations were achieved four days later, at a sirolimus dose of 16-18 mg orally daily. Rifampin was discontinued after nine days and the sirolimus dose was adjusted accordingly, maintaining therapeutic levels throughout follow-up. The patient suffered a flare of chronic skin graft versus host disease requiring etanercept, high-dose systemic steroids, and topical steroids. Conclusion To the best of our knowledge, this is the first report describing the management of sirolimus during the transition from voriconazole inhibition to rifampin induction. Clinicians should be aware of potential drug

  14. Safety and tolerability of deferasirox in pediatric hematopoietic stem cell transplant recipients: one facility's five years' experience of chelation treatment.

    Science.gov (United States)

    Maximova, Natalia; Gregori, Massimo; Simeone, Roberto; Sonzogni, Aurelio; Boz, Giulia; Fucile, Carmen; Marini, Valeria; Martelli, Antonietta; Mattioli, Francesca

    2017-09-08

    42 pediatric patients with iron overload, who underwent liver biopsy and DFX treatment after hematopoietic stem cell transplantation were included in the study group. The patients were divided into two groups diversified according to deferasirox trough plasma concentrations (DFX C trough ) with cut-off equal to10 mcg/mL. The average dose of DFX was 25.9 mg/kg in the DFX C trough 10 mcg/mL group ( p =0,0003). The mean duration of DFX treatment was 135.7 days in the DFX C trough 10 mcg/mL group ( p 10 mcg/mL group ( p 10 mcg/mL group had ductopenia which was complete in 47.6% of them and severe in 52.4%. All patients with particularly high C trough (> 25 mcg/mL) were found to have total ductopenia. 90.5% of all deferasirox-related adverse events and 100% of major adverse events occurred in the DFX C trough > 10 mcg/mL group. In the DFX C trough 10 mcg/mL group. We would recommend a close monitoring in pediatric hematopoietic transplant recipients subjected to deferasirox-based therapy because we have observed a high incidence of adverse events and discontinuation of chelation treatment.

  15. Evaluation of a Stenotrophomonas maltophilia bacteremia cluster in hematopoietic stem cell transplantation recipients using whole genome sequencing

    Directory of Open Access Journals (Sweden)

    Stefanie Kampmeier

    2017-11-01

    Full Text Available Abstract Background Stenotrophomonas maltophilia ubiquitously occurs in the hospital environment. This opportunistic pathogen can cause severe infections in immunocompromised hosts such as hematopoietic stem cell transplantation (HSCT recipients. Between February and July 2016, a cluster of four patients on the HSCT unit suffered from S. maltophilia bloodstream infections (BSI. Methods For epidemiological investigation we retrospectively identified the colonization status of patients admitted to the ward during this time period and performed environmental monitoring of shower heads, shower outlets, washbasins and toilets in patient rooms. We tested antibiotic susceptibility of detected S. maltophilia isolates. Environmental and blood culture samples were subjected to whole genome sequence (WGS-based typing. Results Of four patients with S. maltophlilia BSI, three were found to be colonized previously. In addition, retrospective investigations revealed two patients being colonized in anal swab samples but not infected. Environmental monitoring revealed one shower outlet contaminated with S. maltophilia. Antibiotic susceptibility testing of seven S. maltophlia strains resulted in two trimethoprim/sulfamethoxazole resistant and five susceptible isolates, however, not excluding an outbreak scenario. WGS-based typing did not result in any close genotypic relationship among the patients’ isolates. In contrast, one environmental isolate from a shower outlet was closely related to a single patient’s isolate. Conclusion WGS-based typing successfully refuted an outbreak of S. maltophilia on a HSCT ward but uncoverd that sanitary installations can be an actual source of S. maltophilia transmissions.

  16. INVASIVE CANDIDA INFECTIONS IN PATIENTS WITH HAEMATOLOGICAL MALIGNANCIES AND HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS: CURRENT EPIDEMIOLOGY AND THERAPEUTIC OPTIONS.

    Directory of Open Access Journals (Sweden)

    Corrado Girmenia

    2011-03-01

    Full Text Available In the last decades, the global epidemiological impact of invasive candidiasis (IC in patients with hematologic malignancies (HM and in hematopoietic stem cell transplant (HSCT recipients has decreased and the incidence of invasive aspergillosis  exceeded that of Candida infections. The use of prevention strategies, first of all antifungal prophylaxis with triazoles,  contributed to the reduction of IC in these populations as demonstrated by several  epidemiological studies. However, relatively little is known about the current epidemiological patterns of IC in HM and HSCT populations, because recent epidemiological data almost exclusively derive from retrospective experiences and few prospective data are available. Several prospective, controlled studies in the prophylaxis of invasive fungal diseases have been conducted in both the HM and HSCT setting. On the contrary, most of the prospective controlled trials that demonstrated the efficacy of the antifungal drugs echinocandins and voriconazole in the treatment of candidemia and invasive candidiasis mainly involved  patients with underlying conditions other than HM or  HSCT.  For these reasons, international guidelines provided specific indications for the prophylaxis strategies in HM and HSCT patients, whereas the  recommendations on therapy of documented Candida infections are based on the results observed in the general population and should be considered with caution.

  17. Mixed germ-cell testicular tumor in a liver transplant recipient

    Directory of Open Access Journals (Sweden)

    Mehdi Salehipour

    2012-01-01

    Full Text Available The development of malignancies after solid organ transplants is a well-known complication. Cancer is associated with significant consequences for the organ transplant patient. It is expected that cancer will surpass cardiovascular complications as the leading cause of death in transplant patients within the next few years. We report on a 36-year-old male patient who developed mixed germ-cell testicular tumor seven years after liver transplantation for alcoholic cirrhosis. He was treated with orchiectomy, retroperitoneal lymph node dissection and post-operative chemotherapy.

  18. How Does Influenza A (H1N1 Infection Proceed in Allogeneic Stem Cell Transplantation Recipients?

    Directory of Open Access Journals (Sweden)

    Sinem Civriz Bozdağ

    2012-03-01

    Full Text Available Clinical course of H1N1 infection in Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT patients is contraversial. We report three AHSCT patients who were infected with Influenza A/H1N1 infection. All of the patients were diagnosed with different hematological diagnosis and were at different stages of transplantation.All of them were treated with oseltamivir,zanamivir was switched with oseltamivir in one patient. All of the three patients were survived without any complication. Swine flu, can display with different courses and progress with bacterial or other viral infections in immunsupressed patients.

  19. 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.

  20. Murine cytomegalovirus immediate-early 1 gene expression correlates with increased GVHD after allogeneic hematopoietic cell transplantation in recipients reactivating from latent infection.

    Directory of Open Access Journals (Sweden)

    Senthilnathan Palaniyandi

    Full Text Available The success of allogeneic (allo hematopoietic cell transplantation (HCT is limited by its treatment related complications, mostly graft versus host disease (GVHD and fungal and viral infections. CMV reactivation after HCT has been associated with increased morbidity and mortality, and a causal relation between GVHD, immunosuppressive therapy and vice versa has been postulated. Using a low GVHD severity murine HCT model, we assessed the role of MCMV reactivation and GVHD development. BALB/c mice were infected with either murine CMV (MCMV or mock and monitored for 25 weeks to establish latency, followed by sublethal irradiation conditioning and infusion of bone marrow plus splenocytes from either syngeneic (syn BALB/c or allo B10.D2 donors. Engraftment of allo donor cells was confirmed by PCR for D2Mit265 gene product size. Day+100 mortality and overall GVHD severity in allo MCMV pre-infected recipients was higher than in allo mock controls. Pathologic changes of lung and liver GVHD in immediate-early gene 1 (IE1 positive recipients were significantly increased compared to mock controls, and were only slightly increased in IE1 negative. No significant gut injury was seen in any group. Aggravated lung injury in IE1 positive recipients correlated with higher BAL cell counts both for total cells and for CD4+ T cells when compared with mock controls, and also with protein expression of lung IFN-gamma and liver TNF. No evidence for CMV specific morphologic changes was seen on histopathology in any organ of IE1 positive recipients, suggesting that CMV reactivation is related to increased GVHD severity but does not require active CMV disease, strengthening the concept of a reciprocal relationship between CMV and GVHD.

  1. IgM anti-recipient ABO antibodies predict acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Zaimoku, Yoshitaka; Takami, Akiyoshi; Sato, Hidehiro; Utsumi, Maki; Nakao, Shinji

    2013-07-01

    Passenger lymphocyte syndrome (PLS) presents as transient immune hemolysis due to anti-recipient ABO antibodies produced by donor B-lymphocytes accompanying minor or bidirectional ABO incompatible allogeneic hematopoietic stem cell transplantation (HSCT). We monitored both IgM and IgG type anti-recipient ABO antibodies in 18 consecutive HSCT recipients with hematological malignancies. Five of these patients (28%) developed transient immune hemolysis due to PLS after a median of 19 days post-HSCT. This response was associated with the detection of IgM and IgG anti-recipient ABO antibodies after a median of 16 and 22 days post-HSCT, respectively. All five patients subsequently developed acute graft-versus-host disease (GVHD) grades II-IV, and three died due to transplant-related mortality (TRM) within 1 year after HSCT, while in contrast, of the 13 patients without PLS, three (23%) developed grades II-IV acute GVHD (p ABO antibody may be an early predictor of acute GVHD and poor survival after minor or bidirectional ABO incompatible HSCT.

  2. Residual stresses and strength of multilayer tape cast solid oxide fuel and electrolysis half-cells

    DEFF Research Database (Denmark)

    Charlas, Benoit; Frandsen, Henrik Lund; Brodersen, Karen

    2015-01-01

    -cells with the electrolyte on the compressive side corresponds to the strength of the support. With the loading in the other direction (electrolyte on the tensile side), the origin of the failure is in a different layer for MTC3 (fuel electrode) and for MTC4 (barrier layer). In order to decrease the tensile residual...... coefficient (TEC) mismatch between the layers, cumulated from high temperature, induces significant residual stresses in the half-cells. Furthermore, it has been observed that MTC half-cells with 4 layers (MTC4: support, fuel electrode, electrolyte and barrier layer) are sometimes more fragile to handle than...

  3. Simultaneous Penile and Signet Ring Cell Bladder Carcinoma in Renal Transplant Recipient: A First Case

    Directory of Open Access Journals (Sweden)

    Francesca Manassero

    2009-01-01

    Full Text Available The incidence and prevalence of cancer increase with time after transplantation. Therefore, a risk-adapted screening process is very important in order to identify low-grade malignancies early in their development. This provides the opportunity to initiate appropriate immunosuppressive regimens depending on the tumor type and stage of development. The first case presented is one of a 65-year-old patient with a double genitourinary carcinoma (penis and bladder. The patient received kidney transplantation 7 years prior to this event. After adequate surgical treatment (partial amputation of the penis for squamous cell carcinoma and complete transurethral resection of bladder adenocarcinoma, the patient was noted to be free of tumor recurrence and had functioning renal graft with a 2-year follow-up.

  4. Dynamical system modeling to simulate donor T cell response to whole exome sequencing-derived recipient peptides: Understanding randomness in alloreactivity incidence following stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Vishal Koparde

    Full Text Available Quantitative relationship between the magnitude of variation in minor histocompatibility antigens (mHA and graft versus host disease (GVHD pathophysiology in stem cell transplant (SCT donor-recipient pairs (DRP is not established. In order to elucidate this relationship, whole exome sequencing (WES was performed on 27 HLA matched related (MRD, & 50 unrelated donors (URD, to identify nonsynonymous single nucleotide polymorphisms (SNPs. An average 2,463 SNPs were identified in MRD, and 4,287 in URD DRP (p<0.01; resulting peptide antigens that may be presented on HLA class I molecules in each DRP were derived in silico (NetMHCpan ver2.0 and the tissue expression of proteins these were derived from determined (GTex. MRD DRP had an average 3,670 HLA-binding-alloreactive peptides, putative mHA (pmHA with an IC50 of <500 nM, and URD, had 5,386 (p<0.01. To simulate an alloreactive donor cytotoxic T cell response, the array of pmHA in each patient was considered as an operator matrix modifying a hypothetical cytotoxic T cell clonal vector matrix; each responding T cell clone's proliferation was determined by the logistic equation of growth, accounting for HLA binding affinity and tissue expression of each alloreactive peptide. The resulting simulated organ-specific alloreactive T cell clonal growth revealed marked variability, with the T cell count differences spanning orders of magnitude between different DRP. Despite an estimated, uniform set of constants used in the model for all DRP, and a heterogeneously treated group of patients, higher total and organ-specific T cell counts were associated with cumulative incidence of moderate to severe GVHD in recipients. In conclusion, exome wide sequence differences and the variable alloreactive peptide binding to HLA in each DRP yields a large range of possible alloreactive donor T cell responses. Our findings also help understand the apparent randomness observed in the development of alloimmune responses.

  5. Psychosocial risk predicts high readmission rates for hematopoietic cell transplant recipients.

    Science.gov (United States)

    Richardson, Daniel R; Huang, Ying; McGinty, Heather L; Elder, Patrick; Newlin, Joanna; Kirkendall, Cyndi; Andritsos, Leslie; Benson, Don; Blum, William; Efebera, Yvonne; Penza, Sam; Hofmeister, Craig; Jaglowski, Samantha; Klisovic, Rebecca; Vasu, Sumithira; William, Basem; Devine, Steven; Rosko, Ashley E

    2018-02-14

    Hematopoietic cell transplantation (HCT) is an intensive treatment resulting in disease control however subsequent psychosocial distress is common. Screening for psychosocial risk factors that contribute to morbidity is underutilized; moreover, the value in screening is uncertain. We performed a retrospective study of 395 HCT patients who were screened for psychosocial risk using the Transplant Evaluation Rating Scale (TERS). Patients were classified by psychosocial risk as no-risk (TERS = 26.5, 52%) vs. at-risk (TERS > 26.5, 48%), with at-risk patients stratified by cumulative deficits into mild risk (TERS = 27-35.5, 39%) and moderate risk (TERS > 35.5, 9%). At-risk patients were more likely to be readmitted within 90 days (mild risk HR = 1.62, p = 0.02; moderate risk HR = 2.50, p = 0.002). Prior psychiatric history (HR = 1.81, p = 0.002) and poor coping skills (HR = 1.64, p = 0.04) also influenced readmission. At-risk patients were more likely to be readmitted for infection (no-risk = 12% vs. at-risk = 25%, p = 0.002). Pre-HCT screening with the TERS did not predict survival or length of stay although at-risk patients are at a heighted risk of readmission. Implementing strategies to reduce readmission in higher risk patients is warranted.

  6. The Changing Epidemiology of Bloodstream Infections and Resistance in Hematopoietic Stem Cell Transplantation Recipients

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    Mücahit Yemişen

    2016-08-01

    Full Text Available Objective: Patients receiving hematopoietic stem cell transplantation (HSCT are exposed to highly immunosuppressive conditions and bloodstream infections (BSIs are one of the most common major complications within this period. Our aim, in this study, was to evaluate the epidemiology of BSIs in these patients retrospectively. Materials and Methods: The epidemiological properties of 312 patients with HSCT were retrospectively evaluated. Results: A total of 312 patients, followed between 2000 and 2011, who underwent autologous (62% and allogeneic (38% HSCT were included in the study. The most common underlying malignancies were multiple myeloma (28% and Hodgkin lymphoma (21.5%. A total of 142 (45% patients developed at least 1 episode of BSI and 193 separate pathogens were isolated from the blood cultures. There was a trend of increase in the numbers of BSIs in 2005-2008 and a relative increase in the proportion of gram-positive infections in recent years (2009-2011, and central venous catheter-related BSI was found to be most common source. Coagulase-negative staphylococci (49.2% and Acinetobacter baumannii (8.8% were the most common pathogens. Extended-spectrum beta-lactamase-producing strains were 23% and 22% among Escherichia coli and Klebsiella spp. isolates, respectively. Quinolone resistance was detected in 10% of Enterobacteriaceae. Resistance to carbapenems was not detected in Enterobacteriaceae, while it was seen at 11.1% and 23.5% in Pseudomonas and Acinetobacter strains, respectively. Conclusion: A shift was detected from gram-negative bacteria to gram-positive in the etiology over the years and central lines were the most common sources of BSIs.

  7. Mild hypothermic culture conditions affect residual host cell protein composition post-Protein A chromatography.

    Science.gov (United States)

    Goey, Cher Hui; Bell, David; Kontoravdi, Cleo

    2018-01-30

    Host cell proteins (HCPs) are endogenous impurities, and their proteolytic and binding properties can compromise the integrity, and, hence, the stability and efficacy of recombinant therapeutic proteins such as monoclonal antibodies (mAbs). Nonetheless, purification of mAbs currently presents a challenge because they often co-elute with certain HCP species during the capture step of protein A affinity chromatography. A Quality-by-Design (QbD) strategy to overcome this challenge involves identifying residual HCPs and tracing their source to the harvested cell culture fluid (HCCF) and the corresponding cell culture operating parameters. Then, problematic HCPs in HCCF may be reduced by cell engineering or culture process optimization. Here, we present experimental results linking cell culture temperature and post-protein A residual HCP profile. We had previously reported that Chinese hamster ovary cell cultures conducted at standard physiological temperature and with a shift to mild hypothermia on day 5 produced HCCF of comparable product titer and HCP concentration, but with considerably different HCP composition. In this study, we show that differences in HCP variety at harvest cascaded to downstream purification where different residual HCPs were present in the two sets of samples post-protein A purification. To detect low-abundant residual HCPs, we designed a looping liquid chromatography-mass spectrometry method with continuous expansion of a preferred, exclude, and targeted peptide list. Mild hypothermic cultures produced 20% more residual HCP species, especially cell membrane proteins, distinct from the control. Critically, we identified that half of the potentially immunogenic residual HCP species were different between the two sets of samples.

  8. Earlier low-dose TBI or DST overcomes CD8+ T-cell-mediated alloresistance to allogeneic marrow in recipients of anti-CD40L.

    Science.gov (United States)

    Takeuchi, Yasuo; Ito, Hiroshi; Kurtz, Josef; Wekerle, Thomas; Ho, Leon; Sykes, Megan

    2004-01-01

    Treatment with a single injection of anti-CD40L (CD154) monoclonal antibody (mAb) and fully mismatched allogeneic bone marrow transplant (BMT) allows rapid tolerization of CD4+ T cells to the donor. The addition of in vivo CD8 T-cell depletion leads to permanent mixed hematopoietic chimerism and tolerance. We now describe two approaches that obviate the requirement for CD8 T-cell depletion by rapidly tolerizing recipient CD8 T cells in addition to CD4 cells. Administration of donor-specific transfusion (DST) to mice receiving 3 Gy total body irradiation (TBI), BMT and anti-CD40L mAb on day 0 uniformly led to permanent mixed chimerism and tolerance, compared with only 40% of mice receiving similar treatment without DST. In the absence of DST, moving the timing of 3 Gy TBI to day -1 or day -2 instead of day 0 led to rapid (by 2 weeks) induction of CD8+ cell tolerance, and also permitted uniform achievement of permanent mixed chimerism and donor-specific tolerance in recipients of anti-CD40L and BMT on day 0. These nontoxic regimens overcome CD8+ and CD4+ T-cell-mediated alloresistance without requiring host T-cell depletion, permitting the induction of permanent mixed chimerism and tolerance.

  9. Residual stresses in a co-sintered SOC half-cell during post-sintering cooling

    DEFF Research Database (Denmark)

    Charlas, Benoit; Chatzichristodoulou, Christodoulos; Brodersen, Karen

    2014-01-01

    on the loading conditions, the additional stress needed to break the cells can indeed be smaller due to the initial thermo-mechanical stress state. The residual stresses can for a bilayer cell be approximated by estimating the temperature at which elastic stresses start to build up during the cooling, i.......e. the reference temperature (Tref) or the strain difference based on the curvature. This approximation gives good results for bilayers with a defined cooling temperature profile, where the curvature of the bilayer defines a unique balance between the two unknown residual stress states in the two layers...... simulation taking into account the elastic response and creep of each layer. The model is validated by measuring the curvature and residual stresses of multi-layer cells....

  10. Relationship between Mixed Donor–Recipient Chimerism and Disease Recurrence after Hematopoietic Cell Transplantation for Sickle Cell Disease

    NARCIS (Netherlands)

    Abraham, Allistair; Hsieh, Matthew; Eapen, Mary; Fitzhugh, Courtney; Carreras, Jeanette; Keesler, Daniel; Guilcher, Gregory; Kamani, Naynesh; Walters, Mark C.; Boelens, Jaap J.; Tisdale, John; Shenoy, Shalini

    2017-01-01

    Mixed donor chimerism after hematopoietic cell transplantation for sickle cell disease (SCD) can result in resolution of disease symptoms, but symptoms recur when donor chimerism is critically low. The relationship between chimerism, hemoglobin S (HbS) level, and symptomatic disease was correlated

  11. Efeito residual de apresentações comerciais dos larvicidas temefos e Bacillus thuringiensis israelensis sobre larvas de Aedes aegypti em recipientes com renovação de água Residual effect of commercial applications of larvicides temefos and Bacillus thuringiensis israelensis on Aedes aegypti larvae in recipients with water renewal

    Directory of Open Access Journals (Sweden)

    Ricardo José Soares Pontes

    2005-08-01

    Full Text Available Avaliou-se o efeito residual do temefos (apresentações comerciais A, B, C e Bacillus thuringiensis israelensis (D e E sobre larvas de Aedes aegypti, em recipientes com renovação de água. Utilizaram-se 44 béqueres de 1.000ml (8 para cada apresentação e 4 controles. Em cada béquer introduziram-se diariamente 25 larvas. Após 24 horas, contavam-se as larvas mortas, esvaziavam-se os béqueres até 200ml, repunha-se o volume original e acrescentavam-se novas larvas. A duração do efeito residual máximo (100% de mortalidade foi: A-19; B-39; C-40; D-8; E-19 dias. A razão de mortalidade permaneceu equivalente entre todos os larvicidas durante 25 dias; B e C mostraram RM 2,40 vezes maior do que E entre 46-95 dias; B, comparado com A, mostrou RM 1,90-7,51 vezes maior entre 26-95 dias. Conclui-se pela maior eficácia de duas apresentações do temefos, mesmo em uma situação epidemiológica de longa exposição ao produto e com renovação de água dos recipientes.The residual effect of temefos (commercial applications A, B and C and Bacillus thuringiensis israelensis (D and E on Aedes aegypti larvae was evaluated, in recipients with water renewal. Forty-four beakers of 1,000ml each (8 for each application and 4 controls were used. In each beaker, 25 larvae were introduced daily. After 24 hours, the dead larvae were counted, the beakers emptied to 200ml and refilled to original volume, with addition of new larvae. The duration of the maximum residual effect (100% of mortality was: A-19; B-39; C-40; D-8; E-19 days. The mortality ratio of all applications remained equivalent for 25 days; B, C and E maintained MR equivalent up to 45 days; B and C showed MR 2.40 times greater than E, between 46-95 days; B, compared with A, showed MR 1.90-7.51 times greater between 26-95 days. The conclusion was greater effectiveness of two presentations of temefos, even in an epidemiological situation with long exposure to the product and renewal of water in

  12. Correlation between residual level of DNA double-strand breaks and the radiosensitivity of cancer cells

    International Nuclear Information System (INIS)

    Sun Jianxiang; Sun Weijian; Sui Jianli; Zhou Pingkun

    2008-01-01

    Objective: To understand the variation of the DNA double-strand break rejoining capacity among different cultured cancer cell lines and the primary cancer cells from brain cancer patients, and to explore the predictor of radiotherapy responses of cancers. Methods: DNA double-strand breaks (DSBs) were induced by 60 Co γ-irradiation. Pulsed-field gel electrophoresis was used to analyze the initial production and rejoining of DNA DSBs. Radiosensitivity was determined by in vitro assay of clonogenic-forming capacity. Results: A wide variation of radiosensitivity, e.g. the survival parameter of Do varied from 0.65 to 2.15 Gy, was displayed among the eight cell lines derived from different type of cancers. Although differential level of initial DNA DSBs induced by 20 Gy γ-rays was observed among various cell lines, it was not correlated with the radiosensitivity. The deficiency of DNA DSB rejoining in radiosensitive cell lines was shown either in the early rapid-rejoining phase (SX-10 cells) or in the late slow-rejoining phase (A2780 cells). A significant relationship was observed between the residual level of DNA DSBs measured at 2 h post-20 Gy irradiation and the cellular radiosensitivity (D 0 or SF 2 ). The kinetic curves of rejoining DNA DSBs in the primary human brain tumor cells indicated a variation on DSB rejoining capacity among different individual tumor. The residual level of DNA DSBs after 2 h of rejoining post 20 Gy irradiation in primary human brain tumor cells is compatible to the results obtained in vitro culture cancer cell lines. Conclusions: The residual level of DNA DSBs is correlated with radioresistance of cancer cells, and the residual DNA damage is a useful parameter in predicting the response of tumor tissue to radiotherapy. (authors)

  13. In Silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem Cell Transplant Donors and Recipients: Understanding the Quantitative Immunobiology of Allogeneic Transplantation

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    Max eJameson-Lee

    2014-11-01

    Full Text Available Donor T cell mediated graft versus host effects (GVH may result from the aggregate alloreactivity to minor histocompatibility antigens (mHA presented by the HLA molecules in each donor-recipient pair undergoing stem cell transplantation (SCT. Whole exome sequencing has previously demonstrated a large number of nonsynonymous single nucleotide polymorphisms (SNP present in HLA-matched recipients of SCT donors (GVH direction. The nucleotide sequence flanking each of these SNPs was obtained and the amino acid sequence determined. All the possible nonameric-peptides incorporating the variant amino acid resulting from these SNPs were interrogated in-silico for their likelihood to be presented by the HLA class I molecules using the Immune Epitope Database stabilized matrix method (SMM and NetMHCpan algorithms. The SMM algorithm predicted that a median of 18,396 peptides weakly bound HLA class I molecules in individual SCT recipients, and 2,254 peptides displayed strong binding. A similar library of presented peptides was identified when the data was interrogated using the NetMHCpan algorithm. The bioinformatic algorithm presented here demonstrates that there may be a high level of mHA variation in HLA-matched individuals, constituting an HLA-specific alloreactivity potential.

  14. ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients

    DEFF Research Database (Denmark)

    Maertens, Johan; Cesaro, Simone; Maschmeyer, Georg

    2016-01-01

    The 5th European Conference on Infections in Leukaemia (ECIL-5) meeting aimed to establish evidence-based recommendations for the prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in non-HIV-infected patients with an underlying haematological condition, including allogeneic HSCT recipients. R...

  15. Removing residual DNA from Vero-cell culture-derived human rabies vaccine by using nuclease.

    Science.gov (United States)

    Li, Si-Ming; Bai, Fu-Liang; Xu, Wen-Juan; Yang, Yong-Bi; An, Ying; Li, Tian-He; Yu, Yin-Hang; Li, De-Shan; Wang, Wen-Fei

    2014-09-01

    The clearance of host cell DNA is a critical indicator for Vero-cell culture-derived rabies vaccine. In this study, we evaluated the clearance of DNA in Vero-cell culture-derived rabies vaccine by purification process utilizing ultrafiltration, nuclease digestion, and gel filtration chromatography. The results showed that the bioprocess of using nuclease decreased residual DNA. Dot-blot hybridization analysis showed that the residual host cell DNA was rabies vaccine was less than 0.1 ng/ml protein. The residual nuclease could not paly the biologically active role of digestion of DNA. Experiments of stability showed that the freeze-drying rabies virus vaccine was stable and titers were >5.0 IU/ml. Immunogenicity test and protection experiments indicated mice were greatly induced generation of neutralizing antibodies and invoked protective effects immunized with intraperitoneal injections of the rabies vaccine. These results demonstrated that the residual DNA was removed from virus particles and nuclease was removed by gel filtration chromatography. The date indicated that technology was an efficient method to produce rabies vaccine for human use by using nuclease. Copyright © 2014 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  16. Automated multimodal spectral histopathology for quantitative diagnosis of residual tumour during basal cell carcinoma surgery

    NARCIS (Netherlands)

    Boitor, R. (Radu); Kong, K. (Kenny); Shipp, D. (Dustin); Varma, S. (Sandeep); Koloydenko, A. (Alexey); Kulkarni, K. (Kusum); Elsheikh, S. (Somaia); Bakker Schut, T. (Tom); P.J. Caspers (Peter); G.J. Puppels (Gerwin); M.J.G. Van Der Wolf (Martin J. G.); Sokolova, E. (Elena); T.E.C. Nijsten (Tamar); Salence, B. (Brogan); H. Williams; Notingher, I. (Ioan)

    2017-01-01

    textabstractMultimodal spectral histopathology (MSH), an optical technique combining tissue auto-fluorescence (AF) imaging and Raman micro-spectroscopy (RMS), was previously proposed for detection of residual basal cell carcinoma (BCC) at the surface of surgically-resected skin tissue. Here we

  17. Recruitment of Donor T Cells to the Eyes During Ocular GVHD in Recipients of MHC-Matched Allogeneic Hematopoietic Stem Cell Transplants

    Science.gov (United States)

    Herretes, Samantha; Ross, Duncan B.; Duffort, Stephanie; Barreras, Henry; Yaohong, Tan; Saeed, Ali M.; Murillo, Juan C.; Komanduri, Krishna V.; Levy, Robert B.; Perez, Victor L.

    2015-01-01

    Purpose. The primary objective of the present study was to identify the kinetics and origin of ocular infiltrating T cells in a preclinical model of graft-versus-host disease (GVHD) that induces eye tissue damage. Methods. Graft-versus-host disease was induced using an major histocompatibility complex (MHC)-matched, minor histocompatibility-mismatched hematopoietic stem cell transplant (HSCT) model. This approach, which utilized congenic and EGFP-labeled donor populations, mimics a matched, clinically unrelated donor (MUD) cell transplant. Systemic and ocular GVHD were assessed at varying time points using clinical examination, intravital microscopy, immune phenotype via flow cytometric analyses, and immunohistochemical staining. Results. Following transplant, we observed characteristic changes in GVHD-associated immune phenotype as well as clinical signs present in recipients post transplant. Notably, the kinetics of the systemic changes and the ocular damage paralleled what is observed clinically, including damage to the cornea as well as the conjunctiva and lacrimal gland. Importantly, the infiltrate contained predominantly donor CD4 as well as CD8 T cells with an activated phenotype and macrophages together with effector cytokines consistent with the presence of a TH1 alloreactive population. Conclusions. Overall, the findings here unequivocally demonstrated that donor T cells compose part of the corneal and ocular adnexa infiltrate in animals undergoing ocular GVHD. In total, the results describe a novel and promising preclinical model characterized by both systemic and ocular changes as detected in significant numbers of patients undergoing GVHD following allo-HSCT, which can help facilitate dissecting the underlying immune mechanisms leading to damage associated with ocular GVHD. PMID:25655798

  18. Recruitment of Donor T Cells to the Eyes During Ocular GVHD in Recipients of MHC-Matched Allogeneic Hematopoietic Stem Cell Transplants.

    Science.gov (United States)

    Herretes, Samantha; Ross, Duncan B; Duffort, Stephanie; Barreras, Henry; Yaohong, Tan; Saeed, Ali M; Murillo, Juan C; Komanduri, Krishna V; Levy, Robert B; Perez, Victor L

    2015-04-01

    The primary objective of the present study was to identify the kinetics and origin of ocular infiltrating T cells in a preclinical model of graft-versus-host disease (GVHD) that induces eye tissue damage. Graft-versus-host disease was induced using an major histocompatibility complex (MHC)-matched, minor histocompatibility-mismatched hematopoietic stem cell transplant (HSCT) model. This approach, which utilized congenic and EGFP-labeled donor populations, mimics a matched, clinically unrelated donor (MUD) cell transplant. Systemic and ocular GVHD were assessed at varying time points using clinical examination, intravital microscopy, immune phenotype via flow cytometric analyses, and immunohistochemical staining. Following transplant, we observed characteristic changes in GVHD-associated immune phenotype as well as clinical signs present in recipients post transplant. Notably, the kinetics of the systemic changes and the ocular damage paralleled what is observed clinically, including damage to the cornea as well as the conjunctiva and lacrimal gland. Importantly, the infiltrate contained predominantly donor CD4 as well as CD8 T cells with an activated phenotype and macrophages together with effector cytokines consistent with the presence of a TH1 alloreactive population. Overall, the findings here unequivocally demonstrated that donor T cells compose part of the corneal and ocular adnexa infiltrate in animals undergoing ocular GVHD. In total, the results describe a novel and promising preclinical model characterized by both systemic and ocular changes as detected in significant numbers of patients undergoing GVHD following allo-HSCT, which can help facilitate dissecting the underlying immune mechanisms leading to damage associated with ocular GVHD.

  19. [Clinical study of low cytomegalovirus viral load thresholds for preemptive antiviral therapy in hematopoietic cell transplant recipients].

    Science.gov (United States)

    Li, L; Wang, Y; Yan, C H; Huang, X J

    2018-03-01

    Objective: To investigate the threshold of cytomegalovirus (CMV) DNAemia for preemptive antiviral therapy in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Viral load between 1×10(3) copies/ml and 5×10(3) copies/ml was defined as low viral load by real time Q-PCR. Clinical data and outcome were collected. Results: A total of 95 allo-HSCT recipients with low viral load from September 2014 to February 2015 were recruited in this study. The control group included 37 patients who received preemptive initial antiviral therapy. The other 58 patients didn't received antiviral treatment after positive viremia was confirmed. During monitoring, CMV viremia was cleared spontaneously in 17 patients of study group. Among 41 patients with continuous positive viremia in study group, 26 patients received antiviral therapy after second positivity including 18 with viral load >5×10(3) copies/ml, 2 with fever but still low viral load, 2 with hemorrhagic cystitis and low viral load, 4 with continuous low viral load. Eleven patients received antiviral therapy after the third positivity including 5 with viral load >5×10(3) copies/ml, 1 low viral load patient with fever and diarrhea, 5 with continuous low viral load. Only 4 patients received antiviral therapy after the fourth positivity of >5×10(3) copies/ml. In the study group, 35 cases received ganciclovir and 6 cases received foscarnet. The incidence of neutropenia did not differ significantly between study and control groups [minimum of neutrophil count: (1.63±0.41)×10(9)/L vs. (1.58±0.36)×10(9)/L]. The proportion of viral load greater than 5×10(3) copies/ml in the first week was comparable in two groups. Successful viral clearance rate was not statistically different ( P =0.87). Of all 95 patients, no CMV diseases developed, neither did patient die of CMV infection. Conclusions: Spontaneous clearance of viremia occurs in some patients receiving allo-HSCT with low CMV viral load

  20. Successful Desensitization of T cell Flow Cytometry Crossmatch Positive Renal Transplant Recipients Using Plasmapheresis and Super High-Dose Intravenous Immunoglobulin

    Directory of Open Access Journals (Sweden)

    Yoichi Kakuta, MD, PhD

    2018-01-01

    Full Text Available Background. High-dose IVIG (2 g/kg alone or low-dose IVIG (100 mg/kg in conjunction with plasma exchange is typically administered as a renal transplantation desensitization therapy. Herein, we monitored changes in T cell and B cell flow cytometry crossmatch (FCXM to assess the effects of short-term super high-dose IVIG (4 g/kg administration with plasmapheresis before living-donor renal transplantation. Methods. Seventeen patients, each showing positive T cell FCXM (median ratio, ≥ 1.4 after 2 rounds of double-filtration plasmapheresis, received 4-day regimens of IVIG (1 g/kg per day over 1-week periods. T cell and B cell FCXM determinations were obtained after every IVIG dose and again up to 4 weeks after initiating IVIG to ascertain negative conversion of T cell FCXM (median ratio < 1.4. The primary study endpoint was the percentage of patients achieving T cell FCXM-negative status after the 4-dose IVIG regimen. Results. Upon completion (4 g/kg total or discontinuation of IVIG administration, 8 (47.1% of 17 patients displayed negative T cell FCXM. Based on Kaplan-Meier estimates, the cumulative T cell FCXM-negative conversion rate 4 weeks after IVIG administration initiation was 60.3%. The T cell FCXM-negative conversion rates after cumulative doses of 1, 2, 3, and 4 g/kg IVIG were 29.4%, 35.3%, 56.3%, and 46.7%, respectively. Conclusions. Desensitization of donor-specific antibody-positive renal transplant recipients seems achievable in only a subset of recipients through IVIG dosing (1 g/kg × 4 within 1 week after double-filtration plasmapheresis. The T cell FCXM-negative conversion rate resulting from a cumulative IVIG dose of 3 g/kg or greater surpassed that attained via conventional single-dose IVIG (2 g/kg protocol. This short-term high-dose IVIG desensitization protocol may be an alternative to conventional protocols for recipients with donor-specific antibody.

  1. A new one-platform flow cytometric method for residual cell counting in platelet concentrates.

    Science.gov (United States)

    Schmidt, Michael; Spengler, Hans-Peter; Lambrecht, Bernd; Hourfar, Michael K; Seifried, Erhard; Tonn, Torsten

    2009-12-01

    According to German regulations and guidelines, residual red blood cells (rRBCs) and residual white blood cells (rWBCs) must number fewer than 3 x 10(9) cells/unit and 1 x 10(6) cells/unit in platelet concentrates (PCs), respectively. Due to low levels of residual cells in final products, there is still a need for fast, reliable, and sensitive methods of automated detection of these cell types. In Part A, 21 PCs were spiked with predetermined numbers of red blood cells (RBCs) and white blood cells (WBCs). The linearity, precision, and accuracy of the BD Thrombo Count assay (BD Biosciences Europe) were tested and validated according to international guidelines. Finally in Part B, 100 PCs prepared from pooled buffy coats were tested by the BD Thrombo Count assay and compared with other methods, including Nageotte (rWBCs) and Neubauer (rRBCs) counting chambers and the flow cytometric BD LeucoCOUNT (Becton Dickinson) assay (rWBCs). The unspecific background of blank PC samples was fewer than 0.02 cells/microL for WBCs and fewer than 34 cells/microL for RBCs (mean, 21). Linear regression and precision analyses of spiked PC samples were determined for both WBCs (r(2) = 0.992; range, 0.6-6.0 WBCs/microL) and RBCs (r(2) = 0.999; 800-8000 RBCs/microL). No carryover of cells or drift in results was detected in the automated sample acquisition mode. Analysis according to statistical methods of Bland and Altman demonstrated a high correlation between BD Thrombo Count and the Neubauer manual counting chamber. This novel flow cytometric test is a quick and reliable single-tube assay that has been demonstrated as a potential alternative for the existing manual microscopic counting procedures that are both time-consuming and laborious.

  2. Quantitative detection of residual E. coli host cell DNA by real-time PCR.

    Science.gov (United States)

    Lee, Dong Hyuck; Bae, Jung Eun; Lee, Jung Hee; Shin, Jeong Sup; Kim, In Seop

    2010-10-01

    E. coli has been widely used as a host system to manufacture recombinant proteins for human therapeutic use. Among impurities to be eliminated during the downstream process, residual host cell DNA is a major interest for safety. Residual E. coli host cell DNA in the final products are usually determined using conventional slot blot hybridization assay or total DNA Threshold assay, although these methods are time consuming, expensive, and relatively insensitive. Therefore a sensitive real-time PCR assay for specific detection of residual E. coli DNA was developed and compared with slot blot hybridization assay and Threshold assay to validate the overall capability of these methods. Specific primer pair for amplification of the E. coli 16S rRNA gene was selected to improve the sensitivity, and E. coli host cell DNA was quantified by use of SYBR Green 1. The detection limit of real-time PCR assay in the optimized condition was calculated to be 0.042 pg genomic DNA, which is much higher than those of slot blot hybridization assay and Threshold assay of which detection limit were 2.42 and 3.73 pg genomic DNA, respectively. The real-time PCR assay was validated to be more reproducible, accurate, and precise than slot blot hybridization assay and Threshold assay. The real-time PCR assay may be a useful tool for quantitative detection and clearance validation of residual E. coli DNA during the manufacturing process for recombinant therapeutics.

  3. Insulin Induces Phosphorylation of Serine Residues of Translationally Controlled Tumor Protein in 293T Cells

    Directory of Open Access Journals (Sweden)

    Jeehye Maeng

    2015-04-01

    Full Text Available Insulin induces the activation of Na,K-ATPase while translationally controlled tumor protein (TCTP inhibits this enzyme and the associated pump activity. Because binding of insulin with its membrane receptor is known to mediate the phosphorylation of multiple intracellular proteins, phosphorylation of TCTP by insulin might be related to the sodium pump regulation. We therefore examined whether insulin induces TCTP phosphorylation in embryonic kidney 293T cells. Using immunoprecipitation and Western blotting, we found that insulin phosphorylates serine (Ser residues of TCTP. Following fractionation of the insulin-treated cells into cytosol and membrane fractions, phosphorylated TCTP at its Ser residue (p-Ser-TCTP was detected exclusively in the cytosolic part and not in the membrane fraction. Phosphorylation of TCTP reached maximum in about 10 min after insulin treatment in 293T cells. In studies of cell-type specificity of insulin-mediated phosphorylation of TCTP, insulin did not phosphorylate TCTP in HeLa cells. Computational prediction and immunoprecipitation using several constructs having Ser to Ala mutation at potential p-Ser sites of TCTP revealed that insulin phosphorylated the serine-9 and -15 residues of TCTP. Elucidations of how insulin-mediated TCTP phosphorylation promotes Na,K-ATPase activation, may offer potential therapeutic approaches to diseases associated with vascular activity and sodium pump dysregulation.

  4. Hexa-arginine enhanced uptake and residualization of selective high affinity ligands by Raji lymphoma cells

    Directory of Open Access Journals (Sweden)

    Mirick Gary

    2009-04-01

    Full Text Available Abstract Background A variety of arginine-rich peptide sequences similar to those found in viral proteins have been conjugated to other molecules to facilitate their transport into the cytoplasm and nucleus of targeted cells. The selective high affinity ligand (SHAL (DvLPBaPPP2LLDo, which was developed to bind only to cells expressing HLA-DR10, has been conjugated to one of these peptide transduction domains, hexa-arginine, to assess the impact of the peptide on SHAL uptake and internalization by Raji cells, a B-cell lymphoma. Results An analog of the SHAL (DvLPBaPPP2LLDo containing a hexa-arginine peptide was created by adding six D-arginine residues sequentially to a lysine inserted in the SHAL's linker. SHAL binding, internalization and residualization by Raji cells expressing HLA-DR10 were examined using whole cell binding assays and confocal microscopy. Raji cells were observed to bind two fold more 111In-labeled hexa-arginine SHAL analog than Raji cells treated with the parent SHAL. Three fold more hexa-arginine SHAL remained associated with the Raji cells after washing, suggesting that the peptide also enhanced residualization of the 111In transported into cells. Confocal microscopy showed both SHALs localized in the cytoplasm of Raji cells, whereas a fraction of the hexa-arginine SHAL localized in the nucleus. Conclusion The incorporation of a hexa-D-arginine peptide into the linker of the SHAL (DvLPBaPPP2LLDo enhanced both the uptake and residualization of the SHAL analog by Raji cells. In contrast to the abundant cell surface binding observed with Lym-1 antibody, the majority of (DvLPBaPPP2LArg6AcLLDo and the parent SHAL were internalized. Some of the internalized hexa-arginine SHAL analog was also associated with the nucleus. These results demonstrate that several important SHAL properties, including uptake, internalization, retention and possibly intracellular distribution, can be enhanced or modified by conjugating the SHALs to a

  5. Assessment of the immunogenicity of residual host cell protein impurities of OsrHSA.

    Science.gov (United States)

    Abiri, Naghmeh; Pang, Jianlei; Ou, Jiquan; Shi, Bo; Wang, Xianghong; Zhang, Sucai; Sun, Yunxia; Yang, Daichang

    2018-01-01

    Human serum albumin (HSA) is the most abundant protein in human plasma and is widely used at high doses for treating various diseases. Recombinant HSA is an alternative approach to plasma-derived HSA, providing increased safety and an unlimited supply. However, the safety of the residual host cell proteins (HCPs) co-purified with Oryza sativa HSA (OsrHSA) remains to be determined. An animal system was used to assess the immunogenicity of OsrHSA and its residual HCPs. Low immunogenicity and immunotoxicity of the residual HCPs at a dose of 25 μg/kg, equivalent to 25 times the clinical dosage of HSA, were observed. An anti-drug-antibody (ADA) analysis revealed that anti-HSA, anti-OsrHSA or anti-HCP antibodies developed with a low frequency in pHSA and OsrHSA treatments, but the titers were as low as 1.0-2.0. Furthermore, the titer and the incidence of the specific antibodies were not significantly different between the pHSA and OsrHSA groups, indicating that OsrHSA presents similar immunogenicity to that of pHSA. More importantly, no cytokines were stimulated after the administration of OsrHSA and the residual HCPs, suggesting that there was no risk of a cytokine storm. These results demonstrated that the residual HCPs from OsrHSA have low immunogenicity, indicating that the rice endosperm is one of the best hosts for plant molecular pharming.

  6. [Information and consent forms for hematopoietic stem cell transplantation donors and recipients: Guidelines from the Franchophone society of bone marrow transplantation and cellular therapy (SFGM-TC)].

    Science.gov (United States)

    Bruno, Bénédicte; Thibert, Jean-Baptiste; Bancillon, Nelly; Desbos, Anna; Fawaz, Abir; Fournier, Isabelle; Genty, Carole; Issarni, Dominique; Leveille, Sandrine; Premel, Christelle; Polomeni, Alice; Renault, Myriam; Tarillon, Sylvie; Wallart, Anne; Yakoub-Agha, Ibrahim; Bordessoule, Dominique

    2016-11-01

    Within the context of the SFGM-TC's 6th workshop series on the harmonization of clinical practices, our workshop proposes a standardization of the informed consent process for hematopoietic stem cell donors and recipients leading up to an autologous or allogenic transplantation. All informed consent was for bone marrow or peripheral stem cell donors, and mononuclear/lymphocyte donors according to usual procedures. The informed consent for autologous and allogenic related or unrelated adults and pediatric transplantation patients have been included. A first step has been conducted for collecting in advance the informed consent forms used routinely in all francophone transplantation centers. In a second step, a comprehensive version has been re-written by a multidisciplinary team. For the purposes of understanding the risks and advantages, language has been carefully considered and streamlined. In the third step, texts were sent to stem cell transplantation experts, experts at the French biomedical agency (agence de la biomédecine [ABM]), law specialists, members of the ethical committee of the French society of hematology and several transplant recipients to be edited and proofread. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  7. A 31-residue peptide induces aggregation of tau's microtubule-binding region in cells

    Science.gov (United States)

    Stöhr, Jan; Wu, Haifan; Nick, Mimi; Wu, Yibing; Bhate, Manasi; Condello, Carlo; Johnson, Noah; Rodgers, Jeffrey; Lemmin, Thomas; Acharya, Srabasti; Becker, Julia; Robinson, Kathleen; Kelly, Mark J. S.; Gai, Feng; Stubbs, Gerald; Prusiner, Stanley B.; Degrado, William F.

    2017-09-01

    The self-propagation of misfolded conformations of tau underlies neurodegenerative diseases, including Alzheimer's. There is considerable interest in discovering the minimal sequence and active conformational nucleus that defines this self-propagating event. The microtubule-binding region, spanning residues 244-372, reproduces much of the aggregation behaviour of tau in cells and animal models. Further dissection of the amyloid-forming region to a hexapeptide from the third microtubule-binding repeat resulted in a peptide that rapidly forms fibrils in vitro. We show that this peptide lacks the ability to seed aggregation of tau244-372 in cells. However, as the hexapeptide is gradually extended to 31 residues, the peptides aggregate more slowly and gain potent activity to induce aggregation of tau244-372 in cells. X-ray fibre diffraction, hydrogen-deuterium exchange and solid-state NMR studies map the beta-forming region to a 25-residue sequence. Thus, the nucleus for self-propagating aggregation of tau244-372 in cells is packaged in a remarkably small peptide.

  8. Selenium Protects Retinal Cells from Cisplatin-Induced Alterations in Carbohydrate Residues.

    Science.gov (United States)

    Akşit, Dilek; Yazıcı, Alper; Akşit, Hasan; Sarı, Esin S; Yay, Arzu; Yıldız, Onur; Kılıç, Adil; Ermiş, Sıtkı S; Seyrek, Kamil

    2016-07-01

    Investigate alterations in the expression and localization of carbohydrate units in rat retinal cells exposed to cisplatin toxicity. The aim of the study was to evaluate putative protective effects of selenium on retinal cells subjected to cisplatin. Animal experiment. Eighteen healthy Wistar rats were divided into three equal groups: 1. Control, 2. Cisplatin and 3. Cisplatin+selenium groups. After anesthesia, the right eye of each rat was enucleated. Histochemically, retinal cells of control groups reacted with α-2,3-bound sialic acid-specific Maackia amurensis lectin (MAA) strongly, while cisplatin reduced the staining intensity for MAA. However, selenium administration alleviated the reducing effect of cisplatin on the binding sites for MAA in retinal cells. The staining intensity for N-acetylgalactosamine (GalNAc residues) specific Griffonia simplicifolia-1 (GSL-1) was relatively slight in control animals and cisplatin reduced this slight staining for GSL-1 further. Selenium administration mitigated the reducing effect of cisplatin on the binding sites for GSL-1. A diffuse staining for N-acetylglucosamine (GlcNAc) specific wheat germ agglutinin (WGA) was observed throughout the retina of the control animals. In particular, cells localized in the inner plexiform and photoreceptor layers are reacted strongly with WGA. Compared to the control animals, binding sites for WGA in the retina of rats given cisplatin were remarkably decreased. However, the retinal cells of rats given selenium reacted strongly with WGA. Cisplatin reduces α-2,3-bound sialic acid, GlcNAc and GalNAc residues in certain retinal cells. However, selenium alleviates the reducing effect of cisplatin on carbohydrate residues in retinal cells.

  9. Selenium Protects Retinal Cells from Cisplatin-Induced Alterations in Carbohydrate Residues

    Directory of Open Access Journals (Sweden)

    Dilek Akşit

    2016-08-01

    Full Text Available Background: Investigate alterations in the expression and localization of carbohydrate units in rat retinal cells exposed to cisplatin toxicity. Aims: The aim of the study was to evaluate putative protective effects of selenium on retinal cells subjected to cisplatin. Study Design: Animal experiment. Methods: Eighteen healthy Wistar rats were divided into three equal groups: 1. Control, 2. Cisplatin and 3. Cisplatin+selenium groups. After anesthesia, the right eye of each rat was enucleated. Results: Histochemically, retinal cells of control groups reacted with α-2,3-bound sialic acid-specific Maackia amurensis lectin (MAA strongly, while cisplatin reduced the staining intensity for MAA. However, selenium administration alleviated the reducing effect of cisplatin on the binding sites for MAA in retinal cells. The staining intensity for N-acetylgalactosamine (GalNAc residues specific Griffonia simplicifolia-1 (GSL–1 was relatively slight in control animals and cisplatin reduced this slight staining for GSL-1 further. Selenium administration mitigated the reducing effect of cisplatin on the binding sites for GSL-1. A diffuse staining for N-acetylglucosamine (GlcNAc specific wheat germ agglutinin (WGA was observed throughout the retina of the control animals. In particular, cells localized in the inner plexiform and photoreceptor layers are reacted strongly with WGA. Compared to the control animals, binding sites for WGA in the retina of rats given cisplatin were remarkably decreased. However, the retinal cells of rats given selenium reacted strongly with WGA. Conclusion: Cisplatin reduces α-2,3-bound sialic acid, GlcNAc and GalNAc residues in certain retinal cells. However, selenium alleviates the reducing effect of cisplatin on carbohydrate residues in retinal cells.

  10. Maribavir prophylaxis for prevention of cytomegalovirus disease in recipients of allogeneic stem-cell transplants: a phase 3, double-blind, placebo-controlled, randomised trial.

    Science.gov (United States)

    Marty, Francisco M; Ljungman, Per; Papanicolaou, Genovefa A; Winston, Drew J; Chemaly, Roy F; Strasfeld, Lynne; Young, Jo-Anne H; Rodriguez, Tulio; Maertens, Johan; Schmitt, Michael; Einsele, Hermann; Ferrant, Augustin; Lipton, Jeffrey H; Villano, Stephen A; Chen, Hongzi; Boeckh, Michael

    2011-04-01

    Available drugs against cytomegalovirus have adverse effects that compromise their prophylactic use in recipients of allogeneic stem-cell transplants. We assessed the safety, tolerability, and antiviral activity of oral maribavir in such patients. In this placebo-controlled, randomised, double-blind, multicentre phase 3 study, we enrolled adult patients recipient-seropositive or donor-seropositive for cytomegalovirus who had undergone allogeneic stem-cell transplantation. Patients were recruited from 90 centres in Canada, Europe, and the USA. After engraftment, patients were stratified by recipient cytomegalovirus serostatus and conditioning regimen (myeloablative or reduced-intensity) and assigned (2:1) by masked computer-generated randomisation sequence to receive maribavir 100 mg twice daily or placebo for up to 12 weeks, with weekly blood cytomegalovirus surveillance. If the virus was detected, administration of study drug was stopped and pre-emptive anticytomegalovirus treatment started. The primary endpoint was cytomegalovirus disease within 6 months of transplantation. Analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov, NCT00411645. Between December, 2006, and May, 2008, 681 patients were enrolled and assigned to receive maribavir (454) or placebo (227). The incidence of cytomegalovirus disease within 6 months was 20 of 454 (4%) for the maribavir group and 11 of 227 (5%) for the placebo group (OR 0.90; 95% CI 0.42-1.92). During the 100 days following transplantation, cytomegalovirus infection rates as measured by pp65 antigenaemia were lower in the maribavir group (26.4%) than in the placebo group (34.8%; OR 0.67; 0.47-0.95), but not when measured by plasma cytomegalovirus DNA PCR (27.8%vs 30.4%; OR 0·88; 0.62-1.25), nor by initiation of treatment against cytomegalovirus (30.6%vs 37.4%; OR 0.73, 0.52-1.03). Maribavir was well tolerated: most adverse events, including incident acute graft-versus-host disease and neutropenia

  11. Donor-Recipient Matching for KIR Genotypes Reduces Chronic GVHD and Missing Inhibitory KIR Ligands Protect against Relapse after Myeloablative, HLA Matched Hematopoietic Cell Transplantation.

    Directory of Open Access Journals (Sweden)

    Rehan Mujeeb Faridi

    Full Text Available Allogeneic hematopoietic cell transplantation (HCT can be curative for many hematologic diseases. However, complications such as graft-versus-host disease (GVHD and relapse of primary malignancy remain significant and are the leading causes of morbidity and mortality. Effects of killer Ig-like receptors (KIR-influenced NK cells on HCT outcomes have been extensively pursued over the last decade. However, the relevance of the reported algorithms on HLA matched myeloablative HCT with rabbit antithymocyte globulin (ATG is used for GVHD prophylaxis remains elusive. Here we examined the role of KIR and KIR-ligands of donor-recipient pairs in modifying the outcomes of ATG conditioned HLA matched sibling and unrelated donor HCT.The study cohort consisted of 281 HLA matched sibling and unrelated donor-recipient pairs of first allogeneic marrow or blood stem cell transplantation allocated into 'discovery' (135 pairs and 'validation' (146 pairs cohorts. High resolution HLA typing was obtained from the medical charts and KIR gene repertoires were obtained by a Luminex® based SSO method. All surviving patients were followed-up for a minimum of two years. KIR and HLA class I distributions of HCT pairs were stratified as per applicable definitions and were tested for their association with cause specific outcomes [acute GVHD grade II-IV (aGVHD, chronic GVHD needing systemic therapy (cGVHD and relapse] using a multivariate competing risks regression model as well as with survival outcomes [relapse-free survival (RFS, cGVHD & relapse free survival (cGRFS and overall survival (OS] by multivariate Cox proportional hazards regression model. A significant association between KIR genotype mismatching (KIR-B/x donor into KIR-AA recipient or vice versa and cGVHD was found in both discovery (p = 0.001; SHR = 2.78; 95%CI: 1.50-5.17 and validation cohorts (p = 0.005; SHR = 2.61; 95%CI: 1.33-5.11. High incidence of cGVHD associated with KIR genotype mismatching was

  12. Donor-Recipient Matching for KIR Genotypes Reduces Chronic GVHD and Missing Inhibitory KIR Ligands Protect against Relapse after Myeloablative, HLA Matched Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Faridi, Rehan Mujeeb; Kemp, Taylor J; Dharmani-Khan, Poonam; Lewis, Victor; Tripathi, Gaurav; Rajalingam, Raja; Daly, Andrew; Berka, Noureddine; Storek, Jan; Masood Khan, Faisal

    2016-01-01

    Allogeneic hematopoietic cell transplantation (HCT) can be curative for many hematologic diseases. However, complications such as graft-versus-host disease (GVHD) and relapse of primary malignancy remain significant and are the leading causes of morbidity and mortality. Effects of killer Ig-like receptors (KIR)-influenced NK cells on HCT outcomes have been extensively pursued over the last decade. However, the relevance of the reported algorithms on HLA matched myeloablative HCT with rabbit antithymocyte globulin (ATG) is used for GVHD prophylaxis remains elusive. Here we examined the role of KIR and KIR-ligands of donor-recipient pairs in modifying the outcomes of ATG conditioned HLA matched sibling and unrelated donor HCT. The study cohort consisted of 281 HLA matched sibling and unrelated donor-recipient pairs of first allogeneic marrow or blood stem cell transplantation allocated into 'discovery' (135 pairs) and 'validation' (146 pairs) cohorts. High resolution HLA typing was obtained from the medical charts and KIR gene repertoires were obtained by a Luminex® based SSO method. All surviving patients were followed-up for a minimum of two years. KIR and HLA class I distributions of HCT pairs were stratified as per applicable definitions and were tested for their association with cause specific outcomes [acute GVHD grade II-IV (aGVHD), chronic GVHD needing systemic therapy (cGVHD) and relapse] using a multivariate competing risks regression model as well as with survival outcomes [relapse-free survival (RFS), cGVHD & relapse free survival (cGRFS) and overall survival (OS)] by multivariate Cox proportional hazards regression model. A significant association between KIR genotype mismatching (KIR-B/x donor into KIR-AA recipient or vice versa) and cGVHD was found in both discovery (p = 0.001; SHR = 2.78; 95%CI: 1.50-5.17) and validation cohorts (p = 0.005; SHR = 2.61; 95%CI: 1.33-5.11). High incidence of cGVHD associated with KIR genotype mismatching was applicable

  13. Depletion of Treg cells inhibits minimal residual disease after surgery of HPV16-associated tumours

    Czech Academy of Sciences Publication Activity Database

    Šímová, Jana; Bubeník, Jan; Bieblová, Jana; Rosalia, Rodney Alexander; Frič, Jan; Reiniš, Milan

    2006-01-01

    Roč. 29, č. 6 (2006), s. 1567-1571 ISSN 1019-6439 R&D Projects: GA ČR(CZ) GA301/04/0492 EU Projects: European Commission(XE) 18933 - CLINIGENE Grant - others:Liga proti rakovině(CZ) XX Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV16 * residual tumour disease * Treg cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.556, year: 2006

  14. HPV16-associated tumours: Therapy of surgical minimal residual disease with dendritic cell-based vaccines

    Czech Academy of Sciences Publication Activity Database

    Reiniš, Milan; Indrová, Marie; Mendoza, Luis; Mikyšková, Romana; Bieblová, Jana; Bubeník, Jan; Šímová, Jana

    2004-01-01

    Roč. 25, č. 4 (2004), s. 1165-1170 ISSN 1019-6439 R&D Projects: GA MZd NC7148; GA ČR GA301/04/0492; GA ČR GA301/01/0985; GA AV ČR IAA5052203 Institutional research plan: CEZ:AV0Z5052915 Keywords : HPV 16 * minimal residual tumour disease * dendritic cells Subject RIV: EC - Immunology Impact factor: 3.056, year: 2004

  15. Bio-electrospraying and droplet-based microfluidics: control of cell numbers within living residues

    Energy Technology Data Exchange (ETDEWEB)

    Hong Jongin; DeMello, Andrew J [Nanostructured Materials and Devices Group, Department of Chemistry, Imperial College London, Exhibition Road, London SW7 2AZ (United Kingdom); Jayasinghe, Suwan N, E-mail: a.demello@imperial.ac.u, E-mail: s.jayasinghe@ucl.ac.u [BioPhysics Group, Department of Mechanical Engineering, University College London, Torrington Place, London WC1E 7JE (United Kingdom)

    2010-04-15

    Bio-electrospraying (BES) has demonstrated great promise as a rapidly evolving strategy for tissue engineering and regenerative biology/medicine. Since its discovery in 2005, many studies have confirmed that cells (immortalized, primary and stem cells) and whole organisms (Danio rerio, Xenopus tropicalis, Caenorhabditis elegans to Drosophila) remain viable post-bio-electrospraying. Although this bio-protocol has achieved much, it suffers from one crucial problem, namely the ability to precisely control the number of cells within droplets and or encapsulations. If overcome, BES has the potential to become a high-efficiency biotechnique for controlled cell encapsulation, a technique most useful for a wide range of applications in biology and medicine ranging from the forming of three-dimensional cultures to an approach for treating diseases such as type I diabetes. In this communication, we address this issue by demonstrating the coupling of BES with droplet-based microfluidics for controlling live cell numbers within droplets and residues. (communication)

  16. The Epstein-Barr virus DNA load in the peripheral blood of transplant recipients does not accurately reflect the burden of infected cells.

    Science.gov (United States)

    Fink, Susanne; Tsai, Ming-Han; Schnitzler, Paul; Zeier, Martin; Dreger, Peter; Wuchter, Patrick; Bulut, Olcay C; Behrends, Uta; Delecluse, Henri-Jacques

    2017-01-01

    Transplant recipients frequently exhibit an increased Epstein-Barr virus (EBV) load in the peripheral blood. Here, we quantitated the EBV-infected cells in the peripheral blood of these patients and defined the mode of viral infection, latent or lytic. These data indicated that there is no strong correlation between the number of infected cells and the EBV load (EBVL). This can be explained by a highly variable number of EBV copies per infected cell and by lytic replication in some cells. The plasma of these patients did not contain any free infectious viruses, but contained nevertheless EBV DNA, sometimes in large amounts, that probably originates from cell debris and contributed to the total EBVL. Some of the investigated samples carried a highly variable number of infected cells in active latency, characterized by an expression of the Epstein-Barr nuclear antigens (EBNA2) protein. However, a third of the samples expressed neither EBNA2 nor lytic proteins. Patients with an increased EBVL represent a heterogeneous group of patients whose infection cannot be characterized by this method alone. Precise characterization of the origin of an increased EBVL, in particular, in terms of the number of EBV-infected cells, requires additional investigations including the number of EBV-encoded small RNA-positive cells. © 2016 Steunstichting ESOT.

  17. Effect of T-cell-epitope matching at HLA-DPB1 in recipients of unrelated-donor haemopoietic-cell transplantation: a retrospective study

    Science.gov (United States)

    Fleischhauer, Katharina; Gooley, Theodore; Malkki, Mari; Bardy, Peter; Bignon, Jean-Denis; Dubois, Valérie; Horowitz, Mary M; Madrigal, J Alejandro; Morishima, Yasuo; Oudshoorn, Machteld; Ringden, Olle; Spellman, Stephen; Velardi, Andrea; Zino, Elisabetta; Petersdorf, Effie W

    2013-01-01

    Summary Background The risks after unrelated-donor haemopoietic-cell transplantation with matched HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 alleles between donor and recipient (10/10 matched) can be decreased by selection of unrelated donors who also match for HLA-DPB1; however, such donors are difficult to find. Classification of HLA-DPB1 mismatches based on T-cell-epitope groups could identify mismatches that might be tolerated (permissive) and those that would increase risks (non-permissive) after transplantation. We did a retrospective study to compare outcomes between permissive and non-permissive HLA-DPB1 mismatches in unrelated-donor haemopoietic-cell transplantation. Methods HLA and clinical data for unrelated-donor transplantations submitted to the International Histocompatibility Working Group in haemopoietic-cell transplantation were analysed retrospectively. HLA-DPB1 T-cell-epitope groups were assigned according to a functional algorithm based on alloreactive T-cell crossreactivity patterns. Recipients and unrelated donors matching status were classified as HLA-DPB1 match, non-permissive HLA-DPB1 mismatch (those with mismatched T-cell-epitope groups), or permissive HLA-DPB1 mismatch (those with matched T-cell-epitope groups). The clinical outcomes assessed were overall mortality, non-relapse mortality, relapse, and severe (grade 3–4) acute graft-versus-host disease (aGvHD). Findings Of 8539 transplantations, 5428 (64%) were matched for ten of ten HLA alleles (HLA 10/10 matched) and 3111 (36%) for nine of ten alleles (HLA 9/10 matched). Of the group overall, 1719 (20%) were HLA-DPB1 matches, 2670 (31%) non-permissive HLA-DPB1 mismatches, and 4150 (49%) permissive HLA-DPB1 mismatches. In HLA 10/10-matched transplantations, non-permissive mismatches were associated with a significantly increased risk of overall mortality (hazard ratio [HR] 1·15, 95% CI 1·05–1·25; p=0·002), non-relapse mortality (1·28, 1·14–1·42; pHLA-DPB1 mismatches and HLA-DPB1

  18. Optimization of therapeutic proteins to delete T-cell epitopes while maintaining beneficial residue interactions.

    Science.gov (United States)

    Parker, Andrew S; Griswold, Karl E; Bailey-Kellogg, Chris

    2011-04-01

    Exogenous enzymes, signaling peptides, and other classes of nonhuman proteins represent a potentially massive but largely untapped pool of biotherapeutic agents. Adapting a foreign protein for therapeutic use poses numerous design challenges. We focus here on one significant problem: modifying the protein to mitigate the immune response mounted against "non-self" proteins, while not adversely affecting the protein's stability or therapeutic activity. In order to propose such variants suitable for experimental evaluation, this paper develops a computational method to select sets of mutations predicted to delete immunogenic T-cell epitopes, as evaluated by a 9-mer potential, while simultaneously maintaining important residues and residue interactions, as evaluated by one- and two-body potentials. While this design problem is NP-hard, we develop an integer programming approach that works very well in practice. We demonstrate the effectiveness of our approach by developing plans for biotherapeutic proteins that, in previous studies, have been partially deimmunized via extensive experimental characterization and modification of limited segments. In contrast, our global optimization technique considers an entire protein and accounts for all residues, residue interactions, and epitopes in proposing candidates worth subjecting to experimental evaluation.

  19. Impact of adjuvanted H1N1 vaccine on cell-mediated rejection in heart transplant recipients.

    Science.gov (United States)

    Schaffer, S A; Husain, S; Delgado, D H; Kavanaugh, L; Ross, H J

    2011-12-01

    During the H1N1 influenza virus pandemic, vaccination of high risk groups including solid-organ transplant recipients was advised. A retrospective case control study of 60 heart transplant patients, 15 having received the H1N1 virus antigen and ASO3 adjuvant vaccine (GlaxoSmithKline, Mississauga, ON, Canada) within 21 days and 45 having not been vaccinated, all undergoing routine surveillance endmyocardial biopsies, was performed. The overall rate of cellular rejection (all grades) was not statistically different between groups; however, acute cellular rejection, ≥grade 2 (1990 ISHLT criteria), was more frequent among those having recently vaccinated (control: 1/45 vs. 6/15, p = 0.001). On multivariate analysis, the only risk factor found to be associated with acute cellular rejection was recent H1N1 viral antigen and adjuvant vaccination (OR 26.5: 95% CI 02.59-270.5). Vaccine adjuvants increase host response to vaccine antigens by immune upregulation potentially increasing risk of rejection in solid-organ transplant recipients. The potential hazard of vaccination this study raises must be weighed with the clear benefit vaccination has proven to be. ©Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

  20. Variable EBV DNA Load Distributions and Heterogeneous EBV mRNA Expression Patterns in the Circulation of Solid Organ versus Stem Cell Transplant Recipients

    Directory of Open Access Journals (Sweden)

    A. E. Greijer

    2012-01-01

    Full Text Available Epstein-Barr virus (EBV driven post-transplant lymphoproliferative disease (PTLD is a heterogeneous and potentially life-threatening condition. Early identification of aberrant EBV activity may prevent progression to B-cell lymphoma. We measured EBV DNA load and RNA profiles in plasma and cellular blood compartments of stem cell transplant (SCT; n=5, solid organ transplant recipients (SOT; n=15, and SOT having chronic elevated EBV-DNA load (n=12. In SCT, EBV DNA was heterogeneously distributed, either in plasma or leukocytes or both. In SOT, EBV DNA load was always cell associated, predominantly in B cells, but occasionally in T cells (CD4 and CD8 or monocytes. All SCT with cell-associated EBV DNA showed BARTs and EBNA1 expression, while LMP1 and LMP2 mRNA was found in 1 and 3 cases, respectively. In SOT, expression of BARTs was detected in all leukocyte samples. LMP2 and EBNA1 mRNA was found in 5/15 and 2/15, respectively, but LMP1 mRNA in only 1, coinciding with severe PTLD and high EBV DNA. Conclusion: EBV DNA is differently distributed between white cells and plasma in SOT versus SCT. EBV RNA profiling in blood is feasible and may have added value for understanding pathogenic virus activity in patients with elevated EBV-DNA.

  1. Susceptibility to Cutaneous Squamous Cell Carcinoma in Renal Transplant Recipients Associates with Genes Regulating Melanogenesis Independent of their Role in Pigmentation

    Directory of Open Access Journals (Sweden)

    Per A. Andresen

    2013-01-01

    Full Text Available The highly polymorphic melanocortin 1 receptor ( MC1R gene plays a crucial role in pigmentation. Variants of the gene have been implicated in risk of cutaneous squamous cell carcinoma (SCC in the general population. In renal transplant (RT recipients these cancers are more aggressive and very common. To evaluate the risk of SCC relative to MC1R and the pigmentation-associated genes ASIP, TYR , and TYRP1 , a group of 217 RT recipients with and without SCC was genotyped. Associations with SCC risk were indicated in carriers of the red hair color associated MC1R variant p.Arg151Cys (OR= 1.99; 1.05–-3.75, and in carriers of two of any of the MC1R variants disclosed (OR = 2.36; 1.08–5.15. These associations appeared independent of traditionally protective phenotypes, also supported by the stratifications from skin phototype and hair color. A tendency towards an increased SCC risk was observed for a specific ASIP haplotype (OR = 1.87; 0.91–3.83, while no such associations were observed for the TYR and TYRP1 variants. Thus, the risk of developing SCC in RT patients is modulated by MC1R variation irrespective of phenotypes considered to be protective. Heterozygous combinations of MC1R variants appear to be more relevant in assessing SCC risk than the effects of variants individually.

  2. Response to antiviral therapy in haematopoietic stem cell transplant recipients with cytomegalovirus (CMV) reactivation according to the donor CMV serological status.

    Science.gov (United States)

    Servais, S; Dumontier, N; Biard, L; Schnepf, N; Resche-Rigon, M; Peffault de Latour, R; Scieux, C; Robin, M; Meunier, M; Xhaard, A; Sicre de Fontbrune, F; Le Goff, J; Socié, G; Simon, F; Mazeron, M-C

    2016-03-01

    Pre-emptive antiviral treatment efficiently prevents occurrence of cytomegalovirus (CMV) disease in allogeneic stem cell transplant recipients. However, successive treatment courses can be necessary. The current study was aimed at determining factors that could influence the response to antiviral treatment, in particular the donor CMV serostatus. A total of 147 consecutive CMV-seropositive recipients (R+) were included and prospectively monitored for 6 months after transplantation. Reactivation of CMV occurred in 111 patients, 61 of 78 with a CMV-positive donor (D+) and in 50 of 69 with a CMV-negative donor (D-) (p 0.45). Baseline viral loads and initial viral doubling times did not differ between D+/R+ and D-/R+. Fifteen D+/R+ and four D-/R+ had self-resolving CMV infections. A total of 92 patients received antiviral treatment and 81 (88%) had a significant decrease in CMV load under therapy. Repeated CMV episodes were observed in 67% of those and were significantly more frequent in D-/R+ than in D+/R+ (p antivirals were found in two D-/R+. Donor CMV serostatus influenced neither CMV reactivation occurrence nor the kinetics of CMV DNA load in the early phase of CMV replication but had a significant impact on response to antiviral therapy. Virological drug-resistance remained rare. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  3. Fully human broadly neutralizing monoclonal antibodies against influenza A viruses generated from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient.

    Science.gov (United States)

    Hu, Weibin; Chen, Aizhong; Miao, Yi; Xia, Shengli; Ling, Zhiyang; Xu, Ke; Wang, Tongyan; Xu, Ying; Cui, Jun; Wu, Hongqiang; Hu, Guiyu; Tian, Lin; Wang, Lingling; Shu, Yuelong; Ma, Xiaowei; Xu, Bianli; Zhang, Jin; Lin, Xiaojun; Bian, Chao; Sun, Bing

    2013-01-20

    Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarily targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. The oral iron chelator deferasirox might improve survival in allogeneic hematopoietic cell transplant (alloHSCT) recipients with transfusional iron overload.

    Science.gov (United States)

    Sivgin, Serdar; Baldane, Suleyman; Akyol, Gulsah; Keklik, Muzaffer; Kaynar, Leylagül; Kurnaz, Fatih; Pala, Cigdem; Zararsiz, Gokmen; Cetin, Mustafa; Eser, Bulent; Unal, Ali

    2013-10-01

    Iron overload (IO) has been shown to be an important cause of mortality and morbidity in patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). This study aimed to evaluate the possible effect of oral iron-chelation treatment (deferasirox) on survival in alloHSCT recipients in the posttransplant period. A total of 80 alloHSCT recipients with IO were analyzed, retrospectively. Pretransplant and posttransplant data were obtained from the patients' files. Patients were divided into two groups. Group 1; patients who did not receive any chelator treatment due to side effects or compliance problems. These patients were treated by phlebotomy. Group 2 consisted of patients who received deferasirox treatment. The median treatment duration with deferasirox was 122 days (min-max:91-225). The iron chelating treatment significantly reduced serum ferritin levels administered at a dosage of 20-30 mg/kg/day (pdeferasirox (Exjade) treatment may improve survival in patients with iron overload who underwent alloHSCT. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Fully human broadly neutralizing monoclonal antibodies against influenza A viruses generated from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient

    International Nuclear Information System (INIS)

    Hu, Weibin; Chen, Aizhong; Miao, Yi; Xia, Shengli; Ling, Zhiyang; Xu, Ke; Wang, Tongyan; Xu, Ying; Cui, Jun; Wu, Hongqiang; Hu, Guiyu; Tian, Lin; Wang, Lingling; Shu, Yuelong; Ma, Xiaowei; Xu, Bianli; Zhang, Jin; Lin, Xiaojun; Bian, Chao; Sun, Bing

    2013-01-01

    Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarily targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine.

  6. Fully human broadly neutralizing monoclonal antibodies against influenza A viruses generated from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Weibin [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Chen, Aizhong [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Miao, Yi [Shanghai Xuhui Central Hospital, Shanghai 200031 (China); Xia, Shengli [Center for Disease Control and Prevention of Henan Province, Zhengzhou 450016 (China); Ling, Zhiyang; Xu, Ke; Wang, Tongyan [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Xu, Ying; Cui, Jun; Wu, Hongqiang; Hu, Guiyu; Tian, Lin; Wang, Lingling [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Shu, Yuelong [Chinese Center for Disease Control and Prevention, Beijing 102206 (China); Ma, Xiaowei [Hualan Biological Bacterin Company, Xinxiang 453003 (China); Xu, Bianli; Zhang, Jin [Center for Disease Control and Prevention of Henan Province, Zhengzhou 450016 (China); Lin, Xiaojun, E-mail: linxiaojun@hualan.com [Hualan Biological Bacterin Company, Xinxiang 453003 (China); Bian, Chao, E-mail: cbian@sibs.ac.cn [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Sun, Bing, E-mail: bsun@sibs.ac.cn [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)

    2013-01-20

    Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarily targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine.

  7. Islet autoantibodies and residual beta cell function in type 1 diabetes children followed for 3-6 years

    DEFF Research Database (Denmark)

    Sørensen, Jesper Sand; Vaziri-Sani, Fariba; Maziarz, M

    2012-01-01

    To test if islet autoantibodies at diagnosis of type 1 diabetes (T1DM) and after 3-6 years with T1D predict residual beta-cell function (RBF) after 3-6 years with T1D.......To test if islet autoantibodies at diagnosis of type 1 diabetes (T1DM) and after 3-6 years with T1D predict residual beta-cell function (RBF) after 3-6 years with T1D....

  8. Peripheral Red Blood Cell Split Chimerism as a Consequence of Intramedullary Selective Apoptosis of Recipient Red Blood Cells in a Case of Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Marco Marziali

    2014-08-01

    Full Text Available Allogeneic cellular gene therapy through hematopoietic stem cell transplantation is the only radical cure for congenital hemoglobinopathies like thalassemia and sickle cell anemia. Persistent mixed hematopoietic chimerism (PMC has been described in thalassemia and sickle cell anemia. Here, we describe the clinical course of a 6-year-old girl who had received bone marrow transplant for sickle cell anemia. After the transplant, the patient showed 36% donor hematopoietic stem cells in the bone marrow, whereas in the peripheral blood there was evidence of 80%  circulating donor red blood cells (RBC. The analysis of apoptosis at the Bone Marrow  level suggests that Fas might contribute to the cell death of host erythroid precursors. The increase in NK cells and the regulatory T cell population observed in this patient suggests that these cells might contribute to the condition of mixed chimerism.

  9. Effects of bone marrow stromal cells and umbilical cord blood-derived stromal cells on daunorubicin-resistant residual Jurkat cells.

    Science.gov (United States)

    Liang, X; Hao, L; Chen, X; Zhang, X; Kong, P; Peng, X; Gao, L; Zhang, C; Wang, Q

    2010-11-01

    To observe the effects of the hematopoietic inductive microenvironment (HIM) simulated by stromal cells of different origins on daunorubicin-resistant residual Jurkat cells (Jurkat/DNR cells). Jurkat/DNR cells were cultured and identified. Human umbilical cord blood-derived stromal cells (UCBDSCs) and normal human bone marrow stromal cells (BMSCs) were isolated and cocultured with Jurkat/DNR cells. Jurkat/DNR cells were collected after 14 days of coculture and analyzed with regard to cell proliferation and differentiation abilities, apoptosis, drug sensitivity, and MRD1 multidrug resistance gene mRNA expression. UCBDSC-simulated HIM suppressed proliferation and promoted apoptosis, differentiation, and drug sensitivity of Jurkat/DNR cells more significantly than BMSC-simulated HIM. Both BMSCs and UCBDSCs reconstruct the leukemic HIM and reverse drug resistance in Jurkat/DNR cells. UCBDSCs reconstruct the leukemic HIM and reverse drug resistance more significantly than BMSCs. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. Diagnosis of Plasma Cell Dyscrasias and Monitoring of Minimal Residual Disease by Multiparametric Flow Cytometry

    Science.gov (United States)

    Soh, Kah Teong; Tario, Joseph D.; Wallace, Paul K.

    2018-01-01

    Synopsis Plasma cell dyscrasia (PCD) is a heterogeneous disease which has seen a tremendous change in outcomes due to improved therapies. Over the last few decades, multiparametric flow cytometry has played an important role in the detection and monitoring of PCDs. Flow cytometry is a high sensitivity assay for early detection of minimal residual disease (MRD) that correlates well with progression-free survival and overall survival. Before flow cytometry can be effectively implemented in the clinical setting sample preparation, panel configuration, analysis, and gating strategies must be optimized to ensure accurate results. Current consensus methods and reporting guidelines for MRD testing are discussed. PMID:29128071

  11. Monitoring of intracellular adenosine triphosphate in CD4(+) T cells to predict the occurrence of cytomegalovirus disease in kidney transplant recipients.

    Science.gov (United States)

    Pérez-Jacoiste Asín, María Asunción; Fernández-Ruiz, Mario; López-Medrano, Francisco; Aquilino, Carolina; González, Esther; Ruiz-Merlo, Tamara; Gutiérrez, Eduardo; San Juan, Rafael; Paz-Artal, Estela; Andrés, Amado; Aguado, José Maria

    2016-10-01

    The measurement of intracellular concentrations of adenosine triphosphate (iATP) in phytohemagglutinin-stimulated CD4(+) T cells constitutes a surrogate marker for post-transplant cell-mediated immunity (CMI). This assay has shown suboptimal accuracy for predicting infection after kidney transplantation (KT). We hypothesize that its predictive capacity depends on the specific contribution of the CMI to host-pathogen interactions. We assessed iATP levels in 100 KT recipients at baseline and months 1, 3, and 6 (363 measurements). No association was found between iATP at month 1 and the risk for overall or bacterial infection, although such association was evident for cytomegalovirus (CMV) disease (multivariate-adjusted hazard ratio [per 50-unit increment]: 0.83; P-value = 0.048). There were no significant differences in mean iATP between stable patients (319.4 ng/ml) and those developing overall (304.1 ng/ml) or bacterial infection (346.9 ng/ml) over the 45 days following monitoring. However, iATP was significantly lower in patients who developed CMV disease (223.5 ng/ml; P-values <0.002). The optimal cutoff (265 ng/ml) for predicting CMV disease in patients not receiving antiviral prophylaxis yielded sensitivity, specificity, positive, and negative predictive values of 85.7%, 68.3%, 15.2%, and 98.6%, respectively. In conclusion, a non-pathogen-specific monitoring of CMI by means of iATP informs the risk of CMV disease in KT recipients. © 2016 Steunstichting ESOT.

  12. ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients.

    Science.gov (United States)

    Maertens, Johan; Cesaro, Simone; Maschmeyer, Georg; Einsele, Hermann; Donnelly, J Peter; Alanio, Alexandre; Hauser, Philippe M; Lagrou, Katrien; Melchers, Willem J G; Helweg-Larsen, Jannik; Matos, Olga; Bretagne, Stéphane; Cordonnier, Catherine

    2016-09-01

    The 5th European Conference on Infections in Leukaemia (ECIL-5) meeting aimed to establish evidence-based recommendations for the prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in non-HIV-infected patients with an underlying haematological condition, including allogeneic HSCT recipients. Recommendations were based on the grading system of the IDSA. Trimethoprim/sulfamethoxazole given 2-3 times weekly is the drug of choice for the primary prophylaxis of PCP in adults ( A-II: ) and children ( A-I: ) and should be given during the entire period at risk. Recent data indicate that children may benefit equally from a once-weekly regimen ( B-II: ). All other drugs, including pentamidine, atovaquone and dapsone, are considered second-line alternatives when trimethoprim/sulfamethoxazole is poorly tolerated or contraindicated. The main indications of PCP prophylaxis are ALL, allogeneic HSCT, treatment with alemtuzumab, fludarabine/cyclophosphamide/rituximab combinations, >4 weeks of treatment with corticosteroids and well-defined primary immune deficiencies in children. Additional indications are proposed depending on the treatment regimen. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Genome-wide screening of Escherichia coli genes involved in execution and promotion of cell-to-cell transfer of non-conjugative plasmids: rodZ (yfgA) is essential for plasmid acceptance in recipient cells.

    Science.gov (United States)

    Kurono, Naomi; Matsuda, Ayako; Etchuya, Rika; Sobue, Rina; Sasaki, Yumi; Ito, Miki; Ando, Tsuyako; Maeda, Sumio

    2012-04-27

    Acquisition of new genetic traits by horizontal gene transfer is a bacterial strategy for adaptation to the environment. We previously showed that Escherichia coli can transmit non-conjugative plasmids laterally in a co-culture containing strains with and without the plasmid. In this study, using the Keio collection, a comprehensive library of E. coli knock-out mutants for non-essential genes, we screened for genes responsible for the execution and promotion of cell-to-cell plasmid transfer in recipient cells. By stepwise screening of 'transfer-down' mutants, two essential genes and six promoting genes were obtained. One of the essential genes was priA, which is involved in DNA replication. This priA mutant was also unable to be transformed by artificial transformation methods, probably due to the deficiency of the plasmid maintenance function. The other essential gene was rodZ (yfgA), a gene involved in the regulation of rod-shaped structure of E. coli cells. This rodZ mutant was transformable by all three methods of artificial transformation tested, suggesting that this gene is essential for cell-to-cell plasmid transfer but not for artificial transformation. These are the first data that suggest that rodZ plays an essential role in DNA acquisition. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Identification of critical residues of linear B cell epitope on Goodpasture autoantigen.

    Directory of Open Access Journals (Sweden)

    Xiao-yu Jia

    Full Text Available The autoantigen of anti-glomerular basement membrane (GBM disease has been identified as the non-collagenous domain 1 of α3 chain of type IV collagen, α3(IVNC1. Our previous study revealed a peptide on α3(IVNC1 as a major linear epitope for B cells and potentially nephrogenic, designated as P14 (α3129-150. This peptide has also been proven to be the epitope of auto-reactive T cells in anti-GBM patients. This study was aimed to further characterize the critical motif of P14.16 patients with anti-GBM disease and positive anti-P14 antibodies were enrolled. A set of truncated and alanine substituted peptides derived from P14 were synthesized. Circulating antibodies against the peptides were detected by enzyme linked immunosorbent assay (ELISA.We found that all sera with anti-P14 antibodies reacted with the 13-mer sequence in the C-terminus of P14 (P14c exclusively. The level of antibodies against P14 was highly correlated with the level of antibodies against P14c (r=0.970, P<0.001. P14c was the core immunogenic region and the amino acid sequence (ISLWKGFSFIMFT was highly hydrophobic. Each amino acid residue in P14c was sequentially replaced by alanine. Three residues of glycine142, phenylalanine143, and phenylalanine145 were identified crucial for antibody binding based on the remarkable decline (P<0.001 of antibody reaction after each residue replacement.We defined GFxF (α3142, 143,145 as the critical motif of P14. It may provide some clues for understanding the etiology of anti-GBM disease.

  15. IMPACT OF PRETRANSPLANT DONOR AND RECIPIENT CYTOMEGALOVIRUS SEROSTATUS ON OUTCOME FOR MULTIPLE MYELOMA PATIENTS UNDERGOING REDUCED INTENSITY CONDITIONING ALLOGENEIC STEM CELL TRANSPLANTATION.

    Directory of Open Access Journals (Sweden)

    Jean Elcheikh

    2013-04-01

    Full Text Available To investigate the impact of pre-transplant CMV serostatus of donor or recipient on outcome of patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-SCT for Multiple Myeloma (MM. To our knowledge no data are available in the literature about this issue. We retrospectively followed 99 consecutive patients who underwent reduced-intensity conditioning (RIC Allo-SCT for MM in our cancer centre at Marseille between January 2000 and January 2012. Based upon CMV serostatus, patients were classified as low risk (donor [D]-/recipient [R]- 17 patients (17.1%, intermediate risk (D+/R 14 patients (14.1%, or high risk – either (D-/R+ 31 patients (31.3% or (D+/R+, 37 patients (37.3%. Cumulative incidence of CMV reactivation was 39% with a median time of 61 days (26–318. Three patients (3% developed CMV disease. Two factors were associated with CMV reactivation: CMV serostatus group (low: 0% vs intermediate: 29% vs high: 50%; p=0.001 and the presence of grade II–IV acute GvHD (Hazard Ratio: HR=2.1 [1.1–3.9]. Thirty-six of the 39 patients (92% with CMV reactivation did not present positive detection of CMV after a 21-day median duration preemptive treatment with ganciclovir. Cumulative incidence of day 100 grade II–IV acute GvHD, 1-year chronic GvHD and day 100 transplantation related mortality (TRM were 37%, 36% and 9%, respectively. CMV reactivation and serostatus were not associated with increased GvHD and TRM or short survival. Only the presence of acute GvHD as a time dependent variable was significantly associated with increased TRM (p=0.005. Two-year overall and progression free survival were 56% and 34%, respectively. Donor and recipient CMV serostatus and acute GvHD are independent factors for increased CMV reactivation in high-risk MM patients undergoing RIC Allo-SCT. However, we did not find any influence of CMV reactivation on post transplantation outcome. CMV monitoring and pre-emptive treatment strategy could in

  16. Impact of pretransplant donor and recipient cytomegalovirus serostatus on outcome for multiple myeloma patients undergoing reduced intensity conditioning allogeneic stem cell transplantation.

    Science.gov (United States)

    El-Cheikh, Jean; Devillier, Raynier; Crocchiolo, Roberto; Fürst, Sabine; Calmels, Boris; Faucher, Catherine; Stoppa, Anne Marie; Granata, Angela; Castagna, Luca; Ladaique, Patrick; Lemarie, Claude; Bouabdallah, Reda; Zandotti, Christine; Merlin, Michele; Berger, Pierre; Chabannon, Christian; Blaise, Didier

    2013-01-01

    Scope of the study was to investigate the impact of pre-transplant CMV serostatus of the donor and/or recipient on the outcome of patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-SCT) for Multiple Myeloma (MM). To our knowledge no data are available in the literature about this issue. We retrospectively followed 99 consecutive patients who underwent reduced-intensity conditioning (RIC) Allo-SCT for MM in our cancer center at Marseille between January 2000 and January 2012. Based upon CMV serostatus, patients were classified as low risk (donor [D]-/recipient [R] -) 17 patients (17.1%), intermediate risk (D+/R) 14 patients (14.1%), or high risk - either (D-/R+) 31 patients (31.3%) or (D+/R+), 37 patients (37.3%). Cumulative incidence of CMV reactivation was 39% with a median time of 61 days (26-318). Three patients (3%) developed CMV disease. Two factors were associated with CMV reactivation: CMV serostatus group (low: 0% vs. intermediate: 29% vs. high: 50%; p=0.001) and the presence of grade II-IV acute GvHD (Hazard Ratio: HR=2.1 [1.1-3.9]). Thirty-six of the 39 patients (92%) with CMV reactivation did not present positive detection of CMV after a 21-day median duration preemptive treatment with ganciclovir. Cumulative incidence of day 100 grade II-IV acute GvHD, 1-year chronic GvHD and day 100 transplantation related mortality (TRM) were 37%, 36% and 9%, respectively. CMV reactivation and serostatus were not associated with increased GvHD and TRM or short survival. Only the presence of acute GvHD as a time dependent variable was significantly associated with increased TRM (p=0.005). Two-year overall and progression free survival were 56% and 34%, respectively. Donor and recipient CMV serostatus and acute GvHD are independent factors for increased CMV reactivation in high-risk MM patients undergoing RIC Allo-SCT. However, we did not find any influence of CMV reactivation on post transplantation outcome. CMV monitoring and pre

  17. 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....

  18. Strategies for Empiric Management of Pediatric Fever and Neutropenia in Patients With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: A Systematic Review of Randomized Trials.

    Science.gov (United States)

    Robinson, Paula D; Lehrnbecher, Thomas; Phillips, Robert; Dupuis, L Lee; Sung, Lillian

    2016-06-10

    To describe treatment failure and mortality rates with different antibiotic regimens and different management strategies for empirical treatment of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic stem-cell transplantation (HSCT) recipients. We conducted a systematic review and performed searches of MEDLINE, Embase, PubMed, and Cochrane Central Register of Controlled Trials. Studies were included if pediatric patients had cancer or were HSCT recipients and the intervention was related to the management of FN. Strategies synthesized were monotherapy versus aminoglycoside-containing combination therapy; antipseudomonal penicillin monotherapy versus fourth-generation cephalosporin monotherapy; inpatient versus outpatient management; oral versus intravenous antibiotics; and addition of colony-stimulating factors. Of 11,469 citations screened, 68 studies randomly assigning 7,265 episodes were included. When compared with monotherapy, aminoglycoside-containing combination therapy did not decrease treatment failures (risk ratio, 1.13; 95% CI, 0.92 to 1.38; P = 0.23), and no difference in mortality was observed. Antipseudomonal penicillin and fourth-generation cephalosporin monotherapy were associated with similar failure and mortality rates. Outpatient management and oral antibiotics were safe in low-risk FN with no infection-related mortality observed in any patient and no significant differences in outcomes compared with inpatient management and intravenous therapy. Therapeutic colony-stimulating factors were associated with a 1.42-day reduction in hospitalization (95% CI, 0.62 to 2.22 days; P pediatric randomized trials of FN management. Monotherapy for high-risk FN and outpatient and oral management for low-risk FN are effective strategies. These findings will provide the basis for guideline recommendations in pediatric FN. © 2016 by American Society of Clinical Oncology.

  19. Stromal Cell-Derived Factor 1 Gene Polymorphism Is Associated with Susceptibility to Adverse Long-Term Allograft Outcomes in Non-Diabetic Kidney Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Chung-Jieh Wang

    2014-07-01

    Full Text Available Although the genetic polymorphism of Stromal Cell-Derived Factor 1 (SDF-1 is associated with higher mortality of liver allograft recipients, the role of SDF-1 in the modulation of renal allograft outcomes is unclear. Between March 2000 and January 2008, we recruited 252 non-diabetic renal transplant recipients (RTRs. Baseline characteristics and blood chemistry were recorded. Genomic DNA extraction with polymerase chain reaction-restriction fragment length polymorphism was utilized to analyze the genetic polymorphisms of SDF-1 (rs1801157. The influence of SDF-1 on an adverse renal allograft outcome, defined as either a doubling of serum creatinine, graft failure, or patient death was evaluated. Sixteen patients with the SDF-1 AA/AG genotype and nine with the SDF-1 GG genotype reached an adverse outcome. According to Kaplan-Meier analysis, patients carrying the SDF-1 AA/AG genotype or A allele showed a significantly higher risk of reaching an adverse outcome than those carrying the SDF-1 GG genotype or G allele (p = 0.041; p = 0.0051, respectively; log rank test. Stepwise multivariate Cox proportional regression analysis revealed that patients carrying the SDF-1 AA/AG genotype and A allele had a 2.742-fold (95% CI. 1.106–6.799, p = 0.03 and 2.306-fold (95% CI. 1.254–4.24, p = 0.008 risk of experiencing an adverse outcome. The SDF-1 AA/AG genotype and A allele have a detrimental impact on the long-term outcome of RTRs.

  20. Hepatitis B reactivation in HBsAg-negative/HBcAb-positive allogeneic haematopoietic stem cell transplant recipients: risk factors and outcome.

    Science.gov (United States)

    Mikulska, M; Nicolini, L; Signori, A; Rivoli, G; Del Bono, V; Raiola, A M; Di Grazia, C; Dominietto, A; Varaldo, R; Ghiso, A; Bacigalupo, A; Viscoli, C

    2014-10-01

    HBsAg-negative/HBcAb-positive haematopoietic stem cell transplant (HSCT) recipients are at high risk of hepatitis B virus (HBV) reactivation. Allogeneic HSCT recipients from years 2000 to 2010 were evaluated in order to study the impact of being HBsAg-negative/HBcAb-positive in this population. Overall, 137 of 764 patients (18%) were HBsAg-negative/HBcAb-positive before HSCT. Overall survival, non-relapse mortality (NRM), acute and chronic graft-vs.-host disease were similar in HBcAb-positive and HBcAb-negative patients. Reactivation occurred in 14 patients (10%) within a median of 19 months after HSCT (range 9-77). Cause-specific hazard for reactivation was decreased in the case of an HBV-immune/exposed donor (HRadjusted = 0.12; 95% CI, 0.02-0.96; p 0.045) and increased in patients who received rituximab treatment (HRadjusted = 2.91; 95%CI, 0.77-10.97; p 0.11). Competing risk analyses documented a protective role of an HBV-immune/exposed donor (p 0.041) and an increased probability associated with the length of treatment with cyclosporine (p <0.001) and treatment with rituximab (but not with low-dose rituximab prophylaxis, p <0.001 at each landmark point). No differences in overall survival and NRM were found between patients with and without HBV reactivation. The donor's immunity was independently and consistently associated with a decreased risk of HBV reactivation, while rituximab and cyclosporine treatments increased the probability. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

  1. Cytomegalovirus pre-emptive therapy after hematopoietic stem cell transplantation in the era of real-time quantitative PCR: comparison with recipients of solid organ transplants.

    Science.gov (United States)

    Panagou, E; Zakout, G; Keshani, J; Smith, C; Irish, D; Mackinnon, S; Kottaridis, P; Fielding, A; Griffiths, P D

    2016-06-01

    Cytomegalovirus (CMV) continues to be an important complication of hematopoietic stem cell transplantation and solid organ transplantation. In this study, 314 patients who underwent hematopoietic stem cell transplantation between January 2003 and October 2011 were tested serially for CMV DNA by real-time quantitative polymerase chain reaction (qPCR) for 90 days post transplantation. Patients with CMV viremia >3000 genomes/mL (equivalent to 2520 IU/mL) received pre-emptive therapy and were compared with previously published data from solid organ transplant (SOT) patients monitored and treated in exactly the same way. After stem cell transplant (SCT), 48% of patients developed at least 1 episode of viremia. The median duration of a viremic episode was 25 days and the peak viral load (VL) was 4784 genomes/mL whole blood (equivalent to 4019 IU/mL). The data demonstrated that recipients with positive CMV serostatus were at increased risk of developing viremia, with 0% of donor-negative/recipient-negative (D-R-), 3.7% of D+R-, 79.5% of D-R+, and 74.2% of D+R+ groups developing viremia over follow-up (adjusted hazard ratio for D+R- vs. D+R+ group 0.03; 95% confidence interval 0.004, 0.18; P = 0.0013). In contrast with SOT patients, where 58/74 (78%) D+R- patients had viremia, a low risk of CMV infection was seen after stem cell transplantation (1/27; 3.7%). As both groups of patients, the previously published SOT patients and the present hematopoietic SCT patients, were monitored using the same protocol and qPCR assay with pre-emptive therapy administered at the same VL cutoffs, the distinct differences seen cannot be explained by differences in testing or management and thus emphasize distinct aspects of the natural history of CMV infection post transplant in these 2 patient groups. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Effect of lipopolysaccharide mutations on recipient ability of Salmonella typhimurium for incompatibility group H plasmids.

    Science.gov (United States)

    Sherburne, C; Taylor, D E

    1997-01-01

    Previous investigations of the incompatibility group F, P, and I plasmid systems revealed the important role of the outer membrane components in the conjugal transfer of these plasmids. We have observed variability in transfer frequency of three incompatibility group H plasmids (IncHI1 plasmid R27, IncHI2 plasmid R478, and a Tn7 derivative of R27, pDT2454) upon transfer into various Salmonella typhimurium lipopolysaccharide (LPS) mutants derived from a common parental strain, SL1027. Recipients with truncated outer core via the rfaF LPS mutation increased the transfer frequency of the IncH plasmids by up to a factor of 10(3). Mutations which resulted in the truncation of the residues following 3-deoxy-D-manno-octulosonic acid, such as the rfaE and rfaD mutations, decreased the transfer frequency to undetectable levels. Addition of phosphorylethanolamine, a component of wild-type LPS, to the media decreased the frequency of transfer of R27 into wild-type and rfaF LPS mutant recipients tested. Reversing the direction of transfer, by mating LPS mutant donors with wild-type recipients, did not affect the frequency of transfer compared to the standard matings of wild-type donor with LPS mutant recipient. These findings demonstrate that conjugation interactions affected by LPS mutation are not specific for the recipient cell. Our results suggest that LPS mutation does not affect conjugation via altered pilus binding but affects some later steps in the conjugative process, and alteration of transfer frequency by O-phosphorylethanolamine and LPS truncation is due to charge-related interactions between the donor and recipient cell. PMID:9006054

  3. Fluorescence histochemistry of peptide hormone-producing cells: observations on the phenanthrenequinone method for the demonstration of arginine residues.

    Science.gov (United States)

    Sundler, F; Håkanson, R

    1978-07-12

    Phenanthrenequinone is a sensitive and specific fluorescence histochemical reagent for monosubstituted guanidines. It is probable that it selectively demonstrates the guanidino group of arginine residues of proteins and peptides. Phenanthrenequinone induces moderate to intense fluorescence in gastric chief cells, parenchymal cells of the pancreas, and certain peptide hormone-producing cell types such as the GH cells of the adenohypophysis and the glucagon cells of the pancreatic islets. Similar fluorescence spectra were obtained from an arginine-containing peptide in a histochemical model and from the GH cells of the adenohypophysis following exposure to phenanthrenequinone. We conclude that the cells demonstrated with this reagent store peptides or proteins rich in arginine.

  4. Tuberculosis in postchemotherapy residual masses in germ cell tumor of the testis

    Directory of Open Access Journals (Sweden)

    Rajesh Bansal

    2011-01-01

    Full Text Available Residual masses following chemotherapy in testicular tumors have been characterized as necrosis, mature or immature teratoma, and malignant tumors. Twenty four patients had retroperitoneal lymph node dissection for postchemotherapy residual masses between January 2000 and December 2008. We report two patients; one with late relapse and other with postchemotherapy residual mass, who had tuberculosis. Tumor markers were normal, and PET scan showed increased uptake in residual mass. There are no previous reports of tuberculosis in postchemotherapy residual masses.

  5. Etiopathogenesis of type 1 diabetes mellitus: prognostic factors for the evolution of residual β cell function

    Directory of Open Access Journals (Sweden)

    Dib Sergio A

    2009-12-01

    Full Text Available Abstract Type 1A diabetes mellitus (T1ADM is a progressive autoimmune disease mediated by T lymphocytes with destruction of beta cells. Up to now, we do not have precise methods to assess the beta cell mass, "in vivo" or "ex-vivo". The studies about its genetic susceptibility show strong association with class II antigens of the HLA system (particularly DQ. Others genetics associations are weaker and depend on the population studied. A combination of precipitating events may occur at the beginning of the disease. There is a silent loss of immune-mediated beta cells mass which velocity has an inverse relation with the age, but it is influenced by genetic and metabolic factors. We can predict the development of the disease primarily through the determination of four biochemically islet auto antibodies against antigens like insulin, GAD65, IA2 and Znt8. Beta cell destruction is chronically progressive but at clinical diagnosis of the disease a reserve of these cells still functioning. The goal of secondary disease prevention is halt the autoimmune attack on beta cells by redirecting or dampening the immune system. It is remains one of the foremost therapeutic goals in the T1ADM. Glycemic intensive control and immunotherapeutic agents may preserve beta-cell function in newly diagnosed patients with T1ADM. It may be assessed through C-peptide values, which are important for glycemic stability and for the prevention of chronic complications of this disease. This article will summarize the etiopathogenesis mechanisms of this disease and the factors can influence on residual C-peptide and the strategies to it preservation.

  6. Distribution of residual cancer cells in the bowel wall after neoadjuvant chemoradiation in patients with rectal cancer.

    Science.gov (United States)

    Duldulao, Marjun P; Lee, Wendy; Streja, Leanne; Chu, Peiguo; Li, Wenyan; Chen, Zhenbin; Kim, Joseph; Garcia-Aguilar, Julio

    2013-02-01

    The standard treatment for locally advanced rectal cancer is preoperative chemoradiation and total mesorectal excision. After surgery, tumors are classified according to the depth of tumor invasion, nodal involvement, and tumor regression grade. However, these staging systems do not provide information about the distribution of residual cancer cells within the bowel wall. This study aimed to determine the distribution of residual cancer cells in each layer of the bowel wall in rectal cancer specimens. This was a secondary analysis of data from a prospective phase II study. This study was performed in a multi-institutional setting. Included were 153 patients with stage II or stage III rectal cancer. Patients were treated with chemoradiation and surgery. The surgical specimen tumor tissue was analyzed, and the distribution of residual cancer cells in each layer of the bowel wall was determined. Statistical analysis was used to examine the correlation of residual cancer cells in each layer of the bowel wall with the clinical/pathologic stage and tumor regression grade. Forty-two of 153 (27%) patients had complete response in the bowel wall (ypT0). Of the remaining 111 patients who had residual cancer cells, 5 (3%) were ypTis, 12 (8%) were ypT1, 41 (27%) were ypT2, 50 (33%) were ypT3, and 3 (2%) were ypT4. Of the 94 patients with ypT2-4 tumors, 12 (13%) had cancer cells in the mucosa, and 53 (56%) had cancer cells in the submucosa; 92 (98%) had cancer cells in the muscularis propria. Pretreatment cT correlated with the distribution of residual cancer cells. Tumor regression grade was not associated with the distribution of residual cancer cells after chemoradiation. : Patients received different chemotherapy regimens. Residual cancer cells in rectal cancer specimens after chemoradiation are preferentially located close to the invasive front. This should be considered when designing strategies to diagnose complete pathologic response and when investigating the

  7. Characteristics comparisons of bacteremia in allogeneic and autologous hematopoietic stem cell-transplant recipients with levofloxacin prophylaxis and influence on resistant bacteria emergence

    Directory of Open Access Journals (Sweden)

    Ching-Hsun Wang

    2018-02-01

    Conclusion: Levofloxacin prophylaxis in HSCT recipients is associated with the emergence of fluoroquinolone-resistant Gram-negative bacteria. The risk factors and clinical outcomes of bacteremia differ between allo- and auto-HSCT recipients, and these differences should be taken into account when designing strategies to prevent bacteremia.

  8. Profiling the effects of process changes on residual host cell proteins in biotherapeutics by mass spectrometry.

    Science.gov (United States)

    Schenauer, Matthew R; Flynn, Gregory C; Goetze, Andrew M

    2013-01-01

    An advanced liquid chromatography/mass spectrometry (MS) platform was used to identify and quantify residual Escherichia coli host cell proteins (HCPs) in the drug substance (DS) of several peptibodies (Pbs). Significantly different HCP impurity profiles were observed among different biotherapeutic Pbs as well as one Pb purified via multiple processes. The results can be rationally interpreted in terms of differences among the purification processes, and demonstrate the power of this technique to sensitively monitor both the quantity and composition of residual HCPs in DS, where these may represent a safety risk to patients. The breadth of information obtained using MS is compared to traditional multiproduct enzyme-linked immunosorbent assay (ELISA) values for total HCP in the same samples and shows that, in this case, the ELISA failed to detect multiple HCPs. The HCP composition of two upstream samples was also analyzed and used to demonstrate that HCPs that carry through purification processes to be detectable in DS are not always among those that are the most abundant upstream. Compared to ELISA, we demonstrate that MS can provide a more comprehensive, and accurate, characterization of DS HCPs, thereby facilitating process development as well as more rationally assessing potential safety risks posed by individual, identified HCPs. © 2013 American Institute of Chemical Engineers.

  9. Residual on column host cell protein analysis during lifetime studies of protein A chromatography.

    Science.gov (United States)

    Lintern, Katherine; Pathak, Mili; Smales, C Mark; Howland, Kevin; Rathore, Anurag; Bracewell, Daniel G

    2016-08-26

    Capacity reduction in protein A affinity chromatography with extended cycling during therapeutic antibody manufacture is well documented. Identification of which residual proteins remain from previous cycles during the lifetime of these adsorbent materials is required to understand their role in this ageing process, but represents a significant metrological challenge. Scanning electron microscopy (SEM) and liquid chromatography mass spectrometry (LC-MS/MS) are combined to detect and map this phenomenon of protein carry-over. We show that there is a morphological change at the surface of the agarose resin, revealing deposits on the polymer fibres increasing with cycle number. The amount of residual host cell proteins (HCPs) by LC-MS/MS present on the resin is shown to increase 10-fold between 50 and 100 cycles. During this same period the functional class of the predominant HCPs associated with the resin increased in diversity, with number of proteins identified increasing 5-fold. This ageing is observed in the context of the product quality of the eluate HCP and protein A leachate concentration remaining constant with cycle number. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

  10. CMV-specific T-cell immunity in solid organ transplant recipients at low risk of CMV infection. Chronology and applicability in preemptive therapy.

    Science.gov (United States)

    Mena-Romo, Juan Damián; Pérez Romero, Pilar; Martín-Gandul, Cecilia; Gentil, Miguel Ángel; Suárez-Artacho, Gonzalo; Lage, Ernesto; Sánchez, Magdalena; Cordero, Elisa

    2017-10-01

    To characterize whether the CMV-specific cellular immune response can be used as a predictor of the control of CMV infection and disease and determine thresholds in solid organ transplant (SOT) recipients seropositive for CMV (R+). The CMV-specific T-cell response was characterized using intracellular cytokine staining and the evolution of clinical and virological parameters were recorded during the first year after transplantation. Besides having positive CMV serology, only 28.4% patients had positive immunity (CD8 + CD69 + IFN-γ + ≥0.25%) at 2 weeks after transplantation. These patients had less indication of preemptive treatment (p = 0.025) and developed less high grade (≥2000 IU/ml) CMV replication episodes (p = 0.006) than patients with no immunity. Of the 49 patients with a pretransplant sample, only 22.4% had positive immunity, and had a detectable immune response early after transplantation (median of 3.7 weeks). However, only 50% of patients with negative pretransplant immunity acquired a positive immune response and it was significantly later, at a median of 11 weeks (p immunity. Having CMV-specific CD8 + IFN-γ + cells ≥0.25% before transplant; 0.15% at two weeks or 0.25% at four weeks after transplantation, identifies patients that may spontaneously control CMV infection and may require less monitoring. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  11. 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.

  12. 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......, the standardized incidence ratios for cancers of the tongue, mouth, pharynx, esophagus, liver, and respiratory and urinary tracts and for squamous cell skin carcinoma remained elevated beyond 10 years after the transfusion. CONCLUSIONS: The marked increase in cancer risk shortly after a blood transfusion may...

  13. Allogeneic hematopoietic stem cell transplant recipients and parasitic diseases: A review of the literature of clinical cases and perspectives to screen and follow-up active and latent chronic infections.

    Science.gov (United States)

    Fabiani, Silvia; Fortunato, Simona; Petrini, Mario; Bruschi, Fabrizio

    2017-04-01

    Allogeneic hematopoietic stem cell transplant (HSCT) recipients are at substantial risk for a variety of infections depending upon numerous factors, such as degree of immunosuppression, host factors, and period after transplantation. Bacterial, fungal, viral, as well as parasitic infections can occur with high morbidity and mortality. The aim of this study was to evaluate the magnitude of the occurrence of parasitic infections in allogeneic HSCT recipients. Modalities of transmission, methods of diagnosis, treatment, donor and recipient pre-transplant screening and prevention measures of the most serious parasitic infections have also been discussed. We systematically reviewed literature records on post-transplant (allogeneic HSCT) parasitic infections, identified through PubMed database searching, using no language or time restrictions. Search was concluded on December 31, 2015. In the present review, we only discussed post-transplant parasitic infections in allogeneic HSCT. Only exclusion criteria were absence of sufficient information on the transmission of parasitic infection to the recipient. Autologous HSCT recipients have not been included because of the absence of a proper allogeneic transplantation even in presence of blood or blood product transfusions. The methods and findings of the present review have been reported based on the preferred reporting items for systematic reviews and meta-analysis checklist (PRISMA). Regarding allogeneic HSCT recipients, from data published in the literature the real burden of parasitic infections cannot be really estimated. Nevertheless, a positive trend on publication number exists, probably because of more than one reason: (i) the increasing number of patients transplanted and then treated with immunosuppressive agents, (ii) the "population shift" resulting from immigration and travels to endemic areas, and (iii) the increasing of attention for diagnosis/notification/publication of cases. Considering parasitic

  14. Persistence of recipient human leucocyte antigen (HLA) antibodies and production of donor HLA antibodies following reduced intensity allogeneic haematopoietic stem cell transplantation.

    Science.gov (United States)

    Fasano, Ross M; Mamcarz, Ewelina; Adams, Sharon; Donohue Jerussi, Theresa; Sugimoto, Kyoko; Tian, Xin; Flegel, Willy A; Childs, Richard W

    2014-08-01

    The effects of reduced intensity conditioning (RIC) on human leucocyte antigen (HLA)-alloimmunization and platelet transfusion refractoriness (PTR) following allogeneic haematopoietic stem cell transplantation (Allo-HSCT) are unknown. We studied HLA-alloantibodies in a cohort of 16 patients (eight HLA-alloimmunized with pre-transplant histories of PTR and eight non-alloimmunized controls) undergoing Allo-HSCT using fludarabine/cyclophosphamide-based RIC. Pre- and post-transplant serum samples were analysed for HLA-antibodies and compared to myeloid, T-cell and bone marrow plasma cell chimaerism. Among alloimmunized patients, the duration that HLA-antibodies persisted post-transplant correlated strongly with pre-transplant HLA-antibody mean fluorescence intensity (MFI) and PRA levels (Spearman's rank correlation = 0·954 (P = 0·0048) and 0·865 (P = 0·0083) respectively). Pre-transplant MFI >10,000 was associated with post-transplant HLA antibody persistence >100 d (P = 0·029). HLA-antibodies persisted ≥100 d in 3/8 patients despite recipient chimaerism being undetectable in all lympho-haematopoietic lineages including plasma cells. Post-transplant de-novo HLA-antibodies developed in three control patients with two developing PTR; the donors for two of these patients demonstrated pre-existing HLA-antibodies of equivalent specificity to those in the patient, confirming donor origin. These data show HLA-antibodies may persist for prolonged periods following RIC. Further study is needed to determine the incidence of post-transplant PTR as a consequence of donor-derived HLA alloimmunization before recommendations on donor HLA-antibody screening can be made. © 2014 John Wiley & Sons Ltd.

  15. Residual ß-cell function and microvascular complications in type 1 diabetic patients

    Directory of Open Access Journals (Sweden)

    Gomes M.B.

    2000-01-01

    Full Text Available To determine the influence of residual ß-cell function on retinopathy and microalbuminuria we measured basal C-peptide in 50 type 1 diabetic outpatients aged 24.96 ± 7.14 years, with a duration of diabetes of 9.1 ± 6.2 years. Forty-three patients (86% with low C-peptide (<0.74 ng/ml had longer duration of diabetes than 7 patients (14% with high C-peptide (³0.74 ng/ml (9 (2-34 vs 3 (1-10 years, P = 0.01 and a tendency to high glycated hemoglobin (HBA1 (8.8 (6-17.9 vs 7.7 (6.9-8.7%, P = 0.08. Nine patients (18% had microalbuminuria (two out of three overnight urine samples with an albumin excretion rate (AER ³20 and <200 µg/min and 13 (26% had background retinopathy. No association was found between low C-peptide, microalbuminuria and retinopathy and no difference in basal C-peptide was observed between microalbuminuric and normoalbuminuric patients (0.4 ± 0.5 vs 0.19 ± 0.22 ng/ml, P = 0.61 and between patients with or without retinopathy (0.4 ± 0.6 vs 0.2 ± 0.3 ng/ml, P = 0.43. Multiple regression analysis showed that duration of diabetes (r = 0.30, r2 = 0.09, P = 0.031 followed by HBA1 (r = 0.41, r2 = 0.17, P = 0.01 influenced basal C-peptide, and this duration of diabetes was the only variable affecting AER (r = 0.40, r2 = 0.16, P = 0.004. In our sample of type 1 diabetic patients residual ß-cell function was not associated with microalbuminuria or retinopathy.

  16. Codominant Role of Interferon-γ- and Interleukin-17-Producing T Cells During Rejection in Full Facial Transplant Recipients.

    Science.gov (United States)

    Borges, T J; O'Malley, J T; Wo, L; Murakami, N; Smith, B; Azzi, J; Tripathi, S; Lane, J D; Bueno, E M; Clark, R A; Tullius, S G; Chandraker, A; Lian, C G; Murphy, G F; Strom, T B; Pomahac, B; Najafian, N; Riella, L V

    2016-07-01

    Facial transplantation is a life-changing procedure for patients with severe composite facial defects. However, skin is the most immunogenic of all transplants, and better understanding of the immunological processes after facial transplantation is of paramount importance. Here, we describe six patients who underwent full facial transplantation at our institution, with a mean follow-up of 2.7 years. Seum, peripheral blood mononuclear cells, and skin biopsy specimens were collected prospectively, and a detailed characterization of their immune response (51 time points) was performed, defining 47 immune cell subsets, 24 serum cytokines, anti-HLA antibodies, and donor alloreactivity on each sample, producing 4269 data points. In a nonrejecting state, patients had a predominant T helper 2 cell phenotype in the blood. All patients developed at least one episode of acute cellular rejection, which was characterized by increases in interferon-γ/interleukin-17-producing cells in peripheral blood and in the allograft's skin. Serum monocyte chemotactic protein-1 level was significantly increased during rejection compared with prerejection time points. None of the patients developed de novo donor-specific antibodies, despite a fourfold expansion in T follicular helper cells at 1 year posttransplantation. In sum, facial transplantation is frequently complicated by a codominant interferon-γ/interleukin-17-mediated acute cellular rejection process. Despite that, medium-term outcomes are promising with no evidence of de novo donor-specific antibody development. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  17. Donor-to-Recipient ABO Mismatch Does Not Impact Outcomes of Allogeneic Hematopoietic Cell Transplantation Regardless of Graft Source.

    Science.gov (United States)

    Damodar, Sharat; Shanley, Ryan; MacMillan, Margaret; Ustun, Celalettin; Weisdorf, Daniel

    2017-05-01

    The impact of ABO mismatch has been studied on various hematopoietic cell transplant (HCT) outcomes, including neutrophil and platelet engraftment, pure red cell aplasia, acute and chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), and overall survival (OS). Yet conflicting results have been reported. However, the impact of ABO mismatch on transplant outcomes with various graft types has not been carefully investigated. We analyzed the impact of various graft sources and type of ABO mismatch on transplant outcomes for 1502 patients who underwent HCT at the University of Minnesota between 2000 and 2014: 312 receiving marrow (BM), 475 filgrastim-mobilized blood (peripheral blood stem cell [PBSC]), and 715 umbilical cord blood (UCB) grafts. Neutrophil engraftment by day 28 was marginally less frequent in the bidirectional ABO mismatched transplants receiving UCB, whereas ABO matching had no influence on engraftment in the BM or PBSC cohorts. ABO mismatch led to no significant differences in platelet engraftment irrespective of stem cell source. We observed a modest but not significantly lower incidence of grades II/IV acute GVHD in the bidirectional ABO mismatched transplants in the UCB and the PBSC cohorts but not in the BM group. We found a higher incidence of chronic GVHD in the PBSC group, but it was not significantly lower in the minor ABO mismatched transplants. The incidence of chronic GVHD was similar in the major ABO mismatched transplants receiving BM. We found no significant difference in the OS and NRM between ABO matched and ABO mismatched transplants within each of the 3 graft source groups. Multivariable analysis adjusting for other relevant factors confirmed that ABO match status did not significantly influence the outcomes of either engraftment, acute or chronic GVHD or NRM. We conclude that ABO mismatch does not influence the outcomes of allogeneic HCT, regardless of stem cell source. Copyright © 2017 The American Society for

  18. Kaposi's sarcoma in renal transplant recipients

    African Journals Online (AJOL)

    The cause of the increased frequency of KS among renal transplant recipients is multifactorial: (l) genetic predisposition, i.e. increased incidence of specific lll.A types; (il) chronic immunostimulation in the presence of. T-cell dysfunction; (iil) proliferation of suppressor cells with the production of specific growth factors; and (iv).

  19. Approach to a case of multiple irregular red cell antibodies in a liver transplant recipient: Need for developing competence.

    Science.gov (United States)

    Dara, Ravi C; Tiwari, Aseem K; Pandey, Prashant; Arora, Dinesh

    2015-01-01

    Liver transplant procedure acts as a challenge for transfusion services in terms of specialized blood components, serologic problems, and immunologic effects of transfusion. Red cell alloimmunization in patients awaiting a liver transplant complicate the process by undue delay or unavailability of compatible red blood cell units. Compatible blood units can be provided by well-equipped immunohematology laboratory, which has expertise in resolving these serological problems. This report illustrates resolution of a case with multiple alloantibodies using standard techniques, particularly rare antisera. Our case re-emphasizes the need for universal antibody screening in all patients as part of pretransfusion testing, which helps to identify atypical antibodies and plan for appropriate transfusion support well in time. We recommend that the centers, especially the ones that perform complex procedures like solid organ transplants and hematological transplants should have the necessary immunohematological reagents including rare antisera to resolve complex cases of multiple antibodies as illustrated in this case.

  20. Approach to a case of multiple irregular red cell antibodies in a liver transplant recipient: Need for developing competence

    Directory of Open Access Journals (Sweden)

    Ravi C Dara

    2015-01-01

    Full Text Available Liver transplant procedure acts as a challenge for transfusion services in terms of specialized blood components, serologic problems, and immunologic effects of transfusion. Red cell alloimmunization in patients awaiting a liver transplant complicate the process by undue delay or unavailability of compatible red blood cell units. Compatible blood units can be provided by well-equipped immunohematology laboratory, which has expertise in resolving these serological problems. This report illustrates resolution of a case with multiple alloantibodies using standard techniques, particularly rare antisera. Our case re-emphasizes the need for universal antibody screening in all patients as part of pretransfusion testing, which helps to identify atypical antibodies and plan for appropriate transfusion support well in time. We recommend that the centers, especially the ones that perform complex procedures like solid organ transplants and hematological transplants should have the necessary immunohematological reagents including rare antisera to resolve complex cases of multiple antibodies as illustrated in this case.

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

    Science.gov (United States)

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

    2017-09-15

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

  2. [Errors of red cell concentrates recipients: method of analysis using the adverse events notified to the hemovigilance network in 2009].

    Science.gov (United States)

    Falzone, E; Auroy, Y; Hoffmann, C; Sandid, I; Carlier, M; Benhamou, D; Andreu, G; Lienhart, A

    2012-12-01

    Among the adverse events in the blood transfusion process, transfusion to a "wrong" patient is potentially dangerous, as it can lead to an adverse reaction at least in case of ABO incompatible red cell concentrate. The "Root Cause Analysis" working party of the National Hemovigilance Commission developed a tool to collect this type of adverse event, and tested it on a sample of 43 cases involving red cell concentrates notified between March, 2009 and February, 2010. One hundred and nine failures of a step in the transfusion process were observed, i.e. 2.5 failures per adverse event. Failures may occur early in the process. However, they are mainly found at the time of issuing of the blood component, and further, in the clinical ward. How the failure is eventually detected is not always described when the blood component has been fully transfused, in contrast with the cases where actual transfusion to the wrong patient has been prevented. Knowing the way of failure detection enables an objective approach of the efficacy of the numerous existing safety measures. In this sample, bedside controls (documents check as well as the use of anti-A and anti-B reagents with patient's blood and red cell concentrates) detected the failure in three cases out of 34, which were not detected before, showing an efficacy similar to the administrative control done at reception in the clinical ward. The document, set up to analyse step by step these cases of patient errors, will be used in the future to analyse all similar cases, not only with red cell concentrates, but also with platelet concentrates and fresh frozen plasma, ultimately in order to improve their prevention. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  3. Evaluation of droplet digital PCR for quantification of residual leucocytes in red blood cell concentrates.

    Science.gov (United States)

    Doescher, A; Loges, U; Petershofen, E K; Müller, T H

    2017-11-01

    Enumeration of residual white blood cells in leucoreduced blood components is essential part of quality control. Digital PCR has substantially facilitated quantitative PCR and was thus evaluated for measurements of leucocytes. Target for quantification of leucocytes by digital droplet PCR was the blood group gene RHCE. The SPEF1 gene was added as internal control for the entire assay starting with automated DNA extraction. The sensitivity of the method was determined by serial dilutions of standard samples. Quality control samples were analysed within 24 h, 7 days and 6 months after collection. Routine samples from leucodepleted red blood cell concentrates (n = 150) were evaluated in parallel by flow-cytometry (LeucoCount) and by digital PCR. Digital PCR reliably detected at least 0·4 leucocytes per assay. The mean difference between PCR and flow-cytometric results from 150 units was -0·01 (±1·0). DNA samples were stable for up to at least six months. PCR measurement of leucocytes in samples from plasma and platelet concentrates also provided valid results in a pilot study. Droplet digital PCR to enumerate leucocytes offers an alternative for quality control of leucoreduced blood products. Sensitivity, specificity and reproducibility are comparable to flow-cytometry. The option to collect samples over an extended period of time and the automatization introduce attractive features for routine quality control. © 2017 International Society of Blood Transfusion.

  4. Guideline for the Management of Fever and Neutropenia in Children With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: 2017 Update.

    Science.gov (United States)

    Lehrnbecher, Thomas; Robinson, Paula; Fisher, Brian; Alexander, Sarah; Ammann, Roland A; Beauchemin, Melissa; Carlesse, Fabianne; Groll, Andreas H; Haeusler, Gabrielle M; Santolaya, Maria; Steinbach, William J; Castagnola, Elio; Davis, Bonnie L; Dupuis, L Lee; Gaur, Aditya H; Tissing, Wim J E; Zaoutis, Theo; Phillips, Robert; Sung, Lillian

    2017-06-20

    Purpose To update a clinical practice guideline (CPG) for the empirical management of fever and neutropenia (FN) in children with cancer and hematopoietic stem-cell transplantation recipients. Methods The International Pediatric Fever and Neutropenia Guideline Panel is a multidisciplinary and multinational group of experts in pediatric oncology and infectious diseases that includes a patient advocate. For questions of risk stratification and evaluation, we updated systematic reviews of observational studies. For questions of therapy, we conducted a systematic review of randomized trials of any intervention applied for the empirical management of pediatric FN. The Grading of Recommendation Assessment, Development and Evaluation approach was used to make strong or weak recommendations and to classify levels of evidence as high, moderate, low, or very low. Results Recommendations related to initial presentation, ongoing management, and empirical antifungal therapy of pediatric FN were reviewed; the most substantial changes were related to empirical antifungal therapy. Key differences from our 2012 FN CPG included the listing of a fourth-generation cephalosporin for empirical therapy in high-risk FN, refinement of risk stratification to define patients with high-risk invasive fungal disease (IFD), changes in recommended biomarkers and radiologic investigations for the evaluation of IFD in prolonged FN, and a weak recommendation to withhold empirical antifungal therapy in IFD low-risk patients with prolonged FN. Conclusion Changes to the updated FN CPG recommendations will likely influence the care of pediatric patients with cancer and those undergoing hematopoietic stem-cell transplantation. Future work should focus on closing research gaps and on identifying ways to facilitate implementation and adaptation.

  5. Dendritic cell vaccination in allogeneic stem cell recipients: induction of human cytomegalovirus (HCMV)-specific cytotoxic T lymphocyte responses even in patients receiving a transplant from an HCMV-seronegative donor.

    Science.gov (United States)

    Grigoleit, Gotz Ulrich; Kapp, Markus; Hebart, Holger; Fick, Kerstin; Beck, Robert; Jahn, Gerhard; Einsele, Hermann

    2007-09-01

    Vaccination with peptide-loaded dendritic cells (DCs) has been shown to be potent immunostimulatory therapy for the management of serious infections. After allogeneic stem cell transplant (SCT), a prolonged and severe immune deficiency often leads to infectious complications. Human cytomegalovirus (HCMV) infection is one such life-threatening complication after allogeneic SCT. A phase 1/2 study including 24 allogeneic SCT recipients at high risk for HCMV disease was performed to analyze the feasibility and efficacy of vaccination with HCMV peptide-loaded DCs. No acute adverse effects were observed, and a significant clinical benefit could be demonstrated in comparison to our historical control group. An induction or expansion of HCMV-specific cytotoxic T lymphocytes was observed in 5 patients after DC vaccination.

  6. Comparison of Efficacy and Safety of Caspofungin Versus Micafungin in Pediatric Allogeneic Stem Cell Transplant Recipients: A Retrospective Analysis.

    Science.gov (United States)

    Maximova, Natalia; Schillani, Giulia; Simeone, Roberto; Maestro, Alessandra; Zanon, Davide

    2017-05-01

    The high morbidity and mortality associated with invasive fungal infections (IFIs) provide the rationale for antifungal prophylaxis in immuno-compromised pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Caspofungin and micafungin are antifungal agents of interest for prophylaxis of IFIs because of their potency against Candida and minimal toxicity or interactions with other drugs. Few studies have demonstrated the safety and efficacy of such echinocandins as prophylaxis for IFIs in patients undergoing HSCT. This retrospective cohort study compared caspofungin and micafungin for prevention of IFIs in 93 pediatric patients undergoing HSCT for oncological or non-oncological disease. The observation began with the first dose of antifungal agent and ended 3 months after transplantation. Patients in the micafungin group had a higher overall treatment success rate of 87.2 versus 84.8% in the caspofungin group, but the difference was not significant. There were no statistically significant differences in the incidence or type of proven/probable IFIs between the 2 groups. The low incidence of death did not differ statistically between the groups. Patients in the caspofungin group presented more frequently with fever, during and after neutropenia. In both groups, we observed an expected worsening of blood chemistry parameters. There were no adverse events definitely attributable to the two antifungal agents. These results demonstrate good efficacy and tolerability for caspofungin and micafungin. However, better results with respect to the incidence and resolution of fever in the micafungin group may suggest its use in preference to that of caspofungin.

  7. Computed Tomography Findings of Human Polyomavirus BK (BKV)-Associated Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

    International Nuclear Information System (INIS)

    Schulze, M.; Beck, R.; Igney, A.; Vogel, M.; Maksimovic, O.; Claussen, C.D.; Faul, C.; Horger, M.

    2008-01-01

    Background: Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. Purpose: To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). Material and Methods: The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. Results: All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. Conclusion: CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and

  8. Computed Tomography Findings of Human Polyomavirus BK (BKV)-Associated Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

    Energy Technology Data Exchange (ETDEWEB)

    Schulze, M.; Beck, R.; Igney, A.; Vogel, M.; Maksimovic, O.; Claussen, C.D.; Faul, C.; Horger, M. [Dept. of Diagnostic Radiology, Dept. of Internal Medicine-Oncology, and Inst. of Medical Virology, Eberhard-Karls Univ., Tbingen (Germany)

    2008-12-15

    Background: Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. Purpose: To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). Material and Methods: The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. Results: All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. Conclusion: CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and

  9. Computed Tomography Findings of Human Polyomavirus BK (BKV)-Associated Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

    Energy Technology Data Exchange (ETDEWEB)

    Schulze, M.; Beck, R.; Igney, A.; Vogel, M.; Maksimovic, O.; Claussen, C.D.; Faul, C.; Horger, M. (Dept. of Diagnostic Radiology, Dept. of Internal Medicine-Oncology, and Inst. of Medical Virology, Eberhard-Karls Univ., Tbingen (Germany))

    2008-12-15

    Background: Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. Purpose: To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). Material and Methods: The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. Results: All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. Conclusion: CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and

  10. Efficiency of porcine somatic cell nuclear transfer – a retrospective study of factors related to embryo recipient and embryos transferred

    Directory of Open Access Journals (Sweden)

    Yongye Huang

    2013-10-01

    The successful generation of pigs via somatic cell nuclear transfer depends on reducing risk factors in several aspects. To provide an overview of some influencing factors related to embryo transfer, the follow-up data related to cloned pig production collected in our laboratory was examined. (i Spring showed a higher full-term pregnancy rate compared with winter (33.6% vs 18.6%, P = 0.006. Furthermore, a regression equation can be drawn between full-term pregnancy numbers and pregnancy numbers in different months (y = 0.692x−3.326. (ii There were no significant differences detected in the number of transferred embryos between surrogate sows exhibiting full-term development compared to those that did not. (iii Non-ovulating surrogate sows presented a higher percentage of full-term pregnancies compared with ovulating sows (32.0% vs 17.5%, P = 0.004; respectively. (iv Abortion was most likely to take place between Day 27 to Day 34. (v Based on Life Table Survival Analysis, delivery in normally fertilized and surrogate sows is expected to be completed before Day 117 or Day 125, respectively. Additionally, the length of pregnancy in surrogate sows was negatively correlated with the average litter size, which was not found for normally fertilized sows. In conclusion, performing embryo transfer in appropriate seasons, improving the quality of embryos transferred, optimizing the timing of embryo transfer, limiting the occurrence of abortion, combined with ameliorating the management of delivery, is expected to result in the harvest of a great number of surviving cloned piglets.

  11. Highly sensitive in vitro methods for detection of residual undifferentiated cells in retinal pigment epithelial cells derived from human iPS cells.

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    Takuya Kuroda

    Full Text Available Human induced pluripotent stem cells (hiPSCs possess the capabilities of self-renewal and differentiation into multiple cell types, and they are free of the ethical problems associated with human embryonic stem cells (hESCs. These characteristics make hiPSCs a promising choice for future regenerative medicine research. There are significant obstacles, however, preventing the clinical use of hiPSCs. One of the most obvious safety issues is the presence of residual undifferentiated cells that have tumorigenic potential. To locate residual undifferentiated cells, in vivo teratoma formation assays have been performed with immunodeficient animals, which is both costly and time-consuming. Here, we examined three in vitro assay methods to detect undifferentiated cells (designated an in vitro tumorigenicity assay: soft agar colony formation assay, flow cytometry assay and quantitative real-time polymerase chain reaction assay (qRT-PCR. Although the soft agar colony formation assay was unable to detect hiPSCs even in the presence of a ROCK inhibitor that permits survival of dissociated hiPSCs/hESCs, the flow cytometry assay using anti-TRA-1-60 antibody detected 0.1% undifferentiated hiPSCs that were spiked in primary retinal pigment epithelial (RPE cells. Moreover, qRT-PCR with a specific probe and primers was found to detect a trace amount of Lin28 mRNA, which is equivalent to that present in a mixture of a single hiPSC and 5.0×10⁴ RPE cells. Our findings provide highly sensitive and quantitative in vitro assays essential for facilitating safety profiling of hiPSC-derived products for future regenerative medicine research.

  12. Pre-transplant donor-specific T-cell alloreactivity is strongly associated with early acute cellular rejection in kidney transplant recipients not receiving T-cell depleting induction therapy.

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    Elena Crespo

    Full Text Available Preformed T-cell immune-sensitization should most likely impact allograft outcome during the initial period after kidney transplantation, since donor-specific memory T-cells may rapidly recognize alloantigens and activate the effector immune response, which leads to allograft rejection. However, the precise time-frame in which acute rejection is fundamentally triggered by preformed donor-specific memory T cells rather than by de novo activated naïve T cells is still to be established. Here, preformed donor-specific alloreactive T-cell responses were evaluated using the IFN-γ ELISPOT assay in a large consecutive cohort of kidney transplant patients (n = 90, to assess the main clinical variables associated with cellular sensitization and its predominant time-frame impact on allograft outcome, and was further validated in an independent new set of kidney transplant recipients (n = 67. We found that most highly T-cell sensitized patients were elderly patients with particularly poor HLA class-I matching, without any clinically recognizable sensitizing events. While one-year incidence of all types of biopsy-proven acute rejection did not differ between T-cell alloreactive and non-alloreactive patients, Receiver Operating Characteristic curve analysis indicated the first two months after transplantation as the highest risk time period for acute cellular rejection associated with baseline T-cell sensitization. This effect was particularly evident in young and highly alloreactive individuals that did not receive T-cell depletion immunosuppression. Multivariate analysis confirmed preformed T-cell sensitization as an independent predictor of early acute cellular rejection. In summary, monitoring anti-donor T-cell sensitization before transplantation may help to identify patients at increased risk of acute cellular rejection, particularly in the early phases after kidney transplantation, and thus guide decision-making regarding the use of induction

  13. Pathogen response-like recruitment and activation of neutrophils by sterile immunogenic dying cells drives neutrophil-mediated residual cell killing.

    Science.gov (United States)

    Garg, Abhishek D; Vandenberk, Lien; Fang, Shentong; Fasche, Tekele; Van Eygen, Sofie; Maes, Jan; Van Woensel, Matthias; Koks, Carolien; Vanthillo, Niels; Graf, Norbert; de Witte, Peter; Van Gool, Stefaan; Salven, Petri; Agostinis, Patrizia

    2017-05-01

    Innate immune sensing of dying cells is modulated by several signals. Inflammatory chemokines-guided early recruitment, and pathogen-associated molecular patterns-triggered activation, of major anti-pathogenic innate immune cells like neutrophils distinguishes pathogen-infected stressed/dying cells from sterile dying cells. However, whether certain sterile dying cells stimulate innate immunity by partially mimicking pathogen response-like recruitment/activation of neutrophils remains poorly understood. We reveal that sterile immunogenic dying cancer cells trigger (a cell autonomous) pathogen response-like chemokine (PARC) signature, hallmarked by co-release of CXCL1, CCL2 and CXCL10 (similar to cells infected with bacteria or viruses). This PARC signature recruits preferentially neutrophils as first innate immune responders in vivo (in a cross-species, evolutionarily conserved manner; in mice and zebrafish). Furthermore, key danger signals emanating from these dying cells, that is, surface calreticulin, ATP and nucleic acids stimulate phagocytosis, purinergic receptors and toll-like receptors (TLR) i.e. TLR7/8/9-MyD88 signaling on neutrophil level, respectively. Engagement of purinergic receptors and TLR7/8/9-MyD88 signaling evokes neutrophil activation, which culminates into H 2 O 2 and NO-driven respiratory burst-mediated killing of viable residual cancer cells. Thus sterile immunogenic dying cells perform 'altered-self mimicry' in certain contexts to exploit neutrophils for phagocytic targeting of dead/dying cancer cells and cytotoxic targeting of residual cancer cells.

  14. Importance of B cells to development of regulatory T cells and prolongation of tissue allograft survival in recipients receiving autologous bone marrow transplantation.

    Science.gov (United States)

    Gorczynski, Reginald M; Farrokhi, Kaveh; Gorczynski, Christopher; Sadozai, Hassan; Zhu, Fang; Khatri, Ismat

    2018-01-16

    We previously showed that congenic bone marrow transplantation (BMTx) post myeloablation augmented tissue allograft survival in association with increased regulatory T (Treg) cells of both host and bone marrow donor origin. Regulatory B (Breg) cells can also modulate T-cell immunity and B cells may be implicated in the development of Treg cells. Accordingly, we explored the effect of B-cell depletion in vivo on augmented graft survival post BMTx. C57BL/6 mice received BALB/c skin allografts followed 7 days later by myeloablation using cyclophosphamide and busulphan. Mice then received T-cell-depleted bone marrow from CD45.1 congenic donors, and ongoing immunosuppression with rapamycin (to day 28 after BMTx). Control mice received cyclophosphamide and busulphan followed by rapamycin, but not congenic bone marrow. At different times post BMTx, mice received B-cell-depleting antibody treatment, and the effect on both skin graft survival, and induction of Treg cells was assessed. BMTx resulted in significantly prolonged skin graft survival versus control mice, in association with attenuated donor-specific alloreactivity relative to controls, increased splenic Treg cells and significantly diminished anti-donor IgG. In mice receiving infusion of B-depleting antibodies for 12 days from day 15 post BMTx, both graft survival and Treg cell activity were diminished, particularly for functional Treg cells of donor origin. Adoptive transfer of Breg cells from mice harvested at 15 days post BMTx prolonged survival in naive transplanted mice and increased Treg cell levels. Thus, autologous BMTx augmentation of graft survival is dependent in part upon a population of Breg cells that can modulate the function of donor-derived Treg cells. © 2018 John Wiley & Sons Ltd.

  15. Incidence and dynamics of active cytomegalovirus infection in allogeneic stem cell transplant patients according to single nucleotide polymorphisms in donor and recipient CCR5, MCP-1, IL-10, and TLR9 genes.

    Science.gov (United States)

    Corrales, Isabel; Giménez, Estela; Solano, Carlos; Amat, Paula; de la Cámara, Rafael; Nieto, José; Garcia-Noblejas, Ana; Navarro, David

    2015-02-01

    Single nucleotide polymorphisms (SNPs) in genes involved in the activation or regulation of innate and adaptive immune responses may modulate the susceptibility to and the natural history of certain chronic viral infections. The current study aimed to investigate whether donor and recipient SNPs in the chemokine receptor 5 (rs1800023), monocyte chemoattractant protein 1 (rs13900), interleukin-10 (rs1878672), and Toll-like receptor 9 (rs352140) genes would exert any influence on the rate of incidence and features of CMV DNAemia in the allogeneic stem cell transplantation setting. This was a retrospective observational multicenter study. The cohort consisted of 102 non-consecutive allogeneic stem cell transplant recipients. SNP genotyping was performed by allele-specific real-time PCR. CMV surveillance was performed by the pp65 antigenemia assay/and or by real-time PCR. Seventy-three patients developed CMV DNAemia within the first 100 days after transplantation (71.5%). Neither donor nor recipient SNPs were associated significantly with the rate of incidence of active CMV infection, nor with the need for pre-emptive antiviral therapy. Both the duration of CMV DNAemia and the plasma CMV DNA peak load during episodes were significantly higher in patients harboring the donor (but not the recipient) chemokine receptor 5 A/A genotype, than in their A/G and G/G counterparts (P = 0.022 and P = 0.045, respectively). The data reported suggest that SNPs in chemokine receptor 5 may influence the dynamics of CMV infection in the Allo-SCT setting. © 2014 Wiley Periodicals, Inc.

  16. Predictors of viable germ cell tumor in postchemotherapeutic residual retroperitoneal masses

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    Khalid Al Othman

    2014-01-01

    Full Text Available Objective: The aim of this study was to identify predictors of viable germ cell tumor (GCT in postchemotherapeutic residual retroperitoneal masses. Materials and Methods: The pertinent clinical and pathologic data of 16 male patients who underwent postchemotherapeutic retroperitoneal lymph node dissection (PC-RPLND at King Faisal Specialist Hospital and Research Centre between 1994 and 2005 were reviewed retrospectively. It was found that all patients received cisplatin-based chemotherapy for advanced testicular GCT. Results: Out of the 16 male patients, 2 (13%, 8 (50%, and 6 (37% had viable GCT, fibrosis, and teratoma, respectively. Ten (10 of the patients with prechemotherapeutic S1 tumor markers did not have viable GCT, and two of the six patients who had prechemotherapeutic S2 tumor markers have viable GCT. All tumor marker levels normalized after chemotherapy even in patients with viable GCT. Four patients had vascular invasion without viable GCT. Furthermore, four patients had more than 60% embryonal elements in the original pathology, but only 1 had viable GCT at PC-RPLND. Four of the five patients with immature teratoma had teratoma at PC-RPLND but no viable GCT; however, out of the four patients with mature teratoma, one had viable GCT and two had teratoma at PC-RPLND. Of the two patients with viable GCT, one had 100% embryonal cancer in the original pathology, prechemotherapeutic S2 tumor markers, history of orchiopexy, and no vascular invasion; the other patient had yolk sac tumor with 25% embryonal elements and 40% teratoma in the original pathology, and prechemotherapeutic S2 tumor markers. Conclusion: None of the clinical or pathological parameters showed a strong correlation with the presence of viable GCT in PC-RPLND. However, patients with ≥S2 may be at higher risk to have viable GCT. Further studies are needed to clarify this.

  17. In-vitro cancer cell cytotoxicity and alpha amylase inhibition effect of seven tropical fruit residues

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    Priti Gupta

    2014-07-01

    Conclusions: Study suggests that these fruit residues demonstrate promising antidiabetic and anticancer activity that substantiated its ethno medicinal use and may provide new molecules for the treatment of these diseases.

  18. Efficacy of beer fermentation residue containing Saccharomyces cerevisiae cells for ameliorating aflatoxicosis in broilers.

    Science.gov (United States)

    Bovo, F; Franco, L T; Kobashigawa, E; Rottinghaus, G E; Ledoux, D R; Oliveira, C A F

    2015-05-01

    This study aimed to determine the aflatoxin B1 (AFB1) binding capacity of a beer fermentation residue (BFR) containing Saccharomyces cerevisiae cells, and the efficacy of BFR to ameliorate the toxic effects of AFB1 on performance, serum biochemistry, and histology of broilers. The BFR was collected from a microbrewery, and the yeast cells were counted, dried, and milled before it was used in the study. In vitro evaluation of the BFR was conducted using different concentrations of AFB1 (2.0, 4.0, 8.0, 16.0, and 32.0 μg AFB1/mL) and 100 mg/10 mL of BFR at pH 3.0 or 6.0. Two hundred 1-day-old male broilers (Ross 308) were assigned to chick batteries and allowed ad libitum access to feed and water. A completely randomized design was used with 5 replicate pens of 5 chicks assigned to each of 4 dietary treatments from hatch to 21 d, which included: 1) basal diet (BD), with no BFR or AFB1; 2) BD supplemented with 1% BFR; 3) BD supplemented with 2 mg AFB1/kg of feed; and 4) BD supplemented with 2 mg AFB1/kg feed and 1% BFR. Performance variables were determined weekly, while serum analyses were performed on d 14 and 21. At the end of the study, chicks were anesthetized with carbon dioxide, euthanized by cervical dislocation, and the kidney, liver, and bursa of Fabricius were removed for determination of relative weights, and for histological evaluation. In vitro assays showed that the higher the initial AFB1 concentration in solution, the greater the AFB1 amount adsorbed by BFR at both pHs tested. Feed intake, BW gain, and concentrations of albumin, total protein, and globulin increased (P < 0.05) in broilers fed BFR+AFB1 (Diet 4), when compared to the birds receiving only AFB1 (Diet 2). Although BFR was not able to reduce or prevent the effects of AFB1 on relative weights of kidneys and liver, it reduced the severity of histological changes in the liver and kidney caused by AFB1. © 2015 Poultry Science Association Inc.

  19. Identification of residual leukemic cells by flow cytometry in childhood B-cell precursor acute lymphoblastic leukemia - Verification of leukemic state by flow-sorting and molecular/cytogenetic methods

    DEFF Research Database (Denmark)

    Obro, Nina Friesgaard; Ryder, Lars Peter; Madsen, Hans Ole

    2012-01-01

    Reduction in minimal residual disease, measured by real-time quantitative PCR or flow cytometry, predicts prognosis in childhood B-cell precursor acute lymphoblastic leukemia. We explored whether cells reported as minimal residual disease by flow cytometry represent the malignant clone harboring...... immunophenotype and antigen modulation) that highlight important methodological pitfalls. These findings demonstrate that with sufficient experience, flow cytometry is reliable for minimal residual disease monitoring in B-cell precursor acute lymphoblastic leukemia, although rare cases require supplementary PCR...

  20. Serum from CBA/Ca mice vaccinated with irradiated cercariae of Schistosoma mansoni protects naive recipients through the recruitment of cutaneous effector cells

    International Nuclear Information System (INIS)

    McLaren, D.J.; Smithers, S.R.

    1988-01-01

    Passive transfer experiments showed that 76% of the resistance induced in CBA/Ca mice by exposure to radiation-attenuated cercariae of Schistosoma mansoni could be transferred to naive recipients by administration of donor serum. The serum was twice as effective when given to the recipients at the time of cercarial challenge as compared to administration 5 days after challenge, a result which indicates that serum-dependent challenge elimination is probably accomplished in the cutaneous tissues. This view was confirmed by the observation that passive protection could be ablated by administration of a monoclonal antibody which depletes the cutaneous inflammatory reaction to cercarial penetration. Histopathological studies revealed that vaccine serum induced subdermal inflammatory reactions in challenged recipient mice which were identical both in duration and kinetics to those seen in conventionally vaccinated individuals. Challenge larvae, which had transformed from skin-stage to lung-stage parasites, became trapped within such reactions and eventually showed generalized vacuolation consistent with the onset of damage. Some foci were seen to contain degenerated leucocytes, free eosinophil granules and debris which is thought to represent the remnants of dead parasites. These data show that serum-transferred resistance in the vaccinated CBA/Ca mouse model involves the induction of a cutaneous inflammatory response in the recipients. (author)

  1. Morphological and immunological criteria of minimal residual disease detection in children with B-cell precursors acute lymphoblastic leukemia

    Science.gov (United States)

    Beznos, O. A.; Grivtsova, L. Yu; Popa, A. V.; Shervashidze, M. A.; Serebtyakova, I. N.; Tupitsyn, N. N.; Selchuk, V. U.; Grebennikova, O. P.; Titova, G. V.

    2018-01-01

    One of the key factors of prognosis and risk stratification in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is minimal residual disease (MRD). Identification of MRD on the day 15th is one of the most significant in prognosis of the disease. We compared data of a morphological and flow cytometry results of assessment of a bone marrow (BM) at the day 15th of induction chemotherapy in children with BCP-ALL.

  2. Human mastadenovirus type 70: a novel, multiple recombinant species D mastadenovirus isolated from diarrhoeal faeces of a haematopoietic stem cell transplantation recipient.

    Science.gov (United States)

    Hage, Elias; Gerd Liebert, Uwe; Bergs, Sandra; Ganzenmueller, Tina; Heim, Albert

    2015-09-01

    A human mastadenovirus D (HAdV-D) isolated from diarrhoeal faeces of an allogeneic haematopoietic stem cell transplant (SCT) recipient was found to be non-typable by sequencing of loops 1 and 2 of the hexon main neutralization epitope ('imputed serology'). In contrast to HAdV-C, HAdV-D infections are rarely observed in SCT patients. Therefore, the whole genome of this isolate was sequenced and phylogenetically analysed. In addition, microneutralization testing with type-specific antisera was performed. A complete genomic sequence of 35.2 kb in length with a GC content of 57  % was obtained and found to be distantly related to HAdV-D27 (96.25 % identity). Imputed serology implicated a new type with a nucleotide sequence identity of only 96.11 % to HAdV-D37 (loop 1) and 95.76 % to HAdV-D30 and HAdV-D37 (loop 2). Microneutralization testing confirmed that this clinical isolate was not neutralized by HAdV-D37- or HAdV-D30-specific antisera. The penton base gene showed a novel sequence, which clustered with HAdV-D38, but bootscan analysis indicated an intra-penton recombination event with HAdV-D60. Another recombination event was detected within the early gene region E3 with the 12.2 kDa and CR1-α genes derived from HAdV-D58. Moreover, the E4 region was derived from HAdV-D13, but all these genes had evolved significantly from their ancestors. By contrast, the recombinant fibre gene was almost 100 % identical to HAdV-D29. In conclusion, the genomics of this novel HAdV, designated the HAdV-D70 [P70H70F29] prototype, supported the significance of multiple recombinations in the phylogeny of HAdV-D.

  3. Residual deposits (residual soil)

    International Nuclear Information System (INIS)

    Khasanov, A.Kh.

    1988-01-01

    Residual soil deposits is accumulation of new formate ore minerals on the earth surface, arise as a result of chemical decomposition of rocks. As is well known, at the hyper genes zone under the influence of different factors (water, carbonic acid, organic acids, oxygen, microorganism activity) passes chemical weathering of rocks. Residual soil deposits forming depends from complex of geologic and climatic factors and also from composition and physical and chemical properties of initial rocks

  4. Prestin regulation and function in residual outer hair cells after noise-induced hearing loss.

    Directory of Open Access Journals (Sweden)

    Anping Xia

    Full Text Available The outer hair cell (OHC motor protein prestin is necessary for electromotility, which drives cochlear amplification and produces exquisitely sharp frequency tuning. Tecta(C1509G transgenic mice have hearing loss, and surprisingly have increased OHC prestin levels. We hypothesized, therefore, that prestin up-regulation may represent a generalized response to compensate for a state of hearing loss. In the present study, we sought to determine the effects of noise-induced hearing loss on prestin expression. After noise exposure, we performed cytocochleograms and observed OHC loss only in the basal region of the cochlea. Next, we patch clamped OHCs from the apical turn (9-12 kHz region, where no OHCs were lost, in noise-exposed and age-matched control mice. The non-linear capacitance was significantly higher in noise-exposed mice, consistent with higher functional prestin levels. We then measured prestin protein and mRNA levels in whole-cochlea specimens. Both Western blot and qPCR studies demonstrated increased prestin expression after noise exposure. Finally, we examined the effect of the prestin increase in vivo following noise damage. Immediately after noise exposure, ABR and DPOAE thresholds were elevated by 30-40 dB. While most of the temporary threshold shifts recovered within 3 days, there were additional improvements over the next month. However, DPOAE magnitudes, basilar membrane vibration, and CAP tuning curve measurements from the 9-12 kHz cochlear region demonstrated no differences between noise-exposed mice and control mice. Taken together, these data indicate that prestin is up-regulated by 32-58% in residual OHCs after noise exposure and that the prestin is functional. These findings are consistent with the notion that prestin increases in an attempt to partially compensate for reduced force production because of missing OHCs. However, in regions where there is no OHC loss, the cochlea is able to compensate for the excess prestin in

  5. Renal cancer in recipients of kidney transplant

    Directory of Open Access Journals (Sweden)

    Prajwal Dhakal

    2017-03-01

    Full Text Available The aim of our study is to determine characteristics and outcomes of kidney cancer in renal transplant recipients. MEDLINE ® database was searched in June 2015 to identify cases of kidney cancer in renal transplant recipients. We include also a new case. Descriptive statistics were used for analysis. Forty-eight (48 recipients reported in 25 papers met the eligibility criteria. The median age was 47 years (range 9-66; 27% were females. Chronic glomerulonephritis, cystic kidney disease and hypertension were common indications for renal transplant. Among donors 24% were females and the median age was 52.5 years (17- 73; 62% of kidney cancers were donor-derived. The median interval between transplant and cancer diagnosis was shorter for cancer of recipient versus donor origin (150 vs. 210 days. Clear cell carcinoma was diagnosed in 17%. 25% had metastasis at diagnosis. Kidney explantation or excision was done in 90% and 84% of cases with and without metastasis respectively. The median survival was 72 months. Actuarial 1-year and 5-year survival rates were 73.4% and 55.1% respectively. Among the recipients from 7 donors who subsequently developed malignancy, 57% were dead within a year. Kidney transplant recipients have a small risk of kidney cancer, which affects younger patients and occurs within a year of transplant, likely due to immunosuppression. Whether the use of older donors may increase the likelihood needs further investigation. The presence of metastasis, explantation or excision of affected kidney and development of cancer in donors predict outcomes. The results may guide patient education and informed decision-making.

  6. Early recovery of circulating immature B cells in B-lymphoblastic leukemia patients after CD19 targeted CAR T cell therapy: A pitfall for minimal residual disease detection.

    Science.gov (United States)

    Xiao, Wenbin; Salem, Dalia; McCoy, Catharine S; Lee, Daniel; Shah, Nirali N; Stetler-Stevenson, Maryalice; Yuan, Constance M

    2017-09-09

    CD19-targeted chimeric-antigen receptor-modified T-cells (CAR-T) are promising in the treatment of refractory B-lymphoblastic leukemia (B-ALL). Minimal residual disease (MRD) detection by multicolor flow cytometry (FCM) is critical to distinguish B-ALL MRD from regenerating, non-neoplastic B-cell populations. FCM was performed on samples from 9 patients with B-ALL treated with CAR-T. All 9 patients showed response to CAR-T. Additionally, FCM revealed circulating CD10 + B cells, potentially mimicking MRD. Circulating CD10+ B-cells were detected in blood from 3 days to 3 months after CAR-T, comprising 73% (median) of B-cells (52-83%, 95%CI). They expressed CD19, CD10, CD20, bright CD9, CD22, CD24, moderate CD38 and dim CD58, but were CD34 (-), with bright CD45 and polyclonal surface light chain immunoglobulin (sIg) expression. A similar CD10 + B-cell subpopulation was detected by marrow FCM, amidst abundant B-cell precursors. These circulating CD10 + B-cells are compatible with immature B-cells, and are a reflection of B-cell recovery within the marrow. They are immunophenotypically distinguishable from residual B-ALL. Expression of light chain sIg and key surface antigens characterizing regenerating B-cell precursors can distinguish immature B-cells from B-ALL MRD and prevent misdiagnosis. © 2017 International Clinical Cytometry Society. © 2017 International Clinical Cytometry Society.

  7. Characterization and elimination of undesirable protein residues in plant cell walls for enhancing lignin analysis by solution-state 2D gel-NMR methods

    Science.gov (United States)

    Proteins exist in every plant cell wall. Certain protein residues interfere with lignin characterization and quantification. The current solution-state 2D-NMR technique (gel-NMR) for whole plant cell wall structural profiling provides detailed information regarding cell walls and proteins. However, ...

  8. The role of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in the evaluation of residual germ cell tumours

    International Nuclear Information System (INIS)

    Ballok, Z.E.; Scott, A.M.; Hannah, A.; Berlangieri, S.; Tochon-Danguy, H.; Chan, J.G.; Hicks, R.; Burns, I.; McKendrich, J.; Tauro, A.

    1998-01-01

    Full text: The role of FDG-PET is not well established in the assessment of patients with germ cell tumours. The aim of this study was to assess the accuracy of FDG-PET in detecting residual disease in patients with germ cell tumours, and its potential role in patient management. A total of 34 FDG-PET scans in 29 patients (23 patients (IF:22M) with nonseminomatous germ cell tumours (NSGCT), and 6 male patients with advanced seminoma) performed over a 4 yr period were evaluated. Results of FDG-PET studies were compared to pathology or follow-up. For NSGCT patients, pathological evidence of residual high grade tumour was seen in 9 patients on subsequent surgical specimens. FDG-PET studies were true positive in all of these patients. In 8 NSGCT patients pathology revealed fibrosis or teratoma at subsequent surgery: all had negative FDG-PET studies. There were no false positive, nor false negative FDG-PET studies. Resection was not performed in the remaining 6 patients, and on follow-up 2 patients had a progressive clinical course after positive FDG-PET scans, and 2 patients were in clinical remission 3 and 29 months after a negative FDG-PET study, respectively. Two patients were not evaluable. Of the 6 seminoma patients, 5 underwent further chemotherapy /radiotherapy after having abnormal FDG-PET studies due to clinical evidence of disease. The 6th pt with a negative FDG-PET study had stable retroperitoneal lymph node enlargement after 3 years follow-up. In our series FDG-PET was able to predict the presence of high grade malignancy within residual masses in patients with NSGCT and seminoma with a high accuracy. These initial results encourage further evaluation

  9. A direct qPCR method for residual DNA quantification in monoclonal antibody drugs produced in CHO cells.

    Science.gov (United States)

    Hussain, Musaddeq

    2015-11-10

    Chinese hamster ovary (CHO) cells are the host cell of choice for manufacturing of monoclonal antibody (mAb) drugs in the biopharmaceutical industry. Host cell DNA is an impurity of such manufacturing process and must be controlled and monitored in order to ensure drug purity and safety. A conventional method for quantification of host residual DNA in drug requires extraction of DNA from the mAb drug substance with subsequent quantification of the extracted DNA using real-time PCR (qPCR). Here we report a method where the DNA extraction step is eliminated prior to qPCR. In this method, which we have named 'direct resDNA qPCR', the mAb drug substance is digested with a protease called KAPA in a 96-well PCR plate, the protease in the digest is then denatured at high temperature, qPCR reagents are added to the resultant reaction wells in the plate along with standards and controls in other wells of the same plate, and the plate subjected to qPCR for analysis of residual host DNA in the samples. This direct resDNA qPCR method for CHO is sensitive to 5.0fg of DNA with high precision and accuracy and has a wide linear range of determination. The method has been successfully tested with four mAbs drug, two IgG1 and two IgG4. Both the purified drug substance as well as a number of process intermediate samples, e.g., bioreactor harvest, Protein A column eluate and ion-exchange column eluates were tested. This method simplifies the residual DNA quantification protocol, reduces time of analysis and leads to increased assay sensitivity and development of automated high-throughput methods. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. T Cell Determinants Incorporating [beta]-Amino Acid Residues Are Protease Resistant and Remain Immunogenic In Vivo

    Energy Technology Data Exchange (ETDEWEB)

    Webb, Andrew I.; Dunstone, Michelle A.; Williamson, Nicholas A.; Price, Jason D.; Kauwe, Andreade; Chen, Weisan; Oakley, Aaron; Perlmutter, Patrick; McCluskey, James; Aguilar, Marie-Isabel; Rossjohn, Jamie; Purcell, Anthony W. (Monash); (Melbourne); (ANU)

    2010-07-20

    A major hurdle in designing successful epitope-based vaccines resides in the delivery, stability, and immunogenicity of the peptide immunogen. The short-lived nature of unmodified peptide-based vaccines in vivo limits their therapeutic application in the immunotherapy of cancers and chronic viral infections as well as their use in generating prophylactic immunity. The incorporation of {beta}-amino acids into peptides decreases proteolysis, yet its potential application in the rational design of T cell mimotopes is poorly understood. To address this, we have replaced each residue of the SIINFEKL epitope individually with the corresponding {beta}-amino acid and examined the resultant efficacy of these mimotopes. Some analogs displayed similar MHC binding and superior protease stability compared with the native epitope. Importantly, these analogs were able to generate cross-reactive CTLs in vivo that were capable of lysing tumor cells that expressed the unmodified epitope as a surrogate tumor Ag. Structural analysis of peptides in which anchor residues were substituted with {beta}-amino acids revealed the basis for enhanced MHC binding and retention of immunogenicity observed for these analogs and paves the way for future vaccine design using {beta}-amino acids. We conclude that the rational incorporation of {beta}-amino acids into T cell determinants is a powerful alternative to the traditional homologous substitution of randomly chosen naturally occurring {alpha}-amino acids, and these mimotopes may prove particularly useful for inclusion in epitope-based vaccines.

  11. Development of Graft-Site Candidiasis in 3 Solid Organ Transplant Recipients from the Same Donor.

    Science.gov (United States)

    El-Bandar, Nasrin; Kroy, Daniela C; Fuller, Tom Florian; Kramer, Jürgen; Liefeldt, Lutz; Budde, Klemens; Blobel, Conrad; Miller, Kurt; Friedersdorff, Frank

    2017-07-11

    BACKGROUND Graft-site candidiasis rarely develops in solid organ transplant recipients; however, severe life-threatening complications can occur. We report the course of 3 solid organ transplant recipients developing graft-site candidiasis. CASE REPORT All grafts, consisting of 2 kidneys and 1 liver, were procured from a single donor. Patient data were collected from our database. Candida albicans was isolated from a swab taken during multiple-organ recovery. Complications associated with candidiasis occurred in all 3 recipients with preservation of the liver transplant. Both renal transplant recipients had vascular complications, eventually resulting in graft nephrectomy and subsequent return to dialysis. The patients recovered completely without residual effects of their prior fungal infection. CONCLUSIONS Fungal infections in solid organ transplant recipients are rare. Since the sequelae of these infections are serious and usually pertain to more than 1 recipient at a time, antifungal prophylaxis may be warranted in select donors.

  12. Residues 39-56 of Stem Cell Factor Protein Sequence Are Capable of Stimulating the Expansion of Cord Blood CD34+ Cells.

    Science.gov (United States)

    Shen, Bin; Jiang, Wenhong; Fan, Jie; Dai, Wei; Ding, Xinxin; Jiang, Yongping

    2015-01-01

    Stem cell factor (SCF) can stimulate hematopoietic stem cell (HSC) expansion; however, the specific structural region(s) of SCF protein that are critical for this function are still unknown. A novel monoclonal antibody (named 23C8) against recombinant human SCF (rhSCF) was previously found to inhibit the ability of rhSCF to enhance HSC expansion, making it possible to identify the relevant active region to HSC. Eleven polypeptides were synthesized, which were designed to cover the full-length of rhSCF, with overlaps that are at least 3 amino acids long. ELISA was used to identify the polypeptide(s) that specifically react with the anti-SCF. The effects of the synthetic polypeptides on human HSC expansion, or on the ability of the full-length rhSCF to stimulate cell proliferation, were evaluated ex vivo. Total cell number was monitored using hemocytometer whereas CD34+ cell number was calculated based on the proportion determined via flow cytometry on day 6 of culture. Of all polypeptides analyzed, only one, named P0, corresponding to the SCF protein sequence at residues 39-56, was recognized by 23C8 mAb during ELISA. P0 stimulated the expansion of CD34+ cells derived from human umbilical cord blood (UCB). Addition of P0 increased the numbers of total mononucleated cells and CD34+ cells, by ~2 fold on day 6. P0 also showed partial competition against full-length rhSCF in the ex vivo cell expansion assay. Residues 39-56 of rhSCF comprise a critical functional region for its ability to enhance expansion of human UCB CD34+ cells. The peptide P0 is a potential candidate for further development as a synthetic substitute for rhSCF in laboratory and clinical applications.

  13. Recipient government control under pressure

    DEFF Research Database (Denmark)

    Jansson, Johanna

    This paper seeks to contribute to ongoing debates around African countries‟ relations to their external partners. It explores the notion of recipient government control, here defined as the extent to which a recipient government is able to ensure that the outcome of negotiations with its external...

  14. Escherichia coli common pilus (ECP) targets arabinosyl residues in plant cell walls to mediate adhesion to fresh produce plants.

    Science.gov (United States)

    Rossez, Yannick; Holmes, Ashleigh; Lodberg-Pedersen, Henriette; Birse, Louise; Marshall, Jacqueline; Willats, William G T; Toth, Ian K; Holden, Nicola J

    2014-12-05

    Outbreaks of verotoxigenic Escherichia coli are often associated with fresh produce. However, the molecular basis to adherence is unknown beyond ionic lipid-flagellum interactions in plant cell membranes. We demonstrate that arabinans present in different constituents of plant cell walls are targeted for adherence by E. coli common pilus (ECP; or meningitis-associated and temperature-regulated (Mat) fimbriae) for E. coli serotypes O157:H7 and O18:K1:H7. l-Arabinose is a common constituent of plant cell wall that is rarely found in other organisms, whereas ECP is widespread in E. coli and other environmental enteric species. ECP bound to oligosaccharides of at least arabinotriose or longer in a glycan array, plant cell wall pectic polysaccharides, and plant glycoproteins. Recognition overlapped with the antibody LM13, which binds arabinanase-sensitive pectic epitopes, and showed a preferential affinity for (1→5)-α-linked l-arabinosyl residues and longer chains of arabinan as demonstrated with the use of arabinan-degrading enzymes. Functional adherence in planta was mediated by the adhesin EcpD in combination with the structural subunit, EcpA, and expression was demonstrated with an ecpR-GFP fusion and ECP antibodies. Spinach was found to be enriched for ECP/LM13 targets compared with lettuce. Specific recognition of arabinosyl residues may help explain the persistence of E. coli in the wider environment and association of verotoxigenic E. coli with some fresh produce plants by exploitation of a glycan found only in plant, not animal, cells. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Asthma induction in mice leads to appearance of alpha2-3- and alpha2-6-linked sialic acid residues in respiratory goblet-like cells

    DEFF Research Database (Denmark)

    Kirkeby, Svend; Jensen, Niels-Erik Viby; Mandel, Ulla

    2008-01-01

    incubation with the sialic acid detecting agents, while the goblet-like cells expressed both alpha2-3- and alpha2-6-linked sialic acid residues in the asthmatic animals. The lectins but not the antibodies reacted with intestinal goblet cells. Instead, an antibody recognizing a disialoganglioside, stained......Allergic asthmatic inflammation in mice was induced by sensitization with ovalbumin and lipopolysaccharide from Escherichia coli and visualized in the airways of asthmatic mice by spatial and temporal changes of carbohydrates containing sialic acid residues. Immunohistochemistry was used...... to demonstrate binding of lectins and antibodies that detect alpha2-3- and alpha2-6-linked sialic acid residues. After sensitization and challenge, the histology of the lung changed markedly, and goblet-like cells appeared, most likely caused by Clara cell metaplasia. Normal Clara cells showed no reaction after...

  16. STRESS - STRAIN BEHAVIOR OF A GNEISS RESIDUAL SOIL USING THE CUBIC TRIAXIAL CELL

    OpenAIRE

    MARCONI SOARES ALEIXO

    1998-01-01

    O conhecimento do comportamento de solos residuais é de grande importância para projetos geotécnicos no Brasil e, em particular, na região do Rio de Janeiro, tendo em vista que o clima tropical e as características geológicas favorecem a ocorrência de mantos residuais de grande espessura. O presente trabalho trata do estudo do comportamento tensão-deformação de um solo residual proveniente de um perfil de alteração de rocha gnáissica do maciço da Tijuca, Rio de...

  17. Residual expression of reprogramming factors affects the transcriptional program and epigenetic signatures of induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Cesar A Sommer

    Full Text Available Delivery of the transcription factors Oct4, Klf4, Sox2 and c-Myc via integrating viral vectors has been widely employed to generate induced pluripotent stem cell (iPSC lines from both normal and disease-specific somatic tissues, providing an invaluable resource for medical research and drug development. Residual reprogramming transgene expression from integrated viruses nevertheless alters the biological properties of iPSCs and has been associated with a reduced developmental competence both in vivo and in vitro. We performed transcriptional profiling of mouse iPSC lines before and after excision of a polycistronic lentiviral reprogramming vector to systematically define the overall impact of persistent transgene expression on the molecular features of iPSCs. We demonstrate that residual expression of the Yamanaka factors prevents iPSCs from acquiring the transcriptional program exhibited by embryonic stem cells (ESCs and that the expression profiles of iPSCs generated with and without c-Myc are indistinguishable. After vector excision, we find 36% of iPSC clones show normal methylation of the Gtl2 region, an imprinted locus that marks ESC-equivalent iPSC lines. Furthermore, we show that the reprogramming factor Klf4 binds to the promoter region of Gtl2. Regardless of Gtl2 methylation status, we find similar endodermal and hepatocyte differentiation potential comparing syngeneic Gtl2(ON vs Gtl2(OFF iPSC clones. Our findings provide new insights into the reprogramming process and emphasize the importance of generating iPSCs free of any residual transgene expression.

  18. Exposed hydrophobic residues in human immunodeficiency virus type 1 Vpr helix-1 are important for cell cycle arrest and cell death.

    Directory of Open Access Journals (Sweden)

    R Anthony Barnitz

    Full Text Available The human immunodeficiency virus type 1 (HIV-1 accessory protein viral protein R (Vpr is a major determinant for virus-induced G2/M cell cycle arrest and cytopathicity. Vpr is thought to perform these functions through the interaction with partner proteins. The NMR structure of Vpr revealed solvent exposed hydrophobic amino acids along helices 1 and 3 of Vpr, which could be putative protein binding domains. We previously showed that the hydrophobic patch along helix-3 was important for G2/M blockade and cytopathicity. Mutations of the exposed hydrophobic residues along helix-1 were found to reduce Vpr-induced cell cycle arrest and cell death as well. The levels of toxicity during virion delivery of Vpr correlated with G2/M arrest. Thus, the exposed hydrophobic amino acids in the amino-terminal helix-1 are important for the cell cycle arrest and cytopathicity functions of Vpr.

  19. Shedding of HSV-1, HSV-2, CMV, and EBV in the saliva of hematopoietic stem cell transplant recipients at Fundación HOMI - Hospital de la Misericordia, Bogotá, D.C.

    Science.gov (United States)

    Bohórquez, Sonia P; Díaz, Juliana; Rincón, Claudia M; Estupiñán, Marcela; Chaparro, Mauricio; Low-Calle, Ana María; Castellanos, Jaime E

    2016-05-19

    Hematopoietic stem cell transplantation in pediatric patients is an alternative treatment for different diseases. The conditioning regimen for transplant predisposes recipients to the development of infections. Viral infections by herpes simplex virus 1 (HSV-1), herpes simplex virus 2 (HSV-2), human cytomegalovirus (CMV), and Epstein-Barr virus (EBV), are the most common, and the leading cause of morbidity and mortality among these patients. These viruses lie dormant in various cell types and the reactivation of latent infections may lead to asymptomatic viral shedding in saliva. The detection of these viruses in secretions may contribute to understand the behavioral dynamics of these viral infections in transplanted patients, and to the early diagnosis of reactivation.  To assess HSV-1, HSV-2, CMV and EBV viral shedding in the saliva of patients admitted for hematopoietic stem cell transplantation at Fundación HOMI - Hospital de la Misericordia between January and November of 2012.  We evaluated stimulated saliva samples of 17 hematopoietic stem cell transplantation recipients weekly. We performed DNA extraction from saliva, and we evaluated the presence of DNA for HSV-1, HSV-2, CMV, and EBV by PCR.  While we detected HSV-2 and CMV DNA in the saliva of four patients, EBV DNA was detected in nine patients with leukopenia. In contrast, we did not detect HSV-1 DNA in saliva. Additionally, four out of the 17 patients showed a simultaneous shedding of CMV and EBV.  By conventional PCR, we demonstrated asymptomatic HSV-2, CMV, and EBV viral shedding in saliva, associated with leukopenia.

  20. Donor Monoclonal Gammopathy May Cause Lymphoproliferative Disorders in Solid Organ Transplant Recipients.

    Science.gov (United States)

    Felldin, M; Ekberg, J; Polanska-Tamborek, D; Hansson, U; Sender, M; Rizell, M; Svanvik, J; Mölne, J

    2016-09-01

    Prior research on donor monoclonal gammopathy of undetermined significance (MGUS) has been inadequate regarding the risk for lymphoproliferative disease in solid organ transplantation recipients. Seven organ recipients from two different donors developed lymphoproliferative disease. The origin of the malignancy was determined by use of microsatellite analysis, and the plasma of the two donors was analyzed with the use of electrophoresis. The clinical courses of the seven recipients were followed for 36-60 months. One donor transmitted lymphoplasmacytic lymphoma to two kidney recipients and MGUS to a liver recipient, all IgMκ. A second donor caused IgGλ myeloma in two kidney and one liver recipient, and IgGλ gammopathy in a heart recipient. Transplant nephrectomy was performed in three kidney recipients and remission was achieved. The fourth kidney recipient has kept the graft and the disease has progressed. The liver recipient died from myeloma. There were no clinical signs of lymphoproliferative disease in the donors, but retrospective serum analyses showed M-components, IgMκ (37 g/L) and IgGλ (8 g/L). Donors with MGUS may cause donor-transmitted malignancies via passenger lymphocytes/plasma cells in solid organ recipients. The results call for a large register study of the incidence of donor MGUS and lymphoproliferative disease in their recipients. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  1. Celiac lesion T cells recognize epitopes that cluster in regions of gliadins rich in proline residues

    DEFF Research Database (Denmark)

    Arentz-Hansen, Helene; McAdam, Stephen N; Molberg, Øyvind

    2002-01-01

    BACKGROUND & AIMS: Celiac disease is a gluten-induced enteropathy that shows a strong association with HLA-DQ2 and -DQ8. Gluten-specific T cells, invariably restricted by DQ2 or DQ8, can be isolated from celiac lesions. Such gut-derived T cells have a preference for recognition of gluten that has...

  2. Graft Transit Time Has No Effect on Outcome of Unrelated Donor Hematopoietic Cell Transplants Performed in Australia and New Zealand: A Study from the Australasian Bone Marrow Transplant Recipient Registry.

    Science.gov (United States)

    Patton, William Nigel; Nivison-Smith, Ian; Bardy, Peter; Dodds, Anthony; Ma, David; Shaw, Peter John; Kwan, John; Wilcox, Leonie; Butler, Andrew; Carter, John M; Blacklock, Hilary; Szer, Jeffrey

    2017-01-01

    A previous study found that platelet recovery and mortality were worse in recipients of myeloablative bone marrow transplants where graft transit times were longer than 20 hours. This retrospective study of unrelated myeloablative allogeneic transplantation performed within Australia and New Zealand analyzed transplant outcomes according to graft transit times. Of 233 assessable cases, 76 grafts (33%) were sourced from bone marrow (BM) and 157 (67%) from peripheral blood. Grafts sourced from Australia and New Zealand (47% of total) were associated with a median transit time of 6 hours versus 32 hours for overseas sourced grafts (53% of total). Graft transit temperature was refrigerated in 85%, ambient in 6%, and unknown in 9% of cases, respectively. Graft transit times had no significant effect on neutrophil or platelet engraftment, treatment-related mortality, overall survival, and incidence of acute or chronic graft-versus-host disease. Separate analysis of BM grafts, although of reduced power, also showed no significant difference in either neutrophil or platelet engraftment or survival between short and longer transport times. This study gives reassurance that both peripheral blood stem cell and especially BM grafts subjected to long transit times and transported at refrigerated temperatures may not be associated with adverse recipient outcomes. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  3. DUAL PARAMETER FLOW-CYTOMETRY FOR DEOXYRIBONUCLEIC-ACID AND INTERMEDIATE FILAMENT PROTEINS OF RESIDUAL MATURE TERATOMA - ALL TUMOR-CELLS ARE ANEUPLOID

    NARCIS (Netherlands)

    LOOIJENGA, LHJ; OOSTERHUIS, JW; RAMAEKERS, FCS; DEJONG, B; BECK, JLM; SLEIJFER, DT; KOOPS, HS; Dam, A.

    Most testicular germ cell tumors of adults are presumably derived from polyploid carcinoma in situ. Thus, one would expect that even highly differentiated teratoma components are aneuploid and that it is unlikely to find diploid tumor cell (sub)populations. We studied 10 residual mature teratomas

  4. Hormonal, metabolic and cardiovascular responses to hypoglycaemia in Type 1 (insulin-dependent) diabetes with and without residual B cell function

    DEFF Research Database (Denmark)

    Madsbad, S; Hilsted, J; Krarup, T

    1982-01-01

    Hormonal, metabolic and cardiovascular responses to insulin induced hypoglycaemia were investigated in seven Type 1 (insulin-dependent) diabetic patients with residual B cell function, eight Type 1 diabetic patients without B cell function and six healthy subjects. No differences were found between...... the diabetic groups regarding nadir of glucose and rate of recovery to normoglycaemia. The patients with residual B cell function had a glucagon response to hypoglycaemia which was close to that of normal subjects. In patients without B cell function, the glucagon response to hypoglycaemia was present, albeit...... significantly smaller than in the patients with preserved B cell function (0.025 ng/ml, range 0.007-0.042 versus 0.054 ng/ml, range 0.029-0.087). The group without B cell function had signs of an exaggerated rate of lipolysis and ketogenesis compared with the patients with B cell function and the normal...

  5. A Single Coxsackievirus B2 Capsid Residue Controls Cytolysis and Apoptosis in Rhabdomyosarcoma Cells

    DEFF Research Database (Denmark)

    Gullberg, M.; Tolf, C.; Jonsson, N.

    2010-01-01

    genetics, we identified a single amino acid change within the exposed region of the VP1 protein (glutamine to lysine at position 164) as the determinant for the acquired cytolytic trait. Moreover, this cytolytic virus induced apoptosis, including caspase activation and DNA degradation, in RD cells......) was originally isolated from a patient with summer grippe in the 1950s. Later on, CVB2O was adapted to cytolytic replication in rhabdomyosarcoma (RD) cells. Here, we present analyses of the correlation between the adaptive mutations of this RD variant and the cytolytic infection in RD cells. Using reverse....... These findings contribute to our understanding of the host cell adaptation process of CVB2O and provide a valuable tool for further studies of virus-host interactions....

  6. Selenium Protects Retinal Cells from Cisplatin-Induced Alterations in Carbohydrate Residues

    OpenAIRE

    Dilek Akşit; Alper Yazıcı; Hasan Akşit; Esin S. Sarı; Arzu Yay; Onur Yıldız; Adil Kılıç; Sıtkı S. Ermiş; Kamil Seyrek

    2016-01-01

    Background: Investigate alterations in the expression and localization of carbohydrate units in rat retinal cells exposed to cisplatin toxicity. Aims: The aim of the study was to evaluate putative protective effects of selenium on retinal cells subjected to cisplatin. Study Design: Animal experiment. Methods: Eighteen healthy Wistar rats were divided into three equal groups: 1. Control, 2. Cisplatin and 3. Cisplatin+selenium groups. After anesthesia, the right eye of each rat was ...

  7. Real-time amplification of HLA-DQA1 for counting residual white blood cells in filtered platelet concentrates.

    Science.gov (United States)

    Mohammadi, Tamimount; Reesink, Henk W; Vandenbroucke-Grauls, Christina M J E; Savelkoul, Paul H M

    2004-09-01

    BACKGROUND A real-time polymerase chain reaction (PCR) assay based on amplification of a conserved region of the HLA-DQA1 locus was developed and validated to assess its suitability in quantitating low levels of white blood cells (WBCs) in filtered platelet (PLT) concentrates (PCs). To determine the detection limit, serial dilutions of nonfiltered PCs with known quantities of WBCs were prepared. The analytical sensitivity and accuracy of the assay was tested with WBC concentrations ranging from 300 to 0.03 per microL with real-time PCR and flow cytometry. In addition, 126 random PCs were investigated to assess the capacity of the PCR method to quantify residual WBCs in clinical specimens. A sensitivity of 0.2 WBC equivalent per micro L (1.5 x 10(4) WBC equivalents/unit) was achieved. The assay was shown to be accurate and the HLA-DQA1 gene was reproducibly and consistently amplified in all tested samples (coefficient of variance of < 5%). Overall, the results of the PCR assay correlated well with those of the flow cytometry. The PCR assay detected a concentration of 3 WBCs per micro L (approximately 1 x 10(6) WBCs/unit) with 100 percent accuracy. Real-time PCR is rapid, sensitive, accurate, and reproducible. Hence this approach may prove suitable in routine monitoring of residual WBCs in PCs.

  8. Regulated internalization of NMDA receptors drives PKD1-mediated suppression of the activity of residual cell-surface NMDA receptors.

    Science.gov (United States)

    Fang, Xiao-Qian; Qiao, Haifa; Groveman, Bradley R; Feng, Shuang; Pflueger, Melissa; Xin, Wen-Kuan; Ali, Mohammad K; Lin, Shuang-Xiu; Xu, Jindong; Duclot, Florian; Kabbaj, Mohamed; Wang, Wei; Ding, Xin-Sheng; Santiago-Sim, Teresa; Jiang, Xing-Hong; Salter, Michael W; Yu, Xian-Min

    2015-11-19

    Constitutive and regulated internalization of cell surface proteins has been extensively investigated. The regulated internalization has been characterized as a principal mechanism for removing cell-surface receptors from the plasma membrane, and signaling to downstream targets of receptors. However, so far it is still not known whether the functional properties of remaining (non-internalized) receptor/channels may be regulated by internalization of the same class of receptor/channels. The N-methyl-D-aspartate receptor (NMDAR) is a principal subtype of glutamate-gated ion channel and plays key roles in neuronal plasticity and memory functions. NMDARs are well-known to undergo two types of regulated internalization - homologous and heterologous, which can be induced by high NMDA/glycine and DHPG, respectively. In the present work, we investigated effects of regulated NMDAR internalization on the activity of residual cell-surface NMDARs and neuronal functions. In electrophysiological experiments we discovered that the regulated internalization of NMDARs not only reduced the number of cell surface NMDARs but also caused an inhibition of the activity of remaining (non-internalized) surface NMDARs. In biochemical experiments we identified that this functional inhibition of remaining surface NMDARs was mediated by increased serine phosphorylation of surface NMDARs, resulting from the activation of protein kinase D1 (PKD1). Knockdown of PKD1 did not affect NMDAR internalization but prevented the phosphorylation and inhibition of remaining surface NMDARs and NMDAR-mediated synaptic functions. These data demonstrate a novel concept that regulated internalization of cell surface NMDARs not only reduces the number of NMDARs on the cell surface but also causes an inhibition of the activity of remaining surface NMDARs through intracellular signaling pathway(s). Furthermore, modulating the activity of remaining surface receptors may be an effective approach for treating receptor

  9. Circulating microRNA levels predict residual beta cell function and glycaemic control in children with type 1 diabetes mellitus

    DEFF Research Database (Denmark)

    Samandari, Nasim; Mirza, Aashiq H.; Nielsen, Lotte B.

    2017-01-01

    from the Danish Remission Phase Cohort, and profiled for miRNAs. At the same time points, meal-stimulated C-peptide and HbA1c levels were measured and insulin-dose adjusted HbA1c (IDAA1c) calculated. miRNAs that at 3 months after diagnosis predicted residual beta cell function and glycaemic control...... in this subgroup were further validated in the remaining cohort (n = 83). Statistical analysis of miRNA prediction for disease progression was performed by multiple linear regression analysis adjusted for age and sex. Results: In the discovery analysis, six miRNAs (hsa-miR-24-3p, hsa-miR-146a-5p, hsa-miR-194-5p...

  10. DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Borssén, Magnus; Haider, Zahra; Landfors, Mattias

    2016-01-01

    BACKGROUND: Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects....... In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T......-ALL. PROCEDURE: Sixty-five diagnostic T-ALL samples from Nordic pediatric patients treated according to the Nordic Society of Pediatric Hematology and Oncology ALL 2008 (NOPHO ALL 2008) protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation...

  11. Importance of Terminal Amino Acid Residues to the Transport of Oligopeptides across the Caco-2 Cell Monolayer.

    Science.gov (United States)

    Ding, Long; Wang, Liying; Yu, Zhipeng; Ma, Sitong; Du, Zhiyang; Zhang, Ting; Liu, Jingbo

    2017-09-06

    The objective of this paper was to investigate the effects of terminal amino acids on the transport of oligopeptides across the Caco-2 cell monolayer. Ala-based tetra- and pentapeptides were designed, and the N- or C-terminal amino acid residues were replaced by different amino acids. The results showed that the oligopeptides had a wide range of transport permeability across the Caco-2 cell monolayer and could be divided into four categories: non-/poor permeability, low permeability, intermediate permeability, and good permeability. Tetrapeptides with N-terminal Leu, Pro, Ile, Cys, Met, and Val or C-terminal Val showed the highest permeability, with apparent permeability coefficient (P app ) values over 10 × 10 -6 cm/s (p transport of tetrapeptides. Pentapeptides with N- or C-terminal Tyr also showed high permeability levels, with P app values of about 10 × 10 -6 cm/s. The amino acids Glu, Asn, and Thr at the N terminus or Lys, Asp, and Arg at the C terminus were also beneficial for the transport of tetra- and pentapeptides, with P app values ranging from 1 × 10 -6 to 10 × 10 -6 cm/s. In addition, peptides with amino acids replaced at the N terminus generally showed higher permeability than those with amino acids replaced at the C terminus (p transport of oligopeptides across the Caco-2 cell monolayer.

  12. 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.

  13. ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Cesaro, Simone; Dalianis, Tina; Hanssen Rinaldo, Christine; Koskenvuo, Minna; Pegoraro, Anna; Einsele, Hermann; Cordonnier, Catherine; Hirsch, Hans H

    2018-01-01

    To define guidelines for BK polyomavirus (BKPyV)-associated haemorrhagic cystitis (BKPyV-HC) after paediatric and adult HSCT. Review of English literature and evidence-based recommendations by expert consensus. BKPyV-HC occurs in 8%-25% of paediatric and 7%-54% of adult recipients undergoing allogeneic HSCT. Diagnosis requires the triad of cystitis, macro-haematuria and high urine BKPyV loads >7 log10 copies/mL, and exclusion of other relevant aetiologies. BKPyV viraemia is frequent and may serve as a more specific semiquantitative follow-up marker. No randomized controlled trials are available to inform antiviral prophylaxis or treatment. However, hyper-hydration and/or bladder irrigation showed limited prophylactic value. Fluoroquinolones are not effective for prophylaxis or treatment, but rather increase antibiotic resistance. Hyperbaric oxygen or fibrin glue is marginally effective based on small case series from correspondingly equipped centres. Although cidofovir has been reported to improve and/or reduce BKPyV viraemia or viruria, the current data do not support its regular use. BKPyV-HC remains a disabling unmet clinical need in HSCT that requires novel approaches supported by proper clinical trials. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Nutraceutical properties of cumin residue generated from Ayurvedic industries using cell line models.

    Science.gov (United States)

    Arun, K B; Aswathi, U; Venugopal, V V; Madhavankutty, T S; Nisha, P

    2016-10-01

    Spent cumin (SC), generated from Ayurvedic industry, was evaluated for its nutraceutical potential in terms of antioxidant, antidiabetic and anticancer properties, and compared with that of the raw cumin (RC). SC and RC seeds were extracted with ethyl acetate (E) and methanol (M). SCM (methanol extract) were rich in p-coumaric acid, ferulic acid, ellagic acid and cinnamic acid (6.4445, 5.8286, 2.1519, 4.3085 mg/g dry extract). SCM reduced Fe 2+ ion (89.68 µM AA/g dry weight), scavenged DPPH radical (IC 50 -238.6 µg/mL), better α-amylase inhibition (IC 50 -337.22 µg/mL) and glucose uptake activity in 30.7% of L6 cells. SCM inhibited viability, retarded migration area up to 41.02%, arrested cell cycle at S phase and induced apoptosis in 2.45% of HT29 colon cancer cells. The results indicated that dietary interventions using nutraceutical food formulation made out of SC can play a significant role in the prevention and management of degenerative diseases.

  15. Antibody induction versus corticosteroid induction for liver transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Wettergren, André; Wilson, Colin H

    2014-01-01

    . 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...... to identify additional trials. SELECTION CRITERIA: We included all randomised clinical trials assessing immunosuppression with T-cell specific antibody induction versus corticosteroid induction in liver transplant recipients. Our inclusion criteria stated that participants within each included trial should...... (bias) using bias risk domains with definitions. We used trial sequential analysis to control for random errors (play of chance). MAIN RESULTS: We included 10 randomised trials with a total of 1589 liver transplant recipients, which studied the use of T-cell specific antibody induction versus...

  16. Basic oral care for hematology-oncology patients and hematopoietic stem cell transplantation recipients : a position paper from the joint task force of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT)

    NARCIS (Netherlands)

    Elad, Sharon; Raber-Durlacher, Judith E.; Brennan, Michael T.; Saunders, Deborah P.; Mank, Arno P.; Zadik, Yehuda; Quinn, Barry; Epstein, Joel B.; Blijlevens, Nicole M. A.; Waltimo, Tuomas; Passweg, Jakob R.; Correa, M. Elvira P.; Dahllof, Goran; Garming-Legert, Karin U. E.; Logan, Richard M.; Potting, Carin M. J.; Shapira, Michael Y.; Soga, Yoshihiko; Stringer, Jacqui; Stokman, Monique A.; Vokurka, Samuel; Wallhult, Elisabeth; Yarom, Noam; Jensen, Siri Beier

    Hematology-oncology patients undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT) recipients are at risk for oral complications which may cause significant morbidity and a potential risk of mortality. This emphasizes the importance of basic oral care prior to, during and

  17. Basic oral care for hematology-oncology patients and hematopoietic stem cell transplantation recipients: a position paper from the joint task force of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT)

    NARCIS (Netherlands)

    Elad, S.; Raber-Durlacher, J.E.; Brennan, M.T.; Saunders, D.P.; Mank, A.P.; Zadik, Y.; Quinn, B.; Epstein, J.B.; Blijlevens, N.M.A.; Waltimo, T.; Passweg, J.R.; Correa, M.E.P.; Dahllöf, G.; Garming-Legert, K.U.E.; Logan, R.M.; Potting, C.M.J.; Shapira, M.Y.; Soga, Y.; Stringer, J.; Stokman, M.A.; Vokurka, S.; Wallhult, E.; Yarom, N.; Jensen, S.B.

    2015-01-01

    Purpose Hematology-oncology patients undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT) recipients are at risk for oral complications which may cause significant morbidity and a potential risk of mortality. This emphasizes the importance of basic oral care prior to, during

  18. Basic oral care for hematology-oncology patients and hematopoietic stem cell transplantation recipients: a position paper from the joint task force of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT)

    NARCIS (Netherlands)

    Elad, S.; Raber-Durlacher, J.E.; Brennan, M.T.; Saunders, D.P.; Mank, A.P.; Zadik, Y.; Quinn, B.; Epstein, J.B.; Blijlevens, N.M.A.; Waltimo, T.; Passweg, J.R.; Correa, M.E.; Dahllof, G.; Garming-Legert, K.U.; Logan, R.M.; Potting, C.M.J.; Shapira, M.Y.; Soga, Y.; Stringer, J.; Stokman, M.A.; Vokurka, S.; Wallhult, E.; Yarom, N.; Jensen, S.B.

    2015-01-01

    PURPOSE: Hematology-oncology patients undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT) recipients are at risk for oral complications which may cause significant morbidity and a potential risk of mortality. This emphasizes the importance of basic oral care prior to, during

  19. Basic oral care for hematology-oncology patients and hematopoietic stem cell transplantation recipients: a position paper from the joint task force of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT)

    NARCIS (Netherlands)

    Elad, Sharon; Raber-Durlacher, Judith E.; Brennan, Michael T.; Saunders, Deborah P.; Mank, Arno P.; Zadik, Yehuda; Quinn, Barry; Epstein, Joel B.; Blijlevens, Nicole M. A.; Waltimo, Tuomas; Passweg, Jakob R.; Correa, M. Elvira P.; Dahllöf, Göran; Garming-Legert, Karin U. E.; Logan, Richard M.; Potting, Carin M. J.; Shapira, Michael Y.; Soga, Yoshihiko; Stringer, Jacqui; Stokman, Monique A.; Vokurka, Samuel; Wallhult, Elisabeth; Yarom, Noam; Jensen, Siri Beier

    2015-01-01

    Hematology-oncology patients undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT) recipients are at risk for oral complications which may cause significant morbidity and a potential risk of mortality. This emphasizes the importance of basic oral care prior to, during and

  20. Minimal Residual Disease Diagnostics and Chimerism in the Post-Transplant Period in Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Ulrike Bacher

    2011-01-01

    Full Text Available In acute myeloid leukemia (AML, the selection of poor-risk patients for allogeneic hematopoietic stem cell transplantation (HSCT is associated with rather high post-transplant relapse rates. As immunotherapeutic intervention is considered to be more effective before the cytomorphologic manifestation of relapse, post-transplant monitoring gains increasing attention in stem cell recipients with a previous diagnosis of AML. Different methods for detection of chimerism (e.g., microsatellite analysis or quantitative real-time PCR are available to quantify the ratio of donor and recipient cells in the post-transplant period. Various studies demonstrated the potential use of mixed chimerism kinetics to predict relapse of the AML. CD34+-specific chimerism is associated with a higher specificity of chimerism analysis. Nevertheless, a decrease of donor cells can have other causes as well. Therefore, efforts continue to introduce minimal residual disease (MRD monitoring based on molecular mutations in the post-transplant period. The NPM1 (nucleophosmin mutations can be monitored by sensitive quantitative real-time PCR in subsets of stem cell recipients with AML, but for approximately 20% of patients, suitable molecular mutations for post-transplant MRD monitoring are not available so far. This emphasizes the need for an expansion of the panel of MRD markers in the transplant setting.

  1. Association Between Pretransplant Cancer and Survival in Kidney Transplant Recipients.

    Science.gov (United States)

    Dahle, Dag Olav; Grotmol, Tom; Leivestad, Torbjørn; Hartmann, Anders; Midtvedt, Karsten; Reisæter, Anna V; Mjøen, Geir; Pihlstrøm, Hege K; Næss, Hege; Holdaas, Hallvard

    2017-10-01

    Kidney transplantation in recipients with a previous malignancy is often deferred 2 to 5 years after cancer treatment due to fear of cancer recurrence. In Norway, the required waiting period has been 1 year. We compared patient and graft survival of recipients with pretransplant cancer to the outcomes of matched recipients without such cancer (comparators) using Cox regression. From 1963 to 2010, 377 (6.4%) of 5867 recipients had a pretransplant cancer. During a median follow-up of 6.8 years, 256 recipients died, 35 (13.7%) from recurrent cancer and 27 (10.5%) from de novo cancer. Uncensored and death-censored graft loss occurred in 263 and 46 recipients, respectively. All-cause mortality was similar as in comparators (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.93-1.20]; P = 0.40), death-censored graft loss was lower (HR, 0.63; 95% CI, 0.47-0.84; P = 0.002), and uncensored graft loss was similar (HR, 0.99; 95% CI, 0.87-1.12; P = 0.87). Cancer mortality was higher than in comparators (HR, 1.97; 95% CI, 1.51-2.56; P cancer mortality or all-cause mortality (both P > 0.45). Results were similar within cancer subgroups, with most data in patients with a history of kidney cancer, prostate cancer, urothelial cancer, and skin squamous cell carcinoma. Kidney transplant recipients with a pretransplant cancer had a similar overall patient and graft survival as recipients without such cancer. Cancer mortality was increased, particularly during the first 5 years after transplantation. A short waiting period was not associated with mortality.

  2. Primary intracranial leiomyoma in renal transplant recipient

    Directory of Open Access Journals (Sweden)

    Upasana Patel

    2017-01-01

    Full Text Available Leiomyoma, the benign tumor of smooth muscle cell origin, is commonly seen in genitourinary and gastrointestinal tracts. Primary intracranial leiomyoma, however, is extremely rare occurrence. We hereby report a case of Epstein-Barr negative primary intracranial leiomyoma in a middle-aged renal transplant recipient, which mimicked left frontal parasagittal meningioma on neuroimaging. The tumor was completely excised and diagnosis of leiomyoma was clinched on pathological analysis with immunohistochemistry. The patient improved after tumor removal, and no evidence of tumor recurrence was noted on follow-up study after 10 months postsurgically.

  3. Detergent decellularization of heart valves for tissue engineering: toxicological effects of residual detergents on human endothelial cells.

    Science.gov (United States)

    Cebotari, Serghei; Tudorache, Igor; Jaekel, Thomas; Hilfiker, Andres; Dorfman, Suzanne; Ternes, Waldemar; Haverich, Axel; Lichtenberg, Artur

    2010-03-01

    Detergents are powerful agents for tissue decellularization. Despite this, the high toxicity of detergent residua can be a major limitation. This study evaluated the efficacy of detergent removal from decellularized pulmonary valves (PVs) and the consequences of repopulation with human endothelial cells (HECs). Porcine PVs were treated with 1% sodium deoxycholate (SDC), group A; 1% sodium dodecyl sulfate (SDS), group B; and a mixture of 0.5% SDC/0.5% SDS, group C (n = 5 each). After each of 10 succeeding wash cycles (WCs), samples of the washing solution (WS) were analyzed by solid phase extraction and high performance liquid chromatography for the presence of detergents. Metabolic activity of HEC was also assessed in the WS samples (cytotoxicity and MTS assays). Decellularized and washed PVs were reseeded with HEC. Histological analysis demonstrated efficient tissue decellularization in all groups. Detergents' concentration in all WSs decreased exponentially and was below 50 mg/L after 6, 8, and 4 WCs in groups A, B, and C, respectively. This concentration resulted in no significant toxic influence on cell cultures, and scaffolds could be efficiently reseeded with HEC. In conclusion, intensive washing of detergent decellularized valvular scaffolds lowers the residual contamination below a hazardous threshold and allows their successful repopulation with HEC for tissue engineering purposes.

  4. Complete relaxation of residual stresses during reduction of solid oxide fuel cells

    DEFF Research Database (Denmark)

    Frandsen, Henrik Lund; Chatzichristodoulou, Christodoulos; Hendriksen, Peter Vang

    2015-01-01

    , accelerated creep, taking place during the reduction of the anode. This relaxes stresses at a much higher rate (~×104) than creep during operation. The phenomenon has previously been studied by simultaneous loading and reduction. With the recorded high creep rates, the stresses at the time of reduction should...... reduce significantly over minutes. In this work the stresses are measured in-situ before and after the reduction by use of XRD. The phenomenon of accelerated creep has to be considered both in the production of stacks and in the analysis of the stress field in a stack based on anode supported SOFCs.......To asses the reliability of solid oxide fuel cell (SOFC) stacks during operation, the stress field in the stack must be known. During operation the stress field will depend on time as creep processes relax stresses. This work reports further details on a newly discovered creep phenomenon...

  5. Augmentation of transfer of experimental autoimmune thyroiditis (EAT) in mice by irradiation of recipients

    International Nuclear Information System (INIS)

    Williams, W.V.; Kyriakos, M.; Sharp, G.C.; Braley-Mullen, H.

    1987-01-01

    Experimental autoimmune thyroiditis (EAT) can be adoptively transferred to normal syngeneic recipients using spleen cells from susceptible strains of mice primed in vivo with mouse thyroglobulin (MTg) and lipopolysaccharide (LPS) following in vitro activation of spleen cells by culture with MTg. Irradiation of recipient animals markedly augments the severity of thyroiditis induced in this system. Irradiation of recipients does not alter the time course of the development of thyroiditis, nor does it alter the requirement for both in vivo priming and in vitro activation of spleen cells for the development of EAT. Spleen cells from EAT-resistant strains of mice (e.g., Balb/c) do not induce EAT in irradiated recipients. Irradiated recipients develop significant levels of anti-MTg antibodies while unirradiated recipients have little detectable antibody response. The augmenting effect of irradiation can be substantially reversed by transferring naive spleen cells to recipients prior to the transfer of MTg/LPS-primed in vitro-activated spleen cells. In addition athymic CBA/Tufts nude mice develop more severe EAT than CBA/Tufts nude/+ littermates following transfer of activated CBA/J spleen cells. These data suggest that natural suppressor cells may regulate the development of EAT at the effector cell level

  6. Residues essential for Panton-Valentine leukocidin S component binding to its cell receptor suggest both plasticity and adaptability in its interaction surface.

    Directory of Open Access Journals (Sweden)

    Benoit-Joseph Laventie

    Full Text Available Panton-Valentine leukocidin (PVL, a bicomponent staphylococcal leukotoxin, is involved in the poor prognosis of necrotizing pneumonia. The present study aimed to elucidate the binding mechanism of PVL and in particular its cell-binding domain. The class S component of PVL, LukS-PV, is known to ensure cell targeting and exhibits the highest affinity for the neutrophil membrane (Kd∼10(-10 M compared to the class F component of PVL, LukF-PV (Kd∼10(-9 M. Alanine scanning mutagenesis was used to identify the residues involved in LukS-PV binding to the neutrophil surface. Nineteen single alanine mutations were performed in the rim domain previously described as implicated in cell membrane interactions. Positions were chosen in order to replace polar or exposed charged residues and according to conservation between leukotoxin class S components. Characterization studies enabled to identify a cluster of residues essential for LukS-PV binding, localized on two loops of the rim domain. The mutations R73A, Y184A, T244A, H245A and Y250A led to dramatically reduced binding affinities for both human leukocytes and undifferentiated U937 cells expressing the C5a receptor. The three-dimensional structure of five of the mutants was determined using X-ray crystallography. Structure analysis identified residues Y184 and Y250 as crucial in providing structural flexibility in the receptor-binding domain of LukS-PV.

  7. Residual tumour detection in post-treatment granulation tissue by using advanced diffusion models in head and neck squamous cell carcinoma patients.

    Science.gov (United States)

    Fujima, Noriyuki; Yoshida, Daisuke; Sakashita, Tomohiro; Homma, Akihiro; Kudo, Kohsuke; Shirato, Hiroki

    2017-05-01

    To evaluate the detectability of the residual tumour in post-treatment granulation tissue using parameters obtained with an advanced diffusion model in patients with head and neck squamous cell carcinoma (HNSCC) treated by chemoradiation therapy. We retrospectively evaluated 23 patients with HNSCC after the full course of chemoradiation therapy. The diffusion-weighted image (DWI) acquisition used single-shot spin-echo echo-planar imaging with 11 b-values (0-1000). We calculated 10 DWI parameters using a mono-exponential model, a bi-exponential model, a stretched exponential model (SEM), a diffusion kurtosis imaging (DKI) model and a statistical diffusion model (SDM) in the region of interest (ROI) placed on the post-treatment granulation tissue. The presence of residual tumour was determined by histological findings or clinical follow-up. Among the 23 patients, seven patients were revealed to have residual tumour. The univariate analysis revealed significant differences in six parameters between the patients with and without residual tumour. From the receiver operating characteristic curve analysis, the highest area under curve was detected in the center of the Gaussian distribution of diffusion coefficient (D s ) obtained by the SDM. The multivariate analysis revealed that the D s and diffusion heterogeneity (α) obtained by the SEM were predictors for the presence of residual tumour. DWI parameters obtained by advanced fitting models will be one of the diagnostic tools for the detection of residual tumour. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. 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

  9. Lung Cancer Prognosis in Elderly Solid Organ Transplant Recipients.

    Science.gov (United States)

    Sigel, Keith; Veluswamy, Rajwanth; Krauskopf, Katherine; Mehrotra, Anita; Mhango, Grace; Sigel, Carlie; Wisnivesky, Juan

    2015-10-01

    Treatment-related immunosuppression in organ transplant recipients has been linked to increased incidence and risk of progression for several malignancies. Using a population-based cancer cohort, we evaluated whether organ transplantation was associated with worse prognosis in elderly patients with non-small cell lung cancer (NSCLC). Using the Surveillance, Epidemiology, and End Results Registry linked to Medicare claims, we identified 597 patients aged 65 years or older with NSCLC who had received organ transplants (kidney, liver, heart, or lung) before cancer diagnosis. These cases were compared to 114,410 untransplanted NSCLC patients. We compared overall survival (OS) by transplant status using Kaplan-Meier methods and Cox regression. To account for an increased risk of non-lung cancer death (competing risks) in transplant recipients, we used conditional probability function (CPF) analyses. Multiple CPF regression was used to evaluate lung cancer prognosis in organ transplant recipients while adjusting for confounders. Transplant recipients presented with earlier stage lung cancer (P = 0.002) and were more likely to have squamous cell carcinoma (P = 0.02). Cox regression analyses showed that having received a non-lung organ transplant was associated with poorer OS (P transplantation was associated with no difference in prognosis. After accounting for competing risks of death using CPF regression, no differences in cancer-specific survival were noted between non-lung transplant recipients and nontransplant patients. Non-lung solid organ transplant recipients who developed NSCLC had worse OS than nontransplant recipients due to competing risks of death. Lung cancer-specific survival analyses suggest that NSCLC tumor behavior may be similar in these 2 groups.

  10. Kinetic of the CMV-specific T-Cell Immune Response and CMV infection in CMV-seropositive kidney Transplant Recipients Receiving rabbit Anti-Thymocyte Globulin Induction Therapy: a Pilot Study.

    Science.gov (United States)

    Martín-Gandul, Cecilia; Pérez-Romero, Pilar; Mena-Romo, Damián; Molina-Ortega, Alejandro; González-Roncero, Francisco M; Suñer, Marta; Bernal, Gabriel; Cordero, Elisa

    2018-03-23

    Some studies have suggested that rATG treatment may be associated with an increased incidence of CMV infection and delayed CMV immune response. However, the evidences supporting this matter are scarce. This study aims to characterize the kinetic of the CMV-specific T-cell immune response before and after rATG induction therapy and the relationship with the development of CMV infection in CMV-seropositive kidney transplant recipients. An observational prospective study of CMV-seropositive kidney transplant patients that received rATG induction therapy was performed. A pretransplant sample was obtained before the surgery to determine the CMV-specific immunity. CMV viral load (by PCR) and CMV-specific T-cell immune response (by flow cytometry) were determined during the follow-up at 0.5, 1, 2, 3, 6 and 12 months post-transplantation. A total of 23 patients were included in the study. CMV prophylaxis was administrated for a media of 90 days after transplantation. At the end of follow-up, 18 (78.3%) patients had CMV-specific immunity with a median value of 0.31% CD8 + CD69 + INF-γ + T-cells at a median of 16 weeks post-transplantation. Five patients never acquired CMV-specific immunity. No statistically significant association between CMV infection and CMV-specific T-cell immune response (P=0.086) was observed. However, patients with positive pretransplant CMV-specific immunity developed earlier immunity and achieved higher levels of CD8 + CD69 + INF-γ+ T-cells post-transplantation than patients with negative pretransplant immunity. CMV-specific immune monitoring in addition to CMV-serology may be useful to stratify patient's risk of CMV infection before transplantation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Residuation theory

    CERN Document Server

    Blyth, T S; Sneddon, I N; Stark, M

    1972-01-01

    Residuation Theory aims to contribute to literature in the field of ordered algebraic structures, especially on the subject of residual mappings. The book is divided into three chapters. Chapter 1 focuses on ordered sets; directed sets; semilattices; lattices; and complete lattices. Chapter 2 tackles Baer rings; Baer semigroups; Foulis semigroups; residual mappings; the notion of involution; and Boolean algebras. Chapter 3 covers residuated groupoids and semigroups; group homomorphic and isotone homomorphic Boolean images of ordered semigroups; Dubreil-Jacotin and Brouwer semigroups; and loli

  12. Lymphoproliferative response to herpes simplex virus type 1, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, human herpes virus 6, 7, and 8 antigen stimulation in pediatric allogeneic stem cell transplant recipients.

    Science.gov (United States)

    Cheng, Frankie Wai Tsoi; Chan, Paul Kay Sheung; Lee, Vincent; Leung, Wing Kwan; Shing, Ming Kong; Li, Chi Kong; Leung, Ting Fan

    2010-09-01

    We evaluate the recovery of CMI to various herpes viruses by measuring in vitro LPR to specific recall antigens. CMI was evaluated by the in vitro LPR of PBMC to specific purified HSV-1, VZV, CMV, EBV, HHV-6, -7, -8, antigens. Results were expressed as SI. SI > or = 3 was regarded as positive LPR. Serial measurements were taken prospectively from pretransplant till 12-month post-transplant. Thirty-six patients (M = 19; F = 17) with median age 10.5 yr old were recruited. Most transplants were from MSD with PBSC as the stem cell source. Altogether 50% of subjects started to show positive LPR to HSV-1, CMV, and VZV antigens at two-month post-transplant, major upsurges were noted until 6-month post-transplant. Subjects showed positive LPR to EBV, HHV-6, HHV-7, and HHV-8 antigens were all along <50% throughout the study period. The antibody status of donor and recipient for HSV-1, CMV, and VZV were associated with the timing of recovery of CMI. Choice of donor and stem cell source were important determinants of eventual LPR to various herpes viruses at 3-month post-transplant. At 12-month post-transplant, there was no statistical difference in any parameters in affecting LPR to different herpes viruses.

  13. RELATIONSHIPS BETWEEN ABLATION OF DISTINCT HEMATOPOIETIC-CELL SUBSETS AND THE DEVELOPMENT OF DONOR BONE-MARROW ENGRAFTMENT FOLLOWING RECIPIENT PRETREATMENT WITH DIFFERENT ALKYLATING DRUGS

    NARCIS (Netherlands)

    DOWN, JD; BOUDEWIJN, A; DILLINGH, JH; FOX, BW; PLOEMACHER, RE

    1994-01-01

    A number of different alkylating chemotherapeutic agents - busulphan, dimethylbusulphan (DMB), isopropylmethane sulphonate (IMS), melphalan, cyclophosphamide (CY) and bischloroethylnitrosourea (BCNU)- were investigated for their cytotoxic effects on different haemopoietic cell populations in host

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-08-15

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

  15. Effect of the replacement of aspartic acid/glutamic acid residues with asparagine/glutamine residues in RNase He1 from Hericium erinaceus on inhibition of human leukemia cell line proliferation.

    Science.gov (United States)

    Kobayashi, Hiroko; Motoyoshi, Naomi; Itagaki, Tadashi; Suzuki, Mamoru; Inokuchi, Norio

    2015-01-01

    RNase He1 from Hericium erinaceus, a member of the RNase T1 family, has high identity with RNase Po1 from Pleurotus ostreatus with complete conservation of the catalytic sequence. However, the optimal pH for RNase He1 activity is lower than that of RNase Po1, and the enzyme shows little inhibition of human tumor cell proliferation. Hence, to investigate the potential antitumor activity of recombinant RNase He1 and to possibly enhance its optimum pH, we generated RNase He1 mutants by replacing 12 Asn/Gln residues with Asp/Glu residues; the amino acid sequence of RNase Po1 was taken as reference. These mutants were then expressed in Escherichia coli. Using site-directed mutagenesis, we successfully modified the optimal pH for enzyme activity and generated a recombinant RNase He1 that inhibited the proliferation of cells in the human leukemia cell line. These properties are extremely important in the production of anticancer biologics that are based on RNase activity.

  16. Design and characterization of a microbial fuel cell for the conversion of a lignocellulosic crop residue to electricity.

    Science.gov (United States)

    Gregoire, K P; Becker, J G

    2012-09-01

    Agricultural crop residues contain high amounts of biochemical energy as cellulose and lignin. A portion of this biomass could be sustainably harvested for conversion to bioenergy to help offset fossil fuel consumption. In this study, the potential for converting lignocellulosic biomass directly to electricity in a microbial fuel cell (MFC) was explored. Design elements of tubular air cathode MFCs and leach-bed bioreactors were integrated to develop a new solid-substrate MFC in which cellulose hydrolysis, fermentation, and anode respiration occurred in a single chamber. Electricity was produced continuously from untreated corncob pellets for >60 d. Addition of rumen fluid increased power production, presumably by providing growth factors to anode-respiring bacteria. Periodic exposure to oxygen also increased power production, presumably by limiting the diversion of electrons to methanogenesis. In the absence of methanogenesis, bioaugmentation with Geobacter metallireducens further improved MFC performance. Under these conditions, the maximum power density was 230 mW/m(3). Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Conversion of residual organics in corn stover-derived biorefinery stream to bioenergy via microbial fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Borole, Abhijeet P [ORNL; Hamilton, Choo Yieng [ORNL; Schell, Daniel J [National Renewable Energy Laboratory (NREL)

    2012-01-01

    A biorefinery process typically uses about 4-10 times as much water as the amount of biofuel generated. The wastewater produced in a biorefinery process contains residual sugars, 5-furfural, phenolics, and other pretreatment and fermentation byproducts. Treatment of the wastewater can reduce the need for fresh water and potentially add to the environmental benefits of the process. Use of microbial fuel cells (MFCs) for conversion of the various organics present in a post-fermentation biorefinery stream is reported here. The organic loading was varied over a wide range to assess removal efficiency, coulombic efficiency and power production. A coulombic efficiency of 40% was observed for a low loading of 1% (0.66 g/L) and decreased to 1.8% for the undiluted process stream (66.4 g/L organic loading). A maximum power density of 1180 mW/m2 was observed at a loading of 8%. Excessive loading was found to result in poor electrogenic performance. The results indicate that operation of an MFC at an intermediate loading using dilution and recirculation of the process stream can enable effective treatment with bioenergy recovery.

  18. Review of alternative residual contamination guides for the 324 Building B-Cell Cleanout Project. Phase 1

    International Nuclear Information System (INIS)

    Vargo, G.J.; Durham, J.S.; Brackenbush, L.W.

    1995-09-01

    This report provides a proposed residual contamination guide (RCG) for the 324 Building B-Cell Cleanout Project, Phase 1, at the Hanford Site. The RCG is expressed as a fraction of the amount of highly dispersible radioactive material that would result in offsite doses equal to the Pacific Northwest Laboratory radiological risk guidelines following the worst credible accident scenario for release of the holdup material. The proposed RCG is 10 -1 to 10 -2 of the PNL radiological risk guidelines. As part of the development of the RCG, a number of factors were considered. These include the need to provide an appropriate level of flexibility for other activities within the 324 Building that could contribute to the facility's overall radiological risk, uncertainties inherent in safety analyses, and the possible contribution of other 300 Area facilities to overall radiological risk. Because of these factors and the nature of the cleanout project, the RCG is expressed as a range rather than a point value. This report also provides guidance on determining conformance to the RCG, including inspection and measurement techniques, quality assurance requirements, and consideration of uncertainty

  19. Soybean milk residue ensiled with peanut hulls: fermentation acids, cell wall composition, and silage utilization by mixed ruminal microorganisms.

    Science.gov (United States)

    Yang, C-M J

    2005-08-01

    Preservation of soybean milk residue (SMR) by ensiling with peanut hulls (PEH) and subsequent utilization of silage by mixed ruminal microorganisms were investigated. Treatments were combinations of SMR with PEH at the following ratios: 100:0, 78:22, 71:29, and 60:40 (fresh weight basis). After eight weeks of ensiling, silage lactic acid, crude protein, ether extract, and non-fiber carbohydrates were highest when SMR was ensiled alone and reduced as amounts of SMR decreased. Similar trends were observed for silage in vitro dry matter digestibility, and gas and volatile fatty acid production by ruminal microorganisms. Conversely, silage pH, dry matter, neutral detergent fiber, acid detergent fiber, cellulose, and lignin increased accordingly. The ensiling treatment appeared to alter silage cell wall composition. In particular, silage treated with PEH at the low level (78:22) resulted in reduced fiber contents and lignification. The silage (SMR:PEH=78:22) had enhanced efficiency of both silage fermentation and in vitro ruminal fermentation pattern.

  20. Defining the Ail Ligand-Binding Surface: Hydrophobic Residues in Two Extracellular Loops Mediate Cell and Extracellular Matrix Binding To Facilitate Yop Delivery.

    Science.gov (United States)

    Tsang, Tiffany M; Wiese, Jeffrey S; Alhabeil, Jamal A; Usselman, Lisa D; Thomson, Joshua J; Matti, Rafla; Kronshage, Malte; Maricic, Natalie; Williams, Shanedah; Sleiman, Naama H; Felek, Suleyman; Krukonis, Eric S

    2017-04-01

    Yersinia pestis , the causative agent of plague, binds host cells to deliver cytotoxic Yop proteins into the cytoplasm that prevent phagocytosis and generation of proinflammatory cytokines. Ail is an eight-stranded β-barrel outer membrane protein with four extracellular loops that mediates cell binding and resistance to human serum. Following the deletion of each of the four extracellular loops that potentially interact with host cells, the Ail-Δloop 2 and Ail-Δloop 3 mutant proteins had no cell-binding activity while Ail-Δloop 4 maintained cell binding (the Ail-Δloop 1 protein was unstable). Using the codon mutagenesis scheme SWIM (selection without isolation of mutants), we identified individual residues in loops 1, 2, and 3 that contribute to host cell binding. While several residues contributed to the binding of host cells and purified fibronectin and laminin, as well as Yop delivery, three mutations, F80A (loop 2), S128A (loop 3), and F130A (loop 3), produced particularly severe defects in cell binding. Combining these mutations led to an even greater reduction in cell binding and severely impaired Yop delivery with only a slight defect in serum resistance. These findings demonstrate that Y. pestis Ail uses multiple extracellular loops to interact with substrates important for adhesion via polyvalent hydrophobic interactions. Copyright © 2017 American Society for Microbiology.

  1. Epitope analysis of the collagen type V-specific T cell response in lung transplantation reveals an HLA-DRB1*15 bias in both recipient and donor.

    Directory of Open Access Journals (Sweden)

    Melissa R Keller

    Full Text Available BACKGROUND: IL-17-dependent cellular immune responses to the α1 chain of collagen type V are associated with development of bronchiolitis obliterans syndrome after lung transplantation, and with idiopathic pulmonary fibrosis and coronary artery disease, primary indications for lung or heart transplantation, respectively. METHODOLOGY/PRINCIPAL FINDINGS: We found that 30% of the patients awaiting lung transplantation exhibited a strong cell-mediated immune response to col(V. Of these, 53% expressed HLA-DR15, compared to a 28% HLA-DR15 frequency in col(V low-responders (p=0.02. After transplantation, patients with HLA-DR1 and -DR17, not -DR15, developed anti-col(V responses most frequently (p=0.04 and 0.01 vs. controls, respectively. However, recipients of a lung from an HLA-DR15(+donor were at significantly elevated risk of developing anti-col(V responses (p=0.02 and BOS (p=0.03. To determine the molecular basis of this unusual pattern of DR allele bias, a peptide library comprising the collagenous region of the α1(V protein was screened for binding to HLA-DR0101, -DR1501, -DR0301 (DR17 or to HLA-DQ2 (DQA1*0501: DQB1*0201; in linkage disequilibrium with -DR17 and -DQ6 (DQA1*0102: DQB1*0602; linked to -DR15. Eight 15-mer peptides, six DR-binding and two DQ-binding, were identified. HLA-DR15 binding to two peptides yielded the highest binding scores: 650 (where 100 = positive control for p799 (GIRGLKGTKGEKGED, and 193 for p1439 (LRGIPGPVGEQGLPG. These peptides, which also bound weakly to HLA-DR1, elicited responses in both HLA-DR1(+ and -DR15(+ col(V reactive hosts, whereas binding and immunoreactivity of p1049 (KDGPPGLRGFPGDRG was DR15-specific. Remarkably, a col(V-reactive HLA-DR1(+DR15(neg lung transplant patient, whose donor was HLA-DR15(+, responded not only to p799 and p1439, but also to p1049. CONCLUSIONS/SIGNIFICANCE: HLA-DR15 and IPF disease were independently associated with pre-transplant col(V autoimmunity. The increased risk of de

  2. Codominant Role of Interferon-γ– and Interleukin-17–Producing T Cells During Rejection in Full Facial Transplant Recipients

    Science.gov (United States)

    Borges, T. J.; O’Malley, J. T.; Wo, L.; Murakami, N.; Smith, B.; Azzi, J.; Tripathi, S.; Lane, J. D.; Bueno, E. M.; Clark, R. A.; Tullius, S. G.; Chandraker, A.; Lian, C. G.; Murphy, G. F.; Strom, T. B.; Pomahac, B.; Najafian, N.; Riella, L. V.

    2016-01-01

    Facial transplantation is a life-changing procedure for patients with severe composite facial defects. However, skin is the most immunogenic of all transplants, and better understanding of the immunological processes after facial transplantation is of paramount importance. Here, we describe six patients who underwent full facial transplantation at our institution, with a mean followup of 2.7 years. Seum, peripheral blood mononuclear cells, and skin biopsy specimens were collected prospectively, and a detailed characterization of their immune response (51 time points) was performed, defining 47 immune cell subsets, 24 serum cytokines, anti-HLA antibodies, and donor alloreactivity on each sample, producing 4269 data points. In a nonrejecting state, patients had a predominant T helper 2 cell phenotype in the blood. All patients developed at least one episode of acute cellular rejection, which was characterized by increases in interferon-c/interleukin-17–producing cells in peripheral blood and in the allograft’s skin. Serum monocyte chemotactic protein-1 level was significantly increased during rejection compared with prerejection time points. None of the patients developed de novo donor-specific antibodies, despite a fourfold expansion in T follicular helper cells at 1 year posttransplantation. In sum, facial transplantation is frequently complicated by a codominant interferon-γ/interleukin-17–mediated acute cellular rejection process. Despite that, medium-term outcomes are promising with no evidence of de novo donor-specific antibody development. PMID:26749226

  3. N-Succinimidyl guanidinomethyl iodobenzoate protein radiohalogenation agents: Influence of isomeric substitution on radiolabeling and target cell residualization

    International Nuclear Information System (INIS)

    Choi, Jaeyeon; Vaidyanathan, Ganesan; Koumarianou, Eftychia; McDougald, Darryl; Pruszynski, Marek; Osada, Takuya; Lahoutte, Tony; Lyerly, H. Kim; Zalutsky, Michael R.

    2014-01-01

    Introduction: N-succinimidyl 4-guanidinomethyl-3-[ ⁎ I]iodobenzoate ([ ⁎ I]SGMIB) has shown promise for the radioiodination of monoclonal antibodies (mAbs) and other proteins that undergo extensive internalization after receptor binding, enhancing tumor targeting compared to direct electrophilic radioiodination. However, radiochemical yields for [ 131 I]SGMIB synthesis are low, which we hypothesize is due to steric hindrance from the Boc-protected guanidinomethyl group ortho to the tin moiety. To overcome this, we developed the isomeric compound, N-succinimidyl 3-guanidinomethyl-5-[ 131 I]iodobenzoate (iso-[ 131 I]SGMIB) wherein this bulky group was moved from ortho to meta position. Methods: Boc 2 -iso-SGMIB standard and its tin precursor, N-succinimidyl 3-((1,2-bis(tert-butoxycarbonyl)guanidino)methyl)-5-(trimethylstannyl) benzoate (Boc 2 -iso-SGMTB), were synthesized using two disparate routes, and iso-[*I]SGMIB synthesized from the tin precursor. Two HER2-targeted vectors — trastuzumab (Tras) and a nanobody 5 F7 (Nb) — were labeled using iso-[ ⁎ I]SGMIB and [ ⁎ I]SGMIB. Paired-label internalization assays in vitro with both proteins, and biodistribution in vivo with trastuzumab, labeled using the two isomeric prosthetic agents were performed. Results: When the reactions were performed under identical conditions, radioiodination yields for the synthesis of Boc 2 -iso-[ 131 I]SGMIB were significantly higher than those for Boc 2 -[ 131 I]SGMIB (70.7 ± 2.0% vs 56.5 ± 5.5%). With both Nb and trastuzumab, conjugation efficiency also was higher with iso-[ 131 I]SGMIB than with [ 131 I]SGMIB (Nb, 33.1 ± 7.1% vs 28.9 ± 13.0%; Tras, 45.1 ± 4.5% vs 34.8 ± 10.3%); however, the differences were not statistically significant. Internalization assays performed on BT474 cells with 5 F7 Nb indicated similar residualizing capacity over 6 h; however, at 24 h, radioactivity retained intracellularly for iso-[ 131 I]SGMIB-Nb was lower than for [ 125 I]SGMIB-Nb (46

  4. Variable EBV DNA Load Distributions and Heterogeneous EBV mRNA Expression Patterns in the Circulation of Solid Organ versus Stem Cell Transplant Recipients

    NARCIS (Netherlands)

    Greijer, A. E.; Stevens, S. J.; Verkuijlen, S. A.; Juwana, H.; Fleig, S. C.; Verschuuren, E. A.; Hepkema, B. G.; Cornelissen, J. J.; Brooimans, R. A.; Verdonck, L. F.; Middeldorp, J. M.

    2012-01-01

    Epstein-Barr virus (EBV) driven post-transplant lymphoproliferative disease (PTLD) is a heterogeneous and potentially life-threatening condition. Early identification of aberrant EBV activity may prevent progression to B-cell lymphoma. We measured EBV DNA load and RNA profiles in plasma and cellular

  5. Periodontal status and bacteremia with oral viridans streptococci and coagulase negative staphylococci in allogeneic hematopoietic stem cell transplantation recipients: a prospective observational study

    NARCIS (Netherlands)

    Raber-Durlacher, Judith E.; Laheij, Alexa M. G. A.; Epstein, Joel B.; Epstein, Matthew; Geerligs, Gerard M.; Wolffe, Gordon N.; Blijlevens, Nicole M. A.; Donnelly, J. Peter

    2013-01-01

    This study was aimed to investigate whether any association could be found between the presence of an inflamed and infected periodontium (e.g., gingivitis and periodontitis) and the development of bacteremia during neutropenia following allogeneic hematopoietic stem cell transplantation (HSCT).

  6. [Transfer of allogeneic stem cell transplant recipients to the intensive care unit: Guidelines from the Francophone society of marrow transplantation and cellular therapy (SFGM-TC)].

    Science.gov (United States)

    Moreau, Anne-Sophie; Bourhis, Jean-Henri; Contentin, Nathalie; Couturier, Marie-Anne; Delage, Jeremy; Dumesnil, Cécile; Gandemer, Virginie; Hichri, Yosr; Jost, Edgar; Platon, Laura; Jourdain, Mercé; Pène, Frédéric; Yakoub-Agha, Ibrahim

    2016-11-01

    Transferring a patient undergoing an allogeneic stem cell transplantation to the intensive care unit (ICU) is always a challenging situation on a medical and psychological point of view for the patient and his relatives as well as for the medical staff. Despite the progress in hematology and intensive care during the last decade, the prognosis of these patients admitted to the ICU remains poor and mortality is around 50 %. The harmonization working party of the SFGM-TC assembled hematologists and intensive care specialist in order to improve conditions and modalities of the transfer of a patient after allogeneic stem cell transplantation to the ICU. We propose a structured medical form comprising all essential information necessary for optimal medical care on ICU. Copyright © 2016. Published by Elsevier Masson SAS.

  7. Codominant Role of Interferon-γ– and Interleukin-17–Producing T Cells During Rejection in Full Facial Transplant Recipients

    OpenAIRE

    Borges, T. J.; O’Malley, J. T.; Wo, L.; Murakami, N.; Smith, B.; Azzi, J.; Tripathi, S.; Lane, J. D.; Bueno, E. M.; Clark, R. A.; Tullius, S. G.; Chandraker, A.; Lian, C. G.; Murphy, G. F.; Strom, T. B.

    2016-01-01

    Facial transplantation is a life-changing procedure for patients with severe composite facial defects. However, skin is the most immunogenic of all transplants, and better understanding of the immunological processes after facial transplantation is of paramount importance. Here, we describe six patients who underwent full facial transplantation at our institution, with a mean followup of 2.7 years. Seum, peripheral blood mononuclear cells, and skin biopsy specimens were collected prospectivel...

  8. Persistence of Recipient Human Leucocyte Antigen (HLA) Antibodies and Production of Donor HLA antibodies Following Reduced Intensity Allogeneic Haematopoietic Stem Cell Transplantation

    OpenAIRE

    Fasano, Ross M.; Mamcarz, Ewelina; Adams, Sharon; Jerussi, Theresa Donohue; Sugimoto, Kyoko; Tian, Xin; Flegel, Willy A.; Childs, Richard W.

    2014-01-01

    The effects of reduced intensity conditioning (RIC) on human leucocyte antigen (HLA)-alloimmunization and platelet transfusion refractoriness (PTR) following allogeneic haematopoietic stem cell transplantation (Allo-HSCT) are unknown. We studied HLA-alloantibodies in a cohort of 16 patients (8 HLA-alloimmunized with pre-transplant histories of PTR and 8 non-alloimmunized controls) undergoing Allo-HSCT using fludarabine/cyclophosphamide-based RIC. Pre- and post-transplant serum samples were an...

  9. 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.

  10. 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%; Pcloned pups in non-mated recipients were delivered by Caesarean section because the fall in progesterone concentration in these females did not occur until the due date. The present study demonstrated for the first time that mated female dogs can be used as recipients for cloned embryos.

  11. GWAS of 972 autologous stem cell recipients with multiple myeloma identifies 11 genetic variants associated with chemotherapy-induced oral mucositis

    DEFF Research Database (Denmark)

    Coleman, Elizabeth Ann; Lee, Jeannette Y; Erickson, Stephen W

    2015-01-01

    PURPOSE: High-dose chemotherapy and autologous stem cell transplant (ASCT) to treat multiple myeloma (MM) and other cancers carries the risk of oral mucositis (OM) with sequelae including impaired nutritional and fluid intake, pain, and infectious complications. As a result of these problems...... protocol, baseline estimated glomerular filtration rate, and melphalan dose along with baseline serum albumin and female gender predicted 43.6 % of grades 2-4 OM cases. Eleven SNPs located in or near matrix metalloproteinase 13, JPH3, DHRS7C, CEP192, CPEB1/LINC00692, FBN2, ALDH1A1, and DMRTA1/FLJ35282 were...

  12. Augmentation of Recipient Adaptive Alloimmunity by Donor Passenger Lymphocytes within the Transplant

    Directory of Open Access Journals (Sweden)

    Ines G. Harper

    2016-05-01

    Full Text Available Chronic rejection of solid organ allografts remains the major cause of transplant failure. Donor-derived tissue-resident lymphocytes are transferred to the recipient during transplantation, but their impact on alloimmunity is unknown. Using mouse cardiac transplant models, we show that graft-versus-host recognition by passenger donor CD4 T cells markedly augments recipient cellular and humoral alloimmunity, resulting in more severe allograft vasculopathy and early graft failure. This augmentation is enhanced when donors were pre-sensitized to the recipient, is dependent upon avoidance of host NK cell recognition, and is partly due to provision of cognate help for allo-specific B cells from donor CD4 T cells recognizing B cell MHC class II in a peptide-degenerate manner. Passenger donor lymphocytes may therefore influence recipient alloimmune responses and represent a therapeutic target in solid organ transplantation.

  13. Four weeks of treatment with liraglutide reduces insulin dose without loss of glycemic control in type 1 diabetic patients with and without residual beta-cell function

    DEFF Research Database (Denmark)

    Kielgast, Urd; Krarup, Thure; Holst, Jens Juul

    2011-01-01

    OBJECTIVE To investigate the effect of 4 weeks of treatment with liraglutide on insulin dose and glycemic control in type 1 diabetic patients with and without residual ß-cell function. RESEARCH DESIGN AND METHODS Ten type 1 diabetic patients with residual ß-cell function (C-peptide positive) and 19.......1]; P Treatment with liraglutide in type 1 diabetic patients reduces insulin dose with improved or unaltered glycemic control....... activity was performed before (week 0) and during (week 4) treatment. Differences in insulin dose; HbA(1c); time spent with blood glucose 10, and 3.9-9.9 mmol/L; and body weight were evaluated. RESULTS Insulin dose decreased from 0.50 ± 0.06 to 0.31 ± 0.08 units/kg per day (P

  14. Residue processing

    Energy Technology Data Exchange (ETDEWEB)

    Gieg, W.; Rank, V.

    1942-10-15

    In the first stage of coal hydrogenation, the liquid phase, light and heavy oils were produced; the latter containing the nonliquefied parts of the coal, the coal ash, and the catalyst substances. It was the problem of residue processing to extract from these so-called let-down oils that which could be used as pasting oils for the coal. The object was to obtain a maximum oil extraction and a complete removal of the solids, because of the latter were returned to the process they would needlessly burden the reaction space. Separation of solids in residue processing could be accomplished by filtration, centrifugation, extraction, distillation, or low-temperature carbonization (L.T.C.). Filtration or centrifugation was most suitable since a maximum oil yield could be expected from it, since only a small portion of the let-down oil contained in the filtration or centrifugation residue had to be thermally treated. The most satisfactory centrifuge at this time was the Laval, which delivered liquid centrifuge residue and centrifuge oil continuously. By comparison, the semi-continuous centrifuges delivered plastic residues which were difficult to handle. Various apparatus such as the spiral screw kiln and the ball kiln were used for low-temperature carbonization of centrifuge residues. Both were based on the idea of carbonization in thin layers. Efforts were also being made to produce electrode carbon and briquette binder as by-products of the liquid coal phase.

  15. Travel risk assessment, advice and vaccinations in immunocompromised travellers (HIV, solid organ transplant and haematopoeitic stem cell transplant recipients): A review.

    Science.gov (United States)

    Aung, A K; Trubiano, J A; Spelman, D W

    2015-01-01

    International travellers with immunocompromising conditions such as human immunodeficiency virus (HIV) infection, solid organ transplantation (SOT) and haematopoietic stem cell transplantation (HSCT) are at a significant risk of travel-related illnesses from both communicable and non-communicable diseases, depending on the intensity of underlying immune dysfunction, travel destinations and activities. In addition, the choice of travel vaccinations, timing and protective antibody responses are also highly dependent on the underlying conditions and thus pose significant challenges to the health-care providers who are involved in pre-travel risk assessment. This review article provides a framework of understanding and approach to aforementioned groups of immunocompromised travellers regarding pre-travel risk assessment and management; in particular travel vaccinations, infectious and non-infectious disease risks and provision of condition-specific advice; to reduce travel-related mortality and morbidity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Genetically-determined hyperfunction of the S100B/RAGE axis is a risk factor for aspergillosis in stem cell transplant recipients.

    Directory of Open Access Journals (Sweden)

    Cristina Cunha

    Full Text Available Invasive aspergillosis (IA is a major threat to the successful outcome of hematopoietic stem cell transplantation (HSCT, although individual risk varies considerably. Recent evidence has established a pivotal role for a danger sensing mechanism implicating the S100B/receptor for advanced glycation end products (RAGE axis in antifungal immunity. The association of selected genetic variants in the S100B/RAGE axis with susceptibility to IA was investigated in 223 consecutive patients undergoing HSCT. Furthermore, studies addressing the functional consequences of these variants were performed. Susceptibility to IA was significantly associated with two distinct polymorphisms in RAGE (-374T/A and S100B (+427C/T genes, the relative contribution of each depended on their presence in both transplantation counterparts [patient SNP(RAGE, adjusted hazard ratio (HR, 1.97; P = 0.042 and donor SNP(RAGE, HR, 2.03; P = 0.047] or in donors (SNP(S100B, HR, 3.15; P = 7.8e-(4 only, respectively. Functional assays demonstrated a gain-of-function phenotype of both variants, as shown by the enhanced expression of inflammatory cytokines in RAGE polymorphic cells and increased S100B secretion in vitro and in vivo in the presence of the S100B polymorphism. These findings point to a relevant role of the danger sensing signaling in human antifungal immunity and highlight a possible contribution of a genetically-determined hyperfunction of the S100B/RAGE axis to susceptibility to IA in the HSCT setting.

  17. An automated approach to improve efficacy in detecting residual malignant cancer cell for facilitating prognostic assessment of leukemia: an initial study

    Science.gov (United States)

    Qiu, Yuchen; Lu, Xianglan; Tan, Maxine; Li, Shibo; Liu, Hong; Zheng, Bin

    2015-03-01

    The purpose of this study is to investigate the feasibility of applying automatic interphase FISH cells analysis method for detecting the residual malignancy of post chemotherapy leukemia patients. In the experiment, two clinical specimens with translocation between chromosome No. 9 and 22 or No. 11 and 14 were selected from the patients underwent leukemia diagnosis and treatment. The entire slide of each specimen was first digitalized by a commercial fluorescent microscope using a 40× objective lens. Then, the scanned images were processed by a computer-aided detecting (CAD) scheme to identify the analyzable FISH cells, which is accomplished by applying a series of features including the region size, Brenner gradient and maximum intensity. For each identified cell, the scheme detected and counted the number of the FISH signal dots inside the nucleus, using the adaptive threshold of the region size and distance of the labeled FISH dots. The results showed that the new CAD scheme detected 8093 and 6675 suspicious regions of interest (ROI) in two specimens, among which 4546 and 3807 ROI contain analyzable interphase FISH cell. In these analyzable ROIs, CAD selected 334 and 405 residual malignant cancer cells, which is substantially more than those visually detected in a cytogenetic laboratory of our medical center (334 vs. 122, 405 vs. 160). This investigation indicates that an automatic interphase FISH cell scanning and CAD method has the potential to improve the accuracy and efficiency of the prognostic assessment for leukemia and other genetic related cancer patients in the future.

  18. Transcatheter arterial embolization combined with radiofrequency ablation activates CD8+ T-cell infiltration surrounding residual tumors in the rabbit VX2 liver tumors

    Directory of Open Access Journals (Sweden)

    Duan XH

    2016-05-01

    Full Text Available Xu-Hua Duan,1,2 Teng-Fei Li,2 Guo-Feng Zhou,1,* Xin-Wei Han,2,* Chuan-Sheng Zheng,1 Peng-fei Chen,2 Gan-Sheng Feng11Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 2Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, Henan Province, Zhengzhou, People’s Republic of China*These authors contributed equally to this work Purpose: To evaluate the effect of transcatheter arterial embolization (TAE combined with radiofrequency ablation (RFA treatment (TAE + RFA on the expression of heat shock protein 70 (HSP70 in residual tumors and explore the relationship between the HSP70 and CD8+ T-cell infiltrate surrounding residual tumors in the rabbit VX2 liver tumor model.Materials and methods: Animals with VX2 liver tumors were randomized into four groups (control, TAE, RFA, and TAE + RFA with 15 rabbits in each group. Five rabbits in each group were sacrificed on days 1, 3, and 7 after treatment. HSP70 expression and infiltration of CD8+ T-cells in the liver and residual tumors surrounding the necrosis zone were detected by immunohistochemistry staining. The maximal diameters of tumor necrosis, numbers of metastases, and tumor growth rate were compared on day 7 after treatment.Results: TAE + RFA achieved larger maximal diameter of tumor necrosis, lower tumor growth rate, and fewer metastatic lesions, compared with other treatments on day 7. The number of CD8+ T-cells in the TAE + RFA group was significantly higher than in other groups on days 1, 3, and 7. There was a positive correlation between HSP70 expression level and infiltration of CD8+ T-cells surrounding the residual tumor on day 1 (r=0.9782, P=0.012, day 3 (r=0.93, P=0.021, and day 7 (r=0.8934, P=0.034.Conclusion: In the rabbit VX2 liver tumor model, TAE + RFA activated the highest number of CD8+ T-cells surrounding residual tumors. TAE + RFA appears to be a beneficial

  19. Basic oral care for hematology?oncology patients and hematopoietic stem cell transplantation recipients: a position paper from the joint task force of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT)

    OpenAIRE

    Elad, Sharon; Raber-Durlacher, Judith E.; Brennan, Michael T.; Saunders, Deborah P.; Mank, Arno P.; Zadik, Yehuda; Quinn, Barry; Epstein, Joel B.; Blijlevens, Nicole M. A.; Waltimo, Tuomas; Passweg, Jakob R.; Correa, M. Elvira P.; Dahll?f, G?ran; Garming-Legert, Karin U. E.; Logan, Richard M.

    2014-01-01

    Purpose Hematology?oncology patients undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT) recipients are at risk for oral complications which may cause significant morbidity and a potential risk of mortality. This emphasizes the importance of basic oral care prior to, during and following chemotherapy/HSCT. While scientific evidence is available to support some of the clinical practices used to manage the oral complications, expert opinion is needed to shape the current ...

  20. A Retrospective Analysis of Bloodstream Infections in Pediatric Allogeneic Stem Cell Transplant Recipients: The Role of Central Venous Catheters and Mucosal Barrier Injury.

    Science.gov (United States)

    Balian, Chelsea; Garcia, Michelle; Ward, Jessica

    2018-03-01

    Bloodstream infections (BSIs) are a leading cause of morbidity and mortality in children undergoing hematopoietic stem cell transplant (HSCT). Indwelling central venous catheters (CVCs) increase risk for BSIs, yet mucosal barrier injury-associated laboratory-confirmed bloodstream infection (MBI-LCBI) may also occur due to translocation of pathogenic organisms from the gastrointestinal tract into the bloodstream. The purpose of this study was to determine the association between stool organisms and BSIs in children with CVCs who underwent HSCT. We performed a retrospective analysis of 78 children who received allogeneic HSCT over 3 years (2012-2014). Surveillance stool cultures were analyzed pre- and post-HSCT to assess correlations between organisms isolated from stool and CVC cultures. Twenty-four of 78 children experienced 31 BSIs. Fifteen (48%) of these isolates were identified in stool within 30 days of the positive blood culture, and 11 (36%) isolates met criteria for MBI-LCBI. Mucosal barrier injury leads to translocation of pathogenic organisms into the bloodstream and accounts for a significant number of BSIs in children undergoing HSCT. Nursing assessment of mucosal changes during HSCT and interventions to preserve intact mucosa are essential to prevent MBI-LCBI.

  1. Anti-asialo GM1 antiserum treatment of lethally irradiated recipients before bone marrow transplantation: Evidence that recipient natural killer depletion enhances survival, engraftment, and hematopoietic recovery

    International Nuclear Information System (INIS)

    Tiberghien, P.; Longo, D.L.; Wine, J.W.; Alvord, W.G.; Reynolds, C.W.

    1990-01-01

    Natural killer (NK) cells are reported to have an important role in the resistance of lethally irradiated recipients to bone marrow transplantation (BMT). Therefore, we investigated the effects of recipient NK depletion on survival, chimerism, and hematopoietic reconstitution after lethal irradiation and the transplantation of limiting amounts of T-cell-deficient bone marrow (BM). When administered before BMT, anti-asialo GM1 (ASGM1) antiserum treatment, effective in depleting in vivo NK activity, was associated with a marked increase in survival in 3 of 3 allogeneic combinations (BALB/c into C3H/HeN, C57B1/6, or C3B6F1). This enhanced survival was independent of the susceptibility of each recipient strain to accept BALB/c BM. Moreover, recipient anti-ASGM1 treatment was also effective in increasing survival in recipients of syngeneic BM, suggesting that NK cells can adversely affect engraftment independent of genetically controlled polymorphic cell surface determinants. Analysis of chimerism in surviving animals 2 months post-BMT showed that recipient NK depletion significantly increased the level of donor engraftment when high doses of BM were transplanted. These studies also demonstrated that anti-ASGM1 pretreatment mainly resulted in an increase in extramedullary hematopoiesis in the second and third week after irradiation. Anti-ASGM1 treatment also dramatically accelerated the rate of appearance of donor-derived cells with a higher level of donor-cell engraftment apparent at a time when the differences in survival between NK-depleted and control BMT recipients became significant. Peripheral cell counts were also affected by NK depletion, with significantly enhanced platelet and red blood cell recovery and a moderate increase in granulocyte recovery

  2. Anti-asialo GM1 antiserum treatment of lethally irradiated recipients before bone marrow transplantation: Evidence that recipient natural killer depletion enhances survival, engraftment, and hematopoietic recovery

    Energy Technology Data Exchange (ETDEWEB)

    Tiberghien, P.; Longo, D.L.; Wine, J.W.; Alvord, W.G.; Reynolds, C.W. (Program Resources, Inc., Frederick, MD (USA))

    1990-10-01

    Natural killer (NK) cells are reported to have an important role in the resistance of lethally irradiated recipients to bone marrow transplantation (BMT). Therefore, we investigated the effects of recipient NK depletion on survival, chimerism, and hematopoietic reconstitution after lethal irradiation and the transplantation of limiting amounts of T-cell-deficient bone marrow (BM). When administered before BMT, anti-asialo GM1 (ASGM1) antiserum treatment, effective in depleting in vivo NK activity, was associated with a marked increase in survival in 3 of 3 allogeneic combinations (BALB/c into C3H/HeN, C57B1/6, or C3B6F1). This enhanced survival was independent of the susceptibility of each recipient strain to accept BALB/c BM. Moreover, recipient anti-ASGM1 treatment was also effective in increasing survival in recipients of syngeneic BM, suggesting that NK cells can adversely affect engraftment independent of genetically controlled polymorphic cell surface determinants. Analysis of chimerism in surviving animals 2 months post-BMT showed that recipient NK depletion significantly increased the level of donor engraftment when high doses of BM were transplanted. These studies also demonstrated that anti-ASGM1 pretreatment mainly resulted in an increase in extramedullary hematopoiesis in the second and third week after irradiation. Anti-ASGM1 treatment also dramatically accelerated the rate of appearance of donor-derived cells with a higher level of donor-cell engraftment apparent at a time when the differences in survival between NK-depleted and control BMT recipients became significant. Peripheral cell counts were also affected by NK depletion, with significantly enhanced platelet and red blood cell recovery and a moderate increase in granulocyte recovery.

  3. Control of Multidrug-Resistant Pseudomonas aeruginosa in Allogeneic Hematopoietic Stem Cell Transplant Recipients by a Novel Bundle Including Remodeling of Sanitary and Water Supply Systems.

    Science.gov (United States)

    Kossow, Annelene; Kampmeier, Stefanie; Willems, Stefanie; Berdel, Wolfgang E; Groll, Andreas H; Burckhardt, Birgit; Rossig, Claudia; Groth, Christoph; Idelevich, Evgeny A; Kipp, Frank; Mellmann, Alexander; Stelljes, Matthias

    2017-09-15

    Infections by multidrug-resistant Pseudomonas aeruginosa (MDRPa) are an important cause of morbidity and mortality in patients after allogeneic hematopoietic stem cell transplantation (HSCT). Humid environments can serve as a reservoir and source of infection by this pathogen. To minimize the risk of infection from these reservoirs, we performed extensive remodeling of sanitation and water installations as the focus of our hygiene bundle. During the reconstruction of our transplantation unit (April 2011-April 2014) we implemented several technical modifications to reduce environmental contamination by and subsequent spreading of MDRPa, including a newly designed shower drain, disinfecting siphons underneath the sinks, and rimless toilets. During a 3-year study period (2012-2014), we tracked the number of patients affected by MDRPa (colonized and/or infected) and the outcome of infected patients, and monitored the environmental occurrence of this pathogen. We further performed whole-genome sequencing of nosocomial MDRPa strains to evaluate genotypic relationships between isolates. Whereas 31 (9.2%; 18 colonized, 13 infected) patients were affected in 2012 and 2013, the number decreased to 3 in 2014 (17%; 3 colonized, 0 infected). Lethality by MDRPa similarly decreased from 3.6% to 0%. Environmental detection of MDRPa decreased in toilets from 18.9% in 2012-2013 to 6.1% in the following year and from 8.1% to 3.0%, respectively, in shower outlets. Whole-genome sequencing showed close relationships between environmental and patient-derived isolates. Hospital construction measures aimed at controlling environmental contamination by and spread of MDRPa are effective at minimizing the risk of highly lethal MDRPa infections. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  4. Analysis for residual host cell proteins and DNA in process streams of a recombinant protein product expressed in Escherichia coli cells.

    Science.gov (United States)

    Rathore, Anurag Singh; Sobacke, S E; Kocot, T J; Morgan, D R; Dufield, R L; Mozier, N M

    2003-08-21

    Analyses of crude samples from biotechnology processes are often required in order to demonstrate that residual host cell impurities are reduced or eliminated during purification. In later stages of development, as the processes are further developed and finalized, there is a tremendous volume of testing required to confirm the absence of residual host cell proteins (HCP) and DNA. Analytical tests for these components are very challenging since (1). they may be present at levels that span a million-fold range, requiring substantial dilutions; (2). are not a single component, often existing as fragments and a variety of structures; (3). require high sensitivity for final steps in process; and (4). are present in very complex matrices including other impurities, the product, buffers, salts and solvents. Due to the complex matrices and the variety of potential analytes, the methods of analysis are not truly quantitative for all species. Although these limitations are well known, the assays are still very much in demand since they are required for approval of new products. Methods for final products, described elsewhere, focus on approaches to achieve regulatory requirements. The study described herein will describe the technical rationale for measuring the clearance of HCP and DNA in the entire bioprocessing to purification from an Escherichia coli-derived expression system. Three analytical assays, namely, reversed-phase high-performance liquid chromatography (RP-HPLC), enzyme-linked immunosorbent assay (ELISA), and Threshold Total DNA Assay, were utilized to quantify the protein product, HCP and DNA, respectively. Product quantification is often required for yield estimation and is useful since DNA and HCP results are best expressed as a ratio to product for calculation of relative purification factors. The recombinant E. coli were grown to express the protein of interest as insoluble inclusion bodies (IB) within the cells. The IB were isolated by repeated

  5. Residues 28 to 39 of the Extracellular Loop 1 of Chicken Na+/H+ Exchanger Type I Mediate Cell Binding and Entry of Subgroup J Avian Leukosis Virus.

    Science.gov (United States)

    Guan, Xiaolu; Zhang, Yao; Yu, Mengmeng; Ren, Chaoqi; Gao, Yanni; Yun, Bingling; Liu, Yongzhen; Wang, Yongqiang; Qi, Xiaole; Liu, Changjun; Cui, Hongyu; Zhang, Yanping; Gao, Li; Li, Kai; Pan, Qing; Zhang, Baoshan; Wang, Xiaomei; Gao, Yulong

    2018-01-01

    Chicken Na + /H + exchanger type I (chNHE1), a multispan transmembrane protein, is a cellular receptor of the subgroup J avian leukosis virus (ALV-J). To identify the functional determinants of chNHE1 responsible for the ALV-J receptor activity, a series of chimeric receptors was created by exchanging the extracellular loops (ECL) of human NHE1 (huNHE1) and chNHE1 and by ECL replacement with a hemagglutinin (HA) tag. These chimeric receptors then were used in binding and entry assays to map the minimal ALV-J gp85-binding domain of chNHE1. We show that ECL1 of chNHE1 (chECL1) is the critical functional ECL that interacts directly with ALV-J gp85; ECL3 is also involved in ALV-J gp85 binding. Amino acid residues 28 to 39 of the N-terminal membrane-proximal region of chECL1 constitute the minimal domain required for chNHE1 binding of ALV-J gp85. These residues are sufficient to mediate viral entry into ALV-J nonpermissive cells. Point mutation analysis revealed that A30, V33, W38, and E39 of chECL1 are the key residues mediating the binding between chNHE1 and ALV-J gp85. Further, the replacement of residues 28 to 39 of huNHE1 with the corresponding chNHE1 residues converted the nonfunctional ALV-J receptor huNHE1 to a functional one. Importantly, soluble chECL1 and huECL1 harboring chNHE1 residues 28 to 39 both could effectively block ALV-J infection. Collectively, our findings indicate that residues 28 to 39 of chNHE1 constitute a domain that is critical for receptor function and mediate ALV-J entry. IMPORTANCE chNHE1 is a cellular receptor of ALV-J, a retrovirus that causes infections in chickens and serious economic losses in the poultry industry. Until now, the domains determining the chNHE1 receptor function remained unknown. We demonstrate that chECL1 is critical for receptor function, with residues 28 to 39 constituting the minimal functional domain responsible for chNHE1 binding of ALV-J gp85 and efficiently mediating ALV-J cell entry. These residues are

  6. An optimized single chain TCR scaffold relying on the assembly with the native CD3-complex prevents residual mispairing with endogenous TCRs in human T-cells

    Science.gov (United States)

    Knies, Diana; Klobuch, Sebastian; Xue, Shao-An; Birtel, Matthias; Echchannaoui, Hakim; Yildiz, Oezlem; Omokoko, Tana; Guillaume, Philippe; Romero, Pedro; Stauss, Hans; Sahin, Ugur; Herr, Wolfgang; Theobald, Matthias; Thomas, Simone; Voss, Ralf-Holger

    2016-01-01

    Immunotherapy of cancer envisions the adoptive transfer of T-cells genetically engineered with tumor-specific heterodimeric α/β T-cell receptors (TCRα/β). However, potential mispairing of introduced TCRα/β-chains with endogenous β/α-ones may evoke unpredictable autoimmune reactivities. A novel single chain (sc)TCR format relies on the fusion of the Vα-Linker-Vβ-fragment to the TCR Cβ-domain and coexpression of the TCR Cα-domain capable of recruiting the natural CD3-complex for full and hence, native T-cell signaling. Here, we tested whether such a gp100(280-288)- or p53(264-272) tumor antigen-specific scTCR is still prone to mispairing with TCRα. In a human Jurkat-76 T-cell line lacking endogenous TCRs, surface expression and function of a scTCR could be reconstituted by any cointroduced TCRα-chain indicating mispairing to take place on a molecular basis. In contrast, transduction into human TCRα/β-positive T-cells revealed that mispairing is largely reduced. Competition experiments in Jurkat-76 confirmed the preference of dcTCR to selfpair and to spare scTCR. This also allowed for the generation of dc/scTCR-modified cytomegalovirus/tumor antigen-bispecific T-cells to augment T-cell activation in CMV-infected tumor patients. Residual mispairing was prevented by strenghtening the Vα-Li-Vβ-fragment through the design of a novel disulfide bond between a Vα- and a linker-resident residue close to Vβ. Multimer-stainings, and cytotoxicity-, IFNγ-secretion-, and CFSE-proliferation-assays, the latter towards dendritic cells endogenously processing RNA-electroporated gp100 antigen proved the absence of hybrid scTCR/TCRα-formation without impairing avidity of scTCR/Cα in T-cells. Moreover, a fragile cytomegalovirus pp65(495-503)-specific scTCR modified this way acquired enhanced cytotoxicity. Thus, optimized scTCR/Cα inhibits residual TCR mispairing to accomplish safe adoptive immunotherapy for bulk endogenous TCRα/β-positive T-cells. PMID:27028870

  7. E119D Neuraminidase Mutation Conferring Pan-Resistance to Neuraminidase Inhibitors in an A(H1N1)pdm09 Isolate From a Stem-Cell Transplant Recipient.

    Science.gov (United States)

    L'Huillier, Arnaud G; Abed, Yacine; Petty, Tom J; Cordey, Samuel; Thomas, Yves; Bouhy, Xavier; Schibler, Manuel; Simon, Audrey; Chalandon, Yves; van Delden, Christian; Zdobnov, Evgeny; Boquete-Suter, Patricia; Boivin, Guy; Kaiser, Laurent

    2015-12-01

    An influenza A(H1N1)pdm09 infection was diagnosed in a hematopoietic stem cell transplant recipient during conditioning regimen. He was treated with oral oseltamivir, later combined with intravenous zanamivir. The H275Y neuraminidase (NA) mutation was first detected, and an E119D NA mutation was identified during zanamivir therapy. Recombinant wild-type (WT) E119D and E119D/H275Y A(H1N1)pdm09 NA variants were generated by reverse genetics. Susceptibility to NA inhibitors (NAIs) was evaluated with a fluorometric assay using the 2'-(4-methylumbelliferyl)-α-D-N-acetylneuraminic acid (MUNANA) substrate. Susceptibility to favipiravir (T-705) was assessed using plaque reduction assays. The NA affinity and velocity values were determined with NA enzymatic studies. We identified an influenza A(H1N1)pdm09 E119D mutant that exhibited a marked increase in the 50% inhibitory concentrations against all tested NAIs (827-, 25-, 286-, and 702-fold for zanamivir, oseltamivir, peramivir, and laninamivir, respectively). The double E119D/H275Y mutation further increased oseltamivir and peramivir 50% inhibitory concentrations by 790- and >5000-fold, respectively, compared with the WT. The mutant viruses remained susceptible to favipiravir. The NA affinity and velocity values of the E119D variant decreased by 8.1-fold and 4.5-fold, respectively, compared with the WT. The actual emergence of a single NA mutation conferring pan-NAI resistance in the clinical setting reinforces the pressing need to develop new anti-influenza strategies. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Residual risk

    African Journals Online (AJOL)

    ing the residual risk of transmission of HIV by blood transfusion. An epidemiological approach assumed that all HIV infections detected serologically in first-time donors were pre-existing or prevalent infections, and that all infections detected in repeat blood donors were new or incident infections. During 1986 - 1987,0,012%.

  9. Effects of Hematopoietic Stem Cell Age on CML Disease Progression

    National Research Council Canada - National Science Library

    Dorshkind, Kenneth

    2006-01-01

    ...:22 chromosomal translocation and then transplanted into young recipients. The data indicate that recipients of the young,transduced bone marrow cells presented with myeloid and lymphoid leukemias...

  10. Radiation-induced DNA damage in tumors and normal tissues. II. Influence of dose, residual DNA damage and physiological factors in oxygenated cells

    International Nuclear Information System (INIS)

    Zhang, H.; Wheeler, K.T.

    1994-01-01

    Detection and quantification of hypoxic cells in solid tumors is important for many experimental and clinical situations. Several laboratories, including ours, have suggested that assays which measure radiation-induced DNA strand breaks and DNA-protein crosslinks (DPCs) might be used to detect or quantify hypoxic cells in tumors and normal tissues. Recently, we demonstrated the feasibility of using an alkaline elution assay that measures strand breaks and DPCs to detect and/or quantify hypoxic cells in tissues. For this approach to be valid, DPCs must not be formed to any great extent in irradiated oxygenated cells, and the formation and repair of strand breaks and DPCs in oxygenated cells must not be modified appreciably by physiological factors (e.g., temperature, pH and nutrient depletion) that are often found in solid tumors. To address these issues, two sets of experiments were performed. In one set of experiments, oxygenated 9L cells in tissue culture, subcutaneous 9L tumors and rat cerebella were irradiated with doses of 15 or 50 Gy and allowed to repair until the residual strand break damage was low enough to detect DPCs. In another set of experiments, oxygenated exponentially growing or plateau-phase 9L cells in tissue culture were irradiated with a dose of 15 Gy at 37 or 20 degrees C, while the cells were maintained at a pH of either 6.6 or 7.3. DNA-protein crosslinks were formed in oxygenated cells about 100 times less efficiently than in hypoxic cells. In addition, temperature, pH, nutrient depletion and growth phase did not appreciably alter the formation and repair of strand breaks or the formation of DPCs in oxygenated 9L cells. These results support the use of this DNA damage assay for the detection and quantification of hypoxic cells in solid tumors. 27 refs., 5 tabs

  11. Residual basins

    International Nuclear Information System (INIS)

    D'Elboux, C.V.; Paiva, I.B.

    1980-01-01

    Exploration for uranium carried out over a major portion of the Rio Grande do Sul Shield has revealed a number of small residual basins developed along glacially eroded channels of pre-Permian age. Mineralization of uranium occurs in two distinct sedimentary units. The lower unit consists of rhythmites overlain by a sequence of black shales, siltstones and coal seams, while the upper one is dominated by sandstones of probable fluvial origin. (Author) [pt

  12. Total body irradiation in hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Fundagul Andic

    2014-06-01

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

  13. Design and validation of a new method to detect and quantify residual host cell DNA in human recombinant erythropoietin (rEPO).

    Science.gov (United States)

    Zamanian, Shima; Mohammadi-Yeganeh, Samira; Kia, Vahid; Kaghazian, Hooman; Paryan, Mahdi

    2017-10-21

    During the purification of human recombinant erythropoietin (rEPO) from host cells, residual DNA may remain in final products. This contamination is a risk factor for patients and may result in the inactivation of some tumor suppressor genes or activation of oncogenes if its concentration is more than the standard defined by WHO. Based on WHO's criteria, acceptable level of residual DNA in biopharmaceuticals is less than 10-100 pg/dose. In this study, we have designed a sensitive and specific quantitative real-time polymerase chain reaction (PCR) assay for the detection of residual DNA in human rEPO products. All reported sequences of CHO's GAPDH gene were retrieved from GenBank, and a multiple alignment was performed using Mega 6 software to find conserved regions of the gene. Primers and probe were designed by AlleleID7 software for the highly conserved region. Quantitative real-time PCR showed an R 2 value more than 0.99 and the efficiency equal to 101% indicating a highly accurate and efficiency of the reaction, respectively. Based on the standard curve, the limit of detection of the assay was determined to be 10 copies/µL (0.00967 fg/µL). In addition, the inter- and intra-assay of the test were determined to be 1.14% and 0.65%, respectively, which are in acceptable range according to the WHO's guidelines.

  14. Residual β-cell function and the insulin-like growth factor system in Danish children and adolescents with type 1 diabetes

    DEFF Research Database (Denmark)

    Sorensen, Jesper S; Birkebaek, Niels H; Bjerre, Mette

    2015-01-01

    CONTEXT: C-peptide-positive adults with type 1 diabetes (T1D) have higher circulating total and free IGF-1 and lower IGF binding protein 1 (IGFBP-1) than C-peptide-negative patients. Whether this is also the case in children remains unknown. OBJECTIVE: The objective of the study was to examine...... the IGF system in children/adolescents with and without residual β-cell function (RBF). DESIGN AND PATIENTS: This was a cross-sectional study containing 136 prepubertal (hereof 15 RBF positive) and 206 pubertal (hereof 42 RBF positive) children/adolescents with T1D for 3-6 years as well as 40 prepubertal...

  15. Suppression of adoptive antituberculosis immunity by normal recipient animals

    International Nuclear Information System (INIS)

    Lefford, M.J.

    1983-01-01

    Adoptive immunity is poorly expressed in normal syngeneic mice. This phenomenon was studied by using experimental antituberculosis immunity as a model system representing pure cell-mediated immunity. Expression of adoptive immunity was facilitated by pretreating recipients with sublethal ionizing radiation (500 rads) or high doses (200 mg/kg) of cyclophosphamide or by using adult thymectomized, lethally irradiated, bone-marrow-reconstituted (TXB) mice. Adult thymectomy was less effective, and a low dose of cyclophosphamide (20 mg/kg) was completely ineffective. The beneficial effect of sublethal irradiation was reduced over time; it persisted for 4 weeks and was absent after 8 weeks. Attempts to restore the suppressed state of normal mice to sublethally irradiated mice by using normal spleen or thymus cells did not succeed. Even in rats, which express adoptive antituberculosis immunity without immunosuppressive treatment, the use of sublethally irradiated or TXB recipients potentiated adoptive immunity. It was concluded that suppression of adoptive immunization in normal recipient mice is mediated predominantly, if not exclusively, by T lymphocytes that are sensitive to a number of immunosuppressive agents. The suppressor cells are long-lived and can be regenerated from precursors that are resistant to 500 but not to 900 rads of ionizing radiation

  16. Stereotactic Body Radiation Therapy Can Be Used Safely to Boost Residual Disease in Locally Advanced Non-Small Cell Lung Cancer: A Prospective Study

    Energy Technology Data Exchange (ETDEWEB)

    Feddock, Jonathan, E-mail: jmfedd0@uky.edu [Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky (United States); Arnold, Susanne M. [Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky (United States); Department of Medical Oncology, University of Kentucky, Lexington, Kentucky (United States); Shelton, Brent J. [Department of Biostatistics, University of Kentucky, Lexington, Kentucky (United States); Sinha, Partha; Conrad, Gary [Department of Radiology, University of Kentucky, Lexington, Kentucky (United States); Chen, Li [Department of Biostatistics, University of Kentucky, Lexington, Kentucky (United States); Rinehart, John [Department of Medical Oncology, University of Kentucky, Lexington, Kentucky (United States); McGarry, Ronald C. [Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky (United States)

    2013-04-01

    Purpose: To report the results of a prospective, single-institution study evaluating the feasibility of conventional chemoradiation (CRT) followed by stereotactic body radiation therapy (SBRT) as a means of dose escalation for patients with stage II-III non-small cell lung cancer (NSCLC) with residual disease. Methods and Materials: Patients without metastatic disease and with radiologic evidence of limited residual disease (≤5 cm) within the site of the primary tumor and good or complete nodal responses after standard CRT to a target dose of 60 Gy were considered eligible. The SBRT boost was done to achieve a total combined dose biological equivalent dose >100 Gy to the residual primary tumor, consisting of 10 Gy × 2 fractions (20 Gy total) for peripheral tumors, and 6.5 Gy × 3 fractions (19.5 Gy total) for medial tumors using the Radiation Therapy Oncology Group protocol 0813 definitions. The primary endpoint was the development of grade ≥3 radiation pneumonitis (RP). Results: After a median follow-up of 13 months, 4 patients developed acute grade 3 RP, and 1 (2.9%) developed late and persistent grade 3 RP. No patients developed grade 4 or 5 RP. Mean lung dose, V2.5, V5, V10, and V20 values were calculated for the SBRT boost, and none were found to significantly predict for RP. Only advancing age (P=.0147), previous smoking status (P=.0505), and high CRT mean lung dose (P=.0295) were significantly associated with RP development. At the time of analysis, the actuarial local control rate at the primary tumor site was 82.9%, with only 6 patients demonstrating recurrence. Conclusions: Linear accelerator-based SBRT for dose escalation of limited residual NSCLC after definitive CRT was feasible and did not increase the risk for toxicity above that for standard radiation therapy.

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

    Science.gov (United States)

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

    2017-11-21

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

  18. Positively charged residues at the five-fold symmetry axis of cell culture-adapted foot-and-mouth disease virus permit novel receptor interactions.

    Science.gov (United States)

    Berryman, Stephen; Clark, Stuart; Kakker, Naresh K; Silk, Rhiannon; Seago, Julian; Wadsworth, Jemma; Chamberlain, Kyle; Knowles, Nick J; Jackson, Terry

    2013-08-01

    Field isolates of foot-and-mouth disease virus (FMDV) have a restricted cell tropism which is limited by the need for certain RGD-dependent integrin receptors. In contrast, cell culture-adapted viruses use heparan sulfate (HS) or other unidentified molecules as receptors to initiate infection. Here, we report several novel findings resulting from cell culture adaptation of FMDV. In cell culture, a virus with the capsid of the A/Turkey/2/2006 field isolate gained the ability to infect CHO and HS-deficient CHO cells as a result of a single glutamine (Q)-to-lysine (K) substitution at VP1-110 (VP1-(Q)110(K)). Using site-directed mutagenesis, the introduction of lysine at this same site also resulted in an acquired ability to infect CHO cells by type O and Asia-1 FMDV. However, this ability appeared to require a second positively charged residue at VP1-109. CHO cells express two RGD-binding integrins (α5β1 and αvβ5) that, although not used by FMDV, have the potential to be used as receptors; however, viruses with the VP1-(Q)110(K) substitution did not use these integrins. In contrast, the VP1-(Q)110(K) substitution appeared to result in enhanced interactions with αvβ6, which allowed a virus with KGE in place of the normal RGD integrin-binding motif to use αvβ6 as a receptor. Thus, our results confirmed the existence of nonintegrin, non-HS receptors for FMDV on CHO cells and revealed a novel, non-RGD-dependent use of αvβ6 as a receptor. The introduction of lysine at VP1-110 may allow for cell culture adaptation of FMDV by design, which may prove useful for vaccine manufacture when cell culture adaptation proves intractable.

  19. Optimization and validation of DNA extraction and real-time PCR assay for the quantitative measurement of residual host cell DNA in biopharmaceutical products.

    Science.gov (United States)

    Hu, B; Sellers, J; Kupec, J; Ngo, W; Fenton, S; Yang, T-Y; Grebanier, A

    2014-01-01

    Host cell DNA contamination occurs during the production of biopharmaceuticals and must be controlled and monitored for the purity and safety of the drug products. A sodium iodide-based DNA extraction and a subsequent real time PCR assay were developed and validated for the quantitative measurement of residual host cell DNA impurity in monoclonal antibody therapeutic products. A sodium iodide-based commercial kit was optimized for the removal of interfering matrices. Several incubation steps from the kit protocol were combined and a neutralization buffer was introduced to protein digestion step to eliminate any precipitation from the detergent. The elimination of the two washing steps significantly reduced assay variability from loss of DNA pellets. The optimized DNA extraction procedure can recover DNA close to 100% for DNA concentrations from 10 to 100,000pg/mL. Of the published sequences of repetitive interspersed nuclear elements, we identified a nucleotide mismatch from the published CHO probe. Correction of this nucleotide increased DNA amplification by a thousand fold. The optimized assay was further validated for the quantitation of residual CHO DNA according to ICH guidelines with preset assay acceptance criteria. The method met all assay acceptance criteria and was found linear, accurate and precise for the quantitation of residual CHO in the linear range of 10-100,000pg DNA/mL. LOQ was measured at 10pg DNA/mL and LOD at 1pg DNA/mL. No matrix interference to our validated assay was detected from bioreactor harvest, Protein A eluate or eluate from ion exchange columns. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Demographic and epidemiologic characterization of transfusion recipients from four US regions: evidence from the REDS-III recipient database.

    Science.gov (United States)

    Karafin, Matthew S; Bruhn, Roberta; Westlake, Matt; Sullivan, Marian T; Bialkowski, Walter; Edgren, Gustaf; Roubinian, Nareg H; Hauser, Ronald G; Kor, Daryl J; Fleischmann, Debra; Gottschall, Jerome L; Murphy, Edward L; Triulzi, Darrell J

    2017-12-01

    Blood transfusion is one of the most common medical procedures during hospitalization in the United States. To understand the benefits of transfusion while mitigating potential risks, a multicenter database containing detailed information on transfusion incidence and recipient outcomes would facilitate research. The Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) program has developed a comprehensive transfusion recipient database utilizing data from hospital electronic health records at 12 participating hospitals in four geographic regions. Inpatient and outpatient data on transfusion recipients from January 1, 2013 to December 31, 2014 included patient age, sex, ethnicity, primary diagnosis, type of blood product provided, issue location, pretransfusion and post-transfusion hemoglobin (Hgb), and hospital outcomes. Transfusion incidence per encounter was calculated by blood product and various patient characteristics. During the 2-year study period, 80,362 (12.5%) inpatient encounters involved transfusion. Among inpatients, the most commonly transfused blood products were red blood cells (RBCs; 10.9% of encounters), followed by platelets (3.2%) and plasma (2.9%). Among patients who received transfusions, the median number of RBC units was one, the pretransfusion Hgb level was 7.6 g/dL, and the Hgb increment per unit was 1.4 g/dL. Encounter mortality increased with patient age, the number of units transfused, and the use of platelet or plasma products. The most commonly reported transfusion reaction was febrile nonhemolytic. The database contains comprehensive data regarding transfusion use and patient outcomes. The current report describes an evaluation of the first 2 years of a planned, 4-year, linked blood donor-component-recipient database, which represents a critical new resource for transfusion medicine researchers. © 2017 AABB.

  1. The long and the short of telomeres in bone marrow recipient SCID patients

    OpenAIRE

    Sarzotti-Kelsoe, Marcella; Daniell, Xiaoju G.; Whitesides, John F.; Buckley, Rebecca H.

    2011-01-01

    Telomeres are noncoding DNA regions at the end of the chromosomes that are crucial for genome stability. Since telomere length decreases with cell division, they can be used as a signature of cell proliferation history. T-cell reconstitution in severe combined immunodeficiency (SCID) subjects, recipients of T-cell-depleted, allogeneic-related bone marrow cells, is due to the development and maturation of donor T-cell precursors in the infant’s vestigial thymus and to homeostatic proliferation...

  2. Intestinal parasitic infections in renal transplant recipients.

    Science.gov (United States)

    Azami, Mehdi; Sharifi, Mehran; Hejazi, Sayed Hossein; Tazhibi, Mehdi

    2010-01-01

    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.

  3. 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.

  4. Cross-phosphorylation of bacterial serine/threonine and tyrosine protein kinases on key regulatory residues

    Directory of Open Access Journals (Sweden)

    Lei eShi

    2014-09-01

    Full Text Available Bacteria possess protein serine/threonine and tyrosine kinases which resemble eukaryal kinases in their capacity to phosphorylate multiple substrates. We hypothesized that the analogy might extend further, and bacterial kinases may also undergo mutual phosphorylation and activation, which is currently considered as a hallmark of eukaryal kinase networks. In order to test this hypothesis, we explored the capacity of all members of four different classes of serine/threonine and tyrosine kinases present in the firmicute model organism Bacillus subtilis to phosphorylate each other in vitro and interact with each other in vivo. The interactomics data suggested a high degree of connectivity among all types of kinases, while phosphorylation assays revealed equally wide-spread cross-phosphorylation events. Our findings suggest that the Hanks-type kinases PrkC, PrkD and YabT exhibit the highest capacity to phosphorylate other B. subtilis kinases, while the BY-kinase PtkA and the two-component-like kinases RsbW and SpoIIAB show the highest propensity to be phosphorylated by other kinases. Analysis of phosphorylated residues on several selected recipient kinases suggests that most cross-phosphorylation events concern key regulatory residues. Therefore, cross-phosphorylation events are very likely to influence the capacity of recipient kinases to phosphorylate substrates downstream in the signal transduction cascade. We therefore conclude that bacterial serine/threonine and tyrosine kinases probably engage in a network-type behavior previously described only in eukaryal cells.

  5. Monitoring Immune Responses in Organ Recipients by Flow Cytometry

    Directory of Open Access Journals (Sweden)

    Al-Mukhalafi Zuha

    2001-01-01

    Full Text Available Allograft rejection remains a major barrier to successful organ transplan-tation. Cellular and humoral immune responses play a critical role in mediating graft rejection. During the last few years, monoclonal antibodies have been used as a new specific therapeutic approach in the prevention of allograft rejection. Recently, the technology of flow cytometry has become a useful tool for monitoring immunological responses in transplant recipients. The application of this valuable tool in clinical transplantation at the present time is aimed at, i determining the extent of immuno-suppressive therapy through T-cell receptor analysis of cellular components, ii monitoring levels of alloreactive antibodies to identify high-risk recipients (sensitized patients in the pre-operative period and iii to predict rejection by monitoring their development post-operatively. In future, further development of this technology may demonstrate greater benefit to the field of organ transplantation.

  6. RESIDUAL RISK ASSESSMENTS - RESIDUAL RISK ...

    Science.gov (United States)

    This source category previously subjected to a technology-based standard will be examined to determine if health or ecological risks are significant enough to warrant further regulation for Coke Ovens. These assesments utilize existing models and data bases to examine the multi-media and multi-pollutant impacts of air toxics emissions on human health and the environment. Details on the assessment process and methodologies can be found in EPA's Residual Risk Report to Congress issued in March of 1999 (see web site). To assess the health risks imposed by air toxics emissions from Coke Ovens to determine if control technology standards previously established are adequately protecting public health.

  7. Antigen-driven CD4+ T cell and HIV-1 dynamics: residual viral replication under highly active antiretroviral therapy

    NARCIS (Netherlands)

    Ferguson, N. M.; DeWolf, F.; Ghani, A. C.; Fraser, C.; Donnelly, C. A.; Reiss, P.; Lange, J. M.; Danner, S. A.; Garnett, G. P.; Goudsmit, J.; Anderson, R. M.

    1999-01-01

    Antigen-induced stimulation of the immune system can generate heterogeneity in CD4+ T cell division rates capable of explaining the temporal patterns seen in the decay of HIV-1 plasma RNA levels during highly active antiretroviral therapy. Posttreatment increases in peripheral CD4+ T cell counts are

  8. Recipient Related Prognostic Factors for Graft Survival after Kidney Transplantation. A Single Center Experience

    Directory of Open Access Journals (Sweden)

    Alina Daciana ELEC

    2012-09-01

    Full Text Available Background and Aim. Advanced chronic kidney disease (CKD severely impairs life expectancy and quality of life in affected patients. Considering its benefits, renal transplantation currently represents the optimal treatment solution for end stage kidney disease patients. Pre-transplant assessment aims to maximize the graft and patient survival by identifying potential factors influencing the post-transplant outcome. The aim of this study has been to analyze recipient related prognostic factors bearing an impact on graft survival. Material and Methods. We analyzed the graft outcomes of 426 renal transplantations performed at the Clinical Institute of Urology and Renal Transplantation of Cluj-Napoca, between January 2004 and December 2008. Variables related to recipient and to potential donor/recipient prognostic factors were studied using univariate and multivariate analysis. Results. Graft survivals at 1, 3, 5 and 7 years were 94.01%, 88.37%, 82.51% and 78.10%, respectively. Chronic rejection (41.11% and death with a functioning graft (18.88% were the main causes of graft loss. In uni and multivariate analysis the recipient related variables found to influence the renal graft outcome were: peritoneal dialysis, pre transplant residual diuresis, grade I hypertension, severe iliac vessel atheromatosis, ischemic heart disease, stroke history, dyslipidemia and denutrition. The worst graft outcomes have been found for recipients on peritoneal dialysis, with anuria, hypotension, severe iliac atheromatosis, ischemic heart disease, stroke history, dyslipidemia and a poor nutritional status. Conclusion. The type of dialysis, the pre transplant residual diuresis, recipient arterial blood pressure, iliac vessel atheromatosis, ischemic heart disease, stroke history, dyslipidemia and denutrition significantly influence graft survival.

  9. Roles of Arginine and Lysine Residues in the Translocation of a Cell-Penetrating Peptide from 13C, 31P and 19F Solid-State NMR

    Science.gov (United States)

    Su, Yongchao; Doherty, Tim; Waring, Alan J.; Ruchala, Piotr; Hong, Mei

    2009-01-01

    Cell-penetrating peptides (CPPs) are small cationic peptides that cross the cell membrane while carrying macromolecular cargoes. We use solid-state NMR to investigate the structure and lipid interaction of two cationic residues, Arg10 and Lys13, in the CPP penetratin. 13C chemical shifts indicate that Arg10 adopts a rigid β-strand conformation in the liquid-crystalline state of anionic lipid membranes. This behavior contrasts with all other residues observed so far in this peptide, which adopt a dynamic β-turn conformation with coil-like chemical shifts at physiological temperature. Low-temperature 13C-31P distances between the peptide and the lipid phosphates indicate that both the Arg10 guanidinium Cζ and the Lys13 Cε lie in close proximity to the lipid 31P (4.0 - 4.2 Å), proving the existence of charge-charge interaction for both Arg10 and Lys13 in the gel-phase membrane. However, since lysine substitution in CPPs are known to reduce their translocation ability, we propose that low temperature stabilizes both lysine and arginine interactions with the phosphates, whereas at high temperature the lysine-phosphate interaction is much weaker than the arginine-phosphate interaction. This is supported by the unusually high rigidity of the Arg10 sidechain and its β-strand conformation at high temperature. The latter is proposed to be important for ion pair formation by allowing close approach of the lipid headgroups to guanidinium sidechains. 19F and 13C spin diffusion experiments indicate that penetratin is oligomerized into β-sheets in gel-phase membranes. These solid-state NMR data indicate that guanidinium-phosphate interactions exist in penetratin, and guanidinium groups play a stronger structural role than ammonium groups in the lipid-assisted translocation of CPPs across liquid-crystalline cell membranes. PMID:19364134

  10. Roles of arginine and lysine residues in the translocation of a cell-penetrating peptide from (13)C, (31)P, and (19)F solid-state NMR.

    Science.gov (United States)

    Su, Yongchao; Doherty, Tim; Waring, Alan J; Ruchala, Piotr; Hong, Mei

    2009-06-02

    Cell-penetrating peptides (CPPs) are small cationic peptides that cross the cell membrane while carrying macromolecular cargoes. We use solid-state NMR to investigate the structure and lipid interaction of two cationic residues, Arg(10) and Lys(13), in the CPP penetratin. (13)C chemical shifts indicate that Arg(10) adopts a rigid beta-strand conformation in the liquid-crystalline state of anionic lipid membranes. This behavior contrasts with all other residues observed so far in this peptide, which adopt a dynamic beta-turn conformation with coil-like chemical shifts at physiological temperature. Low-temperature (13)C-(31)P distances between the peptide and the lipid phosphates indicate that both the Arg(10) guanidinium Czeta atom and the Lys(13) Cepsilon atom are close to the lipid (31)P (4.0-4.2 A), proving the existence of charge-charge interaction for both Arg(10) and Lys(13) in the gel-phase membrane. However, since lysine substitution in CPPs is known to weaken their translocation ability, we propose that the low temperature stabilizes interactions of both lysine and arginine with the phosphates, whereas at high temperatures, the lysine-phosphate interaction is much weaker than the arginine-phosphate interaction. This is supported by the unusually high rigidity of the Arg(10) side chain and its beta-strand conformation at high temperatures. The latter is proposed to be important for ion pair formation by allowing close approach of the lipid headgroups to guanidinium side chains. (19)F and (13)C spin diffusion experiments indicate that penetratin is oligomerized into beta-sheets in gel-phase membranes. These solid-state NMR data indicate that guanidinium-phosphate interactions exist in penetratin, and guanidinium groups play a stronger structural role than ammonium groups in the lipid-assisted translocation of CPPs across liquid-crystalline cell membranes.

  11. The atherogenic dyslipidemia ratio [log(TG/HDL-C] is associated with residual vascular risk, beta-cell function loss and microangiopathy in type 2 diabetes females

    Directory of Open Access Journals (Sweden)

    Hermans Michel P

    2012-10-01

    Full Text Available Abstract Background Atherogenic dyslipidemia (AD, defined as low HDL-C plus elevated triglycerides (TG, comorbid to T2DM, increases cardiometabolic risk for CAD even when LDL-C is at target. In T2DM males, AD was shown to correlate with β-cell function loss, yet it is not established whether this applies across gender. Aim To establish the prevalence and severity of AD in T2DM females, and to determine how it relates to cardiometabolic phenotype, glucose homeostasis, micro- and macrovascular complications, and 10-year absolute CV risk (UKPDS Risk Engine. Methods 340 T2DM females were ranked according to quintiles (Q of the continuous variable log(TG/HDL-C, with AD prevalence defined as HDL-C -1 plus TG ≥150 mg.dL-1, and β-cell function assessed with HOMA. Results AD prevalence was 35%; mean HDL-C and TG were 52 (15 and 160 (105 mg.dL-1. AD was significantly related to central fat, metabolic syndrome, sedentarity and skeletal sarcopenia, as well as to hsCRP, fibrinogen, uric acid, cystatin-C, Big ET-1, and 10-year UKPDS CV risk. AD correlated stepwise with lower β-cell function and hyperbolic product, and with accelerated loss of residual insulin secretion, higher HbA1c and prevalent microangiopathy. Conclusions log(TG/HDL-C is a simple means to grade AD and residual macrovascular risk in T2DM females. This ratio associates with major non-LDL cardiometabolic variables and ranks predicted CAD risk. In addition, log(TG/HDL-C identifies worsening glucose homeostasis, poorer glycemic control, and prevalent microangiopathy.

  12. Impact of age on the cancer-specific survival of patients with localized renal cell carcinoma: martingale residual and competing risks analysis.

    Directory of Open Access Journals (Sweden)

    Muyan Cai

    Full Text Available BACKGROUND: Age at diagnosis has been shown to be an independent prognostic factor of localized renal cell carcinoma (RCC in several studies. We used contemporary statistical methods to reevaluate the effect of age on the cancer-specific survival (CSS of localized RCC. METHODS AND FINDINGS: 1,147 patients with localized RCC who underwent radical nephrectomy between 1993 and 2009 were identified in our four institutions. The association between age and CSS was estimated, and the potential threshold was identified by a univariate Cox model and by martingale residual analysis. Competing risks regression was used to identify the independent impact of age on CSS. The median age was 52 years (range, 19-84 years. The median follow-up was 61 months (range, 6-144 months for survivors. A steep increasing smoothed martingale residual plot indicated an adverse prognostic effect of age on CSS. The age cut-off of 45 years was most predictive of CSS on univariate Cox analysis and martingale residual analysis (p = 0.005. Age ≤45 years was independently associated with a higher CSS rate in the multivariate Cox regression model (HR = 1.59, 95% CI = 1.05-2.40, p = 0.027 as well as in competing risks regression (HR = 3.60, 95% CI = 1.93-6.71, p = 0.001. CONCLUSIONS: Increasing age was associated with a higher incidence of cancer-specific mortality of localized RCC. Age dichotomized at 45 years would maximize the predictive value of age on CSS, and independently predict the CSS of patients with localized RCC.

  13. Impact of age on the cancer-specific survival of patients with localized renal cell carcinoma: martingale residual and competing risks analysis.

    Science.gov (United States)

    Cai, Muyan; Wei, Jinhuan; Zhang, Zhiling; Zhao, Hongwei; Qiu, Yunqiao; Fang, Yong; Gao, Zhenli; Cao, Jiazheng; Chen, Wei; Zhou, Fangjian; Xie, Dan; Luo, Junhang

    2012-01-01

    Age at diagnosis has been shown to be an independent prognostic factor of localized renal cell carcinoma (RCC) in several studies. We used contemporary statistical methods to reevaluate the effect of age on the cancer-specific survival (CSS) of localized RCC. 1,147 patients with localized RCC who underwent radical nephrectomy between 1993 and 2009 were identified in our four institutions. The association between age and CSS was estimated, and the potential threshold was identified by a univariate Cox model and by martingale residual analysis. Competing risks regression was used to identify the independent impact of age on CSS. The median age was 52 years (range, 19-84 years). The median follow-up was 61 months (range, 6-144 months) for survivors. A steep increasing smoothed martingale residual plot indicated an adverse prognostic effect of age on CSS. The age cut-off of 45 years was most predictive of CSS on univariate Cox analysis and martingale residual analysis (p = 0.005). Age ≤45 years was independently associated with a higher CSS rate in the multivariate Cox regression model (HR = 1.59, 95% CI = 1.05-2.40, p = 0.027) as well as in competing risks regression (HR = 3.60, 95% CI = 1.93-6.71, p = 0.001). Increasing age was associated with a higher incidence of cancer-specific mortality of localized RCC. Age dichotomized at 45 years would maximize the predictive value of age on CSS, and independently predict the CSS of patients with localized RCC.

  14. Residual nilpotence and residual solubility of groups

    International Nuclear Information System (INIS)

    Mikhailov, R V

    2005-01-01

    The properties of the residual nilpotence and the residual solubility of groups are studied. The main objects under investigation are the class of residually nilpotent groups such that each central extension of these groups is also residually nilpotent and the class of residually soluble groups such that each Abelian extension of these groups is residually soluble. Various examples of groups not belonging to these classes are constructed by homological methods and methods of the theory of modules over group rings. Several applications of the theory under consideration are presented and problems concerning the residual nilpotence of one-relator groups are considered.

  15. The cell wall galactomannan antigen from Malassezia furfur and Malassezia pachydermatis contains beta-1,6-linked linear galactofuranosyl residues and its detection has diagnostic potential.

    Science.gov (United States)

    Shibata, Nobuyuki; Saitoh, Tomomi; Tadokoro, Yukari; Okawa, Yoshio

    2009-10-01

    Lipophilic yeasts of the genus Malassezia are associated with several skin diseases, such as pityriasis versicolor, Malassezia folliculitis, seborrhoeic dermatitis and atopic dermatitis, and are also increasingly associated with catheter-related fungaemia. The cell wall components of pathogenic micro-organisms behave as an antigen and/or ligand of the innate immune response. Live cells of Malassezia furfur and Malassezia pachydermatis did not react with an anti-alpha-1,2-mannoside antibody. However, they showed a strong hydrophobicity and reactivity with an anti-beta-1,3-glucan antibody compared to those of C. albicans. The cell wall polysaccharides of M. furfur and M. pachydermatis were isolated and their structures analysed by (1)H and (13)C NMR experiments. Both polysaccharides were shown to be beta-1,6-linked linear galactofuranosyl polymers with a small amount of mannan. The presence of galactomannan on cells of Malassezia species has not been described previously. The galactomannan did not react with an anti-Aspergillus fumigatus monoclonal antibody which has specificity for beta-1,5-linked galactofuranosyl residues. An anti-M. furfur antibody strongly reacted with the galactomannans of M. furfur and M. pachydermatis, but did not react with the galactomannans of Trichophyton rubrum, A. fumigatus or Fonsecaea pedrosoi. The characteristics of the anti-M. furfur antibody suggest that there is potential for diagnosis of Malassezia infections by antigen detection.

  16. Immunosuppression in the elderly renal allograft recipient

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: The Elderly are the fastest growing part of kidney transplant recipients. The best immunosuppressive strategy is unknown. METHODS: We performed a systematic search of randomized controlled trials and observational studies focused on safety and efficacy of different immunosuppression...... strategies in elderly kidney recipients. Data extraction and risk of bias evaluation were systematically performed. RESULTS: Ten studies were included: 2 randomized clinical trials and 8 observational. A marginal benefit was found for early renal function with delayed tacrolimus or complete tacrolimus...... 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...

  17. DIFFUSION CAPACITY IN HEART-TRANSPLANT RECIPIENTS

    NARCIS (Netherlands)

    GROEN, HJM; BOGAARD, JM; BALK, AHMM; KHO, SG; HOP, WCJ; HILVERING, C

    Preoperative diffusion capacity per liter alveolar volume (Kco) in cardiac transplant recipients with an intrinsic normal lung is within the normal range. In the first postoperative year, Kco showed a significant mean decrease of 12 percent (p

  18. Accuracy of Cochlear Implant Recipients on Speech Reception in Background Music

    Science.gov (United States)

    Gfeller, Kate; Turner, Christopher; Oleson, Jacob; Kliethermes, Stephanie; Driscoll, Virginia

    2012-01-01

    Objectives This study (a) examined speech recognition abilities of cochlear implant (CI) recipients in the spectrally complex listening condition of three contrasting types of background music, and (b) compared performance based upon listener groups: CI recipients using conventional long-electrode (LE) devices, Hybrid CI recipients (acoustic plus electric stimulation), and normal-hearing (NH) adults. Methods We tested 154 LE CI recipients using varied devices and strategies, 21 Hybrid CI recipients, and 49 NH adults on closed-set recognition of spondees presented in three contrasting forms of background music (piano solo, large symphony orchestra, vocal solo with small combo accompaniment) in an adaptive test. Outcomes Signal-to-noise thresholds for speech in music (SRTM) were examined in relation to measures of speech recognition in background noise and multi-talker babble, pitch perception, and music experience. Results SRTM thresholds varied as a function of category of background music, group membership (LE, Hybrid, NH), and age. Thresholds for speech in background music were significantly correlated with measures of pitch perception and speech in background noise thresholds; auditory status was an important predictor. Conclusions Evidence suggests that speech reception thresholds in background music change as a function of listener age (with more advanced age being detrimental), structural characteristics of different types of music, and hearing status (residual hearing). These findings have implications for everyday listening conditions such as communicating in social or commercial situations in which there is background music. PMID:23342550

  19. Accuracy of cochlear implant recipients in speech reception in the presence of background music.

    Science.gov (United States)

    Gfeller, Kate; Turner, Christopher; Oleson, Jacob; Kliethermes, Stephanie; Driscoll, Virginia

    2012-12-01

    This study examined speech recognition abilities of cochlear implant (CI) recipients in the spectrally complex listening condition of 3 contrasting types of background music, and compared performance based upon listener groups: CI recipients using conventional long-electrode devices, Hybrid CI recipients (acoustic plus electric stimulation), and normal-hearing adults. We tested 154 long-electrode CI recipients using varied devices and strategies, 21 Hybrid CI recipients, and 49 normal-hearing adults on closed-set recognition of spondees presented in 3 contrasting forms of background music (piano solo, large symphony orchestra, vocal solo with small combo accompaniment) in an adaptive test. Signal-to-noise ratio thresholds for speech in music were examined in relation to measures of speech recognition in background noise and multitalker babble, pitch perception, and music experience. The signal-to-noise ratio thresholds for speech in music varied as a function of category of background music, group membership (long-electrode, Hybrid, normal-hearing), and age. The thresholds for speech in background music were significantly correlated with measures of pitch perception and thresholds for speech in background noise; auditory status was an important predictor. Evidence suggests that speech reception thresholds in background music change as a function of listener age (with more advanced age being detrimental), structural characteristics of different types of music, and hearing status (residual hearing). These findings have implications for everyday listening conditions such as communicating in social or commercial situations in which there is background music.

  20. SU-E-T-327: Dosimetric Impact of Beam Energy for Intrabeam Breast IORT with Different Residual Cancer Cell Distributions After Surgery

    International Nuclear Information System (INIS)

    Schwid, M; Zhang, H

    2015-01-01

    Purpose: The purpose of this study was to evaluate the dosimetric impact of beam energy to the IORT treatment of residual cancer cells with different cancer cell distributions after breast-conserving surgery. Methods: The three dimensional (3D) radiation doses of IORT using a 4-cm spherical applicator at the energy of 40 keV and 50 keV were separately calculated at different depths of the postsurgical tumor bed. The modified linear quadratic model (MLQ) was used to estimate the radiobiological response of the tumor cells assuming different radio-sensitivities and density distributions. The impact of radiation was evaluated for two types of breast cancer cell lines (α /β=10, and α /β =3.8) at 20 Gy dose prescribed at the applicator surface. Cancer cell distributions in the postsurgical tissue field were assumed to be a Gaussian with the standard deviations of 0.5, 1 and 2 mm respectively, namely the cancer cell infiltrations of 1.5, 3, and 6 mm respectively. The surface cancer cell percentage was assumed to be 0.01%, 0.1%, 1% and 10% separately. The equivalent uniform doses (EUD) for all the scenarios were calculated. Results: The EUDs were found to be dependent on the distributions of cancer cells, but independent of the cancer cell radio-sensitivities and the density at the surface. EUDs of 50 keV are 1% larger than that of 40 keV. For a prescription dose of 20 Gy, EUDs of 50 keV beam are 17.52, 16.21 and 13.14 Gy respectively for 0.5, 1.0 and 2.0 mm of the standard deviation of cancer cell Gaussian distributions. Conclusion: The impact by selected energies of IORT beams is very minimal. When energy is changed from 50 keV to 40 keV, the EUDs are almost the same for the same cancer cell distribution. 40 keV can be safely used as an alternative of 50 keV beam in IORT

  1. SU-E-T-327: Dosimetric Impact of Beam Energy for Intrabeam Breast IORT with Different Residual Cancer Cell Distributions After Surgery

    Energy Technology Data Exchange (ETDEWEB)

    Schwid, M; Zhang, H [Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, IL (United States)

    2015-06-15

    Purpose: The purpose of this study was to evaluate the dosimetric impact of beam energy to the IORT treatment of residual cancer cells with different cancer cell distributions after breast-conserving surgery. Methods: The three dimensional (3D) radiation doses of IORT using a 4-cm spherical applicator at the energy of 40 keV and 50 keV were separately calculated at different depths of the postsurgical tumor bed. The modified linear quadratic model (MLQ) was used to estimate the radiobiological response of the tumor cells assuming different radio-sensitivities and density distributions. The impact of radiation was evaluated for two types of breast cancer cell lines (α /β=10, and α /β =3.8) at 20 Gy dose prescribed at the applicator surface. Cancer cell distributions in the postsurgical tissue field were assumed to be a Gaussian with the standard deviations of 0.5, 1 and 2 mm respectively, namely the cancer cell infiltrations of 1.5, 3, and 6 mm respectively. The surface cancer cell percentage was assumed to be 0.01%, 0.1%, 1% and 10% separately. The equivalent uniform doses (EUD) for all the scenarios were calculated. Results: The EUDs were found to be dependent on the distributions of cancer cells, but independent of the cancer cell radio-sensitivities and the density at the surface. EUDs of 50 keV are 1% larger than that of 40 keV. For a prescription dose of 20 Gy, EUDs of 50 keV beam are 17.52, 16.21 and 13.14 Gy respectively for 0.5, 1.0 and 2.0 mm of the standard deviation of cancer cell Gaussian distributions. Conclusion: The impact by selected energies of IORT beams is very minimal. When energy is changed from 50 keV to 40 keV, the EUDs are almost the same for the same cancer cell distribution. 40 keV can be safely used as an alternative of 50 keV beam in IORT.

  2. 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....

  3. Management for Patients with De Novo or Recurrent Tumors in the Residual Kidney after Surgery for Nonfamilial Bilateral Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Noboru Hara

    2009-01-01

    Full Text Available The tumor de novo in the residual kidney after surgery for nonfamilial bilateral renal cell carcinoma (RCC is problematic. We reviewed 5 patients who experienced such a situation. Three patients had had metachronous bilateral RCC, treated with radical nephrectomy in one kidney and nephron-sparing surgery (NSS in the other. Two patients had had synchronous disease; one patient had received radical nephrectomy and NSS, and the other bilateral NSS. The 5 patients had another solid mass/de novo tumor in the residual kidney 16–88 (mean 46.8 months after surgery. For the tumor de novo in earlier years (1992–1999, one patient underwent surgery and hemodialysis, and the other selected a conservative observation. In recent years (2000–2007, one patient was conservatively observed; the remaining 2 received computerized-tomography-guided radiofrequency ablation, and the local tumors were well controlled postoperatively for 20 and 12 months with their renal function unimpaired. Ablative techniques can potentially strike a balance between oncological and nephrological outcomes in patients with sporadic multiple RCC, successful management of which was difficult previously.

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  5. Microparticles Engineered to Highly Express Peroxisome Proliferator-Activated Receptor-γ Decreased Inflammatory Mediator Production and Increased Adhesion of Recipient Monocytes

    OpenAIRE

    Sahler, Julie; Woeller, Collynn F.; Phipps, Richard P.

    2014-01-01

    Circulating blood microparticles are submicron vesicles released primarily by megakaryocytes and platelets that act as transcellular communicators. Inflammatory conditions exhibit elevated blood microparticle numbers compared to healthy conditions. Direct functional consequences of microparticle composition, especially internal composition, on recipient cells are poorly understood. Our objective was to evaluate if microparticle composition could impact the function of recipient cells, particu...

  6. Residual beta-Cell Function 3-6 Years After Onset of Type 1 Diabetes Reduces Risk of Severe Hypoglycemia in Children and Adolescents

    DEFF Research Database (Denmark)

    Sorensen, J. S.; Johannesen, J.; Pociot, F.

    2013-01-01

    OBJECTIVETo determine the prevalence of residual -cell function (RBF) in children after 3-6 years of type 1 diabetes, and to examine the association between RBF and incidence of severe hypoglycemia, glycemic control, and insulin requirements.RESEARCH DESIGN AND METHODSA total of 342 children (173...... boys) 4.8-18.9 years of age with type 1 diabetes for 3-6 years were included. RBF was assessed by testing meal-stimulated C-peptide concentrations. Information regarding severe hypoglycemia within the past year, current HbA(1c), and daily insulin requirements was retrieved from the medical records....../mol]; P 0.2 nmol/L (mean +/- SE: 1.07 +/- 0.02 vs. 0.93 +/- 0.07 units/kg/day; P diabetes. Children with RBF...

  7. 29 CFR 35.21 - Recipient responsibility to provide notice.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Recipient responsibility to provide notice. 35.21 Section 35.21 Labor Office of the Secretary of Labor NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR....21 Recipient responsibility to provide notice. (a) Notice to other recipients. Where a recipient of...

  8. Real-time amplification of HLA-DQA1 for counting residual white blood cells in filtered platelet concentrates

    NARCIS (Netherlands)

    Mohammadi, Tamimount; Reesink, Henk W.; Vandenbroucke-Grauls, Christina M. J. E.; Savelkoul, Paul H. M.

    2004-01-01

    BACKGROUND A real-time polymerase chain reaction (PCR) assay based on amplification of a conserved region of the HLA-DQA1 locus was developed and validated to assess its suitability in quantitating low levels of white blood cells (WBCs) in filtered platelet (PLT) concentrates (PCs). STUDY DESIGN AND

  9. Residual blood processing by centrifugation, cell salvage or ultrafiltration in cardiac surgery: effects on clinical hemostatic and ex-vivo rheological parameters.

    Science.gov (United States)

    Vonk, Alexander B; Muntajit, Warayouth; Bhagirath, Pranav; van Barneveld, Laurentius J; Romijn, Johannes W; de Vroege, Roel; Boer, Christa

    2012-10-01

    The study compared the effects of three blood concentration techniques after cardiopulmonary bypass on clinical hemostatic and ex-vivo rheological parameters. Residual blood of patients undergoing elective cardiac surgery was processed by centrifugation, cell salvage or ultrafiltration, and retransfused (n = 17 per group). Study parameters included blood loss, (free) hemoglobin, hematocrit, fibrinogen and erythrocyte aggregation, deformability and 2,3-diphosphoglycerate content. Patient characteristics were similar between groups. Ultrafiltration was associated with the highest weight of the transfusion bag [649 ± 261 vs. 320 ± 134 g (centrifugation) and 391 ± 158 g (cell salvage); P blood induced the largest gain in postoperative patient hemoglobin levels when compared to centrifugation and ultrafiltration, and was associated with the largest increase in 2,3-diphosphoglycerate when compared to ultrafiltration (Δ2,3-diphosphoglycerate 1.34 ± 1.92 vs. -0.77 ± 1.56 mmol/l; P = 0.03). Cell salvage is superior with respect to postoperative hemoglobin gain and washout of free hemoglobin when compared to centrifugation or ultrafiltration.

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

    Science.gov (United States)

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

    2017-05-01

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

  11. Oxidation of structural cysteine residues in thioredoxin 1 by aromatic arsenicals enhances cancer cell cytotoxicity caused by the inhibition of thioredoxin reductase 1.

    Science.gov (United States)

    Zhang, Xu; Lu, Jun; Ren, Xiaoyuan; Du, Yatao; Zheng, Yujuan; Ioannou, Panayiotis V; Holmgren, Arne

    2015-12-01

    Thioredoxin systems, composed of thioredoxin reductase (TrxR), thioredoxin (Trx) and NADPH, play important roles in maintaining cellular redox homeostasis and redox signaling. Recently the cytosolic Trx1 system has been shown to be a cellular target of arsenic containing compounds. To elucidate the relationship of the structure of arsenic compounds with their ability of inhibiting TrxR1 and Trx1, and cytotoxicity, we have investigated the reaction of Trx1 system with seven arsenic trithiolates: As(Cys)3, As(GS)3, As(Penicillamine)3, As(Mercaptoethanesulfonate)3, As(Mercaptopurine)3, As(2-mercaptopyridine)3 and As(2-mercaptopyridine N-oxide)3. The cytotoxicity of these arsenicals was consistent with their ability to inhibit TrxR1 in vitro and in cells. Unlike other arsenicals, As(Mercaptopurine)3 which did not show inhibitory effects on TrxR1 had very weak cytotoxicity, indicating that TrxR1 is a reliable drug target for arsenicals. Moreover, the two aromatic compounds As(2-mercaptopyridine)3 and As(2-mercaptopyridine N-oxide)3 showed stronger cytotoxicity than the others. As(2-mercaptopyridine)3 which selectively oxidized two structural cysteines (Cys62 and Cys69) in Trx1 showed mild improvement in cytotoxicity. As(2-mercaptopyridine N-oxide)3 oxidized all the Cys residues in Trx1, exhibiting the strongest cytotoxicity. Oxidation of Trx1 by As(2-mercaptopyridine)3 and As(2-mercaptopyridine N-oxide)3 affected electron transfer from NADPH and TrxR1 to peroxiredoxin 1 (Prx1), which could result in the reactive oxygen species elevation and trigger cell death process. These results suggest that oxidation of structural cysteine residues in Trx1 by aromatic group in TrxR1-targeting drugs may sensitize tumor cells to cell death, providing a novel approach to regulate cellular redox signaling and also a basis for rational design of new anticancer agents. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Adipose Stem Cell-Based Therapeutic Targeting of Residual Androgens in African Americans with Bone-Metastatic Prostate Cancer

    Science.gov (United States)

    2015-11-01

    reduce or circumvent PC, especially among AA-men. 15. SUBJECT TERMS Prostate cancer, health disparity, stem cells, hormone inactivating enzymes, CRPC...aggressive CaP in AA patients [8, 9]. Family history accounts for 5-10% of total CaP cases [8, 9], and it does not differ among AA, Asian Americans...metastatic CaP [23]. Although initially effective, hormonal therapy is marked by progression to castration-resistant prostate cancer (CRPC) over a period of

  13. Power from wastewater and residual products

    DEFF Research Database (Denmark)

    Krogh-Jeppesen, K.

    2007-01-01

    Microbial fuel cells utilise wastewater and residual products from the pretreatment of straw to generate power. Denmark could lead the way......Microbial fuel cells utilise wastewater and residual products from the pretreatment of straw to generate power. Denmark could lead the way...

  14. SERUM PARAOXONASE ACTIVITY IN RENAL TRANSPLANT RECIPIENTS

    Directory of Open Access Journals (Sweden)

    Saritha Gadicherla

    2017-12-01

    Full Text Available BACKGROUND Serum paraoxonase is an enzyme synthesised in the liver. It is known to prevent atherosclerosis by inhibiting oxidation of lowdensity lipoprotein. Renal transplant recipients have increased tendency for developing atherosclerosis and cardiovascular disease. Reduced activity of serum paraoxonase contributes to accelerated atherosclerosis and increased cardiovascular complications in these patients. The aim of this study was to estimate serum paraoxonase activity in renal transplant recipients and compare it with healthy controls. MATERIALS AND METHODS 30 renal transplant recipients and 30 age and sex matched healthy controls were taken for the study. Serum paraoxonase activity, blood urea, serum creatinine and uric acid were estimated in these groups. The serum paraoxonase activity was correlated with urea, creatinine and uric acid levels. RESULTS Serum paraoxonase activity was reduced in renal transplant recipients compared to healthy controls. There was a negative correlation between paraoxonase activity and the levels of urea, creatinine and uric acid levels. CONCLUSION In this study, the paraoxonase activity was reduced in renal transplant recipients compared to controls. The increased cardiovascular disease in these patients could be due to reduced paraoxonase activity.

  15. Seborrheic dermatitis among Oxford renal transplant recipients.

    Science.gov (United States)

    Lally, A; Casabonne, D; Newton, R; Wojnarowska, F

    2010-05-01

    Seborrheic dermatitis is an inflammatory dermatosis with a prevalence of 1-3% in the general population. It is recognized more commonly in those infected by human immunodeficiency virus (HIV). No studies have looked at Seborrheic dermatitis in the context of immunosuppression secondary to organ transplantation. Therefore, we investigated the prevalence of Seborrheic dermatitis in a renal transplant population and characteristics of those affected. A prospective study of 308 renal transplant recipients (RTRs) was carried out. All participants were examined for Seborrheic dermatitis. Descriptive statistics were employed and associations with Seborrheic dermatitis were examined using Fisher's exact test to calculate P-exact values, and Student's t-test was used to compare mean ages and time since transplantation. Statistical analysis was carried out using SPSS version 14.0 for Windows. Seborrheic dermatitis was identified in 29/308 (9.5%) patients and was more common in males (P-exact = 0.004) and in those who had been transplanted for longer (P = 0.02). The disease was mild-moderate severity in the majority but an unusual flexural appearance was recorded in 7/29 patients. Seborrheic dermatitis was less likely in those taking prednisolone (P-exact = 0.006) or tacrolimus (P-exact = 0.008). Seborrheic dermatitis was significantly associated with cutaneous malignancy, in particular squamous cell carcinoma (P-exact Seborrheic dermatitis is more common than other inflammatory dermatoses in immunosuppressed RTRs, but is not as frequent as in those immunosuppressed secondary to HIV. Degree and duration of exposure to immunosuppression and increased colonization with Malassezia yeast genus are likely be important in the aetiology of Seborrheic dermatitis in RTRs. Further studies are required to clarify this.

  16. Recipient screening in IVF: First data from women undergoing anonymous oocyte donation in Dublin

    Directory of Open Access Journals (Sweden)

    Salma Umme

    2011-04-01

    Full Text Available Abstract Background Guidelines for safe gamete donation have emphasised donor screening, although none exist specifically for testing oocyte recipients. Pre-treatment assessment of anonymous donor oocyte IVF treatment in Ireland must comply with the European Union Tissues and Cells Directive (Directive 2004/23/EC. To determine the effectiveness of this Directive when applied to anonymous oocyte recipients in IVF, we reviewed data derived from selected screening tests performed in this clinical setting. Methods Data from tests conducted at baseline for all women enrolling as recipients (n = 225 in the anonymous oocyte donor IVF programme at an urban IVF referral centre during a 24-month period were analysed. Patient age at programme entry and clinical pregnancy rate were also tabulated. All recipients had at least one prior negative test for HIV, Hepatitis B/C, chlamydia, gonorrhoea and syphilis performed by her GP or other primary care provider before reproductive endocrinology consultation. Results Mean (±SD age for donor egg IVF recipients was 40.7 ± 4.2 yrs. No baseline positive chlamydia, gonorrhoea or syphilis screening results were identified among recipients for anonymous oocyte donation IVF during the assessment interval. Mean pregnancy rate (per embryo transfer in this group was 50.5%. Conclusion When tests for HIV, Hepatitis B/C, chlamydia, gonorrhoea and syphilis already have been confirmed to be negative before starting the anonymous donor oocyte IVF sequence, additional (repeat testing on the recipient contributes no new clinical information that would influence treatment in this setting. Patient safety does not appear to be enhanced by application of Directive 2004/23/EC to recipients of anonymous donor oocyte IVF treatment. Given the absence of evidence to quantify risk, this practice is difficult to justify when applied to this low-risk population.

  17. Recipient screening in IVF: First data from women undergoing anonymous oocyte donation in Dublin

    LENUS (Irish Health Repository)

    Walsh, Anthony PH

    2011-04-20

    Abstract Background Guidelines for safe gamete donation have emphasised donor screening, although none exist specifically for testing oocyte recipients. Pre-treatment assessment of anonymous donor oocyte IVF treatment in Ireland must comply with the European Union Tissues and Cells Directive (Directive 2004\\/23\\/EC). To determine the effectiveness of this Directive when applied to anonymous oocyte recipients in IVF, we reviewed data derived from selected screening tests performed in this clinical setting. Methods Data from tests conducted at baseline for all women enrolling as recipients (n = 225) in the anonymous oocyte donor IVF programme at an urban IVF referral centre during a 24-month period were analysed. Patient age at programme entry and clinical pregnancy rate were also tabulated. All recipients had at least one prior negative test for HIV, Hepatitis B\\/C, chlamydia, gonorrhoea and syphilis performed by her GP or other primary care provider before reproductive endocrinology consultation. Results Mean (±SD) age for donor egg IVF recipients was 40.7 ± 4.2 yrs. No baseline positive chlamydia, gonorrhoea or syphilis screening results were identified among recipients for anonymous oocyte donation IVF during the assessment interval. Mean pregnancy rate (per embryo transfer) in this group was 50.5%. Conclusion When tests for HIV, Hepatitis B\\/C, chlamydia, gonorrhoea and syphilis already have been confirmed to be negative before starting the anonymous donor oocyte IVF sequence, additional (repeat) testing on the recipient contributes no new clinical information that would influence treatment in this setting. Patient safety does not appear to be enhanced by application of Directive 2004\\/23\\/EC to recipients of anonymous donor oocyte IVF treatment. Given the absence of evidence to quantify risk, this practice is difficult to justify when applied to this low-risk population.

  18. Site-directed fluorescence labeling reveals a revised N-terminal membrane topology and functional periplasmic residues in the Escherichia coli cell division protein FtsK.

    Science.gov (United States)

    Berezuk, Alison M; Goodyear, Mara; Khursigara, Cezar M

    2014-08-22

    In Escherichia coli, FtsK is a large integral membrane protein that coordinates chromosome segregation and cell division. The N-terminal domain of FtsK (FtsKN) is essential for division, and the C terminus (FtsKC) is a well characterized DNA translocase. Although the function of FtsKN is unknown, it is suggested that FtsK acts as a checkpoint to ensure DNA is properly segregated before septation. This may occur through modulation of protein interactions between FtsKN and other division proteins in both the periplasm and cytoplasm; thus, a clear understanding of how FtsKN is positioned in the membrane is required to characterize these interactions. The membrane topology of FtsKN was initially determined using site-directed reporter fusions; however, questions regarding this topology persist. Here, we report a revised membrane topology generated by site-directed fluorescence labeling. The revised topology confirms the presence of four transmembrane segments and reveals a newly identified periplasmic loop between the third and fourth transmembrane domains. Within this loop, four residues were identified that, when mutated, resulted in the appearance of cellular voids. High resolution transmission electron microscopy of these voids showed asymmetric division of the cytoplasm in the absence of outer membrane invagination or visible cell wall ingrowth. This uncoupling reveals a novel role for FtsK in linking cell envelope septation events and yields further evidence for FtsK as a critical checkpoint of cell division. The revised topology of FtsKN also provides an important platform for future studies on essential interactions required for this process. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. A Cysteine-Rich Protein Kinase Associates with a Membrane Immune Complex and the Cysteine Residues Are Required for Cell Death.

    Science.gov (United States)

    Yadeta, Koste A; Elmore, James M; Creer, Athena Y; Feng, Baomin; Franco, Jessica Y; Rufian, Jose Sebastian; He, Ping; Phinney, Brett; Coaker, Gitta

    2017-01-01

    Membrane-localized proteins perceive and respond to biotic and abiotic stresses. We performed quantitative proteomics on plasma membrane-enriched samples from Arabidopsis (Arabidopsis thaliana) treated with bacterial flagellin. We identified multiple receptor-like protein kinases changing in abundance, including cysteine (Cys)-rich receptor-like kinases (CRKs) that are up-regulated upon the perception of flagellin. CRKs possess extracellular Cys-rich domains and constitute a gene family consisting of 46 members in Arabidopsis. The single transfer DNA insertion lines CRK28 and CRK29, two CRKs induced in response to flagellin perception, did not exhibit robust alterations in immune responses. In contrast, silencing of multiple bacterial flagellin-induced CRKs resulted in enhanced susceptibility to pathogenic Pseudomonas syringae, indicating functional redundancy in this large gene family. Enhanced expression of CRK28 in Arabidopsis increased disease resistance to P. syringae Expression of CRK28 in Nicotiana benthamiana induced cell death, which required intact extracellular Cys residues and a conserved kinase active site. CRK28-mediated cell death required the common receptor-like protein kinase coreceptor BAK1. CRK28 associated with BAK1 as well as the activated FLAGELLIN-SENSING2 (FLS2) immune receptor complex. CRK28 self-associated as well as associated with the closely related CRK29. These data support a model where Arabidopsis CRKs are synthesized upon pathogen perception, associate with the FLS2 complex, and coordinately act to enhance plant immune responses. © 2017 American Society of Plant Biologists. All Rights Reserved.

  20. ABCB1 modulation does not circumvent drug extrusion from primitive leukemic progenitor cells and may preferentially target residual normal cells in acute myelogenous leukemia.

    NARCIS (Netherlands)

    Raaijmakers, M.H.G.P.; Grouw, P.L.M. de; Reijden, B.A. van der; Witte, T.J.M. de; Jansen, J.H.; Raymakers, R.A.P.

    2006-01-01

    PURPOSE: Acute myelogenous leukemia (AML) is a disease originating from normal hematopoietic CD34+ CD38- progenitor cells. Modulation of the multidrug ATP-binding cassette transporter ABCB1 has not resulted in improved outcome in AML, raising the question whether leukemic CD34+ CD38- cells are

  1. Urinary tract infection in kidney transplant recipients.

    Science.gov (United States)

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

    2017-04-01

    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. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  2. 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

    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.

  3. Effects of sublethal gamma radiation on T and B cell activity in the antibody response of mice

    International Nuclear Information System (INIS)

    Carlson, D.E.; Lubet, R.A.

    1976-01-01

    The relative radiosensitivity of T and B cells was followed in sublethally irradiated mice reconstituted with bone marrow cells, thymus cells, or both, and simultaneously challenged with sheep erythrocytes. Numbers of antibody-forming cells in recipient spleens were determined on days 4 to 8. In this assay the response of mice given bone marrow cells was limited by the amount of residual T cell activity, while the response of mice given thymus cells was limited by the residual B cell activity. Although residual activity of both T and B cells was suppressed in mice given 300 to 700 rad at 80 rad/min, residual B cell activity was consistently lower in these animals. When antibody responses were initiated at intervals after irradiation, B cell activity was clearly limiting by 48 hr after 500 or 600 rad. The activity of both T and B cells was sensitive to differences in dose rate between 8 and 80 rad/min. The 4 to 7 fold dose-rate sensitivity of T cells paralleled that of differentially irradiated nonreconstituted mice. In contrast, dose-rate dependence of B cell activity varied from 10- to 20-fold between 8 and 80 rad/min. These results suggest that radiation suppression of antibody responses in mice is highly dependent upon B cell sensitivity, and that dose-rate dependence of the antibody response may be explained in large part by differential sensitivity of B cells

  4. Medical School Performance, Alumni Membership, and Giving: How Do Scholarship Recipients and Non-Recipients Differ?

    Science.gov (United States)

    Elam, Carol L; Stratton, Terry D; Gilbert, Linda A; Stroth, H I; Vicini, Mary Beth; Wilson, Emery A

    2005-12-01

    This study examines student recipients of merit, need-based, service, or minority scholarships, their performance in medical school, and the relationship to future alumni association membership and financial giving. Retrospective data on grade-point average attained across the four-year curriculum and extracurricular activities reported at graduation were collected on students at the University of Kentucky College of Medicine from 1981-1991. Comparisons of academic performance and participation in institutional activities were made across scholarship recipients and non-recipients. These data were then linked to other data tracking alumni association membership and institutional giving. Compared to other scholarship recipients and non-recipients, merit scholars were more likely to be ranked above their class medians and be involved in extracurricular activities, including membership in Alpha Omega Alpha. However, seven years post-graduation, there was no difference between scholarship recipients and non-recipients in alumni association membership or donations to the medical school. Instead, students graduating in the upper half of their class, as compared to graduates in the lower half, and UKCOM graduates who attended the University of Kentucky as undergraduates, rather than students who attended other in-state or out-of state institutions, were more likely to join the medical alumni association. Alumni association members were more likely than non-members to make donations to the institution. More should be done to ensure that graduates who received scholarships are afforded meaningful ways to give back to the institution that supported them as students.

  5. 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

  6. Phosphorylation of tyrosine residues 31 and 118 on paxillin regulates cell migration through an association with CRK in NBT-II cells.

    Science.gov (United States)

    Petit, V; Boyer, B; Lentz, D; Turner, C E; Thiery, J P; Vallés, A M

    2000-03-06

    Identification of signaling molecules that regulate cell migration is important for understanding fundamental processes in development and the origin of various pathological conditions. The migration of Nara Bladder Tumor II (NBT-II) cells was used to determine which signaling molecules are specifically involved in the collagen-mediated locomotion. We show here that paxillin is tyrosine phosphorylated after induction of motility on collagen. Overexpression of paxillin mutants in which tyrosine 31 and/or tyrosine 118 were replaced by phenylalanine effectively impaired cell motility. Moreover, stimulation of motility by collagen preferentially enhanced the association of paxillin with the SH2 domain of the adaptor protein CrkII. Mutations in both tyrosine 31 and 118 diminished the phosphotyrosine content of paxillin and prevented the formation of the paxillin-Crk complex, suggesting that this association is necessary for collagen-mediated NBT-II cell migration. Other responses to collagen, such as cell adhesion and spreading, were not affected by these mutations. Overexpression of wild-type paxillin or Crk could bypass the migration-deficient phenotype. Both the SH2 and the SH3 domains of CrkII are shown to play a critical role in this collagen-mediated migration. These results demonstrate the important role of the paxillin-Crk complex in the collagen-induced cell motility.

  7. Recipient-matching of Passenger Leukocytes Prolongs Survival of Donor Lung Allografts in Miniature Swine.

    Science.gov (United States)

    Madariaga, Maria Lucia L; Michel, Sebastian G; La Muraglia, Glenn M; Sihag, Smita; Leonard, David A; Farkash, Evan A; Colvin, Robert B; Cetrulo, Curtis L; Huang, Christene A; Sachs, David H; Madsen, Joren C; Allan, James S

    2015-07-01

    Allograft rejection continues to be a vexing problem in clinical lung transplantation, and the role played by passenger leukocytes in the rejection or acceptance of an organ is unclear. We tested whether recipient-matching of donor graft passenger leukocytes would impact graft survival in a preclinical model of orthotopic left lung transplantation. In the experimental group (group 1), donor lungs were obtained from chimeric swine, in which the passenger leukocytes (but not the parenchyma) were major histocompatibility complex-matched to the recipients (n = 3). In the control group (group 2), both the donor parenchyma and the passenger leukocytes were major histocompatibility complex-mismatched to the recipients (n = 3). Lungs harvested from swine previously rendered chimeric by hematopoietic stem cell transplantation using recipient-type cells showed a high degree of passenger leukocyte chimerism by immunohistochemistry and flow cytometry. The chimeric lungs containing passenger leukocytes matched to the lung recipient (group 1) survived on average 107 days (range, 80-156). Control lung allografts (group 2) survived on average 45 days (range, 29-64; P lung allograft survival.

  8. A new in vitro approach to determine acquired tolerance in long-term kidney allograft recipients

    International Nuclear Information System (INIS)

    Reinsmoen, N.L.; Kaufman, D.; Matas, A.; Sutherland, D.E.; Najarian, J.S.; Bach, F.H.

    1990-01-01

    Previous studies indicate some kidney allograft recipients treated with total lymphoid irradiation, cyclosporine, or conventional immunosuppressive therapy demonstrate specific proliferative unresponsiveness in mixed lymphocyte culture (MLC) to donor cells at various times posttransplant. To investigate possible donor-specific hyporeactivity, we have studied 3 patients treated with TLI whose grafts have survived longer than 10 years; 2 patients given the same immunosuppressive protocol but without TLI whose grafts have survived longer than 10 years; and 27 CsA-treated living-related donor and cadaver-allograft recipients 1 year posttransplant. We confirmed previous observations of hyporeactivity of some patients' cells to stimulation by donor cells. In addition, we identified hyporeactivity to stimulation by homozygous typing cells (HTCs) defining the HLA-Dw specificities of the donor cells for all 3 of the 3 TLI patients, 1 of the 2 non-TLI patients, and 9 of the 27 patients 1 year posttransplant. The LRD recipients with donor-specific hyporeactivity as defined by the HTC analysis demonstrated fewer rejection episodes (25% vs. 57%) and lower mean creatinine levels (1.18 vs 1.78 mg/dL) than patients without donor-specific hyporeactivity. These studies demonstrate the feasibility of monitoring the immune status of allograft recipients posttransplant by means of HTC analysis, eliminating the need for pretransplant specimens. This approach provides a possible means to assess which patients may have acquired donor-specific hyporeactivity to their kidney allograft and thus may require less immunosuppression

  9. Soymilk residue (okara as a natural immobilization carrier for Lactobacillus plantarum cells enhances soymilk fermentation, glucosidic isoflavone bioconversion, and cell survival under simulated gastric and intestinal conditions

    Directory of Open Access Journals (Sweden)

    Xia Xiudong

    2016-11-01

    Full Text Available Cell immobilization is an alternative to microencapsulation for the maintenance of cells in a liquid medium. However, artificial immobilization carriers are expensive and pose a high safety risk. Okara, a food-grade byproduct from soymilk production, is rich in prebiotics. Lactobacilli could provide health enhancing effects to the host. This study aimed to evaluate the potential of okara as a natural immobilizer for L. plantarum 70810 cells. The study also aimed to evaluate the effects of okara-immobilized L. plantarum 70810 cells (IL on soymilk fermentation, glucosidic isoflavone bioconversion, and cell resistance to simulated gastric and intestinal stresses. Scanning electron microscopy (SEM was used to show cells adherence to the surface of okara. Lactic acid, acetic acid and isoflavone analyses in unfermented and fermented soymilk were performed by HPLC with UV detection. Viability and growth kinetics of immobilized and free L. plantarum 70810 cells (FL were followed during soymilk fermentation. Moreover, changes in pH, titrable acidity and viscosity were measured by conventional methods. For in vitro testing of simulated gastrointestinal resistance, fermented soymilk was inoculated with FL or IL and an aliquot incubated into acidic MRS broth which was conveniently prepared to simulate gastric, pancreatic juices and bile salts. Survival to simulated gastric and intestinal stresses was evaluated by plate count of colony forming units on MRS agar. SEM revealed that the lactobacilli cells attached and bound to the surface of okara. Compared with FL, IL exhibited a significantly higher specific growth rate, shorter lag phase of growth, higher productions of lactic and acetic acids, a faster decrease in pH and increase in titrable acidity, and a higher soymilk viscosity. Similarly, IL in soymilk showed higher productions of daizein and genistein compared with the control. Compared with FL, IL showed reinforced resistance to simulatedgastric and

  10. SERUM PARAOXONASE ACTIVITY IN RENAL TRANSPLANT RECIPIENTS

    OpenAIRE

    Saritha Gadicherla; Suma M. N; Parveen Doddamani

    2017-01-01

    BACKGROUND Serum paraoxonase is an enzyme synthesised in the liver. It is known to prevent atherosclerosis by inhibiting oxidation of lowdensity lipoprotein. Renal transplant recipients have increased tendency for developing atherosclerosis and cardiovascular disease. Reduced activity of serum paraoxonase contributes to accelerated atherosclerosis and increased cardiovascular complications in these patients. The aim of this study was to estimate serum paraoxonase activity in re...

  11. 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...

  12. Medal of Honor Recipients: 1979-2004

    National Research Council Canada - National Science Library

    Richardson, Glenda

    2004-01-01

    .... Although the Persian Gulf War, Operation Enduring Freedom, and Operation Iraqi Freedom are listed in the Table of Contents, as of this writing, no Medals of Honor have been awarded for actions in these conflicts. For further information, see CRS Report 95-519, "Medal of Honor: History and Issues." This report will be updated as new recipients are named.

  13. 1987 NRSSC Exemplary Program Awards Recipients.

    Science.gov (United States)

    Journal of Rural and Small Schools, 1987

    1987-01-01

    Identifies ten recipients of exemplary program awards and describes each program. Award categories include educational technology, cross-cultural services, preserve/inservice training, special education, family/school/community partnerships, innovative and creative programs, secondary curriculum and instruction, at-risk services, elementary…

  14. 14 CFR 1267.660 - Recipient.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Recipient. 1267.660 Section 1267.660 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE..., corporation, partnership, association, unit of government (except a Federal agency) or legal entity, however...

  15. Urinary tract infection in renal transplant recipients

    African Journals Online (AJOL)

    Abstract. Introduction: Urinary tract infection (UTI) is the commonest bacterial infection occurring in renal transplant recipients, and it is associated with significant morbidity. This study aimed to assess the characteristics of all UTI episodes diagnosed in renal transplant patients who attended regularly for follow up in the ...

  16. 76 FR 19683 - Conservation Program Recipient Reporting

    Science.gov (United States)

    2011-04-08

    ... regulations require agencies that make awards of Federal financial assistance subject to the Transparency Act... registration and reporting requirements into these programs' regulations. These changes, the terms of which are..., 2010. The regulations at 2 CFR part 25 require, with some exceptions, recipients of Federal financial...

  17. 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.

  18. {sup 18}F-FDG PET/CT for detection and localization of residual or recurrent disease in patients with multiple myeloma after stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Derlin, Thorsten; Wisotzki, Christian; Klutmann, Susanne [University Medical Center Hamburg-Eppendorf, Department of Nuclear Medicine, Hamburg (Germany); Weber, Christoph; Habermann, Christian R.; Herrmann, Jochen [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Ayuk, Francis; Wolschke, Christine; Kroeger, Nicolaus [University Medical Center Hamburg-Eppendorf, Clinic for Stem Cell Transplantation, Hamburg (Germany)

    2012-03-15

    The aim of the study was to determine the diagnostic performance of {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT for the detection and localization of residual or recurrent disease in patients with multiple myeloma (MM) after stem cell transplantation. A total of 197 whole-body {sup 18}F-FDG PET/CT scans were performed in 99 patients with MM at different time points in the course of disease after autologous or allogeneic stem cell transplantation. Post-transplant PET/CT scans and clinical remission status as determined by the clinical gold standard (Uniform Response Criteria) were analysed and compared. A total of 576 focal osseous and extramedullary lesions were detected in 79 scans. Additional diffuse bone marrow involvement was detected in 17 patients. {sup 18}F-FDG PET/CT had a sensitivity of 54.6%, a specificity of 82.1%, a positive predictive value of 82.3%, a negative predictive value of 54.2% and an overall accuracy of 65.5%. The sensitivity of {sup 18}F-FDG PET/CT was shown to depend on the disease category according to the Uniform Response Criteria for myeloma. In patients with MM in the post-transplant setting, {sup 18}F-FDG PET/CT may (1) contribute to the detection and localization of disease, (2) provide information about the extent of distinct myeloma manifestations and the total disease burden and (3) add information about the metabolic activity of disease, but (4) has substantially lower sensitivity for this purpose compared to the pretreatment setting. (orig.)

  19. 40 CFR 35.6285 - Recipient payment of response costs.

    Science.gov (United States)

    2010-07-01

    ... ASSISTANCE STATE AND LOCAL ASSISTANCE Cooperative Agreements and Superfund State Contracts for Superfund Response Actions Financial Administration Requirements Under A Cooperative Agreement § 35.6285 Recipient... cost share requirements under Cooperative Agreements. The recipient must comply with the requirements...

  20. Residual oil fly ash induces cytotoxicity and mucin secretion by guinea pig tracheal epithelial cells via an oxidant-mediated mechanism.

    Science.gov (United States)

    Jiang, N; Dreher, K L; Dye, J A; Li, Y; Richards, J H; Martin, L D; Adler, K B

    2000-03-15

    Inhalation of ambient air particulate matter (PM) is associated with pulmonary injury and inflammation. Using primary cultures of guinea pig tracheal epithelial (GPTE) cells as an in vitro model of airway epithelium, we examined effects of exposure to suspensions of six different emission and ambient air PM samples: residual oil fly ash (ROFA) from an electrical power plant; fly ash from a domestic oil burning furnace (DOFA); ambient air dust from St. Louis (STL), Ottawa (OT), and Washington, DC (WDC); and volcanic ash from the eruption of Mount Saint Helens (MSH) in 1980. Effects of these particulates on cell viability (assessed via LDH assay), secretion of mucin (measured by a monoclonal antibody-based ELISA), and steady-state mRNA levels of the mucin gene MUC2 were determined. ROFA was the most toxic of the dusts tested, as it significantly increased LDH release following a 24-h incubation with 50 microg/cm(2) ROFA. ROFA also enhanced MUC2 mRNA after 4-h exposure, and mucin secretion after 8 h. ROFA-induced mucin secretion and cytotoxicity were attenuated by the oxidant scavenger, dimethylthiourea (DMTU). ROFA exposure also depleted cells of glutathione (GSH). Relatedly, depletion of intracellular GSH by treatment of the cells with buthionine sulfoxamine (BSO) also provoked mucin secretion, as well as enhancing the secretory effect of ROFA when the two agents were added together. L-NMA, the nitric oxide synthase (NOS) inhibitor, did not affect ROFA-induced mucin secretion. Of the soluble transition metals in ROFA (nickel, iron, vanadium), only vanadium individually, or combinations of the metals containing vanadium, provoked secretion. The results suggest ROFA enhances mucin secretion and generates toxicity in vitro to airway epithelium via a mechanism(s) involving generation of oxidant stress, perhaps related to depletion of cellular antioxidant capacity. Deleterious effects of inhalation of ROFA in the respiratory tract in vivo may relate to these cellular

  1. Diabetes mellitus in the BB/W rat. Insulitis in pancreatic islet grafts after transplantation in diabetic recipients.

    OpenAIRE

    Weringer, E. J.; Like, A. A.

    1986-01-01

    Spontaneous diabetes mellitus in the BioBreeding/Worcester (BB/W) rat is preceded by lymphocytic insulitis which destroys pancreatic beta cells. Cultured major histocompatibility complex identical pancreatic islets and adrenal cortex derived from diabetes-resistant BB/W donors were transplanted into diabetic recipients with hyperglycemia of variable duration. Islet grafts were the targets of BB/W immune attack and revealed lymphocytic insulitis after transplantation into diabetic recipients e...

  2. Transmission of Angiosarcomas From a Common Multiorgan Donor to Four Transplant Recipients

    DEFF Research Database (Denmark)

    Thoning, J; Liu, Ying; Bistrup, C

    2013-01-01

    We describe the donor tumor transmission of metastatic angiosarcomas to four transplant recipients through transplantation of deceased-donor organs, i.e. kidneys, lung and liver, from an apparently unaffected common female multiorgan donor. Fluorescent in situ hybridization of angiosarcoma cells...

  3. Recurrence of sarcoid granulomas in lung transplant recipients is common and does not affect overall survival

    DEFF Research Database (Denmark)

    Schultz, Hans Henrik Lawaetz; Andersen, Claus Bøgelund; Steinbrüchel, D

    2014-01-01

    Background: Sarcoidosis represents 2,5% of all indications for lung transplantation and criteria are generally assumed to be the same as for pulmonary fibrosis. Recurrence of granulomas in transplanted lungs has earlier been proved to derive from recipient immune cells, but its role in relation t...

  4. Successful treatment of verruca vulgaris with Thuja occidentalis in a renal allograft recipient

    Directory of Open Access Journals (Sweden)

    R Joseph

    2013-01-01

    Full Text Available Human papillomavirus-driven verruca vulgaris infection is common in solid organ transplant recipients and increases the risk for squamous cell carcinoma. The available treatment modalities have limited response. We report a renal allograft recipient who presented with multiple warts not responding to cryotherapy and radiosurgery with one turning malignant, needing amputation of the finger. An extract from Thuja occidentalis (White cedar tree cured the resistant warts on the other fingers, leaving only superficial scars and without affecting allograft function. We have reviewed the pharmacological and clinical properties of T. occidentalis.

  5. Primary prevention of skin dysplasia in renal transplant recipients with photodynamic therapy

    DEFF Research Database (Denmark)

    Togsverd-Bo, K; Omland, S H; Wulf, H C

    2015-01-01

    Organ transplant recipients (OTRs) are at high risk of developing cutaneous squamous cell carcinoma (SCC); prevention includes early treatment of premalignant actinic keratosis (AK). Photodynamic therapy (PDT) is a noninvasive field therapy that reduces new AKs in patients with existing AK...... and delays SCC development in mice. We investigated the effect of repeated PDT over 5 years for primary prophylaxis of skin dysplasia. These data represent an interim analysis of an on-going randomized controlled trial. During 2008-2011, 25 renal transplant recipients with clinically normal skin were...

  6. Adenovirus disease in six small bowel, kidney and heart transplant recipients; pathology and clinical outcome.

    Science.gov (United States)

    Mehta, Vikas; Chou, Pauline C; Picken, Maria M

    2015-11-01

    Adenoviruses are emerging as important viral pathogens in hematopoietic stem cell and solid organ transplant recipients, impacting morbidity, graft survival, and even mortality. The risk seems to be highest in allogeneic hematopoietic stem cell transplant recipients as well as heart, lung, and small bowel transplant recipients. Most of the adenovirus diseases develop in the first 6 months after transplantation, particularly in pediatric patients. Among abdominal organ recipients, small bowel grafts are most frequently affected, presumably due to the presence of a virus reservoir in the mucosa-associated lymphoid tissue. Management of these infections may be difficult and includes the reduction of immunosuppression, whenever possible, combined with antiviral therapy, if necessary. Therefore, an awareness of the pathology associated with such infections is important in order to allow early detection and specific treatment. We reviewed six transplant recipients (small bowel, kidney, and heart) with adenovirus graft involvement from two institutions. We sought to compare the diagnostic morphology and the clinical and laboratory findings. The histopathologic features of an adenovirus infection of the renal graft and one native kidney in a heart transplant recipient included a vaguely granulomatous mixed inflammatory infiltrate associated with rare cells showing a cytopathic effect (smudgy nuclei). A lymphocytic infiltrate, simulating T cell rejection, with admixture of eosinophils was also seen. In the small bowel grafts, there was a focal mixed inflammatory infiltrate with associated necrosis in addition to cytopathic effects. In the heart, allograft adenovirus infection was silent with no evidence of inflammatory changes. Immunohistochemical stain for adenovirus was positive in all grafts and in one native kidney. All patients were subsequently cleared of adenovirus infection, as evidenced by follow-up biopsies, with no loss of the grafts. Adenovirus infection can

  7. 45 CFR 1612.11 - Recipient policies and procedures.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies and procedures. 1612.11 Section... RESTRICTIONS ON LOBBYING AND CERTAIN OTHER ACTIVITIES § 1612.11 Recipient policies and procedures. Each recipient shall adopt written policies and procedures to guide its staff in complying with this part. ...

  8. 45 CFR 1636.5 - Recipient policies, procedures and recordkeeping.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies, procedures and recordkeeping... CORPORATION CLIENT IDENTITY AND STATEMENT OF FACTS § 1636.5 Recipient policies, procedures and recordkeeping. Each recipient shall adopt written policies and procedures to guide its staff in complying with this...

  9. 45 CFR 1609.6 - Recipient policies, procedures and recordkeeping.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies, procedures and recordkeeping... CORPORATION FEE-GENERATING CASES § 1609.6 Recipient policies, procedures and recordkeeping. Each recipient shall adopt written policies and procedures to guide its staff in complying with this part and shall...

  10. 45 CFR 1637.5 - Recipient policies, procedures and recordkeeping.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies, procedures and recordkeeping... CORPORATION REPRESENTATION OF PRISONERS § 1637.5 Recipient policies, procedures and recordkeeping. Each recipient shall adopt written policies and procedures to guide its staff in complying with this part and...

  11. 45 CFR 1639.6 - Recipient policies and procedures.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies and procedures. 1639.6 Section... WELFARE REFORM § 1639.6 Recipient policies and procedures. Each recipient shall adopt written policies and procedures to guide its staff in complying with this part. ...

  12. 45 CFR 1627.8 - Recipient policies, procedures and recordkeeping.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies, procedures and recordkeeping... CORPORATION SUBGRANTS AND MEMBERSHIP FEES OR DUES § 1627.8 Recipient policies, procedures and recordkeeping. Each recipient shall adopt written policies and procedures to guide its staff in complying with this...

  13. 45 CFR 1633.4 - Recipient policies, procedures and recordkeeping.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies, procedures and recordkeeping... CORPORATION RESTRICTION ON REPRESENTATION IN CERTAIN EVICTION PROCEEDINGS § 1633.4 Recipient policies, procedures and recordkeeping. Each recipient shall adopt written policies and procedures to guide its staff...

  14. 45 CFR 1644.5 - Recipient policies and procedures.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies and procedures. 1644.5 Section... DISCLOSURE OF CASE INFORMATION § 1644.5 Recipient policies and procedures. Each recipient shall adopt written policies and procedures to implement the requirements of this part. ...

  15. 45 CFR 1626.12 - Recipient policies, procedures and recordkeeping.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies, procedures and recordkeeping... SERVICES CORPORATION RESTRICTIONS ON LEGAL ASSISTANCE TO ALIENS § 1626.12 Recipient policies, procedures and recordkeeping. Each recipient shall adopt written policies and procedures to guide its staff in...

  16. 45 CFR 1617.4 - Recipient policies and procedures.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies and procedures. 1617.4 Section... CLASS ACTIONS § 1617.4 Recipient policies and procedures. Each recipient shall adopt written policies and procedures to guide its staff in complying with this part. ...

  17. 14 CFR 1274.933 - Summary of recipient reporting responsibilities.

    Science.gov (United States)

    2010-01-01

    ....913 Patent Rights—Retention by the Recipient (Small Business)(Paragraph (h)) Notice of Proposed... Reportable Items Every 12 months 1274.912 Patent Rights—Retention by the Recipient (Large Business)(Paragraph...—Retention by the Recipient (Large Business) (Paragraph (e)(3)(ii)) Disclosure of Subject Inventions Within 2...

  18. 45 CFR 1603.10 - Multi-state recipients.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Multi-state recipients. 1603.10 Section 1603.10 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION STATE ADVISORY COUNCILS § 1603.10 Multi-state recipients. Where a recipient has offices in more than one State...

  19. Glucose tolerance, insulin release, and insulin binding to monocytes in kidney transplant recipients

    International Nuclear Information System (INIS)

    Briggs, W.A.; Wielechowski, K.S.; Mahajan, S.K.; Migdal, S.D.; McDonald, F.D.

    1982-01-01

    In order to evaluate glucose tolerance following renal transplantation, intravenous glucose tolerance tests (IVGTT), with evaluation of hormonal responses to the intravenous glucose load and percent specific 125 I-insulin binding to peripheral blood monocytes, were studied in eight clinically stable kidney transplant recipients. For comparison purposes, identical studies were done in eight control subjects and seven clinically stable hemodialysis patients. One transplant recipient was glucose intolerant, with fasting hyperglycemia, elevated HbA1C, and abnormal glucose decay constant. Impaired pancreatic insulin release appeared to be the major factor accounting for his glucose intolerance. The seven glucose-tolerant transplant recipients had significantly increased insulin release during IVGTT compared to control subjects, and significant correlations were found among insulin release, glucose decay constant, and fasting blood sugar in those patients. Insulin binding to monocytes was significantly greater in transplant recipients than control subjects due to an increase in insulin binding capacity per cell. A significant correlation was found between percent specific 125 I-insulin binding and steroid dose, expressed as mg/kg body weight/day, in those patients. Thus, chronic steroid administration does not cause glucose intolerance in transplant recipients who manifest steroid-associated increases in pancreatic insulin release and cellular insulin binding capacity

  20. Management of leukopenia in kidney and pancreas transplant recipients.

    Science.gov (United States)

    Hartmann, Erica L; Gatesman, Mandy; Roskopf-Somerville, Julie; Stratta, Robert; Farney, Alan; Sundberg, Aimee

    2008-01-01

    Leukopenia is frequently observed in the setting of solid organ transplantation. The risk factors, natural history, and outcomes associated with leukopenia post-transplantation have not been well defined. We retrospectively studied 102 adult kidney and/or pancreas transplant recipients over a one-yr period of time. By defining leukopenia as a white blood cell count leukopenia or neutropenia was 58% (59/102); the first episode occurred at a mean of 91 d post-transplant. A significant increase in the incidence of leukopenia was found in patients who either received alemtuzumab induction (42% with alemtuzumab vs. 9% with rabbit anti-thymocyte globulin induction, p leukopenia was reducing the dose of mycophenolate mofetil and/or valganciclovir. When granulocyte stimulating factors were used, a mean of 3.1 doses were needed to successfully manage the leukopenia. Although leukopenia was a common finding in our study of kidney and/or pancreas transplant recipients, there was no difference in the rates of infection or acute rejection in patients with and without leukopenia.

  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. Strongyloides stercoralis infection in kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Baha A Abdalhamid

    2015-01-01

    Full Text Available 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.

  3. Laparoscopic cholecystectomy in a cardiac transplant recipient.

    Science.gov (United States)

    Pandya, Seema R; Paranjape, Saloni

    2014-04-01

    An increasing number of cardiac transplants are being carried out around the world. With increasing longevity, these patients present a unique challenge to non-transplant anesthesiologists for a variety of transplant related or incidental surgeries. The general considerations related to a cardiac transplant recipient are the physiological and pharmacological problems of allograft denervation, the side-effects of immunosuppression, the risk of infection and the potential for rejection. A thorough understanding of the physiology of a denervated heart, need for direct vasoactive agents and post-transplant morbidities is essential in anesthetic management of such a patient. Here, we describe a case of a heart transplant recipient who presented for a cholecystectomy at our center.

  4. Minimal residual disease (MRD detection with translocations and T-cell receptor and immunoglobulin gene rearrangements in adult acute lymphoblastic leukemia patients: a pilot study

    Directory of Open Access Journals (Sweden)

    Muge Sayitoglu

    2008-09-01

    Full Text Available Objective: Monitoring minimal residual disease has become increasingly important in clinical practice of ALL management. Break-point fusion regions of leukaemia related chromosomal aberrations and rearranged immunoglobulin (Ig and T cell-receptor (TCR genes are used as leukaemia specific markers in genetic studies of MRD.Material and Methods: A total of 31 consecutive patients with newly diagnosed ALL were screened for eligibility criteria. Of those 26 were included in the study. One patient with partial response following induction therapy and four patients who were lost to follow-up after induction were excluded from the study; thus 21 patients were evaluated for MRD by using polymerase chain reaction (PCR, heteroduplex analysis, sequencing and quantitative real time PCR techniques. Results: Chromosomal aberrations were detected in 5 (24% of the patients and were used for MRD monitoring. Three patients had t(9;22 translocation, the other 2 had t(4;11 and t(1;19. MRD-based risk stratification of the16 patients analysed for Ig/TCR rearrangements revealed 3 low-risk, 11 intermediate-risk and 2 high-risk patients.Conclusion: MRD monitoring is progressively getting to be a more important predictive factor in adult ALL patients. As reported by others confirmed by our limited data there is a good correlation between MRD status and clinical outcome in patients receiving chemotherapy. The pilot-study presented here is the first that systematically and consecutively performs a molecular MRD monitoring of ALL patients in Turkey.

  5. History of consolidation is prognostic in acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplantation in minimal residual disease-negative first complete remission.

    Science.gov (United States)

    Rashidi, Armin; Linden, Michael A; DeFor, Todd E; Warlick, Erica; Bejanyan, Nelli; Yohe, Sophia; Weisdorf, Daniel J; Ustun, Celalettin

    2017-10-01

    Prognostic factors among acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) in minimal residual disease (MRD)-negative first complete remission (CR1) are unknown. We retrospectively attempted to answer the following question: In AML patients undergoing allo-HCT in MRD-negative CR1, does a history of prior consolidation provide additional prognostic information? The inclusion criteria were: (i) Age > 18 years, (ii) AML in CR1 after 1-2 cycles of intensive induction chemotherapy, with or without consolidation, (iii) Allo-HCT between 1/2003 and 4/2016 at our institution, (iv) Available standard-sensitivity 4-color flow cytometry results from a bone marrow aspiration at diagnosis and after completion of all previous chemotherapy within one month prior to HCT, (v) Flow cytometry-based MRD-negative status at the time of HCT. A history of prior consolidation was associated with favorable overall survival (Hazard Ratio [95% Confidence Interval]: 0.59 [0.35-0.99], P = .046), relapse-free survival (0.60 [0.37-0.96], P = .036), and relapse (0.50 [0.27-0.92], P = .025). Analysis of potential sources of bias was unrevealing. In AML patients undergoing allo-HCT in MRD-negative CR1, a history of prior consolidation was associated with favorable outcomes. If the path to pre-HCT MRD negativity includes consolidation, it may identify patients with improved prognosis following HCT in MRD-negative state. These results warrant validation in larger cohorts. © 2017 Wiley Periodicals, Inc.

  6. [Urinary lithiasis in renal transplant recipient].

    Science.gov (United States)

    Branchereau, J; Thuret, R; Kleinclauss, F; Timsit, M-O

    2016-11-01

    To report epidemiology and characteristics of urinary lithiasis and its management in kidney allograft at the time of organ procurement or after kidney transplantation. An exhaustive systematic review of the scientific literature was performed in the Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of the following keywords (MESH): urinary lithiasis, stone, kidney transplantation. Publications obtained were selected based on methodology, language, date of publication (last 10 years) and relevance. Prospective and retrospective studies, in English or French, review articles; meta-analysis and guidelines were selected and analyzed. This search found 58 articles. After reading, 37 were included in the text based on their relevance. Frequency of urinary lithiasis in renal transplant recipient is similar to those observed in the general population. Generally, urinary lithiasis of the graft is asymptomatic because of renal denervation after organ procurement and transplantation. Nevertheless, this situation may be at high risk due to the immunosuppressed state of the recipient with a unique functioning kidney. Most of the time, the diagnosis is incidental during routine post-transplantation follow-up. Management of urolithiasis in renal transplant recipient is similar to that performed in general population. Due to its potential severity in transplanted immunosuppressed patients with a sole kidney, urolithiasis requires expert urological management. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Head and Neck Malignancies in Croatian Renal Transplant Recipients

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    Nikolina Bašić-Jukić

    2010-04-01

    Full Text Available 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. A total of 1232 renal transplant recipients have been followed at Department of Dialysis University Hospital Centre Zagreb from 1972 to 2009. Demographic data, localization and disease outcome were evaluated in patients who developed cancer. Twenty one patients (1,7% developed 27 head and neck malignancies. The average time from transplantation to development of cancer was 56,8 months. The mean length of follow-up was 9,4±4,8 years. Eighteen malignancies were cutaneous in origin and 9 were noncutaneous. Of cutaneous malignancies, 88.9% were basal cell carcinoma; one patient had Merkell-cell carcinoma and one patient developed squamous cell carcinoma. Six cases of basocellular skin cancer were recorded in one fair-skin patient. Noncutaneous malignancies involved the oral cavity (2 cases of Kaposi’s sarcoma and one pharyngeal cancer and the thyroid gland in 3 patients each. Two patients had post-transplant lymphoproliferative disorder occurring at the head and neck. One patient had brain tumor. Radical surgery, radiation, and/or chemotherapy were necessary in 33,3% of patients. Immunosuppression was reduced in all patients, and 12 patients were switched from the calcineurin-based immunosuppression to sirolimus. They all have stable graft function. None of the patients died from cancer. Immunosuppression was ceased in one patient with Kaposi’s sarcoma who returned to dialysis and died 10 years later from heart failure. An increased incidence of cancer occurring in the head and neck was recorded. Careful skin examination and oral examination is mandatory for discovering cancer before dissemination. Sirolimus is safe alternative to calcineurin-based immunosuppression in patients who developed head and neck

  8. Polyclonal Recipient nTregs Are Superior to Donor or Third-Party Tregs in the Induction of Transplantation Tolerance

    Directory of Open Access Journals (Sweden)

    Nina Pilat

    2015-01-01

    Full Text Available Induction of donor-specific tolerance is still considered as the “Holy Grail” in transplantation medicine. The mixed chimerism approach is virtually the only tolerance approach that was successfully translated into the clinical setting. We have previously reported successful induction of chimerism and tolerance using cell therapy with recipient T regulatory cells (Tregs to avoid cytotoxic recipient treatment. Treg therapy is limited by the availability of cells as large-scale expansion is time-consuming and associated with the risk of contamination with effector cells. Using a costimulation-blockade based bone marrow (BM transplantation (BMT model with Treg therapy instead of cytoreductive recipient treatment we aimed to determine the most potent Treg population for clinical translation. Here we show that CD4+CD25+ in vitro activated nTregs are superior to TGFβ induced iTregs in promoting the induction of chimerism and tolerance. Therapy with nTregs (but not iTregs led to multilineage chimerism and donor-specific tolerance in mice receiving as few as 0.5 × 106 cells. Moreover, we show that only recipient Tregs, but not donor or third-party Tregs, had a beneficial effect on BM engraftment at the tested doses. Thus, recipient-type nTregs significantly improve chimerism and tolerance and might be the most potent Treg population for translation into the clinical setting.

  9. Immunological Basis for Rapid Progression of Diabetes in Older NOD Mouse Recipients Post BM-HSC Transplantation.

    Directory of Open Access Journals (Sweden)

    Nan Wang

    Full Text Available Type I diabetes (T1D, mediated by autoreactive T cell destruction of insulin-producing islet beta cells, has been treated with bone marrow-derived hematopoietic stem cell (BM-HSC transplantation. Older non-obese diabetic (NOD mice recipients (3m, at disease-onset stage receiving syngeneic BM-HSC progressed more rapidly to end-stage diabetes post-transplantation than younger recipients (4-6w, at disease-initiation stage. FACS analyses showed a higher percentage and absolute number of regulatory T cells (Treg and lower proportion of proliferating T conventional cells (Tcon in pancreatic lymph nodes from the resistant mice among the younger recipients compared to the rapid progressors among the older recipients. Treg distribution in spleen, mesenteric lymph nodes (MLN, blood and thymus between the two groups was similar. However, the percentage of thymic Tcon and the proliferation of Tcon in MLN and blood were lower in the young resistants. These results suggest recipient age and associated disease stage as a variable to consider in BM-HSC transplantation for treating T1D.

  10. Analysis of the distribution of charged residues in the N-terminal region of signal sequences: implications for protein export in prokaryotic and eukaryotic cells.

    OpenAIRE

    von Heijne, G

    1984-01-01

    A statistical analysis of the distribution of charged residues in the N-terminal region of 39 prokaryotic and 134 eukaryotic signal sequences reveals a remarkable similarity between the two samples, both in terms of net charge and in terms of the position of charged residues within the N-terminal region, and suggests that the formyl group on Metf is not removed in prokaryotic signal sequences.

  11. Multinational study in children and adolescents with newly diagnosed type 1 diabetes: association of age, ketoacidosis, HLA status, and autoantibodies on residual beta-cell function and glycemic control 12 months after diagnosis

    DEFF Research Database (Denmark)

    Mortensen, H.B.; Swift, P.G.F.; Holl, R.W.

    2010-01-01

    .005), and by stimulated C-peptide (p IA; p = 0.02) and glutamic acid decarboxylase antibodies (GADA; p = 0.0004) at 1 month. HbA1c at 12 months was predicted by HbA1c at diagnosis (p ... (p = 0.002). Conclusions: Younger age, ketoacidosis at diagnosis, and IA and GADA 1 month after diagnosis were the strongest explanatory factors for residual beta-cell function at 12 months. Glycemic control at 12 months was influenced predominantly by ethnicity, HbA1c at diagnosis, and GADA at 1......Objective: To identify predictors of residual beta-cell function and glycemic control during the first 12 months after the diagnosis of type 1 diabetes (T1D). Subjects and Methods: Clinical information and blood samples were collected from 275 children. HbA1c, antibodies, HLA typing and mixed meal...

  12. p.X654R IDUA variant among Thai individuals with intermediate mucopolysaccharidosis type I and its residual activity as demonstrated in COS-7 cells.

    Science.gov (United States)

    Ngiwsara, Lukana; Ketudat-Cairns, James R; Sawangareetrakul, Phannee; Charoenwattanasatien, Ratana; Champattanachai, Voraratt; Kuptanon, Chulaluck; Pangkanon, Suthipong; Tim-Aroon, Thipwimol; Wattanasirichaigoon, Duangrurdee; Svasti, Jisnuson

    2017-12-28

    Mucopolysaccharidosis type I (MPS I) is a rare autosomal-recessive disorder caused by defects in alpha-L-iduronidase (IDUA), a lysosomal enzyme encoded by the IDUA gene. Herein, we characterized IDUA mutations underlying mucopolysaccharidosis type I intermediate form (Hurler-Scheie syndrome) and its molecular pathogenic mechanisms. Clinical data, activity of the IDUA enzyme in leukocytes, and a mutation of the IDUA gene were analyzed. Pathogenesis associated with an IDUA mutation was further investigated by evaluating the mutant cDNA sequence, protein expression and activity in COS-7 cells. Five unrelated patients were identified to have clinical diagnosis of intermediate form of MPS I (Hurler-Scheie) and exhibited low-to-absent levels of leukocyte IDUA activity. Genetic analysis revealed homozygous c.*1T>C (p.X654R) mutation in two patients and compound heterozygosity between the c.*1T>C and another allele including c.265G>A (p.R89Q), c.935G>A (p.W312X), or c.1138 C>T (p.Q380X), each in a single patient. Sequencing the 3'RACE product of the c.*1T>C (p.X654R) allele indicated a 38-amino acids elongation of the mutant protein. COS-7 cells expressing IDUA with the mutations exhibited extremely low levels or complete absence of enzyme activity compared to wild-type IDUA. Western blot analysis detected no protein in p.W312X and p.Q380X samples, while an elevated molecular mass and a different pattern of protein bands were found in p.X654R specimen compared with the wild type IDUA. Mutational spectrum underlying intermediate MPS I is expanded. Our data suggest that the p.X654R is an intermediate IDUA mutant allele with residual enzyme activity. It can lead to intermediate or milder form of MPS I depending on another associated allele. © 2017 John Wiley & Sons Ltd/University College London.

  13. Detection of antibiotic residues in poultry meat.

    Science.gov (United States)

    Sajid, Abdul; Kashif, Natasha; Kifayat, Nasira; Ahmad, Shabeer

    2016-09-01

    The antibiotic residues in poultry meat can pose certain hazards to human health among them are sensitivity to antibiotics, allergic reactions, mutation in cells, imbalance of intestinal micro biota and bacterial resistance to antibiotics. The purpose of the present paper was to detect antibiotic residue in poultry meat. During the present study a total of 80 poultry kidney and liver samples were collected and tested for detection of different antibiotic residues at different pH levels Eschericha coli at pH 6, 7 and Staphyloccocus aureus at pH 8 & 9. Out of 80 samples only 4 samples were positive for antibiotic residues. The highest concentrations of antibiotic residue found in these tissues were tetracycline (8%) followed by ampicilin (4%), streptomycine (2%) and aminoglycosides (1%) as compared to other antibiotics like sulfonamides, neomycine and gentamycine. It was concluded that these microorganism at these pH levels could be effectively used for detection of antibiotic residues in poultry meat.

  14. Decreased donor-specific cytotoxic T cell precursor frequencies one year after clinical lung transplantation do not reflect transplantation tolerance : A comparison of lung transplant recipients with or without bronchiolitis obliterans syndrome

    NARCIS (Netherlands)

    de Haan, A; van der Gun, [No Value; Hepkema, BG; van der Bij, W; de Leij, LFMH; Prop, J

    2000-01-01

    Background. Decreased in vitro T cell alloreactivity, demonstrated by decreased frequencies of peripheral blood donor-specific T cell precursors, may reflect a tolerant state after transplantation and lower the risk for development of chronic graft dysfunction. It is unknown whether a decrease in

  15. The long and the short of telomeres in bone marrow recipient SCID patients.

    Science.gov (United States)

    Sarzotti-Kelsoe, Marcella; Daniell, Xiaoju G; Whitesides, John F; Buckley, Rebecca H

    2011-04-01

    Telomeres are noncoding DNA regions at the end of the chromosomes that are crucial for genome stability. Since telomere length decreases with cell division, they can be used as a signature of cell proliferation history. T-cell reconstitution in severe combined immunodeficiency (SCID) subjects, recipients of T-cell-depleted, allogeneic-related bone marrow cells, is due to the development and maturation of donor T-cell precursors in the infant's vestigial thymus and to homeostatic proliferation of mature T cells in the peripheral organs. Since T-cell function, thymic output, and T-cell clonal diversity are maintained long term in these patients, we investigated whether donor T-cell engraftment resulted in increased telomere shortening. Our study of seven SCID patients, following successful bone marrow transplantation, demonstrates that the patients' peripheral T cells did not exhibit greater than normal telomere shortening.

  16. 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.

  17. State prison mental heath services recipients perception of care survey.

    Science.gov (United States)

    Way, Bruce B; Sawyer, Don A; Kahkejian, Deborah; Moffitt, Catherine; Lilly, Stephanie N

    2007-12-01

    Studies have demonstrated the importance of patient perceptions' of mental health service quality. No studies, however, could be found that surveyed recipients in prison, despite the rapid growth of patients, and litigation in these settings. Patients were asked to complete an anonymous survey in private, and sealed it in an envelope. Of 613 respondents, most were satisfied (79%), agreed they had sufficient access to therapists (78%), were involved with treatment decisions (84%), and thought the MH services they had received would help them better deal with a crisis and emotional stress (75%). There were differences among mental health programs/housing units. Several of perception questions were significantly correlated with medication compliance, admission to crisis observation cells, and receiving disciplinary infractions. Random samples were requested, but likely only a convenience sample was obtained. However, the positive results suggest the need to strive to enhance patient quality of care ratings.

  18. Reduction and repopulation of recipient T4+ and T8+ T-lymphocytes in allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Gratama, J.W.; van den Bergh, R.L.; Naipal, A.; D'Amaro, J.; Zwaan, F.E.; Jansen, J.; de Gast, G.C.

    1986-01-01

    In eight recipients of allogeneic bone marrow grafts who had sex-mismatched donors, the reduction and subsequent repopulation of T4+ and T8+ T-lymphocytes of recipient origin were studied. The origin of the donor-recipient T4+ and T8+ T cells was studied using quinacrine staining of Y chromatin combined with T-cell typing for T4 and T8. Following chemoradiotherapy and bone marrow transplantation (BMT), T cells reached their nadir at a median of five (range 1-8) days after BMT. T8+ T cells decreased at a faster rate from the peripheral blood than T4+ T cells. The first T cells that appeared in the circulation at day 12 were predominantly T4+, and a large number of them were of recipient origin. Thereafter, they gradually decreased, and the numbers of T cells of donor origin increased. In the patients who had no or only minor complications, T4+ and T8+ T cells of donor origin repopulated the blood at similar rates. This pattern, however, was modified by severe graft-versus-host disease or by cytomegalovirus infection

  19. Eosinophil count, allergies, and rejection in pediatric heart transplant recipients.

    Science.gov (United States)

    Arbon, Kate S; Albers, Erin; Kemna, Mariska; Law, Sabrina; Law, Yuk

    2015-08-01

    Allograft rejection and long-term immunosuppression remain significant challenges in pediatric heart transplantation. Pediatric recipients are known to have fewer rejection episodes and to develop more allergic conditions than adults. A T-helper 2 cell dominant phenotype, manifested clinically by allergies and an elevated eosinophil count, may be associated with immunologic quiescence in transplant recipients. This study assessed whether the longitudinal eosinophil count and an allergic phenotype were associated with freedom from rejection. This single-center, longitudinal, observational study included 86 heart transplant patients monitored from 1994 to 2011. Post-transplant biannual complete blood counts, allergic conditions, and clinical characteristics related to rejection risk were examined. At least 1 episode of acute cellular rejection (ACR) occurred in 38 patients (44%), antibody-mediated rejection (AMR) occurred in 11 (13%), and 49 patients (57%) were diagnosed with an allergic condition. Patients with ACR or AMR had a lower eosinophil count compared with non-rejectors (p = 0.011 and p = 0.022, respectively). In the multivariable regression analysis, the presence of panel reactive antibodies to human leukocyte antigen I (p = 0.014) and the median eosinophil count (p = 0.011) were the only independent covariates associated with AMR. Eosinophil count (p = 0.010) and female sex (p = 0.009) were independent risk factors for ACR. Allergic conditions or young age at transplant were not protective from rejection. This study demonstrates a novel association between a high eosinophil count and freedom from rejection. Identifying a biomarker for low rejection risk may allow a reduction in immunosuppression. Further investigation into the role of the T-helper 2 cell phenotype and eosinophils in rejection quiescence is warranted. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  20. Behçet disease-associated MHC class I residues implicate antigen binding and regulation of cell-mediated cytotoxicity.

    Science.gov (United States)

    Ombrello, Michael J; Kirino, Yohei; de Bakker, Paul I W; Gül, Ahmet; Kastner, Daniel L; Remmers, Elaine F

    2014-06-17

    The HLA protein, HLA-B*51, encoded by HLA-B in MHC, is the strongest known genetic risk factor for Behçet disease (BD). Associations between BD and other factors within the MHC have been reported also, although strong regional linkage disequilibrium complicates their confident disentanglement from HLA-B*51. In the current study, we examined a combination of directly obtained and imputed MHC-region SNPs, directly obtained HLA-B locus types, and imputed classical HLA types with their corresponding polymorphic amino acid residues for association with BD in 1,190 cases and 1,257 controls. SNP mapping with logistic regression of the MHC identified the HLA-B/MICA region and the region between HLA-F and HLA-A as independently associated with BD (P MHC class I (MHC-I) amino acid residues, including anchor residues that critically define the selection and binding of peptides to MHC-I molecules, residues known to influence MHC-I-killer immunoglobulin-like receptor interactions, and a residue located in the signal peptide of HLA-B. The locations of these variants collectively implicate MHC-I peptide binding in the pathophysiology of BD. Furthermore, several lines of evidence suggest a role for altered regulation of cellular cytotoxicity in BD pathogenesis.

  1. Tracing HIV-1 transmission: envelope traits of HIV-1 transmitter and recipient pairs.

    Science.gov (United States)

    Oberle, Corinna S; Joos, Beda; Rusert, Peter; Campbell, Nottania K; Beauparlant, David; Kuster, Herbert; Weber, Jacqueline; Schenkel, Corinne D; Scherrer, Alexandra U; Magnus, Carsten; Kouyos, Roger; Rieder, Philip; Niederöst, Barbara; Braun, Dominique L; Pavlovic, Jovan; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Aubert, Vincent; Trkola, Alexandra; Metzner, Karin J; Günthard, Huldrych F

    2016-09-05

    Mucosal HIV-1 transmission predominantly results in a single transmitted/founder (T/F) virus establishing infection in the new host despite the generally high genetic diversity of the transmitter virus population. To what extent HIV-1 transmission is a stochastic process or driven by selective forces that allow T/F viruses best to overcome bottlenecks in transmission has not been conclusively resolved. Building on prior investigations that suggest HIV-1 envelope (Env) features to contribute in the selection process during transmission, we compared phenotypic virus characteristics of nine HIV-1 subtype B transmission pairs, six men who have sex with men and three male-to-female transmission pairs. All recipients were identified early in acute infection and harbored based on extensive sequencing analysis a single T/F virus allowing a controlled analysis of virus properties in matched transmission pairs. Recipient and transmitter viruses from the closest time point to transmission showed no signs of selection for specific Env modifications such as variable loop length and glycosylation. Recipient viruses were resistant to circulating plasma antibodies of the transmitter and also showed no altered sensitivity to a large panel of entry inhibitors and neutralizing antibodies. The recipient virus did not consistently differ from the transmitter virus in terms of entry kinetics, cell-cell transmission and replicative capacity in primary cells. Our paired analysis revealed a higher sensitivity of several recipient virus isolates to interferon-α (IFNα) which suggests that resistance to IFNα cannot be a general driving force in T/F establishment. With the exception of increased IFNα sensitivity, none of the phenotypic virus properties we investigated clearly distinguished T/F viruses from their matched transmitter viruses supporting the notion that at least in subtype B infection HIV-1 transmission is to a considerable extent stochastic.

  2. IKZF1plusDefines a New Minimal Residual Disease-Dependent Very-Poor Prognostic Profile in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Stanulla, Martin; Dagdan, Elif; Zaliova, Marketa; Möricke, Anja; Palmi, Chiara; Cazzaniga, Giovanni; Eckert, Cornelia; Te Kronnie, Geertruy; Bourquin, Jean-Pierre; Bornhauser, Beat; Koehler, Rolf; Bartram, Claus R; Ludwig, Wolf-Dieter; Bleckmann, Kirsten; Groeneveld-Krentz, Stefanie; Schewe, Denis; Junk, Stefanie V; Hinze, Laura; Klein, Norman; Kratz, Christian P; Biondi, Andrea; Borkhardt, Arndt; Kulozik, Andreas; Muckenthaler, Martina U; Basso, Giuseppe; Valsecchi, Maria Grazia; Izraeli, Shai; Petersen, Britt-Sabina; Franke, Andre; Dörge, Petra; Steinemann, Doris; Haas, Oskar A; Panzer-Grümayer, Renate; Cavé, Hélène; Houlston, Richard S; Cario, Gunnar; Schrappe, Martin; Zimmermann, Martin

    2018-03-02

    Purpose Somatic deletions that affect the lymphoid transcription factor-coding gene IKZF1 have previously been reported as independently associated with a poor prognosis in pediatric B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). We have now refined the prognostic strength of IKZF1 deletions by analyzing the effect of co-occurring deletions. Patients and Methods The analysis involved 991 patients with BCP ALL treated in the Associazione Italiana Ematologia ed Oncologia Pediatrica-Berlin-Frankfurt-Muenster (AIEOP-BFM) ALL 2000 trial with complete information for copy number alterations of IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, Xp22.33/Yp11.31 (PAR1 region; CRLF2, CSF2RA, and IL3RA), and ERG; replication of findings involved 417 patients from the same trial. Results IKZF1 deletions that co-occurred with deletions in CDKN2A, CDKN2B, PAX5, or PAR1 in the absence of ERG deletion conferred the worst outcome and, consequently, were grouped as IKZF1 plus . The IKZF1 plus group comprised 6% of patients with BCP ALL, with a 5-year event-free survival of 53 ± 6% compared with 79 ± 5% in patients with IKZF1 deletion who did not fulfill the IKZF1 plus definition and 87 ± 1% in patients who lacked an IKZF1 deletion ( P ≤ .001). Respective 5-year cumulative relapse incidence rates were 44 ± 6%, 11 ± 4%, and 10 ± 1% ( P ≤ .001). Results were confirmed in the replication cohort, and multivariable analyses demonstrated independence of IKZF1 plus . The IKZF1 plus prognostic effect differed dramatically in analyses stratified by minimal residual disease (MRD) levels after induction treatment: 5-year event-free survival for MRD standard-risk IKZF1 plus patients was 94 ± 5% versus 40 ± 10% in MRD intermediate- and 30 ± 14% in high-risk IKZF1 plus patients ( P ≤ .001). Corresponding 5-year cumulative incidence of relapse rates were 6 ± 6%, 60 ± 10%, and 60 ± 17% ( P ≤ .001). Conclusion IKZF1 plus describes a new MRD-dependent very

  3. Vaccine Therapy With or Without Cryosurgery in Treating Patients With Residual, Relapsed, or Refractory B-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2017-03-21

    Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Adult Diffuse Mixed Cell Lymphoma; Adult Diffuse Small Cleaved Cell Lymphoma; Adult Grade III Lymphomatoid Granulomatosis; Adult Immunoblastic Large Cell Lymphoma; Adult Lymphoblastic Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3 Follicular Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia With Nodal Disease

  4. Three cysteine residues of SLC52A1, a receptor for the porcine endogenous retrovirus-A (PERV-A), play a critical role in cell surface expression and infectivity.

    Science.gov (United States)

    Colon-Moran, Winston; Argaw, Takele; Wilson, Carolyn A

    2017-07-01

    Porcine endogenous retrovirus-A (PERV-A), a gammaretrovirus, infects human cells in vitro, thus raising the potential risk of cross-species transmission in xenotransplantation. Two members of the solute carrier family 52 (SLC52A1 and SLC52A2) are PERV-A receptors. Site-directed mutagenesis of the cDNA encoding SLC52A1 identified that only one of two putative glycosylation signals is occupied by glycans. In addition, we showed that glycosylation of SLC52A1 is not necessary for PERV-A receptor function. We also identified that at a minimum, three cysteine residues are sufficient for SLC52A1 cell surface expression. Mutation of cysteine at position 365 and either of the two cysteine residues in the C-terminal tail at positions 442 or 446 reduced SLC52A1 surface expression and PERV-A infection suggesting that these residues may contribute to overall structural stability and receptor function. Understanding interactions between PERV-A and its cellular receptor may provide novel strategies to prevent zoonotic infection in the setting of xenotransplantation. Published by Elsevier Inc.

  5. Acute Hepatic Allograft Rejection in Pediatric Recipients: Independent Factors

    OpenAIRE

    Dehghani, S. M.; Shahramian, I.; Afshari, M.; Bahmanyar, M.; Ataollahi, M.; Sargazi, A.

    2017-01-01

    Background: Acute cellular rejection (ACR) has a reversible effect on graft and its survival. Objective: To evaluate the relation between ACR and clinical factors in recipients of liver transplant allografts. Methods: 47 consecutive liver recipients were retrospectively studied. Their data were extracted from records and analyzed. Results: 38 (81%) of the 47 recipients experienced ACR during a 24-month follow-up. The rate of rejection was associated with none of the studied factors—recipient’...

  6. 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.

  7. Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011)

    NARCIS (Netherlands)

    Averbuch, D.; Cordonnier, C.; Livermore, D.M.; Mikulska, M.; Orasch, C.; Viscoli, C.; Gyssens, I.C.J.; Kern, W.V.; Klyasova, G.; Marchetti, O.; Engelhard, D.; Akova, M.; Ecil, a.j.v.o.E.E.I.E.E.; Eln, .

    2013-01-01

    The detection of multi-resistant bacterial pathogens, particularly those to carbapenemases, in leukemic and stem cell transplant patients forces the use of old or non-conventional agents as the only remaining treatment options. These include colistin/polymyxin B, tigecycline, fosfomycin and various

  8. Residual gas analysis

    International Nuclear Information System (INIS)

    Berecz, I.

    1982-01-01

    Determination of the residual gas composition in vacuum systems by a special mass spectrometric method was presented. The quadrupole mass spectrometer (QMS) and its application in thin film technology was discussed. Results, partial pressure versus time curves as well as the line spectra of the residual gases in case of the vaporization of a Ti-Pd-Au alloy were demonstrated together with the possible construction schemes of QMS residual gas analysers. (Sz.J.)

  9. Validation of chimerism in pediatric recipients of allogeneic hematopoietic stem cell transplantation (HSCT) a comparison between two methods: real-time PCR (qPCR) vs. variable number tandem repeats PCR (VNTR PCR).

    Science.gov (United States)

    Kletzel, Morris; Huang, Wei; Olszewski, Marie; Khan, Sana

    2013-01-01

    Post-hematopoietic stem cell transplantation (HSCT) chimerism monitoring is important to assess relapse and therapeutic intervention. The purpose of our study is to compare two methods variable number tandem repeats (VNTR) vs. quantitative real- time polymerase chain reaction (qPCR) in terms of determining chimerism. 127 (peripheral blood n=112, bone marrow n=15) samples were simultaneously tested by VNTR using APO-B, D1S80, D1S111, D17S30, gene loci SRY and ZP3 and qPCR using 34 assays (CA001-CA034) that are designed to a bi-allelic insertion/deletion (indel) polymorphism in the human genome. Samples were separated in three subsets: total WBC, T-cell and Myeloid cells. Extraction of DNA was performed then quantified. We analyzed column statistics, paired t-test and regression analysis for both methods. There was complete correlation between the two methods. The simplicity and rapidity of the test results from the qPCR method is more efficient and accurate to assess chimerism.

  10. Basic oral care for hematology-oncology patients and hematopoietic stem cell transplantation recipients: a position paper from the joint task force of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT).

    Science.gov (United States)

    Elad, Sharon; Raber-Durlacher, Judith E; Brennan, Michael T; Saunders, Deborah P; Mank, Arno P; Zadik, Yehuda; Quinn, Barry; Epstein, Joel B; Blijlevens, Nicole M A; Waltimo, Tuomas; Passweg, Jakob R; Correa, M Elvira P; Dahllöf, Göran; Garming-Legert, Karin U E; Logan, Richard M; Potting, Carin M J; Shapira, Michael Y; Soga, Yoshihiko; Stringer, Jacqui; Stokman, Monique A; Vokurka, Samuel; Wallhult, Elisabeth; Yarom, Noam; Jensen, Siri Beier

    2015-01-01

    Hematology-oncology patients undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT) recipients are at risk for oral complications which may cause significant morbidity and a potential risk of mortality. This emphasizes the importance of basic oral care prior to, during and following chemotherapy/HSCT. While scientific evidence is available to support some of the clinical practices used to manage the oral complications, expert opinion is needed to shape the current optimal protocols. This position paper was developed by members of the Oral Care Study Group, Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT) in attempt to provide guidance to the health care providers managing these patient populations. The protocol on basic oral care outlined in this position paper is presented based on the following principles: prevention of infections, pain control, maintaining oral function, the interplay with managing oral complications of cancer treatment and improving quality of life. Using these fundamental elements, we developed a protocol to assist the health care provider and present a practical approach for basic oral care. Research is warranted to provide robust scientific evidence and to enhance this clinical protocol.

  11. 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.

  12. Agricultural pesticide residues

    International Nuclear Information System (INIS)

    Fuehr, F.

    1984-01-01

    The utilization of tracer techniques in the study of agricultural pesticide residues is reviewed under the following headings: lysimeter experiments, micro-ecosystems, translocation in soil, degradation of pesticides in soil, biological availability of soil-applied substances, bound residues in the soil, use of macro- and microautography, double and triple labelling, use of tracer labelling in animal experiments. (U.K.)

  13. Who hires physics bachelor's degree recipients?

    Science.gov (United States)

    White, Susan C.

    2015-04-01

    As we saw last month, over 40% of the students who recently earned bachelor's degrees in physics enter the job market. There are employment opportunities for these graduates in all areas of the economy. When we contact graduates, we ask them where they are working, and we use their responses to compile a list of employers in each state who have recently hired a physics bachelor's degree recipient. We also produce a separate list of firms that have hired three or more physics bachelor's. These lists can be useful tools for students who want to know more about where one can find a job with a bachelor's degree in physics. The lists are available at www.aip.org/whos-hiring-physics-bachelors.

  14. 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.

  15. Viral Infection in Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Jovana Cukuranovic

    2012-01-01

    Full Text Available Viruses are among the most common causes of opportunistic infection after transplantation. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or posttransplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This paper will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens.

  16. Interactions in recovery and in residual injury from sequential treatments of mouse haemopoietic and stromal marrow cell populations, using X-rays, cyclophosphamide and busulphan

    International Nuclear Information System (INIS)

    Qi, D.Y.; Hendry, J.H.; Testa, N.G.

    1991-01-01

    The acute recovery of day 11 CFU-S, iv-CFC and CFU-F in mouse bone marrow, following a test dose of X-rays, cyclophosphamide (CP) or busulphan given to mice previously treated with repeated priming dose X-rays or CP, was in general predictable from the amount of residual injury after the priming doses. A marked exception was iv-CFC after X-rays, which although amplified to near normal levels during the residual injury phase, recovered after the test irradiation from low-levels of CFU-S. The amount of residual injury after sequential treatments of different agents was in general less than expected on the basis of the product of the effects of the individual agents. This was most marked for CP priming treatments, where the long-term recovery of day 11 CFU-S after the test dose remained persistently above control levels. Also, some correlation was found between improved stromal recovery (CFU-F) and the CFU-S content following the sequential treatment protocols. (author). 33 refs.; 3 figs.; 5 tabs

  17. Predictors of hyperparathyroidism in renal transplant recipients

    International Nuclear Information System (INIS)

    Houssaini, T.S.; Arrayahani, M.; Rhou, H.; Amar, Y.; Benamar, L.; Ouzeddoun, N.; Bayahia, R.

    2008-01-01

    The changes in parathyroid hormone secretion after successful renal transplantation remain to be clearly elucidated. Our study was aimed at identifying the predictors of hyperparathyroidism in renal transplant recipients. A retrospective single center study involving 37 renal transplant recipients, with a follow-up of at least one year, was performed. All transplants were performed using kidneys from living related donors. The average age of study patients was 30+-10 years, with a male-female ratio of 1.31. The mean duration on hemodialysis (HD) prior to transplantation was 25+-18 months. All the grafts but one were functional after a mean follow-up of 41+-21 months. We noted a rapid reduction of the mean parathyroid hormone (iPTH) level from 383+-265 pg/ml before transplantation to 125+-67 pg/ml at one year and 108+-66 pg/ml at two years after transplantation (p=0.01). Bivariate analysis revealed that the level of iPTH obtained during follow-up correlated with the duration on HD (p=0.03), the serum creatinine at 24-months (p=0.013), and to the level of iPTH in the first year post transplantation (P=<0.001). Other clinical or laboratory parameters were not predictive of hyperparathyroidism after kidney transplantation. Liner regression showed that only the serum creatinine at 24-months independently correlated with the level of iPTH at last follow-up (p=0.02). Our study suggests that short duration on HD and a functional graft are the main predictors of correction of hyperparathyroidism after renal transplantation. (author)

  18. Multisensory Integration in Cochlear Implant Recipients.

    Science.gov (United States)

    Stevenson, Ryan A; Sheffield, Sterling W; Butera, Iliza M; Gifford, René H; Wallace, Mark T

    Speech perception is inherently a multisensory process involving integration of auditory and visual cues. Multisensory integration in cochlear implant (CI) recipients is a unique circumstance in that the integration occurs after auditory deprivation and the provision of hearing via the CI. Despite the clear importance of multisensory cues for perception, in general, and for speech intelligibility, specifically, the topic of multisensory perceptual benefits in CI users has only recently begun to emerge as an area of inquiry. We review the research that has been conducted on multisensory integration in CI users to date and suggest a number of areas needing further research. The overall pattern of results indicates that many CI recipients show at least some perceptual gain that can be attributable to multisensory integration. The extent of this gain, however, varies based on a number of factors, including age of implantation and specific task being assessed (e.g., stimulus detection, phoneme perception, word recognition). Although both children and adults with CIs obtain audiovisual benefits for phoneme, word, and sentence stimuli, neither group shows demonstrable gain for suprasegmental feature perception. Additionally, only early-implanted children and the highest performing adults obtain audiovisual integration benefits similar to individuals with normal hearing. Increasing age of implantation in children is associated with poorer gains resultant from audiovisual integration, suggesting a sensitive period in development for the brain networks that subserve these integrative functions, as well as length of auditory experience. This finding highlights the need for early detection of and intervention for hearing loss, not only in terms of auditory perception, but also in terms of the behavioral and perceptual benefits of audiovisual processing. Importantly, patterns of auditory, visual, and audiovisual responses suggest that underlying integrative processes may be

  19. 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

  20. 42 CFR 431.808 - Protection of recipient rights.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Protection of recipient rights. 431.808 Section 431... Provisions § 431.808 Protection of recipient rights. Any individual performing activities under the MEQC... is consistent with the provisions of §§ 435.902 and 436.901 of this subchapter concerning the rights...

  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. Development of nuclear technology transfer - Korea as a recipient

    International Nuclear Information System (INIS)

    Sung, N.C.

    1988-01-01

    Korea, as a recipient of nuclear technology transfer, has good experience of progressively building up its indigenous capability of nuclear technology through three stages of technology transfer, namely: technology transfer under the turn-key approach, component approach, and integrated technology transfer with a local prime contractor. Here, each stage of experience of technology transfer, with Korea as a recipient, is presented

  3. Multinational study in children and adolescents with newly diagnosed type 1 diabetes: association of age, ketoacidosis, HLA status, and autoantibodies on residual beta-cell function and glycemic control 12 months after diagnosis

    DEFF Research Database (Denmark)

    Mortensen, H.B.; Swift, P.G.F.; Holl, R.W.

    2010-01-01

    .005), and by stimulated C-peptide (p glutamic acid decarboxylase antibodies (GADA; p = 0.0004) at 1 month. HbA1c at 12 months was predicted by HbA1c at diagnosis (p ethnicity...... (p = 0.002). Conclusions: Younger age, ketoacidosis at diagnosis, and IA and GADA 1 month after diagnosis were the strongest explanatory factors for residual beta-cell function at 12 months. Glycemic control at 12 months was influenced predominantly by ethnicity, HbA1c at diagnosis, and GADA at 1...

  4. Complex multi-block analysis identifies new immunologic and genetic disease progression patterns associated with the residual β-cell function 1 year after diagnosis of type 1 diabetes

    DEFF Research Database (Denmark)

    Andersen, Marie Louise Max; Rasmussen, Morten Arendt; Pörksen, Sven

    2013-01-01

    The purpose of the present study is to explore the progression of type 1 diabetes (T1D) in Danish children 12 months after diagnosis using Latent Factor Modelling. We include three data blocks of dynamic paraclinical biomarkers, baseline clinical characteristics and genetic profiles of diabetes...... related SNPs in the analyses. This method identified a model explaining 21.6% of the total variation in the data set. The model consists of two components: (1) A pattern of declining residual β-cell function positively associated with young age, presence of diabetic ketoacidosis and long duration...

  5. Handling of Solid Residues

    International Nuclear Information System (INIS)

    Medina Bermudez, Clara Ines

    1999-01-01

    The topic of solid residues is specifically of great interest and concern for the authorities, institutions and community that identify in them a true threat against the human health and the atmosphere in the related with the aesthetic deterioration of the urban centers and of the natural landscape; in the proliferation of vectorial transmitters of illnesses and the effect on the biodiversity. Inside the wide spectrum of topics that they keep relationship with the environmental protection, the inadequate handling of solid residues and residues dangerous squatter an important line in the definition of political and practical environmentally sustainable. The industrial development and the population's growth have originated a continuous increase in the production of solid residues; of equal it forms, their composition day after day is more heterogeneous. The base for the good handling includes the appropriate intervention of the different stages of an integral administration of residues, which include the separation in the source, the gathering, the handling, the use, treatment, final disposition and the institutional organization of the administration. The topic of the dangerous residues generates more expectation. These residues understand from those of pathogen type that are generated in the establishments of health that of hospital attention, until those of combustible, inflammable type, explosive, radio-active, volatile, corrosive, reagent or toxic, associated to numerous industrial processes, common in our countries in development

  6. Effect of replacing the aspartic acid/glutamic acid residues of bullfrog sialic acid binding lectin with asparagine/glutamine and arginine on the inhibition of cell proliferation in murine leukemia P388 cells.

    Science.gov (United States)

    Ogawa, Yuko; Iwama, Masanori; Ohgi, Kazuko; Tsuji, Tsutomu; Irie, Masachika; Itagaki, Tadashi; Kobayashi, Hiroko; Inokuchi, Norio

    2002-06-01

    The sialic acid binding lectin from bullfrog oocytes (cSBL) is known to have anti-tumor activity. In a previous report, to elucidate the relationship between the net charge and anti-tumor activity of cSBL, we examined the effect of chemical modifications of cSBL with a water-soluble carbodiimide in the presence of various nucleophiles. The results suggested that the anti-tumor activity and internalization into tumor cells increased with an increase in the net charge of cSBL. However, in the chemically modified cSBL, a modification site was observed on average in two of the carboxyl groups of cSBL. To confirm these previous results and to determine which modified carboxyl group contributes to the increase in anti-tumor activity, we prepared mutants with substitutions of Asn/Gln and Arg at three acidic amino acid residues of cSBL and studied their anti-tumor activity and internalization efficiency. The results showed the enhancing effect of charge on anti-tumor activity and internalization, and suggested that the replacement of D24 and E88 of cSBL with arginine is more effective than that of E97. The double mutant D24RE88R showed comparable anti-tumor activity to the ethylenediamine-modified cSBL reported previously. The mutant was well-characterized as a pure cSBL derivative suitable for studying the mechanism of the anti-tumor action of cSBL.

  7. Prognosis of Kidney Transplant Recipients With Pretransplantation Malignancy: A Nationwide Population-Based Cohort Study in Taiwan.

    Science.gov (United States)

    Chiu, H-F; Chung, M-C; Chung, C-J; Yu, T-M; Shu, K-H; Wu, M-J

    2016-04-01

    The objective of this study was to evaluate the prognosis of kidney transplant recipients with pretransplantation malignancy and the incidence of recurrent malignancy in kidney transplant recipients using claims data from Taiwan's universal health insurance program. A total of 4350 transplant recipients were retrospectively analyzed. The rates of pretransplantation or recurrent malignancy, which was defined by their inclusion in the catastrophic illness patient registry using the International Classification of Diseases, 9th Revision, were evaluated. Cox proportional hazard regression and Kaplan-Meier curves were used for the analyses. In total, there were 4350 kidney transplant recipients, 52.1% of patients were male, the mean age at transplantation was 45.8 years old, and the percentages of diabetes mellitus, hypertension, hepatitis B viral infection, and hepatitis C viral infection were 14%, 63.2%, 4.2%, and 2.4%, respectively. There were 95 patients (2.2%) with pretransplantation malignancy. The top 3 pretransplantation malignancies, in decreasing order, were urinary tract, kidney, and breast cancers. After kidney transplantation, 10 recipients had recurrent cancer. The overall cancer recurrence rate was 10.5%. These 10 cancers included urothelial carcinoma (n = 5), renal cell carcinoma (n = 3), breast cancer (n = 1), and thyroid cancer (n = 1). Eleven recipients had a secondary cancer. Patients without pretransplantation and post-transplantation malignancy had the best survival. Patients with pretransplantation malignancy had a greater occurrence of cancers and increased mortality regardless of whether or not they had recurrence of cancer. Our results suggest the higher risk of cancer, recurrent or secondary, and mortality after kidney transplantation. Adequate waiting time before transplantation and preventive strategies are strongly suggested in kidney transplant recipients with cancer history. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Pandemic 2009 Influenza A (H1N1 virus infection in cancer and hematopoietic stem cell transplant recipients; a multicenter observational study. [v1; ref status: indexed, http://f1000r.es/4bi

    Directory of Open Access Journals (Sweden)

    Maria Cecilia Dignani

    2014-09-01

    Full Text Available Background: During March 2009 a novel Influenza A virus emerged in Mexico. We describe the clinical picture of the pandemic Influenza A (H1N1 Influenza in cancer patients during the 2009 influenza season. Methods: Twelve centers participated in a multicenter retrospective observational study of cancer patients with confirmed infection with the 2009 H1N1 Influenza A virus (influenza-like illness or pneumonia plus positive PCR for the 2009 H1N1 Influenza A virus  in respiratory secretions. Clinical data were obtained by retrospective chart review and analyzed.  Results: From May to August 2009, data of 65 patients were collected. Median age was 51 years, 57 % of the patients were female. Most patients (47 had onco-hematological cancers and 18 had solid tumors. Cancer treatment mainly consisted of chemotherapy (46, or stem cell transplantation (SCT (16. Only 19 of 64 patients had received the 2009 seasonal Influenza vaccine. Clinical presentation included pneumonia (43 and upper respiratory tract infection (22. Forty five of 58 ambulatory patients were admitted. Mechanical ventilation was required in 12 patients (18%. Treatment included oseltamivir monotherapy or in combination with amantadine for a median of 7 days. The global 30-day mortality rate was 18%. All 12 deaths were among the non-vaccinated patients. No deaths were observed among the 19 vaccinated patients. Oxygen saturation <96% at presentation was a predictor of mortality (OR 19.5; 95%CI: 2.28 to 165.9. Conclusions: In our cancer patient population, the pandemic 2009 Influenza A (H1N1 virus was associated with high incidence of pneumonia (66%, and 30-day mortality (18.5%. Saturation <96% was significantly associated with death. No deaths were observed among vaccinated patients.

  9. [Residual neuromuscular blockade].

    Science.gov (United States)

    Fuchs-Buder, T; Schmartz, D

    2017-06-01

    Even small degrees of residual neuromuscular blockade, i. e. a train-of-four (TOF) ratio >0.6, may lead to clinically relevant consequences for the patient. Especially upper airway integrity and the ability to swallow may still be markedly impaired. Moreover, increasing evidence suggests that residual neuromuscular blockade may affect postoperative outcome of patients. The incidence of these small degrees of residual blockade is relatively high and may persist for more than 90 min after a single intubating dose of an intermediately acting neuromuscular blocking agent, such as rocuronium and atracurium. Both neuromuscular monitoring and pharmacological reversal are key elements for the prevention of postoperative residual blockade.

  10. TENORM: Wastewater Treatment Residuals

    Science.gov (United States)

    Water and wastes which have been discharged into municipal sewers are treated at wastewater treatment plants. These may contain trace amounts of both man-made and naturally occurring radionuclides which can accumulate in the treatment plant and residuals.

  11. Variation within the PPARG gene is associated with residual beta-cell function and glycemic control in children and adolescents during the first year of clinical type 1 diabetes

    DEFF Research Database (Denmark)

    Porksen, S.; Nielsen, L.B.; Mortensen, H.B.

    2008-01-01

    Context: Conflicting evidence exists as to whether the Pro12Ala single nucleotide polymorphism of the type 2 diabetes susceptibility gene peroxisome proliferator-activated receptor gamma (PPARG) also confers risk for type 1 diabetes (T1D). Objective: The objective of this study was to investigate...... the PPARG gene in relation to residual beta-cell function and glycemic control in newly diagnosed T1D. Design: Prospective, non-interventional, 12-month follow-up study, conducted in 18 centers in 15 countries. Patients: Two hundred and fifty-seven children and adolescents (aged ... diagnosed T1D. Main outcome measures: Beta-cell function was determined as 90-min meal-stimulated C-peptide (Boost test) 1, 6, and 12 months after diagnosis. Hemoglobin A1c (HbA1c) and daily insulin dose (IU/kg/d) were recorded at 1, 3, 6, 9, and 12 months after diagnosis. Haplotypes within PPARG were...

  12. Residuation in orthomodular lattices

    Directory of Open Access Journals (Sweden)

    Chajda Ivan

    2017-04-01

    Full Text Available We show that every idempotent weakly divisible residuated lattice satisfying the double negation law can be transformed into an orthomodular lattice. The converse holds if adjointness is replaced by conditional adjointness. Moreover, we show that every positive right residuated lattice satisfying the double negation law and two further simple identities can be converted into an orthomodular lattice. In this case, also the converse statement is true and the corresponence is nearly one-to-one.

  13. Perceptual learning and auditory training in cochlear implant recipients.

    Science.gov (United States)

    Fu, Qian-Jie; Galvin, John J

    2007-09-01

    Learning electrically stimulated speech patterns can be a new and difficult experience for cochlear implant (CI) recipients. Recent studies have shown that most implant recipients at least partially adapt to these new patterns via passive, daily-listening experiences. Gradually introducing a speech processor parameter (eg, the degree of spectral mismatch) may provide for more complete and less stressful adaptation. Although the implant device restores hearing sensation and the continued use of the implant provides some degree of adaptation, active auditory rehabilitation may be necessary to maximize the benefit of implantation for CI recipients. Currently, there are scant resources for auditory rehabilitation for adult, postlingually deafened CI recipients. We recently developed a computer-assisted speech-training program to provide the means to conduct auditory rehabilitation at home. The training software targets important acoustic contrasts among speech stimuli, provides auditory and visual feedback, and incorporates progressive training techniques, thereby maintaining recipients' interest during the auditory training exercises. Our recent studies demonstrate the effectiveness of targeted auditory training in improving CI recipients' speech and music perception. Provided with an inexpensive and effective auditory training program, CI recipients may find the motivation and momentum to get the most from the implant device.

  14. Influence of oocyte donor and embryo recipient conditions on cloning efficiency in dogs.

    Science.gov (United States)

    Kim, M J; Oh, H J; Park, J E; Hong, S G; Kang, J T; Koo, O J; Kang, S K; Jang, G; Lee, B C

    2010-08-01

    To determine factors that affect the efficiency of dog cloning by somatic cell nuclear transfer, the present study was performed to investigate 1) the effects of surgical history (non-operated/operated) and parity (nullipara/multipara) on the recovery of in vivo canine oocytes; 2) the effects of surgical history and parity of recipients on the pregnancy and delivery; and 3) the effects of synchronization state (AA, advanced asynchrony; SY, synchrony; RA, retarded asynchrony) between oocytes donor and recipient on the pregnancy and delivery. Oocyte recovery rate was significantly higher in non-operated dogs compared to operated dogs (93.8 vs. 89.6%, P dogs and multiparous dogs. Delivery rate was also significantly higher in non-operated dogs compared to operated dogs (2.8 vs. 1.0%, P dogs than multiparous dogs (3.0 vs. 1.7%, P dogs as experimental dogs and nulliparous dogs as recipient dogs to increase delivery rate after transfer of somatic cell nuclear transferred embryos, but further study is needed to find out appropriate synchrony status at the transfer. Copyright 2010 Elsevier Inc. All rights reserved.

  15. Characterization of Hospital Residuals

    International Nuclear Information System (INIS)

    Blanco Meza, A.; Bonilla Jimenez, S.

    1997-01-01

    The main objective of this investigation is the characterization of the solid residuals. A description of the handling of the liquid and gassy waste generated in hospitals is also given, identifying the source where they originate. To achieve the proposed objective the work was divided in three stages: The first one was the planning and the coordination with each hospital center, in this way, to determine the schedule of gathering of the waste can be possible. In the second stage a fieldwork was made; it consisted in gathering the quantitative and qualitative information of the general state of the handling of residuals. In the third and last stage, the information previously obtained was organized to express the results as the production rate per day by bed, generation of solid residuals for sampled services, type of solid residuals and density of the same ones. With the obtained results, approaches are settled down to either determine design parameters for final disposition whether for incineration, trituration, sanitary filler or recycling of some materials, and storage politics of the solid residuals that allow to determine the gathering frequency. The study concludes that it is necessary to improve the conditions of the residuals handling in some aspects, to provide the cleaning personnel of the equipment for gathering disposition and of security, minimum to carry out this work efficiently, and to maintain a control of all the dangerous waste, like sharp or polluted materials. In this way, an appreciable reduction is guaranteed in the impact on the atmosphere. (Author) [es

  16. Increased osteoprotegerin predicts poor virological outcome during anticytomegalovirus therapy in solid organ transplant recipients.

    Science.gov (United States)

    Ueland, Thor; Rollag, Halvor; Hartmann, Anders; Jardine, Alan; Humar, Atul; Bignamini, Angelo A; Åsberg, Anders; Aukrust, Pål

    2015-01-01

    Cytomegalovirus (CMV) infection involves interaction between endothelial cells and leukocyte subsets that may promote vascular inflammation and lead to treatment failure in infected individuals. Osteoprotegerin is a marker of vascular and systemic inflammation but has not been investigated in relation to treatment outcome during CMV infection. We investigated whether circulating levels of osteoprotegerin are related to features of CMV disease and treatment outcomes during CMV infection in 291 solid organ transplant recipients receiving valganciclovir or ganciclovir in an international multicenter trial of CMV disease treatment (the VICTOR study). Elevated plasma osteoprotegerin was associated with (i) certain disease characteristics including presence of tissue invasive disease (Posteoprotegerin levels in solid organ transplant recipients with CMV infection may reflect vascular inflammation and is associated with late virological outcome in these patients.

  17. Donor-Derived Myeloid Sarcoma in Two Kidney Transplant Recipients from a Single Donor

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    Amudha Palanisamy

    2015-01-01

    Full Text Available We report the rare occurrence of donor-derived myeloid sarcoma in two kidney transplant patients who received organs from a single deceased donor. There was no evidence of preexisting hematologic malignancy in the donor at the time of organ recovery. Both recipients developed leukemic involvement that appeared to be limited to the transplanted organ. Fluorescence in situ hybridization (FISH and molecular genotyping analyses confirmed that the malignant cells were of donor origin in each patient. Allograft nephrectomy and immediate withdrawal of immunosuppression were performed in both cases; systemic chemotherapy was subsequently administered to one patient. Both recipients were in remission at least one year following the diagnosis of donor-derived myeloid sarcoma. These cases suggest that restoration of the immune system after withdrawal of immunosuppressive therapy and allograft nephrectomy may be sufficient to control HLA-mismatched donor-derived myeloid sarcoma without systemic involvement.

  18. 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.

  19. Prostate cancer in renal transplant recipients

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    Benjamin A. Sherer

    Full Text Available ABSTRACT As patients with end-stage renal disease are receiving renal allografts at older ages, the number of male renal transplant recipients (RTRs being diagnosed with prostate cancer (CaP is increasing. Historically, the literature regarding the management of CaP in RTR's is limited to case reports and small case series. To date, there are no standardized guidelines for screening or management of CaP in these complex patients. To better understand the unique characteristics of CaP in the renal transplant population, we performed a literature review of PubMed, without date limitations, using a combination of search terms including prostate cancer, end stage renal disease, renal transplantation, prostate cancer screening, prostate specific antigen kinetics, immuno-suppression, prostatectomy, and radiation therapy. Of special note, teams facilitating the care of these complex patients must carefully and meticulously consider the altered anatomy for surgical and radiotherapeutic planning. Active surveillance, though gaining popularity in the general low risk prostate cancer population, needs further study in this group, as does the management of advance disease. This review provides a comprehensive and contemporary understanding of the incidence, screening measures, risk stratification, and treatment options for CaP in RTRs.

  20. Clinical outcomes in overweight heart transplant recipients.

    Science.gov (United States)

    Jalowiec, Anne; Grady, Kathleen L; White-Williams, Connie

    2016-01-01

    Few studies have examined the impact of patient weight on heart transplant (HT) outcomes. Nine outcomes were compared in 2 groups of HT recipients (N = 347) based on their mean body mass index (BMI) during the first 3 years post-HT. Group 1 consisted of 108 non-overweight patients (BMI <25; mean age 52; 29.6% females; 16.7% minorities). Group 2 consisted of 239 overweight patients (BMI ≥25; mean age 52; 15.9% females; 13.8% minorities). Outcome