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Sample records for receiving dual immunosuppressive

  1. Pulmonary nocardiosis in a patient receiving immunosuppressive agent.

    PubMed

    Aswapokee, P; Aswapokee, N; Chirawong, P; Leelarasamee, A

    1977-09-01

    A 20-year-old woman receiving corticosteroid treatment for systemic lupus erythematosus developed pulmonary nocardiosis with hydrophneumothorax. The organism identified as Nocardia asteroides resisted to sulfonamide and cotrimoxazole but sensitive to chloramphenicaol and streptomycin in vitro. She seemed to respond to chloramphenicol but subsequently had peritonitis and succumbed later. PMID:607422

  2. Initial experience of dual maintenance immunosuppression with steroid withdrawal in vascular composite tissue allotransplantation.

    PubMed

    Diaz-Siso, J R; Fischer, S; Sisk, G C; Bueno, E; Kueckelhaus, M; Talbot, S; Carty, M J; Treister, N S; Marty, F; Milford, E L; Pomahac, B; Tullius, S G

    2015-05-01

    Current immunosuppression in VCA is largely based on the experience in solid organ transplantation. It remains unclear if steroids can be reduced safely in VCA recipients. We report on five VCA recipients who were weaned off maintenance steroids after a median of 2 months (mean: 4.8 months, range 2-12 months). Patients were kept subsequently on a low dose, dual maintenance consisting of tacrolimus and mycophenolate mofetil/mycophenloic acid with a mean follow-up of 43.6 months (median = 40 months, range 34-64 months). Early and late acute rejections responded well to temporarily augmented maintenance, topical immunosuppression, and/or steroid bolus treatment. One late steroid-resistant acute rejection required treatment with thymoglobulin. All patients have been gradually weaned off steroids subsequent to the treatment of acute rejections. Low levels of tacrolimus (<5 ng/mL) appeared as a risk for acute rejections. Although further experience and a cautious approach are warranted, dual-steroid free maintenance immunosuppression appears feasible in a series of five VCA recipients. PMID:25777324

  3. Immunization of Children Receiving Immunosuppressive Therapy for Cancer or Hematopoietic Stem Cell Transplantation

    PubMed Central

    Shetty, Avinash K.; Winter, Mary A.

    2012-01-01

    In the past 3 decades, the number of immunocompromised children has increased steadily because of dramatic improvement in survival rates in certain malignancies as a result of intensive curative treatment regimens and an increase in the number of children undergoing life-saving hematopoietic stem cell transplantation (HSCT). Children receiving immunosuppressive therapy for cancer, as well as HSCT recipients, will benefit from vaccination but warrant close evaluation for a variety of reasons, such as the risk of developing severe infections, serious adverse events following certain vaccines, and decreased vaccine efficacy caused by poor immune response to vaccination. Various professional organizations have published vaccination guidelines for immunocompromised patients. Given their heterogeneity, recommendations for the immunization of immunocompromised patients may not be universally applicable. The safety of many commonly used vaccines has not been established in immunocompromised children. In addition, no large-scale vaccine studies have evaluated the clinical outcome of disease prevention in this population. All killed vaccines are generally safe, while live vaccines may be administered to immunocompromised children in select circumstances, depending on the degree of altered immunocompetence and the underlying primary condition. Healthcare providers should be knowledgeable about the indications, contraindications, and precautions for vaccine administration in immunocompromised patients. To protect immunocompromised patients, all family, household contacts, and healthcare workers should also be immunized with all routinely recommended vaccines. Pediatricians play a crucial role in identifying and effectively communicating the risks and benefits of vaccines to immunocompromised patients and their parents. PMID:23049460

  4. Dual-path NMR receiver using double transceiver microcoils.

    PubMed

    Pourmodheji, Hossein; Ghafar-Zadeh, Ebrahim; Magierowski, Sebastian

    2015-08-01

    We present a fully integrated CMOS dual path front-end receiver for NMR applications. Instead of conventional NMR systems which are using one transceiver coil, we propose a dual-path receiver in which it has two transceiver microcoils. This structure cancels the background signal and consequently improving the sensitivity. Spectral simulations of the dual-path receiver are used to verify cancellation of the background signal in this structure. The front-end receiver contains two differential low-noise amplifiers (LNA), two voltage buffers (for conventional mode), two phase shifters, two variable gain amplifiers (VGA), one differential LNA and voltage buffer at the end. This chain of dual-path receiver is designed for 21 MHz NMR settings. The front-end receiver achieves an input referred noise of 2.7 nV/√Hz and voltage gain of 80 dB. The chip is designed in a 0.13-μm CMOS technology and occupies an area of 1 mm × 2 mm. PMID:26737930

  5. A dual-detector optical receiver for PDM signals detection

    NASA Astrophysics Data System (ADS)

    Chen, Guanyu; Yu, Yu; Zhang, Xinliang

    2016-05-01

    We propose and fabricate a silicon based dual-detector optical receiver, which consists of a two dimensional (2D) grating coupler (GC) and two separate germanium photodetectors (Ge PDs). The 2D GC performs polarization diversity, and thus demultiplexing and detection for polarization division multiplexed (PDM) signals can be achieved. Through a specific design with double-sides illumination, the space charge density can be reduced and the responsivity and saturation power can be improved significantly. The measured dark current, responsivity and bandwidth are 0.86 μA, 1.06 A/W and 36 GHz under 3 V reverse biased voltage, respectively. Both DC currents and eye diagrams are measured for the proposed device and the results validate its performance successfully. The power penalty between the single and dual polarized signals is about 1.9 dB under 10 and 20 Gb/s cases for both the two Ge PDs. The proposed direct detection (DD) for PDM signals with high speed, high responsivity and large saturation power is cost-effective and promising for short reach optical communication.

  6. A dual-detector optical receiver for PDM signals detection.

    PubMed

    Chen, Guanyu; Yu, Yu; Zhang, Xinliang

    2016-01-01

    We propose and fabricate a silicon based dual-detector optical receiver, which consists of a two dimensional (2D) grating coupler (GC) and two separate germanium photodetectors (Ge PDs). The 2D GC performs polarization diversity, and thus demultiplexing and detection for polarization division multiplexed (PDM) signals can be achieved. Through a specific design with double-sides illumination, the space charge density can be reduced and the responsivity and saturation power can be improved significantly. The measured dark current, responsivity and bandwidth are 0.86 μA, 1.06 A/W and 36 GHz under 3 V reverse biased voltage, respectively. Both DC currents and eye diagrams are measured for the proposed device and the results validate its performance successfully. The power penalty between the single and dual polarized signals is about 1.9 dB under 10 and 20 Gb/s cases for both the two Ge PDs. The proposed direct detection (DD) for PDM signals with high speed, high responsivity and large saturation power is cost-effective and promising for short reach optical communication. PMID:27198501

  7. A dual-detector optical receiver for PDM signals detection

    PubMed Central

    Chen, Guanyu; Yu, Yu; Zhang, Xinliang

    2016-01-01

    We propose and fabricate a silicon based dual-detector optical receiver, which consists of a two dimensional (2D) grating coupler (GC) and two separate germanium photodetectors (Ge PDs). The 2D GC performs polarization diversity, and thus demultiplexing and detection for polarization division multiplexed (PDM) signals can be achieved. Through a specific design with double-sides illumination, the space charge density can be reduced and the responsivity and saturation power can be improved significantly. The measured dark current, responsivity and bandwidth are 0.86 μA, 1.06 A/W and 36 GHz under 3 V reverse biased voltage, respectively. Both DC currents and eye diagrams are measured for the proposed device and the results validate its performance successfully. The power penalty between the single and dual polarized signals is about 1.9 dB under 10 and 20 Gb/s cases for both the two Ge PDs. The proposed direct detection (DD) for PDM signals with high speed, high responsivity and large saturation power is cost-effective and promising for short reach optical communication. PMID:27198501

  8. A randomized, controlled trial of everolimus-based dual immunosuppression versus standard of care in de novo kidney transplant recipients.

    PubMed

    Chadban, Steven J; Eris, Josette Marie; Kanellis, John; Pilmore, Helen; Lee, Po Chang; Lim, Soo Kun; Woodcock, Chad; Kurstjens, Nicol; Russ, Graeme

    2014-03-01

    Kidney transplant recipients receiving calcineurin inhibitor-based immunosuppression incur increased long-term risks of cancer and kidney fibrosis. Switch to mammalian target of rapamycin (mTOR) inhibitors may reduce these risks. Steroid or Cyclosporin Removal After Transplant using Everolimus (SOCRATES), a 36-month, prospective, multinational, open-label, randomized controlled trial for de novo kidney transplant recipients, assessed whether everolimus switch could enable elimination of mycophenolate plus either steroids or CNI without compromising efficacy. Patients received cyclosporin, mycophenolate and steroids for the first 14 days then everolimus with mycophenolate and CNIwithdrawal (CNI-WD); everolimus with mycophenolate and steroid withdrawal (steroid-WD); or cyclosporin, mycophenolate and steroids (control). 126 patients were randomized. The steroid WD arm was terminated prematurely because of excess discontinuations. Mean eGFR at month 12 for CNI-WD versus control was 65.1 ml/min/1.73 m2 vs. 67.1 ml/min/1.73 m2 by ITT, which met predefined noninferiority criteria (P=0.026). The CNI-WD group experienced a higher rate of BPAR(31% vs. control 13%, P=0.048) and showed a trend towards higher composite treatment failure (BPAR, graft loss, death, loss to follow-up). The 12 month results from SOCRATES show noninferiority in eGFR, but a significant excess of acute rejection when everolimus was commenced at week 2 to enable a progressive withdrawal of mycophenolate and cyclosporin in kidney transplant recipients. PMID:24279685

  9. Optical design of a dual-polarization receiver for 220-280 GHz

    NASA Astrophysics Data System (ADS)

    Padman, Rachael

    1989-10-01

    A 220-280 GHz dual polarization receiver has been built for the James Clerk Maxwell Telescope. Schottky diode mixers cooled to about 15 K by a closed-cycle refrigerator are used to give DSB noise temperatures of 300 K and 420 K in the two channels. The optical design is based on Gaussian-beam optics, and is frequency independent; it allows the significant higher-order Gaussian modes to propagate unhindered, thus offering the prospect of very high aperture efficiency. The receiver includes a number of novel optical components, including a completely symmetric dual polarization Martin-Puplett interferometer. Measurements of the performance of the optical system are presented.

  10. [Commemorative lecture of receiving Imamura Memorial Prize. Characterization of immunosuppressive macrophages induced in mice infected with Mycobacterium intracellulare].

    PubMed

    Tomioka, H

    1993-12-01

    Functional changes in T lymphocytes and macrophages (M phi s) in host mice during the course of Mycobacterium intracellulare infection were studied. In both strains of mice, BALB/c or C57BL/6 (susceptible to M. avium complex) and CBA/JN or C3H/He (resistant to M. avium complex), the smooth, opaque and dome-shaped colonial (SmD) variants of M. intracellulare were easily eliminated from the sites after week 2 of infection. In contrast, the smooth, transparent and irregularly shaped colonial (SmT) variants showed steady growth in the former strains of mice and persisted for long time even in the latter strains of mice. No difference was found between persistence of the organisms in euthymic (+/+) and athymic (nu/nu) BALB/c mice during the first 4 weeks after infection. Thereafter, more rapid growth was seen in the spleens and lungs of nu/nu mice. Thus, matured T cells may be important for the prevention of the progression of M. intracellulare infection to the terminal state. Next, the profiles of generation and characteristics of splenic M phi s which suppress the Con A mitogenic response of splenic T cells in host CBA/JN or BALB/c mice during the course of M. intracellulare infection were investigated. In M. intracellulare--infected mice, reduction in some cellular functions of host splenic T cells, such as the Con A mitogenic response and mixed leucocyte reaction, were seen around 2 weeks after infection, and this was accompanied by appearance of immunosuppressive M phi s in spleen cells (SPCs).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8301920

  11. Tracking formulas and strategies for a receiver oriented dual-axis tracking toroidal heliostat

    SciTech Connect

    Guo, Minghuan; Wang, Zhifeng; Liang, Wenfeng; Zhang, Xiliang; Zang, Chuncheng; Lu, Zhenwu; Wei, Xiudong

    2010-06-15

    A 4 m x 4 m toroidal heliostat with receiver oriented dual-axis tracking, also called spinning-elevation tracking, was developed as an auxiliary heat source for a hydrogen production system. A series of spinning-elevation tracking formulas have been derived for this heliostat. This included basic tracking formulas, a formula for the elevation angle for heliostat with a mirror-pivot offset, and a more general formula for the biased elevation angle. This paper presents the new tracking formulas in detail and analyzes the accuracy of applying a simplifying approximation. The numerical results show these receiver oriented dual-axis tracking formula approximations are accurate to within 2.5 x 10{sup -6} m in image plane. Some practical tracking strategies are discussed briefly. Solar images from the toroidal heliostat at selected times are also presented. (author)

  12. CASES: A Novel Low-Cost Ground-based Dual-Frequency GPS Software Receiver

    NASA Astrophysics Data System (ADS)

    Haacke, B.; Crowley, G.; Reynolds, A.; Bust, G. S.; Kintner, P. M.; Psaiki, M.; Humphreys, T. E.; Powell, S.; O'Hanlon, B.

    2010-12-01

    GPS receivers can be used for monitoring space weather events such as TEC variations and scintillation. The new CASES GPS sensor developed by ASTRA, Cornell and UTAustin represents a revolutionary advance in dual frequency GPS space-weather monitoring. CASES is a paperback-novel-sized dual-frequency GPS software receiver with robust dual-frequency tracking performance, stand-alone capability, and complete software upgradability. This sensor measures and calculates TEC with a relative accuracy of a few 0.01 TECU at a cadence of up to 100 Hz. It measures amplitude and phase at up to 100 Hz on both L1 and L2, for up to 12 satellites in view. It calculates the scintillation severity indicators S4, τ0, and σφ at a cadence that is user defined. It is able to track through scintillation with {S4, τ0, amplitude} combinations as severe as {0.8, 0.8 seconds, 43 dB-Hz (nominal)} (i.e., commensurate with vigorous post-sunset equatorial scintillation) with a mean time between cycle slips greater than 240 seconds and with a mean time between frequency-unlock greater than 1 hour. Other capabilities and options include: Various data interface solutions; In-receiver and network-wide calibration of biases, and detection and mitigation of multipath; Network-wide automated remote configuration of receivers, quality control, re-processing, archiving and redistribution of data in real-time; Software products for data-processing and visualization. The low price of the sensor means that many more instruments can be purchased on a fixed budget, which will lead to new kinds of opportunities for monitoring and scientific study, including networked applications. Other uses for CASES receivers include geodetic and seismic monitoring, measurement of precipitable water vapor in the troposphere at meso-scale resolution, and educational outreach.

  13. W-band dual-polarization receiver for array of microwave background anisotropy (AMiBA)

    NASA Astrophysics Data System (ADS)

    Hwang, Yuh-Jing; Chen, Ming-Tang; Jiang, Homing; Chu, Tah-Hsiung; Hsieh, Sun-Nieng; Han, Chi-Chian; Patt, Ferdinand; Ho, West; Huang, Yau-Der; Wilson, Warwick

    2004-10-01

    This is to report on our development for a dual-polarization receiver to detect the cosmic microwave background (CMB) in 85 to 105 GHz band. The receiver is based on a MMIC, HEMT-based LNA developed in the Jet Propulsion Laboratory. A W-band, orthomode transducer (OMT) is used for polarization separation. Most of the RF front-end is located in cryogenics environment at 20K. We have developed a MMIC sub-harmonically pumped diode mixer, operating at 42 GHz, for signal down-conversion. The entire base-band, 2 to 18 GHz, is correlated in a lag-correlator system. The receiver design details and the lab test results will be described in this report.

  14. Digital Compensation of IQ Imbalance for Dual-Carrier Double Conversion Receivers

    NASA Astrophysics Data System (ADS)

    Park, Chester Sungchung; Park, Fitzgerald Sungkyung

    A receiver architecture and a digital IQ imbalance compensation method for dual-carrier reception are newly proposed. The impact of IQ imbalance on the baseband signal is mathematically analyzed. Based on the analysis, IQ imbalance parameters are estimated and the coupling effect of IQ imbalance is compensated using digital baseband processing alone. Simulation results show that the proposed IQ imbalance compensation successfully removes IQ imbalance. The deviation from the ideal performance is less than 1dB when it is applied to the 3GPP-LTE carrier aggregation.

  15. Immunosuppressive Medications

    PubMed Central

    2016-01-01

    Immunosuppressive agents are commonly used in the nephrologist’s practice in the treatment of autoimmune and immune-mediated diseases and transplantation, and they are investigational in the treatment of AKI and ESRD. Drug development has been rapid over the past decades as mechanisms of the immune response have been better defined both by serendipity (the discovery of agents with immunosuppressive activity that led to greater understanding of the immune response) and through mechanistic study (the study of immune deficiencies and autoimmune diseases and the critical pathways or mutations that contribute to disease). Toxicities of early immunosuppressive agents, such as corticosteroids, azathioprine, and cyclophosphamide, stimulated intense investigation for agents with more specificity and less harmful effects. Because the mechanisms of the immune response were better delineated over the past 30 years, this specialty is now bestowed with a multitude of therapeutic options that have reduced rejection rates and improved graft survival in kidney transplantation, provided alternatives to cytotoxic therapy in immune-mediated diseases, and opened new opportunities for intervention in diseases both common (AKI) and rare (atypical hemolytic syndrome). Rather than summarizing clinical indications and clinical trials for all currently available immunosuppressive medications, the purpose of this review is to place these agents into mechanistic context together with a brief discussion of unique features of development and use that are of interest to the nephrologist. PMID:26170177

  16. Immunosuppressive Medications.

    PubMed

    Wiseman, Alexander C

    2016-02-01

    Immunosuppressive agents are commonly used in the nephrologist's practice in the treatment of autoimmune and immune-mediated diseases and transplantation, and they are investigational in the treatment of AKI and ESRD. Drug development has been rapid over the past decades as mechanisms of the immune response have been better defined both by serendipity (the discovery of agents with immunosuppressive activity that led to greater understanding of the immune response) and through mechanistic study (the study of immune deficiencies and autoimmune diseases and the critical pathways or mutations that contribute to disease). Toxicities of early immunosuppressive agents, such as corticosteroids, azathioprine, and cyclophosphamide, stimulated intense investigation for agents with more specificity and less harmful effects. Because the mechanisms of the immune response were better delineated over the past 30 years, this specialty is now bestowed with a multitude of therapeutic options that have reduced rejection rates and improved graft survival in kidney transplantation, provided alternatives to cytotoxic therapy in immune-mediated diseases, and opened new opportunities for intervention in diseases both common (AKI) and rare (atypical hemolytic syndrome). Rather than summarizing clinical indications and clinical trials for all currently available immunosuppressive medications, the purpose of this review is to place these agents into mechanistic context together with a brief discussion of unique features of development and use that are of interest to the nephrologist. PMID:26170177

  17. The Pharmacology of Immunosuppression

    PubMed Central

    2009-01-01

    Objective To provide students with a comprehensive, integrated presentation on the pharmacology of immuosuppression. Design Course content on the pharmacology of immunosuppression relating to organ transplantation and treatment of autoimmune disorders was presented in integrated sequence modules that included content from pharmacology, medicinal chemistry, and therapeutics. Weekly recitation sessions and active-learning exercises were incorporated to allow students to apply the information they learned to integrated patient cases and stimulate involvement and critical thinking. Fundamental material related to the components and functions of the immune system was presented to students early in curriculum with courses such as biochemistry, pathophysiology, and immunology/microbiology. Assessment Comprehensive examinations, in-class quizzes, written case submissions, case discussions, review exercises, and group exercises were used to assess student learning. Conclusion Students at South University received a comprehensive and detailed understanding of all aspects relating to immunosuppressive therapy. This was accomplished by integrating instruction on immunosuppressive therapy from various disciplines. PMID:20221337

  18. Optically synchronized dual-channel terahertz signals for high-performance transmitter/receiver system

    NASA Astrophysics Data System (ADS)

    Shimizu, Naofumi; Oh, Kyoung-Hwan; Kohjiro, Satoshi; Kikuchi, Ken'ichi; Wakatsuki, Atsushi; Kukutsu, Naoya; Kado, Yuichi

    2010-02-01

    We developed a high-sweeping-speed optically synchronized dual-channel terahertz signal generator, in which the frequency difference between the two terahertz signals is independent of the frequency of the terahertz signals themselves. This feature is essential for heterodyne detection of terahertz signals with various frequencies. With this generator, a frequency-sweepable terahertz transmitter (Tx)/receiver (Rx) system with a wide dynamic range can be realized without sacrificing the high frequency-sweeping speed. Absorption line measurements for water vapor and nitrous oxide show that the developed Tx/Rx system can detect gas absorption with the optical depth of 0.04 or less. This result indicates the potential of the system as a remote gas sensor and gas analyzer.

  19. GPS/GLONASS Time Transfer with 20-Channel Dual GNSS Receiver

    NASA Technical Reports Server (NTRS)

    Daly, P.; Riley, S.

    1996-01-01

    One of the world's two global navigation systems, the Global Positioning System (GPS), is already fully operational (April 1994) and the other, the Global Navigation Satellite System (GLONASS) will become operational by the end of 1995 or early 1996. Each will offer, independently of the other, precise location and time transfer continuously anywhere in the world and indeed in space itself. Many potential users, in particular the civil aviation community, are keenly interested in a joint GPS/GLONASS operation since it would offer substantial advantages in defining and maintaining the integrity of the navigation aid. Results are presented on the characterization of GPS/GLONASS time comparison using a 20-channel dual receiver developed and constructed at the University of Leeds, UK.

  20. Characterization of dual-electrode CMUTs: demonstration of improved receive performance and pulse echo operation with dynamic membrane shaping.

    PubMed

    Guldiken, Rasim O; Balantekin, Mujdat; Zahorian, Jaime; Degertekin, F Levent

    2008-10-01

    A 1-D dual-electrode CMUT array for intracardiac echocardiography (ICE) with a center frequency of 8 MHz has been designed, fabricated, and used to demonstrate the potential of dual-electrode CMUTs. Using a dual-electrode CMUT, 9 dB higher receive signal level is obtained over the 6 dB fractional bandwidth as compared with a conventional CMUT with an identical center electrode biased close to its collapse voltage. Because the same device shows a 7.4 dB increase in maximum pressure output, 16.4 dB overall improvement in transduction performance has been achieved as compared with conventional CMUT. A net peak output pressure of 1.6 MPa on the dual-electrode CMUT membrane with tone burst excitation at 12 MHz is also reported. The frequency response of the dual-electrode CMUT is similar to that of a conventional CMUT with the same membrane geometry with about 15% increase in the center frequency. Monostatic operation of dual-electrode CMUTs shows that the high performance of the transducer is applicable in typical pulse-echo imaging mode of operation. With dynamic shaping of the CMUT membrane to optimize the transmit-and-receive modes of operation separately during each pulse-echo cycle, dual-electrode CMUT is a highly competitive alternative to its piezoelectric counterparts. PMID:18986882

  1. Immunosuppressive drugs and fertility.

    PubMed

    Leroy, Clara; Rigot, Jean-Marc; Leroy, Maryse; Decanter, Christine; Le Mapihan, Kristell; Parent, Anne-Sophie; Le Guillou, Anne-Claire; Yakoub-Agha, Ibrahim; Dharancy, Sébastien; Noel, Christian; Vantyghem, Marie-Christine

    2015-01-01

    Immunosuppressive drugs are used in the treatment of inflammatory and autoimmune diseases, as well as in transplantation. Frequently prescribed in young people, these treatments may have deleterious effects on fertility, pregnancy outcomes and the unborn child. This review aims to summarize the main gonadal side effects of immunosuppressants, to detail the effects on fertility and pregnancy of each class of drug, and to provide recommendations on the management of patients who are seen prior to starting or who are already receiving immunosuppressive treatment, allowing them in due course to bear children. The recommendations for use are established with a rather low level of proof, which needs to be taken into account in the patient management. Methotrexate, mycophenolate, and le- and teri-flunomide, cyclophosphamide, mitoxanthrone are contraindicated if pregnancy is desired due to their teratogenic effects, as well as gonadotoxic effects in the case of cyclophosphamide. Anti-TNF-alpha and mTOR-inhibitors are to be used cautiously if pregnancy is desired, since experience using these drugs is still relatively scarce. Azathioprine, glucocorticoids, mesalazine, anticalcineurins such as cyclosporine and tacrolimus, ß-interferon, glatiramer-acetate and chloroquine can be used during pregnancy, bearing in mind however that side effects may still occur. Experience is limited concerning natalizumab, fingolimod, dimethyl-fumarate and induction treatments. Conclusion: At the time of prescription, patients must be informed of the possible consequences of immunosuppressants on fertility and of the need for contraception. Pregnancy must be planned and the treatment modified if necessary in a pre-conception time period adapted to the half-life of the drug, imperatively in relation with the prescriber of the immunosuppressive drugs. PMID:26490561

  2. A dual-polarization coherent communication system with simplified optical receiver for UDWDM-PON architecture.

    PubMed

    Zheng, Jianyu; Lu, Feng; Xu, Mu; Zhu, Ming; Khalil, Md Ibrahim; Bao, Xu; Guidotti, Daniel; Liu, Jianguo; Zhu, Ninghua; Chang, Gee-Kung

    2014-12-29

    A dual-polarization coherent heterodyne optical communication system using a simplified and low-cost demodulation scheme, for high-capacity UDWDM-PON access networks, is proposed and demonstrated. In this scheme, the signal light and reference light occupying each of the polarization modes are emitted simultaneously from the transmitter. The random phase fluctuations between the signal light and reference light are obviated completely by means of the application of the phase-correlated orthogonal lights. When the signal light in the each polarization mode is modulated with M-amplitude-shift keying (M-ASK) or M2-quadrature amplitude modulation (M2-QAM), the phase-stable intermediate frequency (IF) signal with M-ASK or M2-QAM modulation in the corresponding polarization mode is available for conversion in the electrical domain by beating the modulated signal light with the un-modulated reference light. A new IF signal with M2 or M4-QAM can be synthesized by the IF signals in both modes as long as the power ratio and time delay between the two-modes optical signals are set at the proper values. This is achieved without using polarization demultiplexing and complicated algorithms and the synthesized IF signal can be received and demodulated directly. A proof-of-concept transmission link with dual-polarization 2-ASK is demonstrated. The experimental results are consistent with theoretical predictions. PMID:25607143

  3. Receivers

    NASA Astrophysics Data System (ADS)

    Donnelly, H.

    1983-07-01

    Before discussing Deep Space Network receivers, a brief description of the functions of receivers and how they interface with other elements of the Network is presented. Different types of receivers are used in the Network for various purposes. The principal receiver type is used for telemetry and tracking. This receiver provides the capability, with other elements of the Network, to track the space probe utilizing Doppler and range measurements, and to receive telemetry, including both scientific data from the onboard experiments and engineering data pertaining to the health of the probe. Another type of receiver is used for radio science applications. This receiver measures phase perturbations on the carrier signal to obtain information on the composition of solar and planetary atmospheres and interplanetary space. A third type of receiver utilizes very long baseline interferometry (VLBI) techniques for both radio science and spacecraft navigation data. Only the telemetry receiver is described in detail in this document. The integration of the Receiver-Exciter subsystem with other portions of the Deep Space Network is described.

  4. Receivers

    NASA Technical Reports Server (NTRS)

    Donnelly, H.

    1983-01-01

    Before discussing Deep Space Network receivers, a brief description of the functions of receivers and how they interface with other elements of the Network is presented. Different types of receivers are used in the Network for various purposes. The principal receiver type is used for telemetry and tracking. This receiver provides the capability, with other elements of the Network, to track the space probe utilizing Doppler and range measurements, and to receive telemetry, including both scientific data from the onboard experiments and engineering data pertaining to the health of the probe. Another type of receiver is used for radio science applications. This receiver measures phase perturbations on the carrier signal to obtain information on the composition of solar and planetary atmospheres and interplanetary space. A third type of receiver utilizes very long baseline interferometry (VLBI) techniques for both radio science and spacecraft navigation data. Only the telemetry receiver is described in detail in this document. The integration of the Receiver-Exciter subsystem with other portions of the Deep Space Network is described.

  5. Dual-pilot tone calibration technique. [to reduce multipath fading effects at mobile satellite link receiver

    NASA Technical Reports Server (NTRS)

    Simon, Marvin K.

    1986-01-01

    Pilot-based calibration techniques are used to reduce the effects of multipath fading in mobile satellite receivers. One of the more recent of these techniques, namely the tone calibration technique (TCT), suggests transmitting double sideband modulation with the pilot tone located at the center of its spectrum where the amplitude and phase characteristics of the channel are most stable. To 'make room' for the pilot in the presence of the Doppler shift, the equivalent low-pass data sidebands must be shaped so as to have zero response in the neighborhood of dc. Other techniques such as transparent tone-in-band (TTIB) similarly 'notch out' a hole in the center of the data spectrum for location of the pilot. An alternate possibility which is at the same time much more bandwidth efficient than TCT is a dual-pilot tone calibration technique (DPTCT) that symmetrically locates a pair of pilots outside the data spectrum near the band edges of the channel. The operation and performance of DPTCT are analyzed, and its effectiveness is compared to that of the single tone TCT technique.

  6. Dual-band RF receiver for GPS-L1 and compass-B1 in a 55-nm CMOS

    NASA Astrophysics Data System (ADS)

    Songting, Li; Jiancheng, Li; Xiaochen, Gu; Zhaowen, Zhuang

    2014-02-01

    A fully integrated dual-band RF receiver with a low-IF architecture is designed and implemented for GPS-L1 and Compass-B1 in a 55-nm CMOS process. The receiver incorporates two independent IF channels with 2 or 4 MHz bandwidth to receive dual-band signals around 1.57 GHz respectively. By implementing a flexible frequency plan, the RF front-end and frequency synthesizer are shared for the dual-band operation to save power consumption and chip area, as well as avoiding LO crosstalk. A digital automatic gain control (AGC) loop is utilized to improve the receiver's robustness by optimizing the conversion gain of the analog-to-digital converter (ADC). While drawing about 20 mA per channel from a 1.2 V supply, this RF receiver achieves a minimum noise figure (NF) of about 1.8 dB, an image rejection (IMR) of more than 35 dB, a maximum voltage gain of about 122 dB, a gain dynamic range of 82 dB, and an maximum input-referred 1 dB compression point of about -36.5 dBm with an active die area of 1.5 × 1.4 mm2 for the whole chip.

  7. Immunosuppressive treatment for kidney transplantation.

    PubMed

    Zivčić-Ćosić, S; Trobonjača, Z; Rački, S

    2011-01-01

    Immunosuppressive treatment minimizes unwanted immune reactivity, but it also leads to complications such as metabolic disorders, cardiovascular diseases and malignant tumours. In this paper we summarise the recent developments in action mechanisms of available immunosuppressive drugs and their usage for renal transplantation. These drugs act at various levels of lymphocytic activation and proliferation, and they may have additive or synergic effects when combined. In the majority of patients, the immunosuppressive protocol includes a calcineurin inhibitor (tacrolimus or cyclosporin), an antimetabolite (mycophenolate mofetil or mycophenolic acid) and a corticosteroid. Most patients also receive induction with monoclonal or polyclonal antilymphocytic antibodies. These immunosuppressive drugs allow a one-year survival of renal allografts in over 90% of cases and an incidence of acute rejection episodes below 15%. In most cases, acute cell-mediated rejection can be reversed with pulse doses of methylprednisolone; less often antilymphocytic antibodies must be applied. Acute humoral rejection can be suppressed with high doses of intravenous immunoglobulines or low doses of cytomegalovirus hyperimmune globuline, in combination with plasmapheresis, to obtain a satisfactory reduction of anti-donor antibodies. This treatment also allows renal transplantation for sensitised recipients, or transplantation against a positive cross match or AB0 incompatibility. Less often, immunoadsorption, alemtuzumab, rituximab or splenectomy are applied. New immunosuppressive drugs and protocols are currently under investigation. Immunosuppressive agents and methods targeting the induction of immune tolerance to the donor organ are especially promising. PMID:22286615

  8. Single-frequency, dual-GNSS versus dual-frequency, single-GNSS: a low-cost and high-grade receivers GPS-BDS RTK analysis

    NASA Astrophysics Data System (ADS)

    Odolinski, Robert; Teunissen, Peter J. G.

    2016-06-01

    The concept of single-frequency, dual-system (SF-DS) real-time kinematic (RTK) positioning has become feasible since, for instance, the Chinese BeiDou Navigation Satellite System (BDS) has become operational in the Asia-Pacific region. The goal of the present contribution is to investigate the single-epoch RTK performance of such a dual-system and compare it to a dual-frequency, single-system (DF-SS). As the SF-DS we investigate the L1 GPS + B1 BDS model, and for DF-SS we take L1, L2 GPS and B1, B2 BDS, respectively. Two different locations in the Asia-Pacific region are analysed with varying visibility of the BDS constellation, namely Perth in Australia and Dunedin in New Zealand. To emphasize the benefits of such a model we also look into using low-cost ublox single-frequency receivers and compare such SF-DS RTK performance to that of a DF-SS, based on much more expensive survey-grade receivers. In this contribution a formal and empirical analysis is given. It will be shown that with the SF-DS higher elevation cut-off angles than the conventional 10° or 15° can be used. The experiment with low-cost receivers for the SF-DS reveals (for the first time) that it has the potential to achieve comparable ambiguity resolution performance to that of a DF-SS (L1, L2 GPS), based on the survey-grade receivers.

  9. Dynamic bandwidth allocation algorithms for local storage based VoD delivery: Comparison between single and dual receiver configurations

    NASA Astrophysics Data System (ADS)

    Abeywickrama, Sandu; Wong, Elaine

    2015-02-01

    The benefits of using distributed caching servers to optimize the traditional video-on-demand delivery have been extensively discussed in literature. In our previous work, we introduced a dual-receiver based dynamic bandwidth allocation algorithm to improve video-on-demand services using a local storage placed within the access network. The main drawback of this algorithm lies in the additional power consumption at the optical network unit that arises from using two receivers. In this paper, we present two novel single-receiver based dynamic bandwidth allocation algorithms to further optimize local storage aided video-on-demand over passive optical networks. The quality-of-service and power performances of the algorithms are critically analyzed using packet level simulations and formulation of power consumption models. We show that the energy-efficiency of a local storage based video-on-demand scheme can be increased without compromising the quality-of-service by the use of single receiver algorithms. Further, we compare the two newly introduced algorithms against dual-receiver based and without local storage schemes to find the most appropriate bandwidth allocation algorithm for local storage based video-on-demand delivery over passive optical networks.

  10. Silicon photonic integrated circuit swept-source optical coherence tomography receiver with dual polarization, dual balanced, in-phase and quadrature detection

    PubMed Central

    Wang, Zhao; Lee, Hsiang-Chieh; Vermeulen, Diedrik; Chen, Long; Nielsen, Torben; Park, Seo Yeon; Ghaemi, Allan; Swanson, Eric; Doerr, Chris; Fujimoto, James

    2015-01-01

    Optical coherence tomography (OCT) is a widely used three-dimensional (3D) optical imaging method with many biomedical and non-medical applications. Miniaturization, cost reduction, and increased functionality of OCT systems will be critical for future emerging clinical applications. We present a silicon photonic integrated circuit swept-source OCT (SS-OCT) coherent receiver with dual polarization, dual balanced, in-phase and quadrature (IQ) detection. We demonstrate multiple functional capabilities of IQ polarization resolved detection including: complex-conjugate suppressed full-range OCT, polarization diversity detection, and polarization-sensitive OCT. To our knowledge, this is the first demonstration of a silicon photonic integrated receiver for OCT. The integrated coherent receiver provides a miniaturized, low-cost solution for SS-OCT, and is also a key step towards a fully integrated high speed SS-OCT system with good performance and multi-functional capabilities. With further performance improvement and cost reduction, photonic integrated technology promises to greatly increase penetration of OCT systems in existing applications and enable new applications. PMID:26203382

  11. Design of high-order HTS dual-band bandpass filters with receiver subsystem for future mobile communication systems

    NASA Astrophysics Data System (ADS)

    Sekiya, N.

    2016-08-01

    We have developed two high-order high-temperature superconducting (HTS) dual-band bandpass filters (BPFs) with a receiver subsystem for future mobile communication systems. They feature stub-loaded hair-pin resonators with two types of microstrip lines between them. One has a six-pole design, and the other has an eight-pole design. Both were designed to operate at 2.15 GHz with a 43-MHz (2%) bandwidth for the lower passband and at 3.50 GHz with a 70-MHz (2%) bandwidth for the upper one. They were fabricated using YBa2Cu3Oy thin film on a CeO2-bufferd r-Al2O3 substrate. The measured results for both filters agree well with the simulated ones. The HTS dual-band BPF receiver subsystem uses a pulse tube cryocooler and a wideband low noise amplifier (LNA). We measured the frequency response of the six-pole dual-band BPF with and without a wideband LNA with a gain of 10 dB. The measured return losses were close.

  12. Digital dual-rate burst-mode receiver for 10G and 1G coexistence in optical access networks.

    PubMed

    Mendinueta, José Manuel Delgado; Mitchell, John E; Bayvel, Polina; Thomsen, Benn C

    2011-07-18

    A digital dual-rate burst-mode receiver, intended to support 10 and 1 Gb/s coexistence in optical access networks, is proposed and experimentally characterized. The receiver employs a standard DC-coupled photoreceiver followed by a 20 GS/s digitizer and the detection of the packet presence and line-rate is implemented in the digital domain. A polyphase, 2 samples-per-bit digital signal processing algorithm is then used for efficient clock and data recovery of the 10/1.25 Gb/s packets. The receiver performance is characterized in terms of sensitivity and dynamic range under burst-mode operation for 10/1.25 Gb/s intensity modulated data in terms of both the packet error rate (PER) and the payload bit error rate (pBER). The impact of packet preamble lengths of 16, 32, 48, and 64 bits, at 10 Gb/s, on the receiver performance is investigated. We show that there is a trade-off between pBER and PER that is limited by electrical noise and digitizer clipping at low and high received powers, respectively, and that a 16/2-bit preamble at 10/1.25 Gb/s is sufficient to reliably detect packets at both line-rates over a burst-to-burst dynamic range of 14,5 dB with a sensitivity of -18.5 dBm at 10 Gb/s. PMID:21934767

  13. Nanoparticles and direct immunosuppression.

    PubMed

    Ngobili, Terrika A; Daniele, Michael A

    2016-05-01

    Targeting the immune system with nanomaterials is an intensely active area of research. Specifically, the capability to induce immunosuppression is a promising complement for drug delivery and regenerative medicine therapies. Many novel strategies for immunosuppression rely on nanoparticles as delivery vehicles for small-molecule immunosuppressive compounds. As a consequence, efforts in understanding the mechanisms in which nanoparticles directly interact with the immune system have been overshadowed. The immunological activity of nanoparticles is dependent on the physiochemical properties of the nanoparticles and its subsequent cellular internalization. As the underlying factors for these reactions are elucidated, more nanoparticles may be engineered and evaluated for inducing immunosuppression and complementing immunosuppressive drugs. This review will briefly summarize the state-of-the-art and developments in understanding how nanoparticles induce immunosuppressive responses, compare the inherent properties of nanomaterials which induce these immunological reactions, and comment on the potential for using nanomaterials to modulate and control the immune system. PMID:27229901

  14. Z45: A new 45-GHz band dual-polarization HEMT receiver for the NRO 45-m radio telescope

    NASA Astrophysics Data System (ADS)

    Nakamura, Fumitaka; Ogawa, Hideo; Yonekura, Yoshinori; Kimura, Kimihiko; Okada, Nozomi; Kozu, Minato; Hasegawa, Yutaka; Tokuda, Kazuki; Ochiai, Tetsu; Mizuno, Izumi; Dobashi, Kazuhito; Shimoikura, Tomomi; Kameno, Seiji; Taniguchi, Kotomi; Shinnaga, Hiroko; Takano, Shuro; Kawabe, Ryohei; Nakajima, Taku; Iono, Daisuke; Kuno, Nario; Onishi, Toshikazu; Momose, Munetake; Yamamoto, Satoshi

    2015-12-01

    We developed a dual-linear-polarization HEMT (High Electron Mobility Transistor) amplifier receiver system of the 45-GHz band (hereafter Z45), and installed it in the Nobeyama 45-m radio telescope. The receiver system is designed to conduct polarization observations by taking the cross-correlation of two linearly polarized components, from which we process full Stokes spectroscopy. We aim to measure the magnetic field strength through the Zeeman effect of the emission line of CCS (JN = 43-32) toward pre-protostellar cores. A linear-polarization receiver system has a smaller contribution of instrumental polarization components to the Stokes V spectra than that of the circular polarization system, so that it is easier to obtain the Stokes V spectra. The receiver has an RF frequency of 42-46 GHz and an intermediate frequency (IF) band of 4-8 GHz. The typical noise temperature is about 50 K, and the system noise temperature ranges from 100 to 150 K over the frequency of 42-46 GHz. The receiver system is connected to two spectrometers, SAM45 and PolariS. SAM45 is a highly flexible FX-type digital spectrometer with a finest frequency resolution of 3.81 kHz. PolariS is a newly developed digital spectrometer with a finest frequency resolution of 60 Hz, and which has a capability to process the full-Stokes spectroscopy. The half-power beam width (HPBW) was measured to be 37″ at 43 GHz. The main beam efficiency of the Gaussian main beam was derived to be 0.72 at 43 GHz. The SiO maser observations show that the beam pattern is reasonably round at about 10% of the peak intensity and the side-lobe level was less than 3% of the peak intensity. Finally, we present some examples of astronomical observations using Z45.

  15. Dual-beam ELF wave generation as a function of power, frequency, modulation waveform, and receiver location

    NASA Astrophysics Data System (ADS)

    Agrawal, D.; Moore, R. C.

    2012-12-01

    Dual-beam ELF wave generation experiments performed at the High-frequency Active Auroral Research Program (HAARP) HF transmitter are used to investigate the dependence of the generated ELF wave magnitude on HF power, HF frequency, modulation waveform, and receiver location. During the experiments, two HF beams transmit simultaneously: one amplitude modulated (AM) HF beam modulates the conductivity of the lower ionosphere at ELF frequencies while a second HF beam broadcasts a continuous waveform (CW) signal, modifying the efficiency of ELF conductivity modulation and thereby the efficiency of ELF wave generation. We report experimental results for different ambient ionospheric conditions, and we interpret the observations in the context of a newly developed dual-beam HF heating model. A comparison between model predictions and experimental observations indicates that the theoretical model includes the essential physics involved in multifrequency HF heating of the lower ionosphere. In addition to the HF transmission parameters mentioned above, the model is used to predict the dependence of ELF wave magnitude on the polarization of the CW beam and on the modulation frequency of the modulated beam. We consider how these effects vary with ambientD-region electron density and electron temperature.

  16. The critically ill immunosuppressed patient

    SciTech Connect

    Parrillo, J.E.; Masur, H. )

    1987-01-01

    This book discusses the papers on the diagnosis and management of immunosuppressed patient. Some of the topics are: life-threatening organ failure in immunosuppressed patients; diagnosis and therapy of respiratory disease in the immunosuppressed patient; CNS complication of immunosuppression; infections; antineoplastic therapy of immunosuppressed patient; radiation therapy-issues in critically ill patient; AIDS; and management of bone marrow transplant patients.

  17. A wideband dual-antenna receiver for wireless recording from animals behaving in large arenas.

    PubMed

    Lee, Seung Bae; Yin, Ming; Manns, Joseph R; Ghovanloo, Maysam

    2013-07-01

    A low-noise wideband receiver (Rx) is presented for a multichannel wireless implantable neural recording (WINeR) system that utilizes time-division multiplexing of pulse width modulated (PWM) samples. The WINeR-6 Rx consists of four parts: 1) RF front end; 2) signal conditioning; 3) analog output (AO); and 4) field-programmable gate array (FPGA) back end. The RF front end receives RF-modulated neural signals in the 403-490 MHz band with a wide bandwidth of 18 MHz. The frequency-shift keying (FSK) PWM demodulator in the FPGA is a time-to-digital converter with 304 ps resolution, which converts the analog pulse width information to 16-bit digital samples. Automated frequency tracking has been implemented in the Rx to lock onto the free-running voltage-controlled oscillator in the transmitter (Tx). Two antennas and two parallel RF paths are used to increase the wireless coverage area. BCI-2000 graphical user interface has been adopted and modified to acquire, visualize, and record the recovered neural signals in real time. The AO module picks three demultiplexed channels and converts them into analog signals for direct observation on an oscilloscope. One of these signals is further amplified to generate an audio output, offering users the ability to listen to ongoing neural activity. Bench-top testing of the Rx performance with a 32-channel WINeR-6 Tx showed that the input referred noise of the entire system at a Tx-Rx distance of 1.5 m was 4.58 μV rms with 8-bit resolution at 640 kSps. In an in vivo experiment, location-specific receptive fields of hippocampal place cells were mapped during a behavioral experiment in which a rat completed 40 laps in a large circular track. Results were compared against those acquired from the same animal and the same set of electrodes by a commercial hardwired recording system to validate the wirelessly recorded signals. PMID:23428612

  18. A Wideband Dual-Antenna Receiver for Wireless Recording From Animals Behaving in Large Arenas

    PubMed Central

    Lee, Seung Bae; Yin, Ming; Manns, Joseph R.

    2014-01-01

    A low-noise wideband receiver (Rx) is presented for a multichannel wireless implantable neural recording (WINeR) system that utilizes time-division multiplexing of pulse width modulated (PWM) samples. The WINeR-6 Rx consists of four parts: 1) RF front end; 2) signal conditioning; 3) analog output (AO); and 4) field-programmable gate array (FPGA) back end. The RF front end receives RF-modulated neural signals in the 403–490 MHz band with a wide bandwidth of 18 MHz. The frequency-shift keying (FSK) PWM demodulator in the FPGA is a time-to-digital converter with 304 ps resolution, which converts the analog pulse width information to 16-bit digital samples. Automated frequency tracking has been implemented in the Rx to lock onto the free-running voltage-controlled oscillator in the transmitter (Tx). Two antennas and two parallel RF paths are used to increase the wireless coverage area. BCI-2000 graphical user interface has been adopted and modified to acquire, visualize, and record the recovered neural signals in real time. The AO module picks three demultiplexed channels and converts them into analog signals for direct observation on an oscilloscope. One of these signals is further amplified to generate an audio output, offering users the ability to listen to ongoing neural activity. Bench-top testing of the Rx performance with a 32-channel WINeR-6 Tx showed that the input referred noise of the entire system at a Tx–Rx distance of 1.5 m was 4.58 μVrms with 8-bit resolution at 640 kSps. In an in vivo experiment, location-specific receptive fields of hippocampal place cells were mapped during a behavioral experiment in which a rat completed 40 laps in a large circular track. Results were compared against those acquired from the same animal and the same set of electrodes by a commercial hardwired recording system to validate the wirelessly recorded signals. PMID:23428612

  19. A high-efficiency, low-noise power solution for a dual-channel GNSS RF receiver

    NASA Astrophysics Data System (ADS)

    Jian, Shi; Taishan, Mo; Jianlian, Le; Yebing, Gan; Chengyan, Ma; Tianchun, Ye

    2012-08-01

    A high-efficiency low-noise power solution for a dual-channel GNSS RF receiver is presented. The power solution involves a DC—DC buck converter and a followed low-dropout regulator (LDO). The pulse-width-modulation (PWM) control method is adopted for better noise performance. An improved low-power high-frequency PWM control circuit is proposed, which halves the average quiescent current of the buck converter to 80 μA by periodically shutting down the OTA. The size of the output stage has also been optimized to achieve high efficiency under a light load condition. In addition, a novel soft-start circuit based on a current limiter has been implemented to avoid inrush current. Fabricated with commercial 180-nm CMOS technology, the DC—DC converter achieves a peak efficiency of 93.1% under a 2 MHz working frequency. The whole receiver consumes only 20.2 mA from a 3.3 V power supply and has a noise figure of 2.5 dB.

  20. Design of a dual-channel multi-mode GNSS receiver with a Σ Δ fractional-N synthesizer

    NASA Astrophysics Data System (ADS)

    Qiang, Long; Yiqi, Zhuang; Yue, Yin; Le, Li; Jin, Wang; Zhenrong, Li; Qiankun, Liu; Lei, Wang

    2012-11-01

    A 72 mW highly integrated dual-channel multimode GNSS (global navigation satellite system) receiver with a Σ Δ fractional-N synthesizer which covers GPS L1 and the Compass B1/B2/B3 band is presented. This chip was fabricated in a TSMC CMOS 0.18 μm process and packaged in a 48-pin 3 × 3 mm2 land grid array chip scale package. This work achieves NF <= 5.3 dB without an external LNA, channel gain = 105 dB for channel one (Compass B2 and B3 band), and channel gain = 110 dB for channel two (GPS L1 and Compass B1 band). Image rejection (IMRR) = 36 dB, phase noise is -115.9 dBc @ 1 MHz and -108.9 dBc @ 1 MHz offset from the carrier for the two channels separately. At the low power consumption, multibands of GNSS are compatible in one chip, which is easy for consumers to use, when two different navigation signals are received simultaneously.

  1. Impact of diabetes on immature platelets fraction and its relationship with platelet reactivity in patients receiving dual antiplatelet therapy.

    PubMed

    Verdoia, Monica; Pergolini, Patrizia; Nardin, Matteo; Rolla, Roberta; Barbieri, Lucia; Schaffer, Alon; Marino, Paolo; Bellomo, Giorgio; Suryapranata, Harry; De Luca, Giuseppe

    2016-08-01

    Contrasting data have been reported so far on the role of reticulated platelets in suboptimal response to antiplatelet therapies. In particular, still unexplored is whether they may contribute to explain the higher risk of thrombotic complications observed in diabetic patients. Aim of the present study was to evaluate the impact of diabetes on the levels of reticulated platelets and its relationship with high residual on-treatment platelet reactivity (HRPR) in patients receiving dual antiplatelet therapy. In patients treated with ASA (100-160 mg) and clopidogrel (75 mg daily) or ticagrelor (90 mg twice a day) platelet reactivity and the reticulated platelets fraction (immature platelets fraction, IPF) were assessed at 30-90 days post-discharge for an acute coronary syndrome or elective PCI. Aggregation was assessed by multiple-electrode aggregometry. We included 386 patients, 158 (40.9 %) diabetics. The percentage of IPF was similar in diabetic and non diabetic patients, both at baseline (3.5 ± 2.5 vs 3.6 ± 2.7 %, p = 0.91) and at 30-90 days re-assessment (3.3 ± 2.1 vs 3.5 ± 2.5 %, p = 0.30), with diabetes not emerging as an independent predictor of IPF above III tertile (adjusted OR [95 %CI] = 0.58 [0.30-1.09], p = 0.10). Diabetic patients displayed an enhanced platelet reactivity and a higher rate of HRPR with ADP antagonists (32.8 vs 22.5 %, p = 0.009). However, no association was found between the percentage of IPF and platelet function (r = -0.004; p = 0.95 for ASPI test, r = -0.04; p = 0.59 for ADP-mediated aggregation), or the rate of HRPR for ADP antagonsist across IPF tertiles. Results were similar for diabetics both receiving clopidogrel and ticagrelor. Diabetic patients display a higher platelet reactivity and suboptimal response to ADP-antagonists. However, the rate of reticulated platelets is neither influenced by diabetic status nor associated with an increased platelet reactivity among diabetic patients

  2. Blind, fast and SOP independent polarization recovery for square dual polarization-MQAM formats and optical coherent receivers.

    PubMed

    Chagnon, Mathieu; Osman, Mohamed; Xu, Xian; Zhuge, Qunbi; Plant, David V

    2012-12-01

    We present both theoretically and experimentally a novel blind and fast method for estimating the State of Polarization (SOP) of a single carrier channel modulated in square Dual Polarization (DP) MQAM format for optical coherent receivers. The method can be used on system startup, for quick channel reconfiguration, or for burst mode receivers. It consists of converting the received waveform from Jones to Stokes space and looping over an algorithm until a unitary polarization derotation matrix is estimated. The matrix is then used to initialize the center taps of the subsequent classical decision-directed stochastic gradient algorithm (DD-LMS). We present experimental comparisons of the initial Bit Error Rate (BER) and the speed of convergence of this blind Stokes space polarization recovery (PR) technique against the common Constant Modulus Algorithm (CMA). We demonstrate that this technique works on any square DP-MQAM format by presenting experimental results for DP-4QAM, -16QAM and -64QAM at varying distances and baud rates. We additionally numerically assess the technique for varying differential group delays (DGD) and sampling offsets on 28 Gbaud DP-4QAM format and show fast polarization recovery for instantaneous DGD as high as 90% of symbol duration. We show that the convergence time of this blind PR technique does not depend on the initial SOP as CMA does and allows switching to DD-LMS faster by more than an order of magnitude. For DP-4QAM, it shows a convergence time of 5.9 ns, which is much smaller than the convergence time of recent techniques using modified CMA algorithms for quicker convergence. BER of the first 20 × 10(3) symbols is always smaller by several factors for DP-16QAM and -64QAM but not always for DP-4QAM. PMID:23262730

  3. Melanoma in Immunosuppressed Patients

    PubMed Central

    Kubica, Agnieszka W.; Brewer, Jerry D.

    2012-01-01

    The immunogenic characteristics of malignant melanoma are intriguing. To date, multiple studies exist regarding the immunogenicity of melanoma. In this article, we summarize data in the literature on the role of immunosuppression in melanoma and discuss several immunocompromised patient populations in detail. A comprehensive PubMed search was conducted with no date limitation. The following search terms were used: melanoma in combination with immunosuppression, immunocompromised, genetics, antigen processing, UV radiation, organ transplantation, organ transplant recipients, lymphoproliferative disease, lymphoma, CLL, NHL, radiation, and HIV/AIDS. Although no formal criteria were used for inclusion of studies, most pertinent studies on the topic were reviewed, with the exception of smaller case reports and case series. The included studies were generally large (≥1000 patients in organ transplant recipient studies; ≥500 patients in lymphoma studies), with a focus on institutional experiences, or population-based national or international epidemiologic studies. Melanoma-induced immunosuppression, the role of UV radiation in melanoma development, and the epidemiology, clinical course, and prognosis of melanoma in immunocompromised patients are highlighted. Organ transplant recipients, patients with lymphoproliferative disorders, patients with iatrogenic immunosuppression, and patients with human immunodeficiency virus infection/AIDS are also highlighted. Recommendations are proposed for the care and monitoring of immunosuppressed patients with melanoma. With better understanding of the molecular microenvironment and clinical course of melanoma in immunosuppressed patients, novel therapies could be developed and outcomes potentially affected in these patients. PMID:23036673

  4. A 4mm spectroscopic dual-beam receiver for the Robert C. Byrd green bank radio telescope

    NASA Astrophysics Data System (ADS)

    White, Steven; Frayer, David; Stennes, Mike; Simon, Robert; Watts, Galen; Norrod, Roger; Bryerton, Eric; Srikanth, Sivasankaran; Pospieszalski, Marian

    2012-09-01

    With a 100-meter aperture, and recent improvements to its surface accuracy and servo system upgrades, the Robert C. Byrd Green Bank Telescope is the most sensitive telescope operating at 90 GHz. A dual-feed heterodyne receiver is developed for observations at the lower frequency end of the 3-4mm atmospheric window (67 to 93 GHz). The science goals are primarily molecular spectroscopic studies of star formation and astrochemistry both internal and external to the Milky Way galaxy. Studies of the structural and physical properties of star-forming, cold-cloud cores will be revolutionized with molecular spectroscopy of the deuterium and other important species within the band. Essential for spectroscopy is the ability to remove slow gain and atmospheric variations. An optical table external to the cooled components rotates into the path of either beam an ambient temperature load, an offset mirror for viewing an internal cold load, or a quarter-wave plate that produces circular polarization for VLBI observations. A composite waveguide window comprised of HDPE, Zitex, and z-cut quartz provides a high-strength, low-loss medium for transmission of the signal to the cooled corrugated feed horn. An orthomode transducer separates the polarization components which are amplified by low noise HEMT amplifiers. Warm W-band MMIC amplifiers are required to compensate a negative gain slope and to reduce noise contributions from the down conversion to the GBT IF frequencies. Initial science results and receiver performance during commissioning observations will be presented along with details of the component design.

  5. Immunosuppression for lung transplantation

    PubMed Central

    Ng, Choo Y.; Madsen, Joren C.; Rosengard, Bruce R.; Allan, James S.

    2010-01-01

    1. ABSTRACT As a result of advances in surgical techniques, immunosuppressive therapy, and postoperative management, lung transplantation has become an established therapeutic option for individuals with a variety of end-stage lung diseases. The current 1-year actuarial survival rate following lung transplantation is approaching 80%. However, the 5- year actuarial survival rate has remained virtually unchanged at approximately 50% over the last 15 years due to the processes of acute and chronic lung allograft rejection (1). Clinicians still rely on a vast array of immunosuppressive agents to suppress the process of graft rejection, but find themselves limited by an inescapable therapeutic paradox. Insufficient immunosuppression results in graft loss due to rejection, while excess immunosuppression results in increased morbidity and mortality from opportunistic infections and malignancies. Indeed, graft rejection, infection, and malignancy are the three principal causes of mortality for the lung transplant recipient. One should also keep in mind that graft loss in a lung transplant recipient is usually a fatal event, since there is no practical means of long-term mechanical support, and since the prospects of re-transplantation are low, given the shortage of acceptable donor grafts. This chapter reviews the current state of immunosuppressive therapy for lung transplantation and suggests alternative paradigms for the management of future lung transplant recipients. PMID:19273152

  6. Immunosuppression during spaceflight deconditioning.

    PubMed

    Levine, D S; Greenleaf, J E

    1998-02-01

    Spaceflight results in immunosuppression which is likely due mainly to neurohumoral factors released in response to intermittent stress effects during flight. However, no major non-physiological health problems have been reported during or following spaceflight, but diseases resulting from immunosuppression could occur on long-duration missions and would include bacterial, fungal, and viral infections in addition to increased incidence of neoplasia and autoimmunity. Pharmacokinetics and pharmacodynamics appear to be altered during spaceflight and, as a consequence, alternative drug administration and dosing procedures will need to be developed. Moderate exercise training enhances immune function, but in-flight exercise may affect immunological parameters and immunity in ways not yet ascertained. Hyperosmolality may enhance some immune parameters, and attenuate others especially when associated with dehydration and exercise. Reducing in-flight stress may attenuate flight-induced immunosuppression, but pharmacological interventions may be essential to prevent undesirable immune responses which may occur on long-duration missions to Mars. PMID:9491259

  7. Immunosuppression During Trypanosomiasis

    PubMed Central

    Goodwin, L. G.; Green, D. G.; Guy, M. W.; Voller, A.

    1972-01-01

    Mice and rabbits infected with Trypanosoma brucei developed much lower agglutinin levels than uninfected animals when injected with sheep erythrocytes. The immunosuppression became more marked as the infection progressed. The infected rabbits produced heterophile agglutinins but the mice did not. PMID:5014242

  8. IINFLUENCE OF THE IMMUNOSUPPRESSANT TACROLIMUS (FK-506) ON THE FLEXURAL STRENGTH OF FEMUR: A STUDY IN RATS

    PubMed Central

    Pithon, Matheus Melo; de Andrade, Ana Carolina Dias Viana; de Brito Rodrigues, Vinícius; dos Santos, Rogério Lacerda

    2015-01-01

    Objective: To evaluate the resistance to femoral fractures among rats treated with the immunosuppressant tacrolimus FK-506 and compare these to untreated rats and rats treated with placebo. Methods: Ninety male Wistar rats were used. The animals were nine weeks old and weighed between 220 g and 280 g. The immunosuppressive agent tacrolimus was used in this study at a dose of 2 mg/kg/day, administered orally. The suspension was administered using an insulin syringe, and the maintenance therapeutic dose was sufficient to maintain the immunosuppressive activity. The animals were randomly divided into three groups (n = 30): group 1, no substance administered; group 2, administration of the immunosuppressant tacrolimus FK-506; and group 3, administration of the vehicle alone. Treatment with FK-506 was administered for 28 days. Total leukocyte counts and differential counts (lymphocytes, monocytes, eosinophils and neutrophils) were evaluated in order to monitor the immunosuppressive effect. Bone densitometry analysis by means of dual-energy x-ray absorptiometry (DXA) was also performed before and after administration of the drug. To evaluate the resistance to flexion, a support device was developed so that mechanical tests using an EMIC universal testing machine could be carried out. Results: The results from the flexion resistance tests showed statistical differences between groups 1 and 2 (p = 0.001) and between groups 2 and 3 (p = 0.001). No statistical difference was found between groups 1 and 3 (p = 0.995). Conclusions: The femurs of rats treated with the immunosuppressive agent had lower mechanical strength than did those of normal rats and those that received placebo. PMID:27022554

  9. Successful treatment of renal allograft and bladder malakoplakia with minimization of immunosuppression and prolonged antibiotic therapy.

    PubMed

    Graves, Angela L; Texler, Michael; Manning, Laurens; Kulkarni, Hemant

    2014-04-01

    Malakoplakia is an unusual granulomatous inflammatory disorder associated with diminished bactericidal action of leucocytes that occurs in immunosuppressed hosts. Cases of renal allograft malakoplakia are generally associated with a poor graft and patient survival. We present the case of a 56-year-old female with allograft and bladder malakoplakia occurring two years after renal transplantation complicated by an early antibody mediated rejection. Following a number of symptomatic urinary tract infections caused by resistant Gram-negative bacilli, a diagnosis of malakoplakia was made by biopsy of a new mass lesion of the renal allograft. Cystoscopy also revealed malakoplakia of the bladder wall. Immunosuppressant regimen was modified. Mycophenolate mofetil was ceased, prednisolone reduced to 5 mg/day and tacrolimus concentrations were carefully monitored to maintain trough serum concentrations of 2-4 μg/L. Concurrently, she received a prolonged course of intravenous antibiotics followed by 13 months of dual oral antibiotic therapy with fosfomycin and faropenem. This joint approach resulted in almost complete resolution of allograft malakoplakia lesions and sustained regression of bladder lesions on cystoscopy with histological resolution in bladder lesions. Her renal function has remained stable throughout the illness. If treated with sustained antimicrobial therapy and reduction of immunosuppression, cases of allograft malakoplakia may not necessarily be associated with poor graft survival. PMID:24460630

  10. Tilting toward immunosuppression

    PubMed Central

    Hotchkiss, Richard S.; Coopersmith, Craig M.; McDunn, Jonathan E.; Ferguson, Thomas A.

    2013-01-01

    The immune response goes haywire during sepsis, a deadly condition triggered by infection. Richard S. Hotchkiss and his colleagues take the focus off of the prevailing view that the key aspect of this response is an exuberant inflammatory reaction. They assess recent human studies bolstering the notion that immunosuppression is also a major contributor to the disease. Many people with sepsis succumb to cardiac dysfunction, a process examined by Peter Ward. He showcases the factors that cause cardiomyocyte contractility to wane during the disease. PMID:19424209

  11. New approaches for immunosuppression

    SciTech Connect

    Eiseman, B.; Hansbrough, J.; Weil, R.

    1980-01-01

    New approaches for experimental immunosuppression have been reviewed. These include the following: (1) cyclosporin A, a metabolite from fungus that suppresses multiplying but not resting T and B lymphocytes and can be used in pulsed manner with interspersed drug-free periods; (2) total lymphoid irradiation (transplantation tolerance in rats has been achieved by pretransplant radiation); (3) thoracic duct drainage, which is being revived following its demonstrated effectiveness in the treatment of some autoimmune diseases; (4) hyperbaric oxygen (HBOX). We have found that HBOX 2 1/2 ATA for five hours daily depresses cell-mediated immunity in mice and that this can be reversed by intravenous administration of autologous macrophages.

  12. Ethanol immunosuppression in vitro

    SciTech Connect

    Kaplan, D.R.

    1986-03-01

    Ethanol in concentrations equivalent to levels achieved by the ingestion of moderate to large amounts of alcoholic beverages has been shown to inhibit mitogen and anti-CD3 stimulated human T lymphocyte proliferation. This inhibition was monophasic suggesting that ethanol affected a single limiting component of T cell proliferation. In experiments designed to test the effect of ethanol on various aspects of proliferation, it was demonstrated that ethanol inhibited the capacity of exogenously supplied interleukin 2 to stimulate proliferation of T cells that had previously acquired interleukin 2 receptors in a monophasic, dose-dependent manner. Moreover, there was no suppression of interleukin 2 production or interleukin 2 receptor acquisition. Thus, ethanol was shown to mediate immunosuppression by a mechanism specific to one component of proliferation. Additive inhibition of T cell proliferation was seen with ethanol plus cyclosporin A which inhibits interleukin 2 production. The level of inhibition with 250 ng/ml cyclosporin A alone was equivalent to the level seen with 62 ng/ml cyclosporin A plus 20 mM (94 mg%) ethanol. Ethanol also suppressed an immune effector mechanism. NK cytotoxicity was depressed in a monophasic, dose-dependent manner. Thus, ethanol might be considered as a possible adjunct in immunosuppressive therapy.

  13. Accuracy analysis on C/A code and P(Y) code pseudo-range of GPS dual frequency receiver and application in point positioning

    NASA Astrophysics Data System (ADS)

    Peng, Xiuying; Fan, Shijie; Guo, Jiming

    2008-10-01

    When the Anti-Spoofing (A-S) is active, the civilian users have some difficulties in using the P(Y) code for precise navigation and positioning. Z-tracking technique is one of the effective methods to acquire the P(Y) code. In this paper, the accuracy of pseudoranges from C/A code and P(Y) code for dual frequency GPS receiver is discussed. The principle of measuring the encrypted P(Y) code is described firstly, then a large data set from IGS tracking stations is utilized for analysis and verification with the help of a precise point positioning software developed by authors. Especially, P(Y) code pseudoranges of civilian GPS receivers allow eliminating/reducing the effect of ionospheric delay and improve the precision of positioning. The point positioning experiments for this are made in the end.

  14. Immunosuppressants in cancer prevention and therapy

    PubMed Central

    Blagosklonny, Mikhail V

    2013-01-01

    Rapalogs such as rapamycin (sirolimus), everolimus, temserolimus, and deforolimus are indicated for the treatment of some malignancies. Rapamycin is the most effective cancer-preventive agent currently known, at least in mice, dramatically delaying carcinogenesis in both normal and cancer-prone murine strains. In addition, rapamycin and everolimus decrease the risk of cancer in patients receiving these drugs in the context of immunosuppressive regimens. In general, the main concern about the use of immunosuppressants in humans is an increased risk of cancer. Given that rapalogs are useful in cancer prevention and therapy, should they be viewed as immunosuppressants or immunostimulators? Or should we reconsider the role of immunity in cancer altogether? In addition to its anti-viral, anti-inflammatory, anti-angiogenic and anti-proliferative effects, rapamycin operates as a gerosuppressant, meaning that it inhibits the cellular conversion to a senescent state (the so-called geroconversion), a fundamental process involved in aging and age-related pathologies including cancer. PMID:24575379

  15. Deoxyspergualin--a novel immunosuppressant.

    PubMed

    Jindal, R M; Tepper, M A; Soltys, K; Cho, S I

    1994-01-01

    DSG appears to have a unique, although as yet undefined, mechanism of action and may be a useful immunosuppressive agent. Because DSG is effective in reducing preformed antibodies in the xenograft situation, it may have a significant advantage in ABO-incompatible grafts in transplant recipients with high panel-reactive antibodies. Most important, DSG may have a definitive role in immunosuppressive therapy for pancreatic grafts. PMID:8183294

  16. Clinical Significance of Enteric Protozoa in the Immunosuppressed Human Population

    PubMed Central

    Stark, D.; Barratt, J. L. N.; van Hal, S.; Marriott, D.; Harkness, J.; Ellis, J. T.

    2009-01-01

    Summary: Globally, the number of immunosuppressed people increases each year, with the human immunodeficiency virus (HIV) pandemic continuing to spread unabated in many parts of the world. Immunosuppression may also occur in malnourished persons, patients undergoing chemotherapy for malignancy, and those receiving immunosuppressive therapy. Components of the immune system can be functionally or genetically abnormal as a result of acquired (e.g., caused by HIV infection, lymphoma, or high-dose steroids or other immunosuppressive medications) or congenital illnesses, with more than 120 congenital immunodeficiencies described to date that either affect humoral immunity or compromise T-cell function. All individuals affected by immunosuppression are at risk of infection by opportunistic parasites (such as the microsporidia) as well as those more commonly associated with gastrointestinal disease (such as Giardia). The outcome of infection by enteric protozoan parasites is dependent on absolute CD4+ cell counts, with lower counts being associated with more severe disease, more atypical disease, and a greater risk of disseminated disease. This review summarizes our current state of knowledge on the significance of enteric parasitic protozoa as a cause of disease in immunosuppressed persons and also provides guidance on recent advances in diagnosis and therapy for the control of these important parasites. PMID:19822892

  17. Dual infections with different Legionella strains.

    PubMed

    Wewalka, G; Schmid, D; Harrison, T G; Uldum, S A; Lück, C

    2014-01-01

    In 2010 a case of a dual infection with Legionella pneumophila serogroup (sg) 1 and sg 3 was identified by culture of a blood sample collected from a female Austrian patient with septic pneumonia. Subsequently all 35 European National Legionella Reference Laboratories were interviewed regarding the frequency of dual infections in legionellosis. The Reference Laboratories in Denmark, the UK and Germany reported the detection of another 14 cases of dual infections with different Legionella strains between 2002 and 2012. Among the 15 cases, there were four cases with different Legionella species, six cases with different L. pneumophila serogroups, and five cases of dual infections with L. pneumophila sg 1 with different MAb-types. The median age of the 15 cases was 56 years and the male to female ratio 1:1.14. Six of the 15 patients were receiving immunosuppressive treatment following organ transplantation (n = 3) or for underlying haematological and solid malignancies (n = 3). Five of the 15 cases died within 30 days following diagnosis. Efforts to detect dual infections with different Legionella strains will improve our ability to correctly elucidate the causative sources of infection and enhance our understanding of the epidemiology of Legionella infections. PMID:23910438

  18. Adverse Effects of Systemic Immunosuppression in Keratolimbal Allograft

    PubMed Central

    Krakauer, M.; Welder, J. D.; Pandya, H. K.; Nassiri, N.; Djalilian, A. R.

    2012-01-01

    Purpose. Keratolimbal allograft (KLAL) is a treatment for limbal stem cell deficiency. One disadvantage is systemic immunosuppression to avoid rejection. Our purpose was to examine the adverse effects of systemic immunosuppression in KLAL. Methods. A retrospective case review of 16 patients with KLAL who received systemic immunosuppression consisting of a corticosteroid, an antimetabolite, and/or a calcineurin inhibitor was performed. Patients were monitored for signs, symptoms, or laboratory evidence of toxicity. Results. Eleven of 16 patients (68%) experienced an adverse effect. The average age of those with adverse effects was 43.5 years and without was 31.4 years. Ten of 11 patients (91%) had resolution during mean followup of 16.4 months. No serious adverse effects occurred. The most common included anemia, hyperglycemia, elevated creatinine, and elevated liver function tests. Prednisone and tacrolimus were responsible for the most adverse effects. Patients with comorbidities were more likely to experience an adverse effect (82% versus 20%, P = 0.036). Conclusions. KLAL requires prolonged systemic immunosuppression. Our data demonstrated that systemic immunosuppression did not result in serious adverse effects in our population and is relatively safe with monitoring for toxicity. In addition, we demonstrated that adverse effects are more likely in older patients with comorbidities. PMID:22523651

  19. Ocular toxoplasmosis in immunosuppressed nonhuman primates

    SciTech Connect

    Holland, G.N.; O'Connor, G.R.; Diaz, R.F.; Minasi, P.; Wara, W.M.

    1988-06-01

    To investigate the role of cellular immunodeficiency in recurrent toxoplasmic retinochoroiditis, six Cynomolgus monkeys (Macaca fascicularis) with healed toxoplasmic lesions of the retina were immunosuppressed by total lymphoid irradiation. Three months prior to irradiation 30,000 Toxoplasma gondii organisms of the Beverley strain had been inoculated onto the macula of eye in each monkey via a pars plana approach. Toxoplasmic retinochoroiditis developed in each animal, and lesions were allowed to heal without treatment. During total lymphoid irradiation animals received 2000 centigrays (cGy) over a 7-week period. Irradiation resulted in an immediate drop in total lymphocyte counts and decreased ability to stimulate lymphocytes by phytohemagglutinin. Weekly ophthalmoscopic examinations following irradiation failed to show evidence of recurrent ocular disease despite persistent immunodeficiency. Four months after irradiation live organisms were reinoculated onto the nasal retina of the same eye in each animal. Retinochoroidal lesions identical to those seen in primary disease developed in five of six animals. Toxoplasma organisms therefore were able to proliferate in ocular tissue following the administration of immunosuppressive therapy. This study fails to support the hypothesis that cellular immunodeficiency alone will initiate recurrent toxoplasmic retinochoroiditis. Results suggest that reactivation of disease from encysted organisms involves factors other than suppression of Toxoplasma proliferation. If reactivation occurs by other mechanisms, however, cellular immunodeficiency then may allow development of extensive disease.

  20. (19)F MRSI of capecitabine in the liver at 7 T using broadband transmit-receive antennas and dual-band RF pulses.

    PubMed

    van Gorp, Jetse S; Seevinck, Peter R; Andreychenko, Anna; Raaijmakers, Alexander J E; Luijten, Peter R; Viergever, Max A; Koopman, Miriam; Boer, Vincent O; Klomp, Dennis W J

    2015-11-01

    Capecitabine (Cap) is an often prescribed chemotherapeutic agent, successfully used to cure some patients from cancer or reduce tumor burden for palliative care. However, the efficacy of the drug is limited, it is not known in advance who will respond to the drug and it can come with severe toxicity. (19)F Magnetic Resonance Spectroscopy (MRS) and Magnetic Resonance Spectroscopic Imaging (MRSI) have been used to non-invasively study Cap metabolism in vivo to find a marker for personalized treatment. In vivo detection, however, is hampered by low concentrations and the use of radiofrequency (RF) surface coils limiting spatial coverage. In this work, the use of a 7T MR system with radiative multi-channel transmit-receive antennas was investigated with the aim of maximizing the sensitivity and spatial coverage of (19)F detection protocols. The antennas were broadband optimized to facilitate both the (1)H (298 MHz) and (19)F (280 MHz) frequencies for accurate shimming, imaging and signal combination. B1(+) simulations, phantom and noise measurements showed that more than 90% of the theoretical maximum sensitivity could be obtained when using B1(+) and B1(-) information provided at the (1)H frequency for the optimization of B1(+) and B1(-) at the (19)F frequency. Furthermore, to overcome the limits in maximum available RF power, whilst ensuring simultaneous excitation of all detectable conversion products of Cap, a dual-band RF pulse was designed and evaluated. Finally, (19)F MRS(I) measurements were performed to detect (19)F metabolites in vitro and in vivo. In two patients, at 10 h (patient 1) and 1 h (patient 2) after Cap intake, (19)F metabolites were detected in the liver and the surrounding organs, illustrating the potential of the set-up for in vivo detection of metabolic rates and drug distribution in the body. PMID:26373355

  1. Hematologic toxicity of immunosuppressive treatment.

    PubMed

    Danesi, R; Del Tacca, M

    2004-04-01

    The administration of immunosuppressive agents may be associated with the occurrence of hematologic toxicity, such as anemia, due to bone marrow suppression or hemolysis, leukopenia, and thrombocytopenia. The administration of azathioprine and mycophenolate mofetil is more frequently associated with bone marrow suppression, while hemolytic-uremic syndrome may occur after administration of cyclosporine, tacrolimus, or muromonab (OKT3) and may be associated with the loss of the allograft. Moreover, microangiopathic hemolytic anemia and thrombocytopenia are rare, but potentially severe, complications of immunosuppressive treatment with tacrolimus and cyclosporine; they are characterized by intravascular hemolysis due to mechanical destruction of red cells as a result of pathological changes in small blood vessels. Viral infections (cytomegalovirus), administration of antiviral agents (gancyclovir), inhibitors of angiotensin-converting enzyme and angiotensin II receptor antagonists, antibacterial agents (sulfamethoxazole and trimethoprim), and allopurinol may aggravate bone marrow suppression, particularly when administered with agents that interfere with purine biosynthesis, including azathioprine and mycophenolate mofetil. PMID:15110637

  2. Sterile post-traumatic immunosuppression.

    PubMed

    Islam, Md Nahidul; Bradley, Benjamin A; Ceredig, Rhodri

    2016-04-01

    After major trauma, the human immune system initiates a series of inflammatory events at the injury site that is later followed by suppression of local inflammation favoring the repair and remodeling of the damaged tissues. This local immune response involves complex interactions between resident cells such as macrophages and dendritic cells, soluble mediators such as cytokines and chemokines, and recruited cells such as neutrophils, monocytes and mesenchymal stromal cells. If of sufficient magnitude, these initial immune responses nevertheless have systemic consequences resulting in a state called post-traumatic immunosuppression (PTI). However, controversy exists regarding the exact immunological changes occurring in systemic compartments triggered by these local immune responses. PTI is one of the leading causes of post-surgical mortality and makes patients vulnerable to hospital-acquired infections, multiple organ failure and many other complications. In addition, hemorrhage, blood transfusion, immunesenescence and immunosuppressant drugs aggravate PTI. PTI has been intensively studied, but published results are frequently cloudy. The purpose of this review is to focus on the contributions made by different responsive modalities to immunosuppression following sterile trauma and to try to integrate these into an overall scheme of PTI. PMID:27195120

  3. Sterile post-traumatic immunosuppression

    PubMed Central

    Islam, Md Nahidul; Bradley, Benjamin A; Ceredig, Rhodri

    2016-01-01

    After major trauma, the human immune system initiates a series of inflammatory events at the injury site that is later followed by suppression of local inflammation favoring the repair and remodeling of the damaged tissues. This local immune response involves complex interactions between resident cells such as macrophages and dendritic cells, soluble mediators such as cytokines and chemokines, and recruited cells such as neutrophils, monocytes and mesenchymal stromal cells. If of sufficient magnitude, these initial immune responses nevertheless have systemic consequences resulting in a state called post-traumatic immunosuppression (PTI). However, controversy exists regarding the exact immunological changes occurring in systemic compartments triggered by these local immune responses. PTI is one of the leading causes of post-surgical mortality and makes patients vulnerable to hospital-acquired infections, multiple organ failure and many other complications. In addition, hemorrhage, blood transfusion, immunesenescence and immunosuppressant drugs aggravate PTI. PTI has been intensively studied, but published results are frequently cloudy. The purpose of this review is to focus on the contributions made by different responsive modalities to immunosuppression following sterile trauma and to try to integrate these into an overall scheme of PTI. PMID:27195120

  4. Acute allograft rejection and immunosuppression: influence on endogenous melatonin secretion.

    PubMed

    Cardell, Markus; Jung, Florian Johannes; Zhai, Wei; Hillinger, Sven; Welp, Andre; Manz, Bernhard; Weder, Walter; Korom, Stephan

    2008-04-01

    Melatonin displays a dose-dependent immunoregulatory effect in vitro and in vivo. Exogenous high-dose melatonin therapy exerted an immunosuppressive effect, abrogating acute rejection (AR), significantly prolonging transplant survival. Endogenous melatonin secretion, in response to heterotopic rat cardiac allograft transplantation (Tx), was investigated during the AR response and under standardized immunosuppressive maintenance therapy with cyclosporin A (CsA) and rapamycin (RPM). Recipients of syngeneic transplants, and recipients of allogeneic grafts, either untreated or receiving immunosuppressive therapy constituted the experimental groups. Endogenous circadian melatonin levels were measured at 07:00, 19:00, and 24:00 hr, using a novel radioimmunoassay (RIA) procedure, under standardized 12-hr-light/dark-conditions (light off: 19:00 hr; light on: 07:00 hr), before and after Tx. Neither the operative trauma, nor the challenge with a perfused allograft or the AR response influenced endogenous melatonin peak secretion. Immunosuppressive therapy with CsA led to a significant increase in peak secretion, measured for days 7 (212 +/- 40.7 pg/mL; P < 0.05), 14 (255 +/- 13.9 pg/mL; P < 0.001), and 21 (219 +/- 34 pg/mL; P < 0.01) after Tx, as compared with naïve animals (155 +/- 25.8 pg/mL). In contrast, treatment with RPM significantly decreased the melatonin peak post-Tx up to day 7 (87 +/- 25.2 pg/mL; P < 0.001), compared with naïve animals (155 +/- 25.8 pg/mL). These findings imply a robust nature of the endogenous circadian melatonin secretion kinetics, even against the background of profound allogeneic stimuli. Immunosuppressive maintenance therapy with CsA and RPM modulated early melatonin secretion, indicating a specific secondary action of these drugs. Further studies are necessary to disclose the long-term effect of immunosuppressive therapy on circadian melatonin secretion in transplant recipients. PMID:18339121

  5. Immunosuppressants

    MedlinePlus

    ... antirejection medicine used at the time of transplant Maintenance drugs: Antirejection medications used for the long term. ... induction drug and the monthly payments are like maintenance drugs. If the down payment is good enough ...

  6. A case for varicella vaccination in the immunosuppressed

    PubMed Central

    Holmes, Michael Vaclav; Atabani, Sowsan F; Khan, Nasser; Steiner, Kate; Haque, Tanzina; Slapak, Gabrielle

    2009-01-01

    A middle-aged man with long-standing Crohn disease maintained in remission on low-dose immunosuppression presented with abdominal pain. Over the following few days he developed a vesicular rash, became dyspnoeic, confused and had two seizures. Despite high-dose intravenous aciclovir, he died. Disseminated varicella zoster virus, the cause of his death, could potentially have been prevented had he received varicella vaccination at an earlier stage. PMID:21686799

  7. Mortality from duck plague virus in immunosuppressed adult mallard ducks

    SciTech Connect

    Goldberg, D.R.; Yuill, T.M.; Burgess, E.C. )

    1990-07-01

    Environmental contaminants contain chemicals that, if ingested, could affect the immunological status of wild birds, and in particular, their resistance to infectious disease. Immunosuppression caused by environmental contaminants, could have a major impact on waterfowl populations, resulting in increased susceptibility to contagious disease agents. Duck plague virus has caused repeated outbreaks in waterfowl resulting in mortality. In this study, several doses of cyclophosphamide (CY), a known immunosuppressant, were administered to adult mallards (Anas platyrhynchos) to determine if a resultant decrease in resistance to a normally sub-lethal strain of duck plague virus would occur, and induce mortality in these birds. Death occurred in birds given CY only, and in birds given virus and CY, but not in those given virus only. There was significantly greater mortality and more rapid deaths in the duck plague virus-infected groups than in groups receiving only the immunosuppressant. A positively correlated dose-response effect was observed with CY mortalities, irrespective of virus exposure. A fuel oil and a crude oil, common environmental contaminants with immunosuppressive capabilities, were tested to determine if they could produce an effect similar to that of CY. Following 28 days of oral oil administration, the birds were challenged with a sub-lethal dose of duck plague virus. No alteration in resistance to the virus (as measured by mortality) was observed, except in the positive CY control group.

  8. Mortality from duck plague virus in immunosuppressed adult mallard ducks

    USGS Publications Warehouse

    Goldberg, D.R.; Yuill, Thomas M.; Burgess, E.C.

    1990-01-01

    Environmental contaminants contain chemicals that, if ingested, could affect the immunological status of wild birds, and in particular, their resistance to infectious disease. Immunosuppression caused by environmental contaminants, could have a major impact on waterfowl populations, resulting in increased susceptibility to contagious disease agents. Duck plague virus has caused repeated outbreaks in waterfowl resulting in mortality. In this study, several doses of cyclophosphamide (CY), a known immunosuppressant, were administered to adult mallards (Anas platyrhynchos) to determine if a resultant decrease in resistance to a normally sub-lethal strain of duck plague virus would occur, and induce mortality in these birds. Death occurred in birds given CY only, and in birds given virus and CY, but not in those given virus only. There was significantly greater mortality and more rapid deaths in the duck plague virus-infected groups than in groups receiving only the immunosuppressant. A positively correlated dose-response effect was observed with CY mortalities, irrespective of virus exposure. A fuel oil and a crude oil, common environmental contaminants with immunosuppressive capabilities, were tested to determine if they could produce an effect similar to that of CY. Following 28 days of oral oil administration, the birds were challenged with a sub-lethal dose of duck plague virus. No alteration in resistance to the virus (as measured by mortality) was observed, except in the positive CY control group.

  9. Immunosuppressant-associated neurotoxicity responding to olanzapine.

    PubMed

    Bourgeois, James A; Hategan, Ana

    2014-01-01

    Immunosuppressants, particularly tacrolimus, can induce neurotoxicity in solid organ transplantation cases. A lower clinical threshold to switch from tacrolimus to another immunosuppressant agent has been a common approach to reverse this neurotoxicity. However, immunosuppressant switch may place the graft at risk, and, in some cases, continuation of the same treatment protocol may be necessary. We report a case of immunosuppressant-associated neurotoxicity with prominent neuropsychiatric manifestation and describe psychiatric intervention with olanzapine that led to clinical improvement while continuing tacrolimus maintenance. PMID:25114826

  10. Immunosuppressive effect of murine cytomegalovirus.

    PubMed Central

    Loh, L; Hudson, J B

    1980-01-01

    Murine cytomegalovirus suppressed the ability of spleen cells to respond to mitogens in vitro. The degree of suppression was proportional to the multiplicity of infection. This effect could not be explained by cytolysis of lymphocytes, an alteration in the kinetics of the response to mitogen, or a direct competition between virions and mitogen molecules for cell-surface receptors. Nor was it due to simple contact between cell and virus, since ultraviolet-inactivated murine cytomegalovirus failed to suppress the response to mitogens. Reconstitution experiments were performed which involved mixing various combinations of infected and uninfected macrophages and lymphocytes. Under these conditions, it was found that the infected macrophages and lymphocytes. Under these conditions, it was found that the infected macrophages had an impaired capacity to mediate the response ot T lymphocytes to concanavalin A. This suggests that murine cytomegalovirus may cause immunosuppression indirectly by interfering with macrophage function. PMID:6244228

  11. [Hepatitis B virus infection in pregnancy and the immunosuppressed patient].

    PubMed

    Riveiro-Barciela, Mar; Buti, María

    2015-01-01

    Hepatitis B virus (HBV) infection continues to be a major public health problem worldwide. Although treatment indications are well established in clinical practice guidelines, there are some risk groups, such as pregnant women and immunosuppressed patients, who require different and specific management of HBV infection. In pregnant women, treatment indication should be individualized and the risk of HBV transmission to the newborn evaluated because cases of vertical transmission continue to be reported, despite active and passive immunoprophylaxis. In patients receiving immunosuppressive therapy, HBV reactivation is associated with high morbidity and mortality, even in patients with past HBV infection, highlighting the importance of screening and the need to evaluate prophylactic therapy in some cases. PMID:25066320

  12. Immunosuppression and Chagas Disease: A Management Challenge

    PubMed Central

    Pinazo, María-Jesús; Espinosa, Gerard; Cortes-Lletget, Cristina; Posada, Elizabeth de Jesús; Aldasoro, Edelweiss; Oliveira, Inés; Muñoz, Jose; Gállego, Montserrat; Gascon, Joaquim

    2013-01-01

    Immunosuppression, which has become an increasingly relevant clinical condition in the last 50 years, modifies the natural history of Trypanosoma cruzi infection in most patients with Chagas disease. The main goal in this setting is to prevent the consequences of reactivation of T. cruzi infection by close monitoring. We analyze the relationship between Chagas disease and three immunosuppressant conditions, including a description of clinical cases seen at our center, a brief review of the literature, and recommendations for the management of these patients based on our experience and on the data in the literature. T. cruzi infection is considered an opportunistic parasitic infection indicative of AIDS, and clinical manifestations of reactivation are more severe than in acute Chagas disease. Parasitemia is the most important defining feature of reactivation. Treatment with benznidazole and/or nifurtimox is strongly recommended in such cases. It seems reasonable to administer trypanocidal treatment only to asymptomatic immunosuppressed patients with detectable parasitemia, and/or patients with clinically defined reactivation. Specific treatment for Chagas disease does not appear to be related to a higher incidence of neoplasms, and a direct role of T. cruzi in the etiology of neoplastic disease has not been confirmed. Systemic immunosuppressive diseases or immunosuppressants can modify the natural course of T. cruzi infection. Immunosuppressive doses of corticosteroids have not been associated with higher rates of reactivation of Chagas disease. Despite a lack of evidence-based data, treatment with benznidazole or nifurtimox should be initiated before immunosuppression where possible to reduce the risk of reactivation. Timely antiparasitic treatment with benznidazole and nifurtimox (or with posaconazole in cases of therapeutic failure) has proven to be highly effective in preventing Chagas disease reactivation, even if such treatment has not been formally

  13. GABAergic neurons in the ventral tegmental area receive dual GABA/enkephalin-mediated inhibitory inputs from the bed nucleus of the stria terminalis.

    PubMed

    Kudo, Takehiro; Konno, Kohtarou; Uchigashima, Motokazu; Yanagawa, Yuchio; Sora, Ichiro; Minami, Masabumi; Watanabe, Masahiko

    2014-06-01

    Activation of mu-opioid receptor (MOR) disinhibits dopaminergic neurons in the ventral tegmental area (VTA) through inhibition of γ-aminobutyric acid (GABA)ergic neurons. This mechanism is thought to play a pivotal role in mediating reward behaviors. Here, we characterised VTA-projecting enkephalinergic neurons in the anterior division of the bed nucleus of the stria terminalis (BST) and investigated their targets by examining MOR expression in the VTA. In the BST, neurons expressing preproenkephalin mRNA were exclusively GABAergic, and constituted 37.2% of the total GABAergic neurons. Using retrograde tracer injected into the VTA, 21.6% of VTA-projecting BST neurons were shown to express preproenkephalin mRNA. Enkephalinergic projections from the BST exclusively formed symmetrical synapses onto the dendrites of VTA neurons. In the VTA, 74.1% of MOR mRNA-expressing neurons were GABAergic, with the rest being glutamatergic neurons expressing type-2 vesicular glutamate transporter mRNA. However, MOR mRNA was below the detection threshold in dopaminergic neurons. By immunohistochemistry, MOR was highly expressed on the extrasynaptic membranes of dendrites in GABAergic VTA neurons, including dendrites innervated by BST-VTA projection terminals. MOR was also expressed weakly on GABAergic and glutamatergic terminals in the VTA. Given that GABAA α1 is expressed at GABAergic BST-VTA synapses on dendrites of GABAergic neurons [T. Kudo et al. (2012) J. Neurosci., 32, 18035-18046], our results collectively indicate that the BST sends dual inhibitory outputs targeting GABAergic VTA neurons; GABAergic inhibition via 'wired' transmission, and enkephalinergic inhibition via 'volume' transmission. This dual inhibitory system provides the neural substrate underlying the potent disinhibitory control over dopaminergic VTA neurons exerted by the BST. PMID:24580812

  14. In Search for Equilibrium: Immunosuppression Versus Opportunistic Infection.

    PubMed

    Yousuf, Tariq; Kramer, Jason; Kopiec, Adam; Jones, Brody; Iskandar, Joy; Ahmad, Khansa; Keshmiri, Hesam; Dia, Muhyaldeen

    2016-02-01

    Post-transplant immunosuppression is necessary to prevent organ rejection. Immunosuppression itself can introduce complications arising from opportunistic infections. We present a case of disseminated blastomycosis manifested only as a skin lesion in an asymptomatic patient post-orthotopic heart transplantation. A 64-year-old female who had recently undergone orthotopic heart transplant for end-stage ischemic cardiomyopathy presented for a scheduled routine cardiac biopsy. The patient had no current complaints other than a crusted plaque noticed at her nasal tip. It initially manifested 6 months after surgery as a pimple that she repeatedly tried to manipulate resulting in redness and crust formation. Her immunosuppressive and prophylactic medications included: mycophenolate, tacrolimus, prednisone, bactrim, acyclovir, valganciclovir, pyrimethamine/sulfadiazine, and fluconazole. On physical examination, she was flushed, with a large and exquisitely tender crusted necrotic lesion involving almost the entire half of the nose anteriorly, the left forehead and right side of the neck. She had decreased air entry over the right lung field as well. A computed tomography (CT) image of the chest was ordered to investigate this concerning physical exam finding in the post-transplant state of this patient on immunosuppressive therapy. Chest CT revealed bilateral nodular pulmonary infiltrates with confluence in the posterior right upper lobe. Blood cultures for aerobic and anerobic organisms were negative. Both excisional biopsy of the nasal cutaneous ulcer and bronchial biopsy demonstrated numerous fungal yeast forms morphologically consistent with Blastomyces. Cultures of both specimens grew Blastomyces dermatitidis, with methicillin-resistant Staphylococcus aureus (MRSA) superinfection of the nose. She received 14 days of intravenous (IV) amphotericin B for disseminated blastomycosis and 7 days of IV vancomycin for MRSA. Her symptoms and cutaneous lesions improved and she

  15. In Search for Equilibrium: Immunosuppression Versus Opportunistic Infection

    PubMed Central

    Yousuf, Tariq; Kramer, Jason; Kopiec, Adam; Jones, Brody; Iskandar, Joy; Ahmad, Khansa; Keshmiri, Hesam; Dia, Muhyaldeen

    2016-01-01

    Post-transplant immunosuppression is necessary to prevent organ rejection. Immunosuppression itself can introduce complications arising from opportunistic infections. We present a case of disseminated blastomycosis manifested only as a skin lesion in an asymptomatic patient post-orthotopic heart transplantation. A 64-year-old female who had recently undergone orthotopic heart transplant for end-stage ischemic cardiomyopathy presented for a scheduled routine cardiac biopsy. The patient had no current complaints other than a crusted plaque noticed at her nasal tip. It initially manifested 6 months after surgery as a pimple that she repeatedly tried to manipulate resulting in redness and crust formation. Her immunosuppressive and prophylactic medications included: mycophenolate, tacrolimus, prednisone, bactrim, acyclovir, valganciclovir, pyrimethamine/sulfadiazine, and fluconazole. On physical examination, she was flushed, with a large and exquisitely tender crusted necrotic lesion involving almost the entire half of the nose anteriorly, the left forehead and right side of the neck. She had decreased air entry over the right lung field as well. A computed tomography (CT) image of the chest was ordered to investigate this concerning physical exam finding in the post-transplant state of this patient on immunosuppressive therapy. Chest CT revealed bilateral nodular pulmonary infiltrates with confluence in the posterior right upper lobe. Blood cultures for aerobic and anerobic organisms were negative. Both excisional biopsy of the nasal cutaneous ulcer and bronchial biopsy demonstrated numerous fungal yeast forms morphologically consistent with Blastomyces. Cultures of both specimens grew Blastomyces dermatitidis, with methicillin-resistant Staphylococcus aureus (MRSA) superinfection of the nose. She received 14 days of intravenous (IV) amphotericin B for disseminated blastomycosis and 7 days of IV vancomycin for MRSA. Her symptoms and cutaneous lesions improved and she

  16. Comparison of the immunosuppressive effect of fractionated total lymphoid irradiation (TLI) vs conventional immunosuppression (CI) in renal cadaveric allotransplantation

    SciTech Connect

    Waer, M.; Vanrenterghem, Y.; Ang, K.K.; van der Schueren, E.; Michielsen, P.; Vandeputte, M.

    1984-02-01

    Beginning in November 1981, eight patients with end stage diabetic nephropathy underwent renal cadaveric transplantation after TLI. Transplantation was done between 2 to 11 days after the end of a fractionated TLI to a total dose of 20 to 30 Gy. During the same observation period, 60 nondiabetic patients with end stage renal disease of different origin also received a cadaveric kidney graft, with a conventional regimen of immunosuppression that consists of anti-lymphocyte-globulin, tapering high doses of prednisone, and azathioprine. Phytohemagglutinin (PHA)-, concanavalin A (con A)-, and pokeweed mitogen (PWM)-induced blastogenesis, as well as the mixed lymphocyte reaction (MLR) and the cell-mediated lympholysis (CML) decreased progressively during the first months after conventional immunosuppression to 50% of the pretransplantation level, and remained there for the first year after transplantation. These tests were much more impaired after TLI and again no recovery occurred during the first year. In the clinic, the more profound immunosuppression in TLI patients was more frequently associated with viral infections (cytomegalovirus and herpes zoster). The incidence of rejections, however, was somewhat less frequent in the TLI-treated group and occurred significantly later. After TLI, the mean cumulative dose of steroids needed for kidney transplantation during the first year after transplantation could be substantially reduced.

  17. Interferon-γ Production by Peripheral Lymphocytes Predicts Survival of Tumor-Bearing Mice Receiving Dual PD-1/CTLA-4 Blockade.

    PubMed

    McNamara, Michael J; Hilgart-Martiszus, Ian; Barragan Echenique, Diego M; Linch, Stefanie N; Kasiewicz, Melissa J; Redmond, William L

    2016-08-01

    Immune checkpoint inhibitors are transforming the way cancer is treated. However, these therapies do not benefit all patients and frequently cause significant immune-related adverse events. Biomarkers that identify patients with a favorable early response to therapy are essential for guiding treatment decisions and improving patient outcomes. In this report of our study, we present evidence that shortly after administration of dual PD-1/CTLA-4 blockade, the proinflammatory capacity of peripheral lymphocytes is predictive of tumor progression and survival outcomes in multiple murine models. Specifically, we observed that the quantity of interferon-γ (IFNγ) produced by peripheral lymphocytes in response to CD3/CD28 stimulation was robustly correlated with subsequent survival outcomes. In the tumor models and early time points assessed in this study, this relationship was considerably more predictive than a host of other potential biomarkers, several of which have been previously reported. Overall, these findings suggest that measuring the capacity of peripheral lymphocytes to produce IFNγ may help identify which patients are benefitting from combination anti-PD-1/anti-CTLA-4 immunotherapy. Cancer Immunol Res; 4(8); 650-7. ©2016 AACR. PMID:27262113

  18. Diverticulitis in immunosuppressed patients: A fatal outcome requiring a new approach?

    PubMed Central

    Brandl, Andreas; Kratzer, Theresa; Kafka-Ritsch, Reinhold; Braunwarth, Eva; Denecke, Christian; Weiss, Sascha; Atanasov, Georgi; Sucher, Robert; Biebl, Matthias; Aigner, Felix; Pratschke, Johann; Öllinger, Robert

    2016-01-01

    Background Diagnosis and treatment of diverticulitis in immunosuppressed patients are more challenging than in immunocompetent patients, as maintenance immunosuppressive therapies may mask symptoms or impair the patient’s ability to counteract the local and systemic infective sequelae of diverticulitis. The purpose of this study was to compare the in-hospital mortality and morbidity due to diverticulitis in immunosuppressed and immunocompetent patients and identify risk factors for lethal outcomes. Methods This retrospective study included consecutive in-patients who received treatment for colonic diverticulitis at our institution between April 2008 and April 2014. Patients were divided into immunocompetent and immunosuppressed groups. Primary end points were mortality and morbidity during treatment. Risk factors for death were evaluated. Results Of the 227 patients included, 15 (6.6%) were on immunosuppressive therapy for solid organ transplantation, autoimmune disease, or cerebral metastasis. Thirteen of them experienced colonic perforation and showed higher morbidity (p = 0.039). Immunosuppressed patients showed longer stays in hospital (27.6 v. 14.5 d, p = 0.016) and in the intensive care unit (9.8 v. 1.1 d, p < 0.001), a higher rate of emergency operations (66% v. 29.2%, p = 0.004), and higher in-hospital mortality (20% v. 4.7%, p = 0.045). Age, perforated diverticulitis with diffuse peritonitis, emergency operation, C-reactive protein > 20 mg/dL, and immunosuppressive therapy were significant predictors of death. Age (hazard ratio [HR] 2.57, p = 0.008) and emergency operation (HR 3.03, p = 0.003) remained significant after multivariate analysis. Conclusion Morbidity and mortality due to sigmoid diverticulitis is significantly higher in immunosuppressed patients. Early diagnosis and treatment considering elective sigmoid resection for patients with former episodes of diverticulitis who are wait-listed for transplant is crucial to prevent death. PMID:27240131

  19. Non-typhoidal Salmonella bacteraemia: Epidemiology, clinical characteristics and its' association with severe immunosuppression

    PubMed Central

    Dhanoa, Amreeta; Fatt, Quek Kia

    2009-01-01

    Background Non-typhoidal Salmonella (NTS) is increasingly recognized as an important pathogen associated with bacteraemia especially in immunosuppressed patients. However, there is limited data specifically describing the clinical characteristics and outcome amongst the immunosuppressed patients. Methods A total of 56,707 blood culture samples and 5,450 stool samples were received by the microbiology laboratory at a tertiary referral hospital in Malaysia, during a 4-year study period. Out of these samples, 55 non-duplicate NTS isolates were identified from blood and 121 from stool. A retrospective analysis of the 55 patients with NTS bacteraemia was then conducted to determine the predominant NTS serovars causing bacteraemia and its' blood invasive potential, epidemiological data, clinical characteristics and antimicrobial susceptibility. Patients were then grouped as immunosuppressed and non-immunosuppressed to determine the association of severe immunosuppression on clinical features. Data was analyzed using the Statistical Package for Social Sciences (SPSS version 15.0) using the non-parametric Mann-Whitney test, Fisher's exact test or Chi-squared test. The odds ratio (OR) and its 95% confidence intervals (CI) were calculated. The P-value < 0.05 (two-tailed) was taken as the level of significance. Results Out of 55 NTS bacteraemia cases identified, 81.8% (45/55) were community-acquired. Salmonella enterica serovar Enteritidis had the highest blood invasiveness. An extra-intestinal focus of infection was noted in 30.9% (17/55) of the patients, most commonly involving the lungs and soft tissue. 90.9% (50/55) of the patients had an underlying disease and 65.5% (36/55) of the patients had severe clinical immunosuppressive condition with malignancy and HIV being the most common. Immunosuppressed patients had higher mortality (P = 0.04), presented more commonly with primary bacteraemia (P = 0.023), leukopenia (P = 0.001) and opportunistic infections (P = 0.01). In

  20. Neurotoxicity of Immunosuppressive Therapies in Organ Transplantation

    PubMed Central

    ANGHEL, Daniela; TANASESCU, Radu; CAMPEANU, Ana; LUPESCU, Ioana; PODDA, Giulio; BAJENARU, Ovidiu

    2013-01-01

    ABSTRACT Immunosuppressive agents have revolutionized clinical transplantation medicine, allowing the avoidance of immune system attack on the transplanted graft. Nevertheless, the use of medications such as cyclosporine, tacrolimus and others also brought the side effects of these drugs. Early identification of drug-induced neurotoxicity in transplanted patients and of its specific causes is important, not only because of patient's poor clinical status but because of concomitant systemic and metabolic disorders which may obscure symptoms. Treatment and prognosis are highly dependent on the type of complication and it's early recognition. This review focuses on the clinical entities of neurotoxicity caused by immunosuppressive drugs in transplanted patients. PMID:24371481

  1. A COLLAGENOUS COLITIS-LIKE CONDITION IN IMMUNOSUPPRESSED INFANT BABOONS

    PubMed Central

    Dons, Eefje M.; Echeverri, Gabriel J.; Rigatti, Lora H.; Klein, Edwin; Montoya, Claudia; Wolf, Roman F.; Ijzermans, Jan N.M.; Cooper, David K.C.; Wagner, Robert

    2011-01-01

    Background Collagenous colitis is a chronic inflammatory bowel disease of unknown etiology. It is fairly common in adult humans, but rare in infants, and has been associated with autoimmune disorders. Case Reports We report four infant baboons (age 7–12 months) that had received a transplant at three months of age and subsequent immunosuppressive therapy for periods of 4–10 months. All presented identical symptoms within a period of four weeks, including weight loss associated with chronic watery diarrhea that was unresponsive to standard antimicrobial treatment. Clinical chemistry evaluations were within normal ranges, viral causes were ruled out, and fecal and blood cultures were repeatedly negative. At necropsy, two infant baboons were found to have a form of collagenous colitis. In the remaining two baboons that had identical clinical features, immunosuppressive therapy was discontinued and treatment with budesonide was initiated. Both baboons recovered and remained well on no medication until the end of follow-up (24 months). Conclusions Collagenous colitis has occasionally been reported in patients with organ transplants. It has been reported only once previously in baboons. The four cases reported here strongly suggest that (i) clinical features as well as histopathological findings of collagenous colitis in baboons are very similar to those in human patients; (ii) it was associated with the immunocompromised state of the baboons, as two non-immunosuppressed age-matched baboons in close proximity did not develop the condition, and (iii) it may have had an infectious origin as all four cases developed within a four week period of time. PMID:22294413

  2. Maintenance pharmacological immunosuppressive strategies in renal transplantation.

    PubMed Central

    Vella, J. P.; Sayegh, M. H.

    1997-01-01

    Current maintenance immunosuppressive regimens for transplantation are based on three classes of drugs: corticosteroids, immunophilin-binding agents (eg, cyclosporin and tacrolimus), and antimetabolites (eg, azathioprine and mycophenolate). Drugs from the various classes inhibit the immune system at different points and are thus synergistic when used in combination. PMID:9338020

  3. Catastrophic gastrointestinal complication of systemic immunosuppression.

    PubMed

    Smith, Lyn Alexandra; Gangopadhyay, Mitali; Gaya, Daniel R

    2015-02-28

    We present a case of acute upper gastrointestinal haemorrhage in a patient with systemic vasculitis immunosuppressed on cyclophosphamide and prednisolone. The patient presented with a diffuse haemorrhagic oesophagitis and a non-specific duodenitis. Biopsies taken from the oesophagus and duodenum demonstrated infection with herpes simplex virus (HSV) and cytomegalovirus (CMV) respectively. Viral infection of the upper gastrointestinal tract is a recognised complication of immunosuppression and HSV is one of the most common pathogens. CMV on the other hand most commonly causes a colitis or less commonly oesophagitis. CMV enteritis is rare as is the synchronous infection with two viral agents in an immunocompromised patient having being described in a few case series only. Viral infection of the gastrointestinal tract in immunocompromised patients should be treated with systemic anti-viral medication and consideration to withdrawal of the immunosuppressive therapy if possible and appropriate. The authors highlight the need for a high suspicion of viral infection in immunosuppressed patients presenting with upper gastrointestinal bleeding. PMID:25741165

  4. The gingival plasma cell infiltrate in renal transplant patients on an immunosuppressive regimen.

    PubMed

    Saether, K; Tollefsen, T; Helgeland, K; Schenck, K

    1998-10-01

    Treatment with immunosuppressive agents inhibits gingival inflammation and progression of periodontitis in humans. We examined the numbers and the isotype distribution of immunoglobulin-producing plasma cells by immunohistochemistry in gingival specimens taken from renal transplant transplant recipients receiving immunosuppressive agents (IS), and from otherwise comparable systemically healthy patients. The immunosuppressed patient group had significantly (P< 0.05) fewer IgG-, IgA-, IgG1-, IgG2-, and IgG4-producing plasma cells in the connective tissue adjacent to the pocket epithelium. The reduced numbers of such patents with quiescent periodontal disease support the contention that high counts of plasma cells are indicative of more severe disease. PMID:9860096

  5. Unusual case of B cell lymphoma after immunosuppressive treatment for psoriasis.

    PubMed

    Nosotti, Lorenzo; Baiocchini, Andrea; Bonifati, Claudio; Visco-Comandini, Ubaldo; Mirisola, Concetta; Del Nonno, Franca

    2015-04-18

    Lymphomas may be induced by the systemic immunosuppressive therapies used to treat psoriasis, such as ciclosporin, methotrexate and tumour necrosis factor (TNF)-α blockers. The biologic agents currently used in psoriasis include alefacept, efalizumab, and the TNF-α antagonists etanercept, infliximab, and adalimumab. Infections and cancer are the main possible consequences of intended or unexpected immunosuppression. We report a 59-year-old man with a history of severe psoriasis vulgaris treated with traditional immunosuppressant drugs followed by anti-TNF-α therapy; the patient was firstly hospitalized for an acute cholestatic toxic hepatitis, which we supposed to be related to adalimumab. The first liver biopsy showed active disease with severe hepatocellular damage caused by heavy lymphocytes infiltrate in portal tracts at in the interface with a not conclusive diagnosis of lymphoproliferative disease. The correct diagnosis of T cell/histiocyte- rich large B cell lymphoma (T/HRBCL) was only reached through a gastric biopsy and a second liver biopsy. T/HRBCL is an uncommon morphologic variant of diffuse large B-cell lymphoma not described until now in psoriatic patients receiving immunosuppressive biologic agents. In psoriatic patients, treated with biologic immunosuppressive agents, the suspect of abdominal lymphoma should always be included as differential diagnosis. Abdominal ultrasound evaluation need therefore to be included in the pre-treatment screening as in the follow-up surveillance. PMID:25914782

  6. Reduction of delayed renal allograft function using sequential immunosuppression.

    PubMed

    Müller, T; Ruffingshofer, D; Bidmon, B; Arbeiter, K; Balzar, E; Aufricht, C

    2001-08-01

    Previous data suggested that outcome in small children with cadaveric renal transplantation might be improved with sequential therapy. This protocol combines augmented immunosuppression [by including antibody induction (ATG)] with avoidance of nephrotoxic medication in the immediate postoperative phase (by delayed start of cyclosporin therapy). In this report, we describe effects of this approach in 12 consecutively transplanted small children of less than 5 years of age (mean 3.2 years) who received a cadaveric renal graft at our institution between 1991 and 1998. Up to 1996 triple therapy (prednisolone, azathioprine, cyclosporin) and since 1997 sequential therapy (prednisolone, azathioprine, ATG until serum creatinine <2 mg/dl, then cyclosporin) was used for immunosuppression. Five children had delayed graft function (45.4%), all of whom were treated with triple therapy including cyclosporin from the very beginning, whereas children treated by the sequential protocol gained immediate graft function (P<0.05). There was no statistical difference between the two protocols concerning frequency or severity of rejections (67% vs. 60%, all steroid responsive), difference in the incidence of either bacterial or viral infections, or between the incidence of hypertension. Although not reaching statistical significance, 1-year graft survival rates also increased from 60% for triple therapy to 80% for sequential therapy. In conclusion, our findings confirm previous studies showing that outcome in small children undergoing renal transplantation may be improved by specially tailored treatment protocols such as sequential therapy. PMID:11519888

  7. In vivo indomethacin reverse exercise-induced immunosuppression in rats.

    PubMed

    Asselin, P; Benquet, C; Krzystyniak, K; Brousseau, P; Savard, R; Fournier, M

    1996-01-01

    The effect of oral indomethacin on the immunosuppressive effect of exercise was examined in exercised untrained female Wistar rats immunized with sheep red blood cell (SRBC) antigens. Intensity of the 1 h exercise was controlled by 0-50 kPa air pressure, generated by a compressor located at the bottom of a water tank, during continuous swimming of the rats, previously immunized with SRBC. After 48-72 h, depending on the ip (intraperitoneal) or iv (intravenous) route of SRBC immunization, the exercise suppressed humoral PFC response and augmented phagocytosis of peritoneum macrophages. These effects occurred only when exercise was performed at 48 h after antigen injection. Animals receiving indomethacin, however, did not show any exercise-related suppression of the PFC response. The data suggest a relationship between exercise-induced immunosuppression and possible increased in vivo prostaglandin synthesis during the intense exercise. Overall, exercise-related suppression of humoral PFC response was dependent on the intensity of the exercise, was time specific, and was reversible by pharmacological blockade of the cyclooxygenase pathway of prostaglandin synthesis. PMID:9023588

  8. CALUTRON RECEIVER

    DOEpatents

    Barnes, S.W.

    1959-06-16

    An improved receiver and receiver mount for calutrons are described. The receiver can be manipulated from outside the tank by a single control to position it with respect to the beam. A door can be operated exteriorly also to prevent undesired portions of the beam from entering the receiver. The receiver has an improved pocket which is more selective in the ions collected. (T.R.H.)

  9. Role of Exclusive Enteral Nutrition in the Preoperative Optimization of Patients With Crohn's Disease Following Immunosuppressive Therapy

    PubMed Central

    Li, Yi; Zuo, Lugen; Zhu, Weiming; Gong, Jianfeng; Zhang, Wei; Gu, Lili; Guo, Zhen; Cao, Lei; Li, Ning; Li, Jieshou

    2015-01-01

    Abstract We conducted a study to evaluate the impact of the exclusive enteral nutrition (EEN) on perioperative outcome in Crohn's disease (CD) patients following immunosuppressive therapy. Patients with CD followed at a referral center between January 2001 and March 2014 who underwent abdominal surgery were identified. Patients were divided into 4 groups: patients not exposed to immunosuppressive agents in the previous 8 weeks before surgery (group 1); patients received immunosuppressive medications without preoperative drug-free interval (group 2); patients had preoperative immunosuppressants-free interval (group 3); patients treated with adding EEN to preoperative immunosuppressants-free interval regimen (group 4). Urgent operation requirement, stoma creation, postoperative complications, readmission, and reoperation were compared in patients among groups. Overall, 708 abdominal surgeries performed in 498 CD patients were identified. Three hundred seventy-six (53.11%) surgeries performed in those receiving preoperative immunosuppressive medications. Compared with other groups, group 2 had increased postoperative complications, more frequent urgent operation, and higher rate of stoma creation. Patients in group 4 were found to have better outcome including lower rate of stoma creation (P < 0.05), and decreased incidence of postoperative complications (P < 0.05) compared with group 2 and group 3. Additionally, decreased urgent operation requirement (P < 0.05) and extended preoperative drug-free interval (P < 0.001) were observed in the group 4 than those in the group 3. Preoperative optimization of CD following immunosuppressive therapy by EEN prolongs the immunosuppressants-free interval, reduces the risk of urgent surgery and reoperation, and most importantly, decreases complications after abdominal surgery. PMID:25654387

  10. New Immunosuppressive Therapies in Uveitis Treatment

    PubMed Central

    Mérida, Salvador; Palacios, Elena; Navea, Amparo; Bosch-Morell, Francisco

    2015-01-01

    Uveitis is an inflammatory process that initially starts in the uvea, but can also affect other adjacent eye structures, and is currently the fourth cause of blindness in developed countries. Corticoids are probably the most widespread treatment, but resorting to other immunosuppressive treatments is a frequent practice. Since the implication of different cytokines in uveitis has been well demonstrated, the majority of recent treatments for this disease include inhibitors or antibodies against these. Nevertheless, adequate treatment for each uveitis type entails a difficult therapeutic decision as no clear recommendations are found in the literature, despite the few protocolized clinical assays and many case-control studies done. This review aims to present, in order, the mechanisms and main indications of the most modern immunosuppressive drugs against cytokines. PMID:26270662

  11. Adherence to immunosuppression: a prospective diary study.

    PubMed

    Gordon, E J; Prohaska, T R; Gallant, M P; Siminoff, L A

    2007-12-01

    Immunosuppression adherence among kidney transplant recipients is essential for graft survival. However, nonadherence is common, jeopardizing graft survival. Besides skipping dosages, little is known about other forms of medication nonadherence and their underlying reasons. This study sought to examine patients' extent of medication adherence over time and reasons for nonadherence. Thirty-nine new kidney transplant recipients were asked to complete a month-long medication-taking diary that included reporting medication nonadherence such as skipped medications, medications taken early or late, taking dosages greater or less than prescribed, and the reason for each occurrence of nonadherence. Of the 20 (51%) patients who completed the diary, 11 (55%) reported at least 1 form of nonadherence. Eleven patients reported taking their immunosuppression at least 1 hour later than the prescribed time, 1 patient reported skipping medication, but no patients reported changing the dosage on their own. Immunosuppression was taken on average 1.5 hours after the prescribed time. Of those patients who took their medications late, there were on average 3.1 occasions of taking it late. The most common reasons for this behavior included health care-related issues, followed by oversleeping, being away from home, work-related barriers, and forgetting. The majority of kidney transplant recipients took medications later than prescribed during 1 month. Future research should determine the clinical impact on graft function of late administration of immunosuppression. Interventions should be designed to better assist kidney recipients with taking medications on time, especially when they are away from home. PMID:18089327

  12. UV-induced immunosuppression in the balance.

    PubMed

    de Gruijl, Frank R

    2008-01-01

    Around 1980, experiments with hairless mice showed us that UV-induced actinic keratoses (AK) and ensuing skin carcinomas did not arise independently: the rate of occurrence in one skin area was increased considerably if AKs had already been induced separately in another distant skin area, i.e. a systemic effect. The ground laying work of Margaret Kripke in the 1970s provided a fitting explanation: UV-induced immunosuppression and tolerance toward the UV-induced tumors. From Kripke's work a new discipline arose: "Photoimmunology." Enormous strides were made in exploring and expanding the effects from UV carcinogenesis to infectious diseases, and in elucidating the mechanisms involved. Stemming from concerns about a depletion of the ozone layer and the general impact of ambient UV radiation, the groups I worked in and closely collaborated with explored the anticipated adverse effects of UV-induced immunosuppression on healthy individuals. An important turning point was brought about in 1992 when the group of Kevin Cooper reported that immunosuppression could be induced by UV exposure in virtually all human subjects tested, suggesting that this is a normal and sound physiological reaction to UV exposure. This reaction could actually protect us from illicit immune responses against our UV-exposed skin, such as observed in idiopathic polymorphic light eruption. This premise has fruitfully rekindled the research on this common "sun allergy," affecting to widely varying degrees about one in five Europeans with indoor professions. PMID:18173695

  13. [The immunosuppressive microenvironment of malignant gliomas].

    PubMed

    Borisov, K E; Sakaeva, D D

    2015-01-01

    The dogma of the central nervous system (CNS) as an immune-privileged site has been substantially revised in recent years. CNS is an immunocompetent organ and actively interacts with the immune system. Microglia plays a leading role in a CNS immune response. However, in malignant gliomas, there is M2-polarization of microglia acquiring immunosuppressive and tumor-supportive properties. It occurs under the influence of tumor cytokines, such as transforming growth factor-β, interleukin-10, and prostaglandin E2. M2-polarized microglia exhibits reduced phagocytic activity, changes in the expression of many cellular determinants, or inverse of their functions, STAT3 activation, and production of immunosuppressive cytokines that suppress the function of cytotoxic CD8+ T cells or CD4+ T-helper cells type I. Myeloid-derived suppressor cells and regulatory T-lymphocytes, which have been recruited from peripheral blood into tumor tissue, also have immunosuppressive properties. The development of new treatment options for malignant gliomas must consider the role of the microenvironment in maintaining tumor vitality and progression. PMID:26841651

  14. Management of immunosuppressant agents following liver transplantation: Less is more

    PubMed Central

    Ascha, Mustafa S; Ascha, Mona L; Hanouneh, Ibrahim A

    2016-01-01

    Immunosuppression in organ transplantation was revolutionary for its time, but technological and population changes cast new light on its use. First, metabolic syndrome (MS) is increasing as a public health issue, concomitantly increasing as an issue for post-orthotopic liver transplantation patients; yet the medications regularly used for immunosuppression contribute to dysfunctional metabolism. Current mainstay immunosuppression involves the use of calcineurin inhibitors; these are potent, but nonspecifically disrupt intracellular signaling in such a way as to exacerbate the impact of MS on the liver. Second, the impacts of acute cellular rejection and malignancy are reviewed in terms of their severity and possible interactions with immunosuppressive medications. Finally, immunosuppressive agents must be considered in terms of new developments in hepatitis C virus treatment, which undercut what used to be inevitable viral recurrence. Overall, while traditional immunosuppressive agents remain the most used, the specific side-effect profiles of all immunosuppressants must be weighed in light of the individual patient. PMID:26839639

  15. CALUTRON RECEIVER

    DOEpatents

    Brunk, W.O.

    1959-09-29

    A description is given for an improved calutron receiver having a face plate lying at an angle to the direction of the entering ion beams but having an opening, the plane of which is substantially perpendicular to that of the entering ion beams. By so positioning the opening in the receiver, the effective area through which the desired material may enter the receiver is increased, and at the same time the effective area through which containattng material may enter the receiver is reduced.

  16. CALUTRON RECEIVER

    DOEpatents

    York, H.F.

    1959-07-01

    A receiver construction is presented for calutrons having two or more ion sources and an individual receiver unit for each source. Design requirements dictate that the face plate defining the receiver entrance slots be placed at an angle to the approaching beam, which means that ions striking the face plate are likely to be scattcred into the entrance slots of other receivers. According to the present invention, the face plate has a surface provided with parallel ridges so disposed that one side only of each ridge's exposed directly to the ion beam. The scattered ions are directed away from adjacent receivers by the ridges on the lace plate.

  17. Multifocal Epstein-Barr Virus-Negative Posttransplantation Lymphoproliferative Disorder Treated With Reduction of Immunosuppression.

    PubMed

    Miyazono, Akinori; Okamoto, Yasuhiro; Nagasako, Hironobu; Hamasaki, Yuko; Shishido, Seiichiro; Yoshioka, Takako; Kawano, Yoshifumi

    2016-09-01

    Posttransplantation lymphoproliferative disorder (PTLD) is associated with significant mortality in kidney transplant recipients. PTLD cases associated with poor prognostic factors that are refractory to reduction of immunosuppression generally require chemotherapy and immunotherapy. We present a patient with PTLD who achieved complete remission after reduction of immunosuppression alone despite having a poor prognosis. A boy with a mutation in the WT1 gene developed bilateral Wilms tumor at 15 months and received a kidney transplant at the age of 4 years. At 13 years of age, the patient's condition was managed with methylprednisolone, tacrolimus, and mycophenolate mofetil. He developed Epstein-Barr virus-negative monomorphic PTLD with numerous nodular lesions in the liver, vertebral bodies, and gastric wall. To reduce immunosuppression, we discontinued mycophenolate mofetil treatment, decreased tacrolimus dosage to 1mg/d, and increased methylprednisolone dosage to 2mg/d. The PTLD lesions drastically diminished in size within several days and disappeared 144 days after reduction of immunosuppression, although the patient had several factors indicating a poor prognosis. As of 13 months after reduction of immunosuppression for PTLD, the transplanted kidney was still functional. We conclude that even when patients with PTLD have a poor prognosis, reduction of immunosuppression alone may result in complete remission when the early response is excellent. PMID:27178679

  18. National Variation in Use of Immunosuppression for Kidney Transplantation: A Call for Evidence-Based Regimen Selection.

    PubMed

    Axelrod, D A; Naik, A S; Schnitzler, M A; Segev, D L; Dharnidharka, V R; Brennan, D C; Bae, S; Chen, J; Massie, A; Lentine, K L

    2016-08-01

    Immunosuppression management in kidney transplantation has evolved to include an increasingly diverse choice of medications. Although informed by patient and donor characteristics, choice of immunosuppression regimen varies widely across transplant programs. Using a novel database integrating national transplant registry and pharmacy fill records, immunosuppression use at 6-12 and 12-24 mo after transplant was evaluated for 22 453 patients transplanted in 249 U.S. programs in 2005-2010. Use of triple immunosuppression comprising tacrolimus, mycophenolic acid or azathioprine, and steroids varied widely (0-100% of patients per program), as did use of steroid-sparing regimens (0-77%), sirolimus-based regimens (0-100%) and cyclosporine-based regimens (0-78%). Use of triple therapy was more common in highly sensitized patients, women and recipients with dialysis duration >5 years. Sirolimus use appeared to diminish over the study period. Patient and donor characteristics explained only a limited amount of the observed variation in regimen use, whereas center choice explained 30-46% of the use of non-triple-therapy immunosuppression. The majority of patients who received triple-therapy (79%), cyclosporine-based (87.6%) and sirolimus-based (84.3%) regimens continued them in the second year after transplant. This population-based study of immunosuppression practice demonstrates substantial variation in center practice beyond that explained by differences in patient and donor characteristics. PMID:26901466

  19. Ten Years Experience With Belatacept-Based Immunosuppression After Kidney Transplantation

    PubMed Central

    Grannas, Gerrit; Schrem, Harald; Klempnauer, Juergen; Lehner, Frank

    2014-01-01

    Background Belatacept was approved for prevention of acute rejection in adult kidney transplantation in 2011 based on two randomized, controlled, multicenter phase 3 studies. Long-term experience over 10 years with belatacept-based immunosuppression after kidney transplantation has not been reported before. Patients and Methods Analyzed were 20 patients who had been included into a randomized multicenter phase 2 study by our institution between March 2001 and November 2002. For 10-year follow-up, three different groups could be analyzed: 1) patients with primary calcineurin inhibitor-based (CNI-based) immunosuppression (n = 5), 2) patients with early switch from a belatacept-based to a CNI-based regimen within the first 14 months (n = 8) and 3) patients with completely CNI-free belatacept immunosuppression (n = 7). Results Fifteen patients received primary belatacept-based immunosuppression and five patients primary cyclosporine A (CyA). Five patients are still on belatacept. Kidney function measured by serum creatinine levels worsened in the CNI group and the belatacept to CNI switch group during long-term follow-up whereas all patients receiving belatacept throughout follow-up showed stable creatinine values. Acute rejections occurred predominantly in the first 12 months after transplantation and were responsible for four of seven switches from belatacept- to CNI-based immunosuppression within the first 14 months. Five of the 20 patients died. Conclusions Belatacept is effective and safe in renal transplant patients and was not associated with graft loss due to chronic allograft nephropathy. Belatacept was well tolerated in all patients and caused less nephrotoxic side effects and was well accepted in most patients. PMID:24578751

  20. Enteric glial cells have specific immunosuppressive properties.

    PubMed

    Kermarrec, Laetitia; Durand, Tony; Neunlist, Michel; Naveilhan, Philippe; Neveu, Isabelle

    2016-06-15

    Enteric glial cells (EGC) have trophic and neuroregulatory functions in the enteric nervous system, but whether they exert a direct effect on immune cells is unknown. Here, we used co-cultures to show that human EGC can inhibit the proliferation of activated T lymphocytes. Interestingly, EGC from Crohn's patients were effective at one EGC for two T cells whereas EGC from control patients required a ratio of 1:1. These data suggest that EGC contribute to local immune homeostasis in the gastrointestinal wall. They also raise the possibility that EGC have particular immunosuppressive properties in inflammatory bowel diseases such as Crohn's disease. PMID:27235353

  1. Radio receivers

    NASA Astrophysics Data System (ADS)

    Bankov, V. N.; Barulin, L. G.; Zhodzishskii, M. I.; Malyshev, I. V.; Petrusinskii, V. V.

    The book is concerned with the design of microelectronic radio receivers and their components based on semiconductor and hybrid integrated circuits. Topics discussed include the hierarchical structure of radio receivers, the synthesis of structural schemes, the design of the principal functional units, and the design of radio receiver systems with digital signal processing. The discussion also covers the integrated circuits of multifunctional amplifiers, analog multipliers, charge-transfer devices, frequency filters, piezoelectronic devices, and microwave amplifiers, filters, and mixers.

  2. CALUTRON RECEIVERS

    DOEpatents

    Lofgren, E.J.

    1958-09-01

    Improvements are described in isotope separation devices of the calutron type and, in particular, deals with a novel caiutron receiver which passes the optimum portions of the ion beam to a collecting chamber. In broad aspects the receiver provides means for pass delimited pontion of the beam and an elongated collecting pocket disposed to receive ions passed by the beam delimiting means. The collecting pocket is transversely partitioned into a plurality of ion receiving compartments respectively defined by a corresponding plurality of separately removable liner elements.

  3. CALUTRON RECEIVERS

    DOEpatents

    Schmidt, F.H.; Stone, K.F.

    1958-09-01

    S>This patent relates to improvements in calutron devices and, more specifically, describes a receiver fer collecting the ion curreot after it is formed into a beam of non-homogeneous isotropic cross-section. The invention embodies a calutron receiver having an ion receiving pocket for separately collecting and retaining ions traveling in a selected portion of the ion beam and anelectrode for intercepting ions traveling in another selected pontion of the ion beam. The electrode is disposed so as to fix the limit of one side of the pontion of the ion beam admitted iato the ion receiving pocket.

  4. Transient immunosuppression stops rejection of virus-transduced enhanced green fluorescent protein in rabbit retina.

    PubMed

    Doi, Kentaro; Kong, Jian; Hargitai, Janos; Goff, Stephen P; Gouras, Peter

    2004-10-01

    The expression of lentivirus-transduced enhanced green fluorescent protein (EGFP) was detectable in rabbit retinal pigment epithelium (RPE) within 3 to 5 days after subretinal injection of the vector. Within 2 to 3 weeks, EGFP-expressing cells were eliminated by rejection. In the current experiments, we monitor serum antibody titers for EGFP before and after transduction and determine whether systemic immunosuppression prevents recognition of EGFP by the immune system. While all control rabbits developed antibodies against EFGP and showed signs of rejection, no such evidence was observed with animals which received immunosuppression. One month of systemic immunosuppression permanently prevented rejection of RPE with EGFP expression. Fluorescence has been maintained for more than a year. If a control eye was injected with the same virus after terminating immunosuppression, both eyes showed signs of rejection. The lack of rejection is not due to tolerance but to a failure of the animals to detect the foreign protein. Detection must depend upon a brief window of time after surgery needed to introduce the vector, perhaps related to a concurrent but transient inflammation. This strategy may be useful in managing other types of rejection in the retina. PMID:15452253

  5. Immunosuppressive serum levels in allogeneic hematopoietic stem cell transplantation: pharmaceutical care contribution

    PubMed Central

    CORRÊA, Paulo M.; Zuckermann., Joice; Fischer, Gustavo B.; Castro., Mauro S.

    2015-01-01

    Background: Cyclosporine and tacrolimus are limited by a narrow therapeutic window. Maintaining immunosuppressive drugs at desired levels may be difficult. Pharmaceutical care emerges as a philosophy of practice that enhances medication use and leads to a better control of serum concentration. Objective: This study aims to evaluate the impact of pharmaceutical care in the maintaining of proper serum levels of immunosuppressive medications in patients who have undergone allo-HSCT. Methods: The study had a quasi-experimental design that included a comparison group. The service model used was pharmacotherapy follow-up, according to an adaptation of the Dader method. The pharmacist consultation was carried out at a day-hospital or at the outpatient hematology clinic as needed. The intervention group consisted of 22 patients seen by a clinical pharmacist. The control group consisted of 44 patients that received standard care. This study aims to evaluate the impact of pharmaceutical care on keeping patient serum levels of cyclosporine and tacrolimus within the desired range. Results: Control group displayed 65% of the proper serum levels of immunosuppressive agents. While In intervention group, the figure was 82% (p = 0.004). Conclusion: The role of the pharmacist in the multidisciplinary team may contribute to a greater success in attaining the patients’ therapeutic targets with regard to the use of immunosuppressant. PMID:27382420

  6. Effects of immunosuppressive drugs on gastrointestinal transit of rats: effects of tacrolimus, cyclosporine, and prednisone.

    PubMed

    Dall'Agnol, D J R; Hauschildt, A T; Lima, M B; Corá, L A; Teixeira, M C B; Américo, M F

    2014-01-01

    Triple immunosuppressive therapy after organ transplantation may cause several gastrointestinal disturbances. It is difficult to identify which drug causes more complications, requiring an appropriate animal model. The aim was to compare the gastrointestinal transit in immunosuppressed rats under triple immunosuppressive therapy. Male rats were immunosuppressed by gavage during 14 days with tacrolimus (n = 10), cyclosporine (n = 12), and prednisone (n = 9). Animals received a magnetic pellet before (control) and after treatment that was monitored at predetermined intervals by AC biosusceptometry, a noninvasive and radiation-free technique. The following parameters were measured: creatinine serum, mean time of gastric emptying (MGET), mean time to reach cecum (MCAT), and mean transit time through small bowel (MSBTT). The differences were analyzed by ANOVA (Tukey). Our results showed that MGET of animals treated with prednisone, cyclosporine, and tacrolimus were reduced compared with control subjects (P < .03, P < .009, and P < .002, respectively). There was no difference in MCAT, whereas MSBTT was longer for tacrolimus and prednisone compared with control subjects (P < .004 and P < .004, respectively). Also, prednisone and tacrolimus presented a reduced MGET (P < .05 and P < .01, respectively) compared with cyclosporine. Our data showed a low serum creatinine level and no difference among groups regarding renal function. In summary, cyclosporine has less effect on the gastrointestinal transit; however, all of these drugs should be carefully prescribed to prevent gastrointestinal symptoms and improve quality of life after transplantation. PMID:25131057

  7. Curing Hepatitis C in Liver Transplant Recipients Is Associated with Changes in Immunosuppressant Use

    PubMed Central

    Saab, Sammy; Rheem, Justin; Jimenez, Melissa; Bau, Sherona; Choi, Gina; Durazo, Francisco; El Kabany, Mohammed; Han, Steven; Farid, Alexander; Jamal, Naadir; Grotts, Jonathan; Elashoff, David; Busuttil, Ronald W.

    2016-01-01

    Background and Aims: All-oral interferon-free antivirals are highly effective in treating recurrent hepatitis C (HCV) infection in liver transplant (LT) recipients. The aim of the study was to assess immunosuppression needs after achieving a sustained viral response (SVR). Methods: We compared immunosuppression needs before and after achieving a SVR in adult LT recipients treated for recurrent HCV infection with all-oral direct acting agents. Results: We identified 52 liver LT treated recipients who achieved a SVR. The median (25th and 75th percentile interquartile range [IQR]) age was 62 years (57.75, 65). Most recipients received tacrolimus (TAC) for their immunosuppressant regimen. After achieving SVR, there was no statistically significant difference in daily dose of TAC unadjusted per weight (p > 0.05). However, there was a statistically significant decrease in daily dose of TAC adjusted per weight, serum levels of TAC, and the product of glomerular filtration rate and TAC. No statistically significant differences in cyclosporine unadjusted/adjusted per weight daily dose or serum levels were noted. Conclusions: Immunosuppression needs were increased for those patients treated with TAC but not cyclosporine. LT recipients prescribed TAC require close monitoring after treatment completion to avoid potential risk of acute rejection. PMID:27047770

  8. Bacillary angiomatosis in an immunosuppressed dog.

    PubMed

    Yager, Julie A; Best, Susan J; Maggi, Ricardo G; Varanat, Mrudula; Znajda, Nadine; Breitschwerdt, Edward B

    2010-08-01

    A dog being treated with immunosuppressive doses of prednisone and azathioprine for pancytopenia of unknown origin, developed, over a 2-week period, multiple erythematous nodular lesions in the skin including footpads. Skin samples revealed lesions identical to those of human bacillary angiomatosis (BA). The nodules were composed of multifocal proliferations of capillaries, each lined by protuberant endothelial cells. The capillary clusters were separated by an oedematous connective tissue, lightly infiltrated with degenerate inflammatory cells, including neutrophils and macrophages. Tissue sections stained with Warthin-Starry silver stain revealed large numbers of positively stained bacilli in the stromal tissue, most heavily concentrated around the proliferating capillaries. Lesions of vascular degeneration and inflammation were evident. Bartonella vinsonii subsp. berkhoffii genotype 1 was independently amplified and sequenced from the blood and the skin tissue. The pathognomonic nature of the histological lesions, demonstration of compatible silver-stained bacilli in the tissue, and identification of B. vinsonii subsp. berkhoffii in the blood and tissue indicates that this is most likely the aetiologic agent responsible for the lesions. Antibiotic therapy was successful in resolving the nodules. It would appear that B. vinsonii subsp berkhoffii, like Bartonella henselae and Bartonella quintana, has the rare ability to induce angioproliferative lesions, most likely in association with immunosuppression. The demonstration of lesions identical to those of human BA in this dog is further evidence that the full range of clinical manifestations of human Bartonella infection occurs also in canines. PMID:20374571

  9. Local brain heavy ion irradiation induced Immunosuppression

    NASA Astrophysics Data System (ADS)

    Lei, Runhong; Deng, Yulin; Huiyang Zhu, Bitlife.; Zhao, Tuo; Wang, Hailong; Yu, Yingqi; Ma, Hong; Wang, Xiao; Zhuang, Fengyuan; Qing, Hong

    Purpose: To investigate the long term effect of acute local brain heavy ion irradiation on the peripheral immune system in rat model. Methodology: Only the brain of adult male Wistar rats were radiated by heavy ions at the dose of 15 Gy. One, two and three months after irradiation, thymus and spleen were analyzed by four ways. Tunel assay was performed to evaluate the percentage of apoptotic cells in thymus and spleen, level of Inflammatory cytokines (IL-2, IL-6, SSAO, and TNF-α) was detected by ELISA assay, the differentiation of thymus T lymphocyte subsets were measured by flow cytometry and the relative expression levels of genes related to thymus immune cell development were measured by using quantitative real-time PCR. Results: Thymus and spleen showed significant atrophy from one month to three months after irradiation. A high level of apoptosis in thymus and spleen were obtained and the latter was more vulnerable, also, high level of inflammatory cytokines were found. Genes (c-kit, Rag1, Rag2 and Sca1) related to thymus lymphocytes’ development were down-regulated. Conclusion: Local area radiation in the rat brain would cause the immunosuppression, especially, the losing of cell-mediated immune functions. In this model, radiation caused inflammation and then induced apoptosis of cells in the immune organs, which contributed to immunosuppression.

  10. Anti-arthritic and immunosuppressive activities of substituted triterpenoidal candidates.

    PubMed

    Alanazi, Amer M; Al-Omar, Mohamed A; Abdulla, Mohamed M; Amr, Abd El-Galil E

    2013-07-01

    We herein report the anti-arthritic and immunosuppressive activities of some synthesized substituted terpenoidal structure. Forty-four triterpenoid derivatives 1-21 containing a carboxylic, ester, amide and ketone groups attached to a triterpene moiety were conveniently synthesized and screened for their anti-arthritic and immunosuppressive activities. Synthetic triterpenoidal structures linked to a different function groups seem to be a promising approach in the search for novel leads for potent anti-arthritic and immunosuppressive agents. The detailed synthetic pathways of obtained compounds and anti-arthritic and immunosuppressive activities were reported. PMID:23603083

  11. Immunosuppressive cells in tumor immune escape and metastasis.

    PubMed

    Liu, Yang; Cao, Xuetao

    2016-05-01

    Tumor immune escape and the initiation of metastasis are critical steps in malignant progression of tumors and have been implicated in the failure of some clinical cancer immunotherapy. Tumors develop numerous strategies to escape immune surveillance or metastasize: Tumors not only modulate the recruitment and expansion of immunosuppressive cell populations to develop the tumor microenvironment or pre-metastatic niche but also switch the phenotype and function of normal immune cells from a potentially tumor-reactive state to a tumor-promoting state. Immunosuppressive cells facilitate tumor immune escape by inhibiting antitumor immune responses and furthermore promote tumor metastasis by inducing immunosuppression, promoting tumor cell invasion and intravasation, establishing a pre-metastatic niche, facilitating epithelial-mesenchymal transition, and inducing angiogenesis at primary tumor or metastatic sites. Numerous translational studies indicate that it is possible to inhibit tumor immune escape and prevent tumor metastasis by blocking immunosuppressive cells and eliminating immunosuppressive mechanisms that are induced by either immunosuppressive cells or tumor cells. Furthermore, many clinical trials targeting immunosuppressive cells have also achieved good outcome. In this review, we focus on the underlying mechanisms of immunosuppressive cells in promoting tumor immune escape and metastasis, discuss our current understanding of the interactions between immunosuppressive cells and tumor cells in the tumor microenvironment, and suggest future research directions as well as potential clinical strategies in cancer immunotherapy. PMID:26689709

  12. CALUTRON RECEIVERS

    DOEpatents

    MacKenzie, K.R.

    1958-09-16

    A novel calutron receiver is described for collecting the constituent material of two closely adjacent selected portions of an ion beam in separate compartments. The receiver is so conntructed that ion scatter and intermixing of the closely adjacent beam portions do nnt occur when the ions strike the receiver structure, and the beam is sharply separated Into the two compartments. In essence, these desirable results are achieved by inclining the adjoining wall of one compartment with respect to the approaching ions to reduce possible rebounding of ions from the compartment into the adjacent compartment.

  13. Streak camera receiver definition study

    NASA Technical Reports Server (NTRS)

    Johnson, C. B.; Hunkler, L. T., Sr.; Letzring, S. A.; Jaanimagi, P.

    1990-01-01

    Detailed streak camera definition studies were made as a first step toward full flight qualification of a dual channel picosecond resolution streak camera receiver for the Geoscience Laser Altimeter and Ranging System (GLRS). The streak camera receiver requirements are discussed as they pertain specifically to the GLRS system, and estimates of the characteristics of the streak camera are given, based upon existing and near-term technological capabilities. Important problem areas are highlighted, and possible corresponding solutions are discussed.

  14. RFI receiver. [deep space network

    NASA Technical Reports Server (NTRS)

    Lay, R.

    1980-01-01

    An S-band radio frequency interference (RFI) receiver to analyze and identify sources of RFI problems in the Deep Space Network DSN tracking stations is described. The RFI receiver is a constant gain, double conversion, open loop receiver with dual sine/cosine channel outputs, providing a total of 20 MHZ monitoring capability. This receiver is computer controlled using a MODCOMP II miniprocessor. The RFI receiver has been designed to operate at a 150 Kelvin system noise temperature accomplished by cascading two low noise field effect transistor (FET) amplifiers for the receiver front-end. The first stage low noise FET amplifier is mounted at the feed horn to minimize any cable losses to achieve a lower system noise temperature. The receiver is tunable over the frequency range of 2150 to 2450 MHz in both sine/cosine output channels with a resolution of 100 kHz.

  15. [Infections and immunosuppressive agents in rheumatology].

    PubMed

    Kahn, M F; Vitale, C; Grimaldi, A

    The authors review the problem of infection occurring in patients with chronic inflammatory rheumatism, e.g. rheumatoid arthritis, and lupus erythematosus, treated with cytolytic drugs for immunodepressive reasons. From their investigation, it seems that there is a high frequency of bacterial and mycotic and viral infections in these patients, but controlled investigations seem to show quite definitely that the frequency of these infections depends on the disease itself. The risk does not seem to be increased by cytolytic drugs. The only exception is herpes which appears in 10 to 20% of patients treated with immunosuppressive agents, as against 2% in a controll series. The other virus diseases did not have an abnormally high frequency. The conclusions are, of course, only of value for the types of treatment used in rheumatology. PMID:183273

  16. Cell Therapy for Parkinson's Disease: A Translational Approach to Assess the Role of Local and Systemic Immunosuppression.

    PubMed

    Aron Badin, R; Vadori, M; Vanhove, B; Nerriere-Daguin, V; Naveilhan, P; Neveu, I; Jan, C; Lévèque, X; Venturi, E; Mermillod, P; Van Camp, N; Dollé, F; Guillermier, M; Denaro, L; Manara, R; Citton, V; Simioni, P; Zampieri, P; D'avella, D; Rubello, D; Fante, F; Boldrin, M; De Benedictis, G M; Cavicchioli, L; Sgarabotto, D; Plebani, M; Stefani, A L; Brachet, P; Blancho, G; Soulillou, J P; Hantraye, P; Cozzi, E

    2016-07-01

    Neural transplantation is a promising therapeutic approach for neurodegenerative diseases; however, many patients receiving intracerebral fetal allografts exhibit signs of immunization to donor antigens that could compromise the graft. In this context, we intracerebrally transplanted mesencephalic pig xenografts into primates to identify a suitable strategy to enable long-term cell survival, maturation, and differentiation. Parkinsonian primates received WT or CTLA4-Ig transgenic porcine xenografts and different durations of peripheral immunosuppression to test whether systemic plus graft-mediated local immunosuppression might avoid rejection. A striking recovery of spontaneous locomotion was observed in primates receiving systemic plus local immunosuppression for 6 mo. Recovery was associated with restoration of dopaminergic activity detected both by positron emission tomography imaging and histological examination. Local infiltration by T cells and CD80/86+ microglial cells expressing indoleamine 2,3-dioxigenase were observed only in CTLA4-Ig recipients. Results suggest that in this primate neurotransplantation model, peripheral immunosuppression is indispensable to achieve the long-term survival of porcine neuronal xenografts that is required to study the beneficial immunomodulatory effect of local blockade of T cell costimulation. PMID:26749114

  17. Monopulse receiver

    NASA Technical Reports Server (NTRS)

    1977-01-01

    A time division multiplexing and a quadraphase combining dual channel system were analyzed, designed, and tested. Analyses performed include the following: (1) boresight error as a function of the error channel bandwidth; (2) error channel interference with the sum channel functions; (3) threshold performance; and (4) error channel crosstalk, linearity, and drift as a function of signal level, Doppler, and environment. Test results indicate that the time division multiplexing system meets the design goals of the program. However, careful selection and alignment of all gain controlled amplifiers are required along with temperature compensation of the angle channel gain. The quadraphase system crosstalk performance is comparatively poor (-15 dB) with respect to the -30 dB requirements and this consequently affects gain tracking performance. Gain tracking was found to be + or - 20 percent rather than the + or - 5 percent specification. Data for the two systems is compared and recommendations are presented.

  18. The portal immunosuppressive storm: relevance to islet transplantation?

    PubMed

    Shapiro, A M James; Gallant, Heather L; Hao, Er Geng; Lakey, Jonathan R T; McCready, Tara; Rajotte, Ray V; Yatscoff, Randall W; Kneteman, Norman M

    2005-02-01

    Outcomes in clinical islet transplantation improved substantially with the introduction of combined sirolimus and tacrolimus immunosuppression. However, multiple islet preparations are often required to achieve insulin independence, suggesting that islet engraftment may not be optimal when these agents are absorbed via the portal vein. The current study was designed to assess the differential concentrations of immunosuppressive drugs within the portal and systemic circulations of a large animal model, to assess the local concentrations of drugs to which islets are exposed early after implantation. Chronic catheters were placed in the portal vein and carotid artery of 6 mongrel dogs, and immunosuppressants were administered orally. Blood samples were drawn simultaneously from portal and systemic catheters, and drug concentrations were analyzed. Peak immunosuppressant levels as well as area under the curve were dramatically elevated in portal blood relative to systemic levels for all drugs tested. This "portal storm" of immunosuppression may be relevant to intrahepatic islet transplantation. PMID:15665744

  19. Management of hepatitis B reactivation in immunosuppressed patients: An update on current recommendations

    PubMed Central

    Bessone, Fernando; Dirchwolf, Melisa

    2016-01-01

    The proportion of hepatitis B virus (HBV) previously exposed patients who receive immunosuppressive treatment is usually very small. However, if these individuals are exposed to potent immunosuppressive compounds, the risk of HBV reactivation (HBVr) increases with the presence of hepatitis B surface antigen (HBsAg) in the serum. Chronic HBsAg carriers have a higher risk than those who have a total IgG anticore as the only marker of resolved/occult HBV disease. The loss of immune control in these patients may results in the reactivation of HBV replication within hepatocytes. Upon reconstitution of the immune system, infected hepatocytes are once again targeted and damaged by immune surveillance in an effort to clear the virus. There are different virological scenarios, and a wide spectrum of associated drugs with specific and stratified risk for the development of HBVr. Some of this agents can trigger a severe degree of hepatocellular damage, including hepatitis, acute liver failure, and even death despite employment of effective antiviral therapies. Currently, HBVr incidence seems to be increasing around the world; a fact mainly related to the incessant appearance of more powerful immunosuppressive drugs launched to the market. Moreover, there is no consensus on the length of prophylactic treatment before the patients are treated with immunosuppressive therapy, and for how long this therapy should be extended once treatment is completed. Therefore, this review article will focus on when to treat, when to monitor, what patients should receive HBV therapy, and what drugs should be selected for each scenario. Lastly, we will update the definition, risk factors, screening, and treatment recommendations based on both current and different HBV management guidelines. PMID:27004086

  20. CALUTRON RECEIVER

    DOEpatents

    Barnes, S.W.

    1959-08-25

    An improvement in a calutron receiver for collecting the isotopes ts described. The electromagnetic separation of the isotopes produces a mass spectrum of closely adjacent beams of ions at the foci regions, and a dividing wall between the two pockets is arranged at an angle. Substantially all of the tons of the less abundant isotope enter one of the pockets and strike one side of the wall directly, while substantially none of the tons entering the other pocket strikes the wall directly.

  1. Neurobehavioral consequences of small molecule-drug immunosuppression.

    PubMed

    Bösche, Katharina; Weissenborn, Karin; Christians, Uwe; Witzke, Oliver; Engler, Harald; Schedlowski, Manfred; Hadamitzky, Martin

    2015-09-01

    60 years after the first successful kidney transplantation in humans, transplant patients have decent survival rates owing to a broad spectrum of immunosuppressive medication available today. Not only transplant patients, but also patients with inflammatory autoimmune diseases or cancer benefit from these life-saving immunosuppressive and anti-proliferative medications. However, this success is gained with the disadvantage of neuropsychological disturbances and mental health problems such as depression, anxiety and impaired quality of life after long-term treatment with immunosuppressive drugs. So far, surprisingly little is known about unwanted neuropsychological side effects of immunosuppressants and anti-proliferative drugs from the group of so called small molecule-drugs. This is partly due to the fact that it is difficult to disentangle whether and to what extent the observed neuropsychiatric disturbances are a direct result of the patient's medical history or of the immunosuppressive treatment. Thus, here we summarize experimental as well as clinical data of mammalian and human studies, with the focus on selected small-molecule drugs that are frequently employed in solid organ transplantation, autoimmune disorders or cancer therapy and their effects on neuropsychological functions, mood, and behavior. These data reveal the necessity to develop immunosuppressive and anti-proliferative drugs inducing fewer or no unwanted neuropsychological side effects, thereby increasing the quality of life in patients requiring long term immunosuppressive treatment. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'. PMID:25529273

  2. Immunosuppressant deoxyspergualin inhibits antigen processing in monocytes.

    PubMed

    Hoeger, P H; Tepper, M A; Faith, A; Higgins, J A; Lamb, J R; Geha, R S

    1994-11-01

    Deoxyspergualin (DSG) is a novel immunosuppressive agent recently shown to bind to the constitutive heat shock protein 70, which is involved in binding and intracellular transport of antigenic peptides. In this study, we show that DSG inhibits the proliferation of PBMCs to the Ags tetanus toxoid and diphtheria toxoid, but not to the mitogens PHA and PMA/ionomycin, nor to the superantigens toxic shock syndrome toxin-1 and staphylococcal enterotoxin A. DSG's effect was specific for monocytes as preincubation of T cells with DSG did not inhibit their proliferation to monocytes pulsed with tetanus toxoid Ag for 16 h, whereas the presence of DSG during Ag pulsing of the monocytes inhibited their ability to stimulate T cell proliferation. DSG did not down-regulate the expression of MHC class II molecules by monocytes, and the inhibitory effect of DSG on T cell proliferation was not reversed by the addition of IL-2, nor by the addition of the costimulatory signals IL-1, IL-6, and anti-CD28. Studies with two human T cell clones, HA1.7 and PF5, specific, respectively, to peptides spanning amino acids 307-319 and 256-270 of influenza hemagglutinin, showed that DSG inhibited the proliferation of the clones to the native hemagglutinin molecule but minimally affected their proliferation to the peptides. These data suggest that DSG interferes with Ag processing and/or presentation. PMID:7930603

  3. Potential of immunosuppressive agents in cerebral ischaemia

    PubMed Central

    Gupta, Yogendra Kumar; Chauhan, Anjali

    2011-01-01

    Ischaemic stroke is a disorder involving multiple mechanisms of injury progression including activation of glutamate receptors, release of proinflammatory cytokines, nitric oxide (NO), free oxygen radicals and proteases. Presently, recombinant tissue plasminogen activator (rtPA) is the only drug approved for the management of acute ischaemic stroke. This drug, however, is associated with limitations like narrow therapeutic window and increased risk of intracranial haemorrhage. A large number of therapeutic agents have been tested including N-methly-D-aspartate (NMDA) receptor antagonist, calcium channel blockers and antioxidants for management of stroke, but none has provided significant neuroprotection in clinical trials. Therefore, searching for other potentially effective drugs for ischaemic stroke management becomes important. Immunosuppressive agents with their wide array of mechanisms have potential as neuroprotectants. Corticosteroids, immunophilin ligands, mycophenolate mofetil and minocycline have shown protective effect on neurons by their direct actions or attenuating toxic effects of mediators of inflammation. This review focuses on the current status of corticosteroids, cyclosporine A, FK506, rapamycin, mycophenolate mofetil and minocycline in the experimental models of cerebral ischaemia. PMID:21321416

  4. Immunosuppressive mechanisms in protein-calorie malnutrition

    SciTech Connect

    Redmond, H.P.; Shou, J.; Kelly, C.J.; Schreiber, S.; Miller, E.; Leon, P.; Daly, J.M. )

    1991-08-01

    Protein-calorie malnutrition (PCM) induces immunosuppression leading to increased mortality rates. Impaired macrophage respiratory burst activity (superoxide anion (O2-) generation) occurs in PCM, but cellular mechanisms are unclear. The major pathway resulting in O2- production involves inositol lipid-dependent signal transduction. This study examined the effect of mild versus severe PCM on macrophage O2- generating signal transduction pathways specific for responses to Candida albicans. Mice (CFW/Swiss Webster: n = 300) were randomized to either control or low protein diets for 3 or 8 weeks. Peritoneal macrophages were harvested for O2- production, mannose-fucose receptor (MFR) expression, membrane phospholipid analysis, arachidonic acid (AA) content, prostaglandin E2 (PGE2) production, and protein kinase C levels. O2- release was impaired in both mild and severe PCM. MFR expression was also decreased at these time points. Inositol lipid content was significantly lower at the 8-week time point only, although PGE2 and AA were significantly higher in the low protein diet group at 3 weeks. Protein kinase C levels were unchanged by PCM. Thus, mild PCM significantly increases macrophage-PGE2 production secondary to increased AA phospholipid content, with subsequent inhibition of O2- and MFR expression. Severe PCM inhibits macrophage (O2-) through depletion of critical membrane phospholipid components with subsequent impairment in signal transduction.

  5. Hepatitis B Reactivation During Immunosuppressive Therapy or Cancer Chemotherapy, Management, and Prevention: A Comprehensive Review-Screened

    PubMed Central

    Tavakolpour, Soheil; Alavian, Seyed Moayed; Sali, Shahnaz

    2016-01-01

    Context Due to the close relationship between the immune system and the hepatitis B virus (HBV) replication, it is essential to monitor patients with current or past HBV infection under any type of immunosuppression. Cancer chemotherapy, immunosuppressive therapies in autoimmune diseases, and immunosuppression in solid organ and stem cell transplant recipients are the major reasons for hepatitis B virus reactivation (HBVr). In this review, the challenges associated with HBVr are discussed according to the latest studies and guidelines. We also discuss the role of treatments with different risks, including anti-CD20 agents, tumor necrosis factor-alpha (TNF-α) inhibitors, and other common immunosuppressive agents in various conditions. Evidence Acquisition Through an electronic search of the PubMed, Google Scholar, and Scopus databases, we selected the studies associated with HBVr in different conditions. The most recent recommendations were collected in order to reach a consensus on how to manage patients at risk of HBVr. Results It was found that the positive hepatitis B surface antigen (HBsAg), the high baseline HBV DNA level, the positive hepatitis B virus e antigen (HBeAg), and an absent or low hepatitis B surface antibody (HBsAb) titer prior to starting treatment are the most important viral risk factors. Furthermore, rituximab, anthracycline, and different types of TNF-α inhibitors were identified as the high-risk therapies. By analyzing the efficiency of prophylaxis on the prevention of HBVr, it was concluded that those with a high risk of antiviral resistance should not be used in long-term immunosuppressants. Receiving HBV antiviral agents at the commencement of immunosuppressant therapy or chemotherapy was demonstrated to be effective in decreasing the risk of HBVr. Prophylaxis could also be initiated before the start of therapy. For most immune suppressive regimes, antiviral therapy should be kept up for at least 6 months after the cessation of

  6. [Current status of oral immunomodulatory and immunosuppressive agents].

    PubMed

    Meller, S; Baran, A M; Braun, S A; Klossowski, N; Homey, B

    2014-02-01

    Various dermatological disorders require treatments with immunosuppressive or immunomodulatory agents. Nevertheless, several studies demonstrate low prescription rates for systemic treatments. This low usage may be a result of physicians' low levels of confidence in administering systemic treatments. However, immunosuppressive treatments represent safe options when potential side effects as well as pharmacological interactions are considered. This review overviews the most important oral immunosuppressive or immunomodulatory agents and summarizes their mode of actions, indications, and adverse effects. Biologics that require intravenous or subcutaneous application are not included, but novel and new agents likely to be released soon are considered. PMID:24549480

  7. Prevention of infection in immunosuppressive patients with autoimmune nephrosis by using an immunostimulating bacterial lysate Broncho-vaxom

    PubMed Central

    Zhang, Miao; Luan, Hong; Zhang, Qian; Wang, Le; Lv, Yong-Man; He, Fan; Chen, Yan; Zeng, Hong-Bing; Yao, Ying; Liu, Qin

    2012-01-01

    The utilization of immunosuppressive agents presents patients with autoimmune nephrosis at a high risk of infection. The present trial was to investigate the efficacy and safety of Broncho-Vaxom on preventing infection in immunosuppressive patients with autoimmune nephrosis. Methods: 40 patients with autoimmune nephrosis were randomly divided into two groups. The control group (20 cases) routinely received corticosteroid and (or) immunosuppressive therapy, while the treatment group (20 cases) received a capsule containing 7 mg Broncho-Vaxom daily for the first 10 d of each month for 3 consecutive months on the basis of conventional corticosteroid and (or) immunosuppressive therapy. The condition of infection and blood lymphocyte were assessed. Results: 4 patients in the treatment group and 5 patients in the control group were lost during the follow-up period. 25% of patients in the treatment group and 40% of patients in the control group suffered infection. There was no difference in the incidence of infection between the two groups (p > 0.05), while Broncho-Vaxom treated patients suffered a shorter infection period and of which fewer patients need to receive antibiotics therapy (p < 0.05). After the treatment with Broncho-Vaxom, the total number of blood T lymphocyte, proportion of CD4+ T lymphocyte, CD4+/CD8+ reduced less and the serum IgG rose more obviously (p < 0.05), but the blood lymphocyte, B lymphocyte, CD8+ T lymphocyte, IgA and IgM have no differences between the two groups (p > 0.05). Conclusion: Broncho-Vaxom might be a good choice for preventing the respiratory infection in nephrosis, especially in the patients under the therapy of immunosuppressive agents. PMID:22922768

  8. Fractionated total lymphoid irradiation as preparative immunosuppression in high risk renal transplantation: clinical and immunological studies

    SciTech Connect

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

    1982-10-01

    Twenty-two patients at high risk to reject renal allografts have been treated with fractionated total lymphoid irradiation (FTLI) prior to transplantation of primary (2), secondary (16) or teritary (4) renal allografts. All patients undergoing retransplantation had rapidly rejected previous grafts. At 24 months following transplantation, 72% of grafts were functioning in the TLI group compared with a 38% graft function in an historical control group of recipients receiving secondary or tertiary grafts and treated with conventional immunosuppression. Important variables in determining success of transplantation following fractionated TLI include the dose of TLI, the interval from radiation to transplantation, and maintenance, post-transplant immunosuppressive therapy. Optimal results were achieved with 2500 rads delivered in 100 rad fractions followed by transplantation within two weeks, and a tapering prednisone schedule and maintenance azathioprine post-transplantation. Seventeen patients had significant complications of the radiation treatment and there was one death, prior to transplantation, associated with pneumonitis. In vitro assessment of immune function demonstrated marked peripheral T cell depletion and loss of in vitro responsiveness to mitogen and allogeneic stimulation following FTLI. The administration of donor bone marrow at the time of transplantation did not produce chimerism. The results suggest that when properly utilized FTLI can produce effective adjunctive immunosuppression for clinical transplantation.

  9. Fractionated total lymphoid irradiation as preparative immunosuppression in high risk renal transplantation

    SciTech Connect

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

    1982-10-01

    Twenty-two patients at high risk to reject renal allografts have been treated with fractionated total lymphoid irradiation (FTLI) prior to transplantation of primary (2), secondary (16) or tertiary (4) renal allografts. All patients undergoing retransplantation had rapidly rejected previous grafts. At 24 months following transplantation, 72% of grafts were functioning in the TLI group compared with a 38% graft function in an historical control group of recipients receiving secondary or tertiary grafts and treated with conventional immunosuppression. Important variables in determining success of transplantation following fractionated TLI include the dose of TLI, the interval from radiation to transplantation, and maintenance post-transplant immunosuppressive therapy. Optimal results were achieved with 2500 rads delivered in 100 rad fractions followed by transplantation within two weeks, and a tapering prednisone schedule and maintenance azathioprine post-transplantation. Seventeen patients had significant complications of the radiation treatment and there was one death, prior to transplantation, associated with pneumonitis. In vitro assessment of immune function demonstrated marked peripheral T cell depletion and loss of in vitro responsiveness to mitogen and allogeneic stimulation following FTLI. The administration of donor bone marrow at the time of transplantation did not produce chimerism. The results suggest that when properly utilized FTLI can produce effective adjunctive immunosuppression for clinical transplantation.

  10. Cytomegalovirus infection impairs immunosuppressive and antimicrobial effector functions of human multipotent mesenchymal stromal cells.

    PubMed

    Meisel, Roland; Heseler, Kathrin; Nau, Julia; Schmidt, Silvia Kathrin; Leineweber, Margret; Pudelko, Sabine; Wenning, Johannes; Zimmermann, Albert; Hengel, Hartmut; Sinzger, Christian; Degistirici, Özer; Sorg, Rüdiger Volker; Däubener, Walter

    2014-01-01

    Human mesenchymal stromal cells (MSC) possess immunosuppressive and antimicrobial effects that are partly mediated by the tryptophan-catabolizing enzyme indoleamine-2,3-dioxygenase (IDO). Therefore MSC represent a promising novel cellular immunosuppressant which has the potential to control steroid-refractory acute graft versus host disease (GvHD). In addition, MSC are capable of reducing the risk of infection in patients after haematopoietic stem cell transplantation (HST). Recent data indicate that signals from the microenvironment including those from microbes may modulate MSC effector functions. As Cytomegalovirus (CMV) represents a prominent pathogen in immunocompromised hosts, especially in patients following HST, we investigated the impact of CMV infection on MSC-mediated effects on the immune system. We demonstrate that CMV-infected MSC lose their cytokine-induced immunosuppressive capacity and are no longer able to restrict microbial growth. IDO expression is substantially impaired following CMV infection of MSC and this interaction critically depends on intact virus and the number of MSC as well as the viral load. Since overt CMV infection may undermine the clinical efficacy of MSC in the treatment of GvHD in transplant patients, we recommend that patients scheduled for MSC therapy should undergo thorough evaluation for an active CMV infection and receive CMV-directed antiviral therapy prior to the administration of MSC. PMID:24782599

  11. Hepatitis B reactivation in the setting of chemotherapy and immunosuppression - prevention is better than cure

    PubMed Central

    Pattullo, Venessa

    2015-01-01

    Due to the inherent relationship between the immune system and the hepatitis B virus (HBV) in exposed and infected individuals, immunomodulation associated with the treatment of solid tumours, haematological malignancies and inflammatory disorders has been linked to HBV reactivation (HBVr). Reactivation of HBV infection in the setting of chemotherapy and immunosuppression may lead to fulminant liver failure and death, but there is a cumulative body of evidence that these are potentially preventable adverse outcomes. As chronic hepatitis B is largely asymptomatic but also endemic worldwide, clinicians caring for patients requiring chemotherapy or immunosuppression need to be vigilant of the potential for HBVr in susceptible individuals. Serological screening and prophylactic and pre-emptive antiviral treatment with a nucleos(t)ide analogue should be considered in appropriate settings. Hepatitis B prevalence is examined in this review article, as are the risks of HBVr in patients receiving chemo- and immunosuppressive therapy. Recommendations regarding screening, monitoring and the role of antiviral prophylaxis are outlined with reference to current international associations’ guidelines and the best available evidence to date. PMID:25954478

  12. Immunosuppression and Chagas disease; experience from a non-endemic country.

    PubMed

    Salvador, F; Sánchez-Montalvá, A; Valerio, L; Serre, N; Roure, S; Treviño, B; Pou, D; Sulleiro, E; Bocanegra, C; Molina, I

    2015-09-01

    Reactivation of Chagas disease in the chronic phase may occur when immunosuppression is established, sometimes resulting in high parasitaemia and severe clinical manifestations such as meningitis and meningoencephalitis. Although this situation is being increasingly described, there is still scarce information. This retrospective observational study was performed in three Tropical Medicine Units of Barcelona (Spain) included in the International Health Programme of the Catalan Health Institute (PROSICS). The objective of the study was to describe epidemiological, clinical, microbiological, prognostic and therapeutic data from patients with Chagas disease and any kind of immunosuppressive condition attended in these three institutions from January 2007 to October 2014. From 1823 patients with Chagas disease attending these three centres during the study period, 38 (2%) had some kind of immunosuppressive condition: 12 patients had human immunodeficiency virus infection, 8 patients had neoplasia, 4 patients underwent organ transplantation and 14 patients had an autoimmune disease. Eight (21.1%) patients had cardiac involvement, and six (15.8%) patients had gastrointestinal involvement. Acute Trypanosoma cruzi infection was detected in two Spanish patients. Thirty-one (81.6%) patients received treatment with benznidazole, of whom 17 (54.8%) had some kind of adverse event. No patient had a severe manifestation or reactivation of Chagas disease. Patients with Chagas disease under immunosuppressive conditions are being increasingly described, especially in non-endemic countries. More information about this topic is required and international consensus in the diagnosis, treatment and follow up of these patients must be established to reduce the morbidity and mortality. PMID:26055418

  13. Clinical Study of Porokeratosis Associated with Immunosuppressive Therapy in Renal Transplant Recipients

    PubMed Central

    Han, Ye Won; Kim, Yeon Jeong; Kim, Hyung Ok

    2008-01-01

    Background The etiology of porokeratosis (PK) remains unknown, but immunosuppression is known to be a factor in the pathogenesis of PK and it may also exacerbate PK. Objective The aim of this study was to examine the clinical characteristics of PK associated with immunosuppressive therapy in renal transplant recipients. Methods A total of 9 renal transplant patients diagnosed with biopsy-proven PK from January 2001 to December 2006 were enrolled. The authors analyzed the patient and medication histories, clinical characteristics, and associated diseases. Results The ages of the 9 patients ranged from 38 to 67 years (mean 52 years). All received multi-drug regimens comprised of two or three immunosuppressive agents (steroids, cyclosporine, mycophenolate mofetil, azathioprine and/or tacrolimus). Times between transplantation and the onset of PK ranged from 2 to 9 years (mean 4.1 years). No family history of PK or a history of intense sun-exposure was elicited. The number of the lesions was less than ten in 8 of the 9. Lesions were mainly located in the extremities, though some affected the trunk or neck (3). Three patients had disseminated superficial actinic PK (DSAP), PK Mibelli, or both types. Associated diseases included verruca (4), recurrent herpes simplex (1), actinic keratosis (1), and cutaneous B cell lymphoma (1). Conclusion The three clinical patterns of PK occurred equally in our patients, namely, coexistent PK Mibelli and DSAP, or the DSAP and Mibelli types as independent forms. Our findings support the notion that the different variants of PK be viewed as parts of a heterogeneous clinical spectrum. Further studies are needed in order to establish the clinical patterns of PK in immunosuppressed patients. PMID:27303185

  14. Some transformations of tacrolimus, an immunosuppressive drug.

    PubMed

    Skytte, Dorthe M; Jaroszewski, Jerzy W; Johansen, Kenneth T; Hansen, Steen Honoré; Hansen, Liselotte; Nielsen, Peter G; Frydenvang, Karla

    2013-02-14

    Transformations of the macrocyclic lactone tacrolimus (1), an important immunosuppressive drug produced by Streptomyces species, are described. These transformation products are primarily of interest as reference substances for drug impurity analyses. Upon action of acid (p-toluenesulfonic acid in toluene), tacrolimus is dehydrated by loss of water from the β-hydroxyketone moiety with partial inversion of configuration at C-8, resulting in formation of 5-deoxy-Δ(5,6)-tacrolimus and 5-deoxy-Δ(5,6)-8-epitacrolimus. The structure of the latter was determined by single-crystal X-ray crystallography. The same products are formed upon action of free radicals (iodine in boiling toluene), along with formation of 8-epitacrolimus. The latter is converted by p-toluenesulfonic acid to 5-deoxy-Δ(5,6)-8-epitacrolimus. Treatment of tacrolimus with weak base (1,5-diazabicyclo[4.3.0]nonene) gives, in addition to 8-epitacrolimus, the open-chain acid corresponding to 5-deoxy-Δ(5,6)-tacrolimus, a rare non-cyclic derivative of tacrolimus. Strong base (t-butoxide) causes pronounced degradation of the molecule. Thermolysis of tacrolimus leads to ring expansion by an apparent [3,3]-sigmatropic rearrangement of the allylic ester moiety with subsequent loss of water from the β-hydroxyketone moiety. ¹H and ¹³C NMR spectra of the obtained compounds, complicated by the presence of amide bond rotamers and ketal moiety tautomers, were assigned by extensive use of 2D NMR techniques. PMID:23238171

  15. The risk of recurrent IgA nephropathy in a steroid-free protocol and other modifying immunosuppression.

    PubMed

    Von Visger, J R; Gunay, Y; Andreoni, K A; Bhatt, U Y; Nori, U S; Pesavento, T E; Elkhammas, E A; Winters, H A; Nadasdy, T; Singh, N

    2014-08-01

    Recurrent glomerulonephritis is an important cause of kidney allograft failure. The effect of immunosuppression on recurrent IgA nephropathy (IgAN) is unclear. We analyzed the impact of steroids and other immunosuppression on the risk of recurrent IgAN post-kidney transplantation. Between June 1989 and November 2008, 3311 kidney transplants were performed at our center. IgAN was the primary disease in 124 patients; of these, 75 (60.5%) patients received steroid-based immunosuppression (15 undergoing late steroid withdrawal), and 49 (39.5%) were maintained on steroid-free immunosuppression. Recurrent IgAN was diagnosed in 27 of 124 (22%) patients in clinically indicated kidney allograft biopsies over a median follow-up of 6.86 ± 5.4 yr. On cox proportional hazards model multivariate analysis, the hazard risk (HR) of IgAN recurrence was significantly higher in patients managed with steroid-free (HR 8.59: 3.03, 24.38, p < 0.001) and sirolimus-based (HR = 3.00:1.16, 7.75, p = 0.024) immunosuppression without antilymphocyte globulin induction (HR = 4.5: 1.77, 11.73, p = 0.002). Mycophenolate use was associated with a lower risk (HR = 0.42: 0.19, 0.95, p = 0.036), whereas cyclosporine did not have a significant impact on the risk of IgAN recurrence (p = 0.61). These results warrant future prospective studies regarding the role of steroids and other immunosuppression drugs in reducing recurrence of IgAN and other glomerulonephritis post-transplant. PMID:24869763

  16. Lung transplant immunosuppression – time for a new approach?

    PubMed Central

    Witt, CA; Puri, V; Gelman, AE; Krupnick, AS; Kreisel, D

    2015-01-01

    Summary Outcomes after lung transplantation remain worse compared to other solid organ transplants, which is in large part due to high rates of graft rejection. Despite emerging data that immune responses to lungs differ from other organs, immunosuppression for lung transplant recipients is still based on strategies established for recipients of other grafts. There exists an urgent need to develop immunosuppressive strategies for lung transplant recipients that take the unique immunological features of this organ into account. PMID:25220652

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

    SciTech Connect

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

    1990-10-01

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

  18. Hyperbaric Oxygen Therapy as a Sole Agent Is Not Immunosuppressant in a Highly Immunogenic Mouse Model

    PubMed Central

    Gassas, Adam; Min, Weixian; Evans, A. Wayne; Carter, Susan; Sándor, George K.; Grunebaum, Eyal

    2011-01-01

    Background. Hyperbaric oxygen (HBO) therapy, which is used for many conditions, may also have immunosuppressive effects and could be used for prevention or treatment of graft-versus-host disease (GvHD). If HBO is immunosuppressant, then we hypothesize that HBO therapy will delay the T-cell mediated skin graft rejection. Methods. C57/BL6 black-coated (H2B) mice received skin graft from CBA (H2D) white-coated mice. Mice were treated with either 19 session of 240 kpa oxygen or 29 session of 300 kpa oxygen, for 90 minutes. Mice were housed either 4 per cage or separately, to prevent friction and mechanical factors that may affect graft survival. Skin grafts were assessed daily. Results. There was no difference in length of graft survival between mice that received either regimens of HBO therapy and mice that did not receive HBO therapy. Conclusions. HBO therapy, as a sole agent, did not delay skin graft rejection in a highly immunogenic mouse model. PMID:22046567

  19. Radiation receiver

    DOEpatents

    Hunt, A.J.

    1983-09-13

    The apparatus for collecting radiant energy and converting same to alternate energy form includes a housing having an interior space and a radiation transparent window allowing, for example, solar radiation to be received in the interior space of the housing. Means are provided for passing a stream of fluid past said window and for injecting radiation absorbent particles in said fluid stream. The particles absorb the radiation and because of their very large surface area, quickly release the heat to the surrounding fluid stream. The fluid stream particle mixture is heated until the particles vaporize. The fluid stream is then allowed to expand in, for example, a gas turbine to produce mechanical energy. In an aspect of the present invention properly sized particles need not be vaporized prior to the entrance of the fluid stream into the turbine, as the particles will not damage the turbine blades. In yet another aspect of the invention, conventional fuel injectors are provided to inject fuel into the fluid stream to maintain the proper temperature and pressure of the fluid stream should the source of radiant energy be interrupted. In yet another aspect of the invention, an apparatus is provided which includes means for providing a hot fluid stream having hot particles disbursed therein which can radiate energy, means for providing a cooler fluid stream having cooler particles disbursed therein, which particles can absorb radiant energy and means for passing the hot fluid stream adjacent the cooler fluid stream to warm the cooler fluid and cooler particles by the radiation from the hot fluid and hot particles. 5 figs.

  20. Radiation receiver

    DOEpatents

    Hunt, Arlon J.

    1983-01-01

    The apparatus for collecting radiant energy and converting same to alternate energy form includes a housing having an interior space and a radiation transparent window allowing, for example, solar radiation to be received in the interior space of the housing. Means are provided for passing a stream of fluid past said window and for injecting radiation absorbent particles in said fluid stream. The particles absorb the radiation and because of their very large surface area, quickly release the heat to the surrounding fluid stream. The fluid stream particle mixture is heated until the particles vaporize. The fluid stream is then allowed to expand in, for example, a gas turbine to produce mechanical energy. In an aspect of the present invention properly sized particles need not be vaporized prior to the entrance of the fluid stream into the turbine, as the particles will not damage the turbine blades. In yet another aspect of the invention, conventional fuel injectors are provided to inject fuel into the fluid stream to maintain the proper temperature and pressure of the fluid stream should the source of radiant energy be interrupted. In yet another aspect of the invention, an apparatus is provided which includes means for providing a hot fluid stream having hot particles disbursed therein which can radiate energy, means for providing a cooler fluid stream having cooler particles disbursed therein, which particles can absorb radiant energy and means for passing the hot fluid stream adjacent the cooler fluid stream to warm the cooler fluid and cooler particles by the radiation from the hot fluid and hot particles.

  1. Immunosuppression Decreases Inflammation and Increases AAV6-hSERCA2a-Mediated SERCA2a Expression

    PubMed Central

    Zhu, Xiaodong; McTiernan, Charles F.; Rajagopalan, Navin; Shah, Hemal; Fischer, David; Toyoda, Yoshiya; Letts, Dustin; Bortinger, Jonathan; Gibson, Gregory; Xiang, Wenyu; McCurry, Kenneth; Mathier, Michael; Glorioso, Joseph C.

    2012-01-01

    Abstract The calcium pump SERCA2a (sarcoplasmic reticulum calcium ATPase 2a), which plays a central role in cardiac contraction, shows decreased expression in heart failure (HF). Increasing SERCA2a expression in HF models improves cardiac function. We used direct cardiac delivery of adeno-associated virus encoding human SERCA2a (AAV6-hSERCA2a) in HF and normal canine models to study safety, efficacy, and the effects of immunosuppression. Tachycardic-paced dogs received left ventricle (LV) wall injection of AAV6-hSERCA2a or solvent. Pacing continued postinjection for 2 or 6 weeks, until euthanasia. Tissue/serum samples were analyzed for hSERCA2a expression (Western blot) and immune responses (histology and AAV6-neutralizing antibodies). Nonpaced dogs received AAV6-hSERCA2a and were analyzed at 12 weeks; a parallel cohort received AAV-hSERCA2a and immunosuppression. AAV-mediated cardiac expression of hSERCA2a peaked at 2 weeks and then declined (to ∼50%; p<0.03, 6 vs. 2 weeks). LV end diastolic and end systolic diameters decreased in 6-week dogs treated with AAV6-hSERCA2a (p<0.05) whereas LV diameters increased in control dogs. Dogs receiving AAV6-hSERCA2a developed neutralizing antibodies (titer ≥1:120) and cardiac cellular infiltration. Immunosuppression dramatically reduced immune responses (reduced inflammation and neutralizing antibody titers <1:20), and maintained hSERCA2a expression. Thus cardiac injection of AAV6-hSERCA2a promotes local hSERCA2a expression and improves cardiac function. However, the hSERCA2a protein level is reduced by host immune responses. Immunosuppression alleviates immune responses and sustains transgene expression, and may be an important adjuvant for clinical gene therapy trials. PMID:22482463

  2. Effects of Immunosuppressants on Immune Response to Vaccine in Inflammatory Bowel Disease

    PubMed Central

    Cao, Yuan; Zhao, Di; Xu, An-Tao; Shen, Jun; Ran, Zhi-Hua

    2015-01-01

    Objective: To evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants). Data Sources: We completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators). The following terms were used: “inflammatory bowel disease (IBD)” OR “Crohn's disease” OR “ulcerative colitis” AND (“vaccination” OR “vaccine”) AND (“corticosteroids” OR “mercaptopurine” OR “azathioprine” OR “methotrexate [MTX]”) AND “immunomodulators.” Study Selection: The inclusion criteria of articles were that the studies: (1) Randomized controlled trials which included patients with a diagnosis of IBD (established by standard clinical, radiographic, endoscopic, and histologic criteria); (2) exposed patients received immunomodulators for maintenance (weight-appropriate doses of 6-mercaptopurine/azathioprine or within 3 months of stopping, 15 mg or more MTX per week or within 3 months of stopping; (3) exposed patients received nonimmunomodulators (no therapy, antibiotics only, mesalazine only, biological agent only such as infliximab, adalimumab, certolizumab or natalizumab or within 3 months of stopping one of these agents). The exclusion criteria of articles were that the studies: (1) History of hepatitis B virus (HBV), influenza or streptococcus pneumoniae infection; (2) patients who had previously been vaccinated against HBV, influenza or streptococcus pneumoniae; (3) any medical condition known to cause immunosuppression (e.g. chronic renal failure and human immunodeficiency virus infection); (4) individuals with positive hepatitis markers or liver cirrhosis; (5) patients with a known allergy to eggs or other components of the vaccines and (6) pregnancy. Results: Patients treated with immunomodulators were

  3. Assessment of Readiness for Clinical Decision Support to Aid Laboratory Monitoring of Immunosuppressive Care at U.S. Liver Transplant Centers

    PubMed Central

    Weir, C.; Evans, R. S.; Staes, C.

    2014-01-01

    Summary Background Following liver transplantation, patients require lifelong immunosuppressive care and monitoring. Computerized clinical decision support (CDS) has been shown to improve post-transplant immunosuppressive care processes and outcomes. The readiness of transplant information systems to implement computerized CDS to support post-transplant care is unknown. Objectives a) Describe the current clinical information system functionality and manual and automated processes for laboratory monitoring of immunosuppressive care, b) describe the use of guidelines that may be used to produce computable logic and the use of computerized alerts to support guideline adherence, and c) explore barriers to implementation of CDS in U.S. liver transplant centers. Methods We developed a web-based survey using cognitive interviewing techniques. We surveyed 119 U.S. transplant programs that performed at least five liver transplantations per year during 2010–2012. Responses were summarized using descriptive analyses; barriers were identified using qualitative methods. Results Respondents from 80 programs (67% response rate) completed the survey. While 98% of programs reported having an electronic health record (EHR), all programs used paper-based manual processes to receive or track immunosuppressive laboratory results. Most programs (85%) reported that 30% or more of their patients used external laboratories for routine testing. Few programs (19%) received most external laboratory results as discrete data via electronic interfaces while most (80%) manually entered laboratory results into the EHR; less than half (42%) could integrate internal and external laboratory results. Nearly all programs had guidelines regarding pre-specified target ranges (92%) or testing schedules (97%) for managing immunosuppressive care. Few programs used computerized alerting to notify transplant coordinators of out-of-range (27%) or overdue laboratory results (20%). Conclusions Use of EHRs is

  4. Fingerprints of transplant tolerance suggest opportunities for immunosuppression minimization.

    PubMed

    Sarwal, Minnie M

    2016-03-01

    HLA incompatible organ transplant tolerance is the holy grail of transplantation. Stable engraftment of an HLA mismatched allograft and life-long tolerance induction, though feasible in highly selected cohorts with depletional protocols, is not ready for generalized application to the entire transplant recipient pool. It has thus been important to harness biomarkers that can uncover mechanisms and tools for monitoring HLA mismatched recipients that develop a state of operational tolerance, during accidental immunosuppression withdrawal secondary to problems of over-immunosuppression (infection or malignancy) or toxicity (mostly cosmetic or cardiovascular). A restricted and unpredictable group of patients can demonstrate a clinical state of operational tolerance, manifested by state of stable graft function of a graft with HLA mismatches between recipient and donor, intact immune responses to third party antigens and no measurable immunosuppression. These patients have served as the basis for the discovery of clinically correlative biomarkers, in distal biofluids (mainly blood), that can define the existing state of operational clinical tolerance. Operationally tolerant patients are rare, as withdrawal of immunosuppression most often results in rejection and graft loss. Nevertheless, operationally tolerant kidney, liver and heart allograft recipients have been reported. The presence of similar biomarker signature profiles in HLA mismatched transplant recipients on immunosuppression, suggests the feasibility of utilizing these biomarkers for educated immunosuppression minimization with a view to retaining immunological quiescence, while reducing the maintenance immunosuppression burden to a "safe" alloimmune threshold. Though clinical operational tolerance is rare, as immunosuppression cessation most often results in increased alloimmunity and rejection, the biomarker profile studies that have harnessed whole genome profiling suggest that the frequency of this state

  5. Management of patients with hepatitis B who require immunosuppressive therapy

    PubMed Central

    Hwang, Jessica P.; Lok, Anna S.-F.

    2014-01-01

    Patients with chronic HBV infection are at risk of reactivation of HBV should they require immunosuppressive therapies for a variety of clinical settings, including chemotherapy for patients with cancer, immunosuppression for solid organ and stem cell transplant recipients, and use of anti-CD20 antibodies, TNF inhibitors, or corticosteroids in patients with oncological, gastrointestinal, rheumatological or dermatological conditions. The key to preventing HBV reactivation is the identification of patients with HBV infection prior to immunosuppressive therapy, initiation of prophylactic antiviral therapy in patients at moderate or high risk of HBV reactivation, and close monitoring of other patients so that antiviral therapy can be initiated at the first sign of HBV reactivation. Unfortunately, many patients infected with HBV are unaware of their infection or risk factors, and physicians often do not have sufficient time to systematically assess patients for risk factors for HBV prior to starting immunosuppressive therapy. In this article, we review the incidence, risk factors and outcomes of HBV reactivation, and the efficacy of antiviral therapy in preventing its occurrence. We also propose an algorithm for managing patients with HBV infection who require immunosuppressive therapy. PMID:24247262

  6. Prevention of Hepatitis B reactivation in the setting of immunosuppression

    PubMed Central

    Pattullo, Venessa

    2016-01-01

    Advances in the treatment of malignant and inflammatory diseases have developed over time, with increasing use of chemotherapeutic and immunosuppressive agents of a range of drug classes with varying mechanism and potency in their effects on the immune system. These advances have been met with the challenge of increased risk of hepatitis B virus (HBV) reactivation in susceptible individuals. The magnitude of risk of HBV reactivation is associated with the individual’s HBV serological status and the potency and duration of immunosuppression. Individuals with chronic hepatitis B (CHB) and previously infected but serologically cleared HBV infection are both susceptible to HBV reactivation. HBV reactivation in the setting of immunosuppression is a potentially life threatening condition leading to liver failure and death in extreme cases. It is important to recognize that HBV reactivation in the setting of immunosuppression is potentially preventable. Therefore, identification of patients at risk of HBV reactivation and institution of prophylactic antiviral therapy prior to initiation of immunosuppression is essential. PMID:27291888

  7. Vaccinations in children on immunosuppressive medications for renal disease.

    PubMed

    Banerjee, Sushmita; Dissanayake, Pathum Vindana; Abeyagunawardena, Asiri Samantha

    2016-09-01

    Renal diseases are often treated with immunosuppressive medications, placing patients at risk of infections, some of which are vaccine-preventable. However, in such patients vaccinations may be delayed or disregarded due to complications of the underlying disease process and challenges in its management. The decision to administer vaccines to immunosuppressed children is a risk-benefit balance as such children may have a qualitatively diminished immunological response or develop diseases caused by the vaccine pathogen. Vaccination may cause a flare-up of disease activity or provocation of graft rejection in renal transplant recipients. Moreover, it cannot be assumed that a given antibody level provides the same protection in immunosupressed children as in healthy ones. We have evaluated the safety and efficacy of licensed vaccines in children on immunosuppressive therapy and in renal transplant recipients. The limited evidence available suggests that vaccines are most effective if given early, ideally before the requirement for immunosuppressive therapy, which may require administration of accelerated vaccine courses. Once treatment with immunosuppressive drugs is started, inactivated vaccines are usually considered to be safe when the disease is quiescent, but supplemental doses may be required. In the majority of cases, live vaccines are to be avoided. All vaccines are generally contraindicated within 3-6 months of a renal transplant. PMID:26450774

  8. Ultraviolet-induced alloantigen-specific immunosuppression in transplant immunity

    PubMed Central

    Hori, Tomohide; Kuribayashi, Kagemasa; Saito, Kanako; Wang, Linan; Torii, Mie; Uemoto, Shinji; Iida, Taku; Yagi, Shintaro; Kato, Takuma

    2015-01-01

    After the first observation of the immunosuppressive effects of ultraviolet (UV) irradiation was reported in 1974, therapeutic modification of immune responses by UV irradiation began to be investigated in the context immunization. UV-induced immunosuppression is via the action of regulatory T cells (Tregs). Antigen-specific Tregs were induced by high-dose UV-B irradiation before antigen immunization in many studies, as it was considered that functional alteration and/or modulation of antigen-presenting cells by UV irradiation was required for the induction of antigen-specific immunosuppression. However, it is also reported that UV irradiation after immunization induces antigen-specific Tregs. UV-induced Tregs are also dominantly transferable, with interleukin-10 being important for UV-induced immunosuppression. Currently, various possible mechanisms involving Treg phenotype and cytokine profile have been suggested. UV irradiation accompanied by alloantigen immunization induces alloantigen-specific transferable Tregs, which have potential therapeutic applications in the transplantation field. Here we review the current status of UV-induced antigen-specific immunosuppression on the 40th anniversary of its discovery. PMID:25815267

  9. Azathioprine as a single immunosuppressive drug in the treatment of myasthenia gravis.

    PubMed

    Cosi, V; Lombardi, M; Erbetta, A; Piccolo, G

    1993-04-01

    We retrospectively evaluated results obtained from azathioprine (AZA) treatment on a selected sample of 40 patients affected by autoimmune myasthenia gravis (MG). Patients received AZA as a single immunosuppressive drug for at least 2 years. Twenty out of 40 patients received also a one-month course of cyclophosphamide (CP) before starting AZA. All patients started immunosuppressive treatment out of myasthenic crisis. After 3, 12 and 24 months of AZA treatment, 82.5%, 92.5% and 97.5% of the patients respectively showed improvement in functional state, disappearance of bulbar involvement, or both. The impressive percentage of short-term positive results did not seem influenced by pre-treatment by CP. Side effects included only minor and transitory gastrointestinal symptoms and reversible cytopenia. Although the patient population was either particularly suitable for AZA treatment or candidate to a better response, our data suggest that AZA might also have good short term effects in a subgroup of MG patients. PMID:8328322

  10. Septic arthritis in the era of immunosuppressive treatments.

    PubMed

    Salar, O; Baker, B; Kurien, T; Taylor, A; Moran, C

    2014-03-01

    Immunosuppressants have been the mainstay of treatment for certain inflammatory joint conditions for many years. Developments in this field, namely biological treatments, have led to a change in the classical presentation of acute bone, joint and soft tissue infections. The normal findings of severe pain and tenderness on examination may be absent or simply mimic a typical exacerbation of the chronic joint condition. A minimally raised white cell count and elevated C-reactive protein in the absence of systemic signs of infection may be interpreted as further evidence for the diagnosis of an exacerbation of inflammatory arthritis. We present a unique case of recurrent polyarticular septic arthritis in a patient treated with immunosuppression for refractory rheumatoid arthritis. We hope this article will enable doctors to appreciate and recognise the changing face of septic arthritis in the modern era of immunosuppressant treatments. PMID:24780657

  11. In vitro study of immunosuppressive effect of apoptotic cells*

    PubMed Central

    Zhang, Wen-jin; Zheng, Shu-sen

    2005-01-01

    Recent studies revealed that apoptotic cells are actively involved in immunosuppression and anti-inflammation. After being phagocytosed by macrophages, apoptotic cells can actively regulate cytokines secretion from lipopolysaccharide (LPS)-stimulated macrophages, in which the secretion of immunosuppressive cytokines such as interleukin-10 (IL-10) is increased while the pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNFα), interleukin-1beta (IL-1β) and leukin-8 (IL-8) are suppressed. In this paper, we first present evidence that phagocytosed apoptotic cells regulate cytokine secretion of LPS-stimulated macrophages, but also inhibit the activation of T lymphocytes stimulated by ConA. These data suggest that apoptotic cells can alter the biological behavior of macrophages which gain immunosuppressive property. PMID:16130196

  12. Cytomegalovirus Pneumonia in Patients with Rheumatic Diseases After Immunosuppressive Therapy: A Single Center Study in China

    PubMed Central

    Xue, Yu; Jiang, Li; Wan, Wei-Guo; Chen, Yu-Ming; Zhang, Jiong; Zhang, Zhen-Chun

    2016-01-01

    Background: Rheumatic diseases involve multiple organs that are affected by immunological mechanisms. Treatment with corticosteroids and immunosuppressive agents may also increase the frequency of infection. Cytomegalovirus (CMV) is a widespread herpes virus and a well-recognized pathogen, which causes an opportunistic and potentially fatal infection in immunocompromised patients. This retrospective study aimed to investigate the clinical and laboratory characteristics of CMV pneumonia in patients with rheumatic diseases after immunosuppressive therapy in a single center in Shanghai, China. Methods: Eight hundred and thirty-four patients with rheumatic diseases who had undergone CMV-DNA viral load tests were included, and the medical records of 142 patients who were positive for CMV-DNA in plasma samples were evaluated. GraphPad Prism version 5.013 (San Diego, CA, USA) was used to conduct statistical analysis. The correlation between CMV-DNA viral loads and lymphocyte counts was assessed using the Spearman rank correlation coefficient test. Significance between qualitative data was analyzed using Pearson's Chi-squared test. The cut-off thresholds for CMV-DNA viral load and lymphocyte count were determined by receiver operating characteristic (ROC) curve analysis. Results: One hundred and forty-two patients had positive CMV viral load tests. Of these 142 patients, 73 patients with CMV pneumonia were regarded as symptomatic, and the other 69 were asymptomatic. The symptomatic group received higher doses of prednisolone (PSL) and more frequently immunosuppressants than the asymptomatic group (P < 0.01). The symptomatic group had lower lymphocyte counts, especially CD4+ T-cells, than the asymptomatic group (P < 0.01). By ROC curve analysis, when CD4+ T-cell count was <0.39 × 109/L, patients with rheumatic diseases were at high risk for symptomatic CMV infection. The CMV-DNA load was significantly higher in the symptomatic patients than that in asymptomatic patients (P

  13. A new potent immunosuppressive isoflavanonol from Campylotropis hirtella.

    PubMed

    Xuan, Bixia; Du, Xing; Li, Xiaoping; Shen, Zhengwu

    2016-06-01

    Four new flavonoids were isolated from Campylotropis hirtella and these are a chromone and a 2H-chromene, an isoflavone and an isoflavanonol. The structures of these compounds were elucidated by extensive spectroscopic measurements. All of the compounds were assessed for immunosuppressive activity. Compound 4 showed very strong T lymphocyte suppression activity (IC50: 0.13 μM) and potent B lymphocyte suppression activity (IC50: 0.26 μM). Due to its potent immunosuppressive activity and lower cytotoxicity, further structure-activity studies will be pursued on this compound. PMID:26221996

  14. Strongyloidiasis in immunosuppressed hosts. Presentation as massive lower gastrointestinal bleeding.

    PubMed

    Powell, R W; Moss, J P; Nagar, D; Melo, J C; Boram, L H; Anderson, W H; Cheng, S H

    1980-08-01

    Two cases of massive lower gastrointestinal hemorrhage in immunosuppressed patients were due to complicated infestation with Strongyloides stercoralis. The very high mortality of disseminated strongyloidiasis may in part be attributed to delays in diagnosis and treatment resulting from the complex life cycle of this nematode. Successful therapy in the cases presented consisted of reduction of corticosteroid dosage, use of thiabendazole in excess of that recommended for uncomplicated infestation, parenterally administered nutrition, multiple transfusion of blood products, and vigorous supportive management. Emphasis is given to proper categorization of patients and measures designed to prevent, detect, and treat hyperinfection in patients in whom immunosuppression is anticipated. PMID:6967302

  15. Prevention of infection caused by immunosuppressive drugs in gastroenterology

    PubMed Central

    Orlicka, Katarzyna; Barnes, Eleanor

    2013-01-01

    Immunosuppressive therapy is frequently used to treat gastrointestinal diseases such as inflammatory bowel disease, autoimmune hepatitis, IgG4-related disease (autoimmune pancreatitis and sclerosing cholangitis) and in the post-transplantation setting. These drugs interfere with the immune system. The main safety concern with their use is the risk of infections. Certain infections can be prevented or their impact minimized. Physicians must adopt preventative strategies and should have a high degree of suspicion to recognize infections early and treat appropriately. This article reviews the risk factors for infections, the mechanism of action of immunosuppressive therapy and proposes preventive strategies. PMID:23819020

  16. Outcome of Hepatitis E Virus Infection in Patients With Inflammatory Arthritides Treated With Immunosuppressants

    PubMed Central

    Bauer, Hélène; Luxembourger, Cécile; Gottenberg, Jacques-Eric; Fournier, Sophie; Abravanel, Florence; Cantagrel, Alain; Chatelus, Emmanuel; Claudepierre, Pascal; Hudry, Christophe; Izopet, Jacques; Fabre, Sylvie; Lefevre, Guillaume; Marguerie, Laurent; Martin, Antoine; Messer, Laurent; Molto, Anna; Pallot-Prades, Béatrice; Pers, Yves-Marie; Roque-Afonso, Anne-Marie; Roux, Christian; Sordet, Christelle; Soubrier, Martin; Veissier, Claire; Wendling, Daniel; Péron, Jean-Marie; Sibilia, Jean

    2015-01-01

    Abstract The clinical presentation and outcome of hepatitis E virus (HEV) infection in inflammatory rheumatic diseases are unknown. We aimed to investigate the severity of acute HEV infection and the risk of chronic viral replication in patients with inflammatory arthritides treated with immunosuppressive drugs. All rheumatology and internal medicine practitioners belonging to the Club Rhumatismes et Inflammation in France were sent newsletters asking for reports of HEV infection and inflammatory arthritides. Baseline characteristics of patients and the course of HEV infection were retrospectively assessed by use of a standardized questionnaire. From January 2010 to August 2013, we obtained reports of 23 cases of HEV infection in patients with rheumatoid arthritis (n = 11), axial spondyloarthritis (n = 5), psoriatic arthritis (n = 4), other types of arthritides (n = 3). Patients received methotrexate (n = 16), antitumor necrosis factor α agents (n = 10), rituximab (n = 4), abatacept (n = 2), tocilizumab (n = 2), and corticosteroids (n = 10, median dose 6 mg/d, range 2–20). All had acute hepatitis: median aspartate and alanine aminotransferase levels were 679 and 1300 U/L, respectively. Eleven patients were asymptomatic, 4 had jaundice. The HEV infection diagnosis relied on positive PCR results for HEV RNA (n = 14 patients) or anti-HEV IgM positivity (n = 9). Median follow-up was 29 months (range 3–55). Treatment included discontinuation of immunosuppressants for 20 patients and ribavirin treatment for 5. Liver enzyme levels normalized and immunosuppressant therapy could be reinitiated in all patients. No chronic infection was observed. Acute HEV infection should be considered in patients with inflammatory rheumatism and elevated liver enzyme values. The outcome of HEV infection seems favorable, with no evolution to chronic hepatitis or fulminant liver failure. PMID:25860212

  17. Black Dot Tinea Capitis in an Immunosuppressed Man

    PubMed Central

    Mendese, Gary W.; Loo, Daniel S.

    2013-01-01

    Tinea capitis is a common superficial fungal infection of the scalp primarily afflicting young children. In adults, this infection may have an atypical presentation that may lead to a delay in diagnosis. The authors present a case report of black dot tinea capitis in an immunosuppressed Asian man with psoriasis and provide a review of the literature. PMID:23710273

  18. The transcription factor BACH2 promotes tumor immunosuppression.

    PubMed

    Roychoudhuri, Rahul; Eil, Robert L; Clever, David; Klebanoff, Christopher A; Sukumar, Madhusudhanan; Grant, Francis M; Yu, Zhiya; Mehta, Gautam; Liu, Hui; Jin, Ping; Ji, Yun; Palmer, Douglas C; Pan, Jenny H; Chichura, Anna; Crompton, Joseph G; Patel, Shashank J; Stroncek, David; Wang, Ena; Marincola, Francesco M; Okkenhaug, Klaus; Gattinoni, Luca; Restifo, Nicholas P

    2016-02-01

    The immune system has a powerful ability to recognize and kill cancer cells, but its function is often suppressed within tumors, preventing clearance of disease. Functionally diverse innate and adaptive cellular lineages either drive or constrain immune reactions within tumors. The transcription factor (TF) BACH2 regulates the differentiation of multiple innate and adaptive cellular lineages, but its role in controlling tumor immunity has not been elucidated. Here, we demonstrate that BACH2 is required to establish immunosuppression within tumors. Tumor growth was markedly impaired in Bach2-deficient mice and coincided with intratumoral activation of both innate and adaptive immunity. However, augmented tumor clearance in the absence of Bach2 was dependent upon the adaptive immune system. Analysis of tumor-infiltrating lymphocytes from Bach2-deficient mice revealed high frequencies of rapidly proliferating effector CD4+ and CD8+ T cells that expressed the inflammatory cytokine IFN-γ. Effector T cell activation coincided with a reduction in the frequency of intratumoral Foxp3+ Tregs. Mechanistically, BACH2 promoted tumor immunosuppression through Treg-mediated inhibition of intratumoral CD8+ T cells and IFN-γ. These findings demonstrate that BACH2 is a key component of the molecular program of tumor immunosuppression and identify therapeutic targets for the reversal of immunosuppression in cancer. PMID:26731475

  19. Effect of Immunosuppressive Therapy on Proteinogram in Rats

    PubMed Central

    Kędzierska, Karolina; Sindrewicz, Krzysztof; Sporniak-Tutak, Katarzyna; Bober, Joanna; Stańczyk-Dunaj, Małgorzata; Dołęgowska, Barbara; Kaliszczak, Robert; Sieńko, Jerzy; Kabat-Koperska, Joanna; Gołembiewska, Edyta; Ciechanowski, Kazimierz

    2016-01-01

    Background It has been observed that the use of immunosuppressive drugs in patients after transplantation of vascularized organs may be associated with changes in the concentration of certain fractions of plasma proteins. The concentration of these proteins was correlated with an increased risk of occurrence of stage 3 chronic kidney disease (CKD). This article examines the effect of the most commonly used immunosuppressive drugs on the concentration of plasma proteins in Wistar rats. Material/methods The study involved 36 rats grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporine A, rapamycin, and prednisone). The rats in all study groups were treated with a 3-drug protocol for 6 months. The treatment dose was adjusted based on available data in the literature. No drugs were administered to the control group. The rats were sacrificed and blood samples collected to determine the concentration of plasma proteins using electrophoresis technique. Results Statistically significant differences were observed between protein concentrations within the studied groups. The differences related to the proteins with masses of 195 kDa, 170 kDa, 103 kDa, and 58 kDa. Conclusions (1) Immunosuppressive drugs caused changes in the proteinogram of plasma proteins. (2) The strongest effect on rat plasma proteins was exerted by a regimen based on rapamycin. Intermediate, weak, and weakest effects were observed in regimens based on cyclosporine A, tacrolimus, and mycophenolate mofetil, respectively. PMID:27288069

  20. Learned immunosuppression: extinction, renewal, and the challenge of reconsolidation.

    PubMed

    Hadamitzky, Martin; Engler, Harald; Schedlowski, Manfred

    2013-03-01

    Behavioral conditioning of immune responses is one of the most impressive examples for the bidirectional communication among the nervous and immune systems. We established a model of behaviorally conditioned immunosuppression employing a conditioned taste aversion (CTA) paradigm in the rat pairing a novel taste (saccharin) as a conditioned stimulus (CS) with the immunosuppressive drug cyclosporine A (CsA) as an unconditioned stimulus (US). By re-presenting the CS during evocation, rats avoid drinking the saccharin. Concomitantly animals display an immunosuppression reflected by an ex vivo reduction in splenic T cell proliferation as well as diminished interleukin-2 and interferon-γ production and cytokine mRNA expression, mimicking the actual effect of the US (CsA). Due to the fact that the kinetics of this behaviorally conditioned immunosuppression are completely unknown, extinction of the conditioned response on the behavioral level (CTA) as well as in the immune response needs to be elucidated together with the neural processes mediating the extinction process. PMID:22791465

  1. Immunosuppressive and anti-inflammatory properties of engineered nanomaterials

    PubMed Central

    Ilinskaya, A N; Dobrovolskaia, M A

    2014-01-01

    Nanoparticle interactions with various components of the immune system are determined by their physicochemical properties such as size, charge, hydrophobicity and shape. Nanoparticles can be engineered to either specifically target the immune system or to avoid immune recognition. Nevertheless, identifying their unintended impacts on the immune system and understanding the mechanisms of such accidental effects are essential for establishing a nanoparticle's safety profile. While immunostimulatory properties have been reviewed before, little attention in the literature has been given to immunosuppressive and anti-inflammatory properties. The purpose of this review is to fill this gap. We will discuss intended immunosuppression achieved by either nanoparticle engineering, or the use of nanoparticles to carry immunosuppressive or anti-inflammatory drugs. We will also review unintended immunosuppressive properties of nanoparticles per se and consider how such properties could be either beneficial or adverse. Linked Articles This article is part of a themed section on Nanomedicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-17 PMID:24724793

  2. Effect of Immunosuppressive Therapy on Proteinogram in Rats.

    PubMed

    Kędzierska, Karolina; Sindrewicz, Krzysztof; Sporniak-Tutak, Katarzyna; Bober, Joanna; Stańczyk-Dunaj, Małgorzata; Dołęgowska, Barbara; Kaliszczak, Robert; Sieńko, Jerzy; Kabat-Koperska, Joanna; Gołembiewska, Edyta; Ciechanowski, Kazimierz

    2016-01-01

    BACKGROUND It has been observed that the use of immunosuppressive drugs in patients after transplantation of vascularized organs may be associated with changes in the concentration of certain fractions of plasma proteins. The concentration of these proteins was correlated with an increased risk of occurrence of stage 3 chronic kidney disease (CKD). This article examines the effect of the most commonly used immunosuppressive drugs on the concentration of plasma proteins in Wistar rats. MATERIAL AND METHODS The study involved 36 rats grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporine A, rapamycin, and prednisone). The rats in all study groups were treated with a 3-drug protocol for 6 months. The treatment dose was adjusted based on available data in the literature. No drugs were administered to the control group. The rats were sacrificed and blood samples collected to determine the concentration of plasma proteins using electrophoresis technique. RESULTS Statistically significant differences were observed between protein concentrations within the studied groups. The differences related to the proteins with masses of 195 kDa, 170 kDa, 103 kDa, and 58 kDa. CONCLUSIONS (1) Immunosuppressive drugs caused changes in the proteinogram of plasma proteins. (2) The strongest effect on rat plasma proteins was exerted by a regimen based on rapamycin. Intermediate, weak, and weakest effects were observed in regimens based on cyclosporine A, tacrolimus, and mycophenolate mofetil, respectively. PMID:27288069

  3. ADMX Receiver and Analysis

    NASA Astrophysics Data System (ADS)

    Malagon, Ana; ADMX Collaboration

    2016-03-01

    ADMX looks for the excess radiation deposited into a cavity from the conversion of a dark matter axion into a microwave photon. The sensitivity of the experiment increases by reducing the background thermal noise and minimizing the electronic noise of the readout system. The axion masses that the experiment can detect are determined by the resonant frequency of the cavity mode of interest, which is tuned using a two rod configuration. One can also increase the search rate by measuring the output from two cavity modes at once, which requires two separate readout schemes. I will discuss the ADMX dual-channel receiver which has been upgraded to have near quantum-limited sensitivity on both channels, and describe how the correct modes are verified, using simulations, in the presence of dense electromagnetic structure. I conclude by describing upgrades to the ADMX analysis which allow for real-time exclusion limits. Supported by DOE Grants DE-FG02-97ER41029, DE-FG02-96ER40956, DE- AC52-07NA27344, DE-AC03-76SF00098, and the Livermore LDRD program.

  4. Changes in the Immune System of Female Wistar Rats After Exposure to Immunosuppressive Treatment During Pregnancy.

    PubMed

    Kabat-Koperska, J; Kolasa-Wołosiuk, A; Wojciuk, B; Wojciechowska-Koszko, I; Roszkowska, P; Krasnodębska-Szponder, B; Paczkowska, E; Safranow, K; Gołembiewska, E; Machaliński, B; Ciechanowski, K

    2016-06-01

    This experimental study assessed the impact of medications frequently used after kidney transplantation on the immune system of pregnant female Wistar rats. The study evaluates medications, both approved and contraindicated during pregnancy in common therapeutic combinations. The study was conducted on 32 female Wistar rats, subjected to immunosuppressive regimens most commonly used in therapy of human kidney transplant recipients (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; and cyclosporine A, everolimus and prednisone). The animals received drugs by oral gavage 2 weeks before pregnancy and at 3 weeks of pregnancy. We found drug regimen-dependent differences in cytometry from spleen. Many subpopulations of lymphocytes were suppressed in rats treated with cyclosporine A, mycophenolate mofetil and prednisone and tacrolimus, mycophenolate mofetil and prednisone; the number of NK cells was increased in group of rats treated with cyclosporine A, everolimus and prednisone. We also found changes in histological examination of thymus and spleen of all treated dams. In cytokine assay, we noticed increasing levels of IL-17 with increasing doses of concanavalin A in control group and in group of dams treated with cyclosporine A, mycophenolate mofetil and prednisone. This increase was blocked in rats treated with tacrolimus, mycophenolate mofetil and prednisone and cyclosporine A, everolimus and prednisone. Qualitative, quantitative and morphological changes of immune system in pharmacologically immunosuppressed females have been observed. Thymus structure, spleen composition and splenocytes IL-17 production were mostly affected in drug regimen-dependent manner. PMID:27007325

  5. 42 CFR 410.30 - Prescription drugs used in immunosuppressive therapy.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Prescription drugs used in immunosuppressive... Other Health Services § 410.30 Prescription drugs used in immunosuppressive therapy. (a) Scope. Payment may be made for prescription drugs used in immunosuppressive therapy that have been approved...

  6. 42 CFR 410.30 - Prescription drugs used in immunosuppressive therapy.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Prescription drugs used in immunosuppressive... Other Health Services § 410.30 Prescription drugs used in immunosuppressive therapy. (a) Scope. Payment may be made for prescription drugs used in immunosuppressive therapy that have been approved...

  7. 42 CFR 410.30 - Prescription drugs used in immunosuppressive therapy.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false Prescription drugs used in immunosuppressive... Other Health Services § 410.30 Prescription drugs used in immunosuppressive therapy. (a) Scope. Payment may be made for prescription drugs used in immunosuppressive therapy that have been approved...

  8. Progressive Outer Retinal Necrosis and Immunosuppressive Therapy in Myasthenia Gravis

    PubMed Central

    Coisy, Solène; Ebran, Jean-Marc; Milea, Dan

    2014-01-01

    Introduction Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. Case Report A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. Conclusion VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment. PMID:24926266

  9. Forging a link between oncogenic signaling and immunosuppression in melanoma.

    PubMed

    Khalili, Jahan S; Hwu, Patrick; Lizée, Gregory

    2013-02-01

    Immunosuppressive tumor microenvironments limit the efficacy of T cell-based immunotherapy. We have recently demonstrated that the inhibition of BRAF(V600E) with vemurafenib relieves interleukin-1 (IL-1)-induced T-cell suppression as mediated by melanoma tumor associated fibroblasts (TAFs). These results suggest that inhibitors of the MAPK pathway in combination with T cell-based immunotherapies may induce long-lasting and durable responses. PMID:23525189

  10. Complications of Immunosuppressive/Immunomodulatory Therapy in Neurological Diseases

    PubMed Central

    Nath, Avindra

    2016-01-01

    Opinion statement The first critical step in the appropriate treatment of neurological infectious disease accompanying immunosuppressive states or immunomodulatory medication is to properly identify the offending organism. Broadly immunosuppressive conditions will predispose to both common and uncommon infectious diseases. There are substantial differences between neurological infectious disorders complicating disturbances of the innate immunity (neutrophils, monocytes and macrophages) and those due to abnormal adaptive immunity (humoral and cellular immunity). Similarly, there are differences in the types of infections with impaired humoral immunity compared to disturbed cellular immunity and between T- and B-cell disorders. HIV/AIDS has been a model of acquired immunosuppression and the nature of opportunistic infections with which it has been associated has been well characterized and generally correlates well with the degree of CD4 lymphopenia. Increasingly, immunotherapies target specific components of the immune system, such as an adhesion molecule or its ligand or surface receptors on a special class of cells. These targeted perturbations of the immune system increase the risk of particular infectious diseases. For instance, natalizumab, an α4β1 integrin inhibitor that is highly effective in multiple sclerosis, increases the risk of progressive multifocal leukoencephalopathy for reasons that still remain unclear. It is likely that other therapies that result in a disruption of a specific component of the immune system will be associated with other unique opportunistic infections. The risk of multiple simultaneous neurological infections in the immunosuppressed host must always be considered, particularly with a failure to respond to a therapeutic regimen. With respect to appropriate and effective therapy, diagnostic accuracy assumes primacy, but occasionally broad spectrum therapy is necessitated. For a number of opportunistic infectious disorders

  11. [Filamentous fungal infections in immunosuppressed patients: prophylaxis and treatment].

    PubMed

    Ruiz-Camps, Isabel; Peghin, Maddalena

    2015-09-01

    Although the incidence of invasive aspergillosis has decreased in haematologic patients and solid organ transplant recipients due to the use of prophylaxis; aspergillosis has emerged in other populations undergoing immunosuppressive drugs where prophylaxis is not well defined presenting different clinical patterns. Voriconazole is the gold standard in the treatment of aspergillosis and probably combined therapy, with voriconazole plus anidulafungin, could have a role in the initial management of the infection. PMID:26365733

  12. Immunosuppression by fractionated total lymphoid irradiation in collagen arthritis

    SciTech Connect

    McCune, W.J.; Buckley, J.A.; Belli, J.A.; Trentham, D.E.

    1982-05-01

    Treatments with fractionated total lymphoid irradiation (TLI) and cyclophosphamide were evaluated for rats injected with type II collagen. Preadministration of TLI and repeated injections of cyclophosphamide suppressed the severity of arthritis and lowered antibody titers to collagen significantly. TLI initiated at the onset of collagen arthritis decreased humoral and cellular responses to collagen but did not affect the severity of arthritis. These data demonstrate that both TLi and cyclophosphamide are immunosuppressive in an experimentally inducible autoimmune disease.

  13. Methylenedioxymethamphetamine ('Ecstasy')-induced immunosuppression: a cause for concern?

    PubMed

    Boyle, Noreen T; Connor, Thomas J

    2010-09-01

    Methylenedioxymethamphetamine (MDMA; 'Ecstasy') is a ring-substituted amphetamine and a popular drug of abuse. In addition to ability to induce euphoria, MDMA abuse is associated with a range of acute and long-term hazardous effects. This paper is focused on once such adverse effect: its ability to negatively impact on functioning of the immune system. Research demonstrates that MDMA has immunosuppressive properties, with both innate and adaptive arms of the immune system being affected. The ability of MDMA to suppress innate immunity is indicated by impaired neutrophil phagocytosis and reduced production of dendritic cell/macrophage-derived pro-inflammatory cytokines including tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-12 and IL-15. MDMA also suppresses innate IFN-gamma production, and considering the role of IFN-gamma in priming antigen-presenting cells, it is not surprising that MDMA reduces MHC class II expression on dendritic cells and macrophages, and inhibits co-stimulatory molecule expression. Paradoxically, studies demonstrate that MDMA elicits pro-inflammatory actions in the CNS by activating microglia, the resident innate immune cells in the brain. In terms of adaptive immunity, MDMA reduces circulating lymphocyte numbers, particularly CD4(+) T-cells; suppresses T-cell proliferation; and skews cytokine production in a Th(2) direction. For the most part, the immunosuppressive effects of MDMA cannot be attributed to a direct action of the drug on immune cells, but rather due to the release of endogenous immunomodulatory substances. In this regard, peripheral beta-adrenoceptors and cholinergic receptors have been shown to mediate some immunosuppressive effects of MDMA. Finally, we discuss emerging evidence indicating that MDMA-induced immunosuppression can translate into significant health risks for abusers. PMID:20718737

  14. The influence of intrauterine exposure to immunosuppressive treatment on changes in the immune system in juvenile Wistar rats

    PubMed Central

    Kabat-Koperska, Joanna; Kolasa-Wołosiuk, Agnieszka; Wojciuk, Bartosz; Wojciechowska-Koszko, Iwona; Roszkowska, Paulina; Krasnodębska-Szponder, Barbara; Paczkowska, Edyta; Safranow, Krzysztof; Gołembiewska, Edyta; Machaliński, Bogusław; Ciechanowski, Kazimierz

    2016-01-01

    Background In our study, we assessed the impact of immunosuppressive drug combinations on changes in the immune system of juvenile Wistar rats exposed to these drugs during pregnancy. We primarily concentrated on changes in two organs of the immune system – the thymus and the spleen. Methods The study was conducted on 40 (32+8) female Wistar rats administered full and half dose of drugs, respectively, subjected to regimens commonly used in therapy of human kidney transplant recipients ([1] cyclosporine A, mycophenolate mofetil, and prednisone; [2] tacrolimus, mycophenolate mofetil, and prednisone; [3] cyclosporine A, everolimus, and prednisone). The animals received drugs by oral gavage 2 weeks before pregnancy and during 3 weeks of pregnancy. Results There were no statistically significant differences in the weight of the thymus and spleen, but changes were found in the results of blood hematology, cytometry from the spleen, and a histologic examination of the examined immune organs of juvenile Wistar rats. In the cytokine assay, changes in the level of interleukine 17 (IL-17) after increasing amounts of concanavaline A were dose-dependent; the increase of IL-17 was blocked after administration of higher doses of immunosuppressive drugs. However, after a reduction of doses, its increase resumed. Conclusion Qualitative, quantitative, and morphological changes in the immune system of infant rats born to pharmacologically immunosuppressed females were observed. Thymus structure, spleen composition, and splenocyte IL-17 production were mostly affected in a drug regimen–dependent manner. PMID:27471376

  15. De novo alloreactive memory CD8+ T cells develop following allogeneic challenge when CNI immunosuppression is delayed.

    PubMed

    Hart-Matyas, M; Gareau, A J; Hirsch, G M; Lee, T D G

    2015-01-01

    Allospecific memory T cells are a recognized threat to the maintenance of solid-organ transplants. Limited information exists regarding the development of alloreactive memory T cells when post-transplant immunosuppression is present. The clinical practice of delaying calcineurin inhibitor (CNI) initiation post-transplant may permit the development of a de novo allospecific memory population. We investigated the development of de novo allospecific memory CD8+ T cells following the introduction of CNI immunosuppression in a murine model using allogeneic cell priming. Recipient mice alloprimed with splenocytes from fully mismatched donors received cyclosporine (CyA), initiated at 0, 2, 6, or 10days post-prime. Splenocytes from recipients were analyzed by flow cytometry or enzyme-linked immunosorbent assay for evidence of memory cell formation. Memory and effector CD8+ T cell development was prevented when CyA was initiated at 0day or 2days post-prime (p<0.001), but not 6days post-prime. Following a boost challenge, these memory CD8+ T cells were capable of producing a similarly sized population of secondary effectors as recipients not treated with CyA (p>0.05). Delaying CyA up to 6days or later post-prime permits the development of functional de novo allospecific memory CD8+ T cells. The development of this potentially detrimental T cell population in patients could be prevented by starting CNI immunosuppression early post-transplant. PMID:25315500

  16. Immunosuppression in cardiac graft rejection: A human in vitro model to study the potential use of new immunomodulatory drugs

    SciTech Connect

    Crescioli, Clara Squecco, Roberta; Cosmi, Lorenzo; Sottili, Mariangela; Gelmini, Stefania; Borgogni, Elisa; Sarchielli, Erica; Scolletta, Sabino; Francini, Fabio; Annunziato, Francesco; Vannelli, Gabriella Barbara; Serio, Mario

    2008-04-01

    CXCL10-CXCR3 axis plays a pivotal role in cardiac allograft rejection, so that targeting CXCL10 without inducing generalized immunosuppression may be of therapeutic significance in allotransplantation. Since the role of resident cells in cardiac rejection is still unclear, we aimed to establish reliable human cardiomyocyte cultures to investigate Th1 cytokine-mediated response in allograft rejection. We used human fetal cardiomyocytes (Hfcm) isolated from fetal hearts, obtained after legal abortions. Hfcm expressed specific cardiac lineage markers, specific cardiac structural proteins, typical cardiac currents and generated ventricular action potentials. Thus, Hfcm represent a reliable in vitro tool for allograft rejection research, since they resemble the features of mature cells. Hfcm secreted CXCL10 in response to IFN{gamma} and TNF{alpha}{alpha}; this effect was magnified by cytokine combination. Cytokine synergy was associated to a significant TNF{alpha}-induced up-regulation of IFN{gamma}R. The response of Hfcm to some currently used immunosuppressive drugs compared to rosiglitazone, a peroxisome proliferator-activated receptor {gamma} agonist and Th1-mediated response inhibitor, was also evaluated. Only micophenolic acid and rosiglitazone halved CXCL10 secretion by Hfcm. Given the pivotal role of IFN{gamma}-induced chemokines in Th1-mediated allograft rejection, these preliminary results suggest that the combined effects of immunosuppressive agents and rosiglitazone could be potentially beneficial to patients receiving heart transplants.

  17. Successful treatment of ileal ulcers caused by immunosuppressants in two organ transplant recipients.

    PubMed

    Guo, Yun-Wei; Gu, Hua-Ying; Abassa, Kodjo-Kunale; Lin, Xian-Yi; Wei, Xiu-Qing

    2016-06-28

    Although gastroduodenal ulcers are common in solid organ transplant patients, there are few reports on multiple giant ulcers in the distal ileum and ileocecal valve caused by immunosuppressants Herein, we report on a liver transplant recipient and a renal transplant recipient with multiple large ulcers in the distal ileum and ileocecal valve who rapidly achieved ulcer healing upon withdrawal of sirolimus or tacrolimus and administration of thalidomide. In case 1, a 56-year-old man with primary hepatocellular carcinoma had received a liver transplantation. Tacrolimus combined with sirolimus and prednisolone was used as the anti-rejection regimen. Colonoscopy was performed because of severe abdominal pain and diarrhea at post-operative month 10. Multiple giant ulcers were found at the ileocecal valve and distal ileum. The ulcers healed rapidly with withdrawal of sirolimus and treatment with thalidomide. There was no recurrence during 2 years of follow-up. In case 2, a 34-year-old man with end-stage kidney disease received kidney transplantation and was put on tacrolimus combined with mycophenolate mofetil and prednisolone as the anti-rejection regimen. Twelve weeks after the operation, the patient presented with hematochezia and severe anemia. Colonoscopy revealed multiple large ulcers in the ileocecal valve and distal ileum, with massive accumulation of fresh blood. The bleeding ceased after treatment with intravenous somatostatin and oral thalidomide. Tacrolimus was withdrawn at the same time. Colonoscopy at week 4 of follow-up revealed remarkable healing of the ulcers, and there was no recurrence of bleeding during 1 year of follow-up. No lymphoma, tuberculosis, or infection of cytomegalovirus, Epstein-Barr virus, or fungus was found in either patient. In post-transplantation cases with ulcers in the distal ileum and ileocecal valve, sirolimus or tacrolimus should be considered a possible risk factor, and withdrawing them or switching to another immunosuppressant

  18. Successful treatment of ileal ulcers caused by immunosuppressants in two organ transplant recipients

    PubMed Central

    Guo, Yun-Wei; Gu, Hua-Ying; Abassa, Kodjo-Kunale; Lin, Xian-Yi; Wei, Xiu-Qing

    2016-01-01

    Although gastroduodenal ulcers are common in solid organ transplant patients, there are few reports on multiple giant ulcers in the distal ileum and ileocecal valve caused by immunosuppressants Herein, we report on a liver transplant recipient and a renal transplant recipient with multiple large ulcers in the distal ileum and ileocecal valve who rapidly achieved ulcer healing upon withdrawal of sirolimus or tacrolimus and administration of thalidomide. In case 1, a 56-year-old man with primary hepatocellular carcinoma had received a liver transplantation. Tacrolimus combined with sirolimus and prednisolone was used as the anti-rejection regimen. Colonoscopy was performed because of severe abdominal pain and diarrhea at post-operative month 10. Multiple giant ulcers were found at the ileocecal valve and distal ileum. The ulcers healed rapidly with withdrawal of sirolimus and treatment with thalidomide. There was no recurrence during 2 years of follow-up. In case 2, a 34-year-old man with end-stage kidney disease received kidney transplantation and was put on tacrolimus combined with mycophenolate mofetil and prednisolone as the anti-rejection regimen. Twelve weeks after the operation, the patient presented with hematochezia and severe anemia. Colonoscopy revealed multiple large ulcers in the ileocecal valve and distal ileum, with massive accumulation of fresh blood. The bleeding ceased after treatment with intravenous somatostatin and oral thalidomide. Tacrolimus was withdrawn at the same time. Colonoscopy at week 4 of follow-up revealed remarkable healing of the ulcers, and there was no recurrence of bleeding during 1 year of follow-up. No lymphoma, tuberculosis, or infection of cytomegalovirus, Epstein-Barr virus, or fungus was found in either patient. In post-transplantation cases with ulcers in the distal ileum and ileocecal valve, sirolimus or tacrolimus should be considered a possible risk factor, and withdrawing them or switching to another immunosuppressant

  19. Phagocytic cell function in response to immunosuppressive therapy.

    PubMed

    Drath, D B; Kahan, B D

    1984-02-01

    The increased incidence of pulmonary infection in human renal allograft recipients is presumably related to antirejection immunosuppressive therapy. To assess immunosuppressive-related disturbances of the immune responses of the lung, we evaluated the functional abilities of the pulmonary alveolar macrophage (PAM) and polymorphonuclear leukocyte (PMN) of rats in chemotaxis, phagocytosis, and superoxide-release assays following 30 days of intraperitoneal administration of cyclosporine, azathioprine, and/or prednisolone sodium succinate. None of these drugs affected superoxide release by stimulated PAMs or PMNs. Except for a transient inhibition by azathioprine, the drugs had no effect on phagocytosis of Staphylococcus aureus by either cell type. On the other hand, cyclosporine inhibited formyl-methionyl-leucyl-phenylalanine (FMLP)-directed chemotaxis by PAMs, and both FMLP and C5a stimulated chemotaxis by PMNs. Azathioprine had more dramatic effects on PAMs than on PMNs and prednisolone at 2 mg/kg inhibited PAMs. The results indicated that, with the exception of chemotaxis, the immunosuppressive agents largely spare nonspecific elements of host defense. PMID:6320765

  20. Opportunistic Infections—Coming to the Limits of Immunosuppression?

    PubMed Central

    Fishman, Jay A.

    2013-01-01

    Possible etiologies of infection in the solid organ recipient are diverse, ranging from common bacterial and viral pathogens to opportunistic pathogens that cause invasive disease only in immunocompromised hosts. The recognition of infectious syndromes in this population is limited by alterations in the clinical manifestations by immunosuppression. The risk of serious infections in the organ transplant patient is determined by the interaction between the patients’ recent and distant epidemiological exposures and all factors that contribute to the patient’s net state of immune suppression. This risk is altered by antimicrobial prophylaxis and changes in immunosuppressive therapies. In addition to the direct effects of infection, opportunistic infections, and the microbiome may adversely shape the host immune responses with diminished graft and patient survivals. Antimicrobial therapies are more complex than in the normal host with a significant incidence of drug toxicity and a propensity for drug interactions with the immunosuppressive agents used to maintain graft function. Rapid and specific microbiologic diagnosis is essential. Newer microbiologic assays have improved the diagnosis and management of opportunistic infections. These tools coupled with assays that assess immune responses to infection and to graft antigens may allow optimization of management for graft recipients in the future. PMID:24086067

  1. Prevention of ultraviolet radiation-induced immunosuppression by sunscreen in Candida albicans-induced delayed-type hypersensitivity

    PubMed Central

    CHEN, QUAN; LI, RUNXIANG; ZHAO, XIAOXIA; LIANG, BIHUA; MA, SHAOYIN; LI, ZHENJIE; ZHU, HUILAN

    2016-01-01

    Ultraviolet (UV) radiation-induced immunosuppression leading to skin cancer has received increased attention in previous years. The present study aimed to investigate the immunoprotection offered by Anthelios sunscreen in a mouse model of Candida albicans-induced delayed-type hypersensitivity. Anthelios sunscreen was applied to the skin on the dorsal skin of BALB/c mice treated with a sub-erythema dose of solar-simulated radiation. Delayed-type hypersensitivity was induced by immunization with Candida albicans. Changes in the skin thickness of the foot pads were measured, and immunosuppression rates were also evaluated. The expression levels of CD207, CD80 and CD86 in the Langerhans cells were semi-quantitatively detected using Western blotting and immunohistochemical assays. The delayed-type hypersensitivity mouse model was successfully established. The minimal erythema doses of UVA and UVB exposure to the mice were 2,000 and 145 mJ/cm2, respectively. The immunosuppression rates in the sunscreen group and non-sunscreen group were 24.39 and 65.85%, respectively (P<0.01). The results of the Western blotting and immunohistochemistry showed that the expression levels of CD207 (P<0.01), CD80 (P<0.05) and CD86 (P<0.01) were higher in the sunscreen group, compared with those in the non-sunscreen group. UV exposure reduced Candida albicans antigen-induced delayed-type hypersensitivity. Anthelios sunscreen was found to protect the skin from immunosuppression through the activation of epidermal Langerhans cells. PMID:27175551

  2. Prevention of ultraviolet radiation‑induced immunosuppression by sunscreen in Candida albicans‑induced delayed‑type hypersensitivity.

    PubMed

    Chen, Quan; Li, Runxiang; Zhao, Xiaoxia; Liang, Bihua; Ma, Shaoyin; Li, Zhenjie; Zhu, Huilan

    2016-07-01

    Ultraviolet (UV) radiation-induced immunosuppression leading to skin cancer has received increased attention in previous years. The present study aimed to investigate the immunoprotection offered by Anthelios sunscreen in a mouse model of Candida albicans‑induced delayed‑type hypersensitivity. Anthelios sunscreen was applied to the skin on the dorsal skin of BALB/c mice treated with a sub‑erythema dose of solar‑simulated radiation. Delayed‑type hypersensitivity was induced by immunization with Candida albicans. Changes in the skin thickness of the foot pads were measured, and immunosuppression rates were also evaluated. The expression levels of CD207, CD80 and CD86 in the Langerhans cells were semi‑quantitatively detected using Western blotting and immunohistochemical assays. The delayed‑type hypersensitivity mouse model was successfully established. The minimal erythema doses of UVA and UVB exposure to the mice were 2,000 and 145 mJ/cm2, respectively. The immunosuppression rates in the sunscreen group and non‑sunscreen group were 24.39 and 65.85%, respectively (P<0.01). The results of the Western blotting and immunohistochemistry showed that the expression levels of CD207 (P<0.01), CD80 (P<0.05) and CD86 (P<0.01) were higher in the sunscreen group, compared with those in the non‑sunscreen group. UV exposure reduced Candida albicans antigen‑induced delayed‑type hypersensitivity. Anthelios sunscreen was found to protect the skin from immunosuppression through the activation of epidermal Langerhans cells. PMID:27175551

  3. African American kidney transplantation survival: the ability of immunosuppression to balance the inherent pre- and post-transplant risk factors.

    PubMed

    Malat, Gregory E; Culkin, Christine; Palya, Aniruddha; Ranganna, Karthik; Kumar, Mysore S Anil

    2009-10-22

    Among organ transplant recipients, the African American population historically has received special attention. This is because secondary to their disposition to certain disease states, for example hypertension, an African American patient has a propensity to reach end-stage renal disease and require renal replacement earlier than a Caucasian patient. Regardless of the initiative to replace dialysis therapy with organ transplantation, the African American patient has many barriers to kidney transplantation, thus extending their time on dialysis and waiting time on the organ transplant list. These factors are among the many negative causes of decreased kidney graft survival, realized before kidney transplantation. Unfortunately, once the African American recipient receives a kidney graft, the literature documents that many post-transplant barriers exist which limit successful outcomes. The primary post-transplant barrier relates to designing proper immunosuppression protocols. The difficulty in designing protocols revolves around (i) altered genetic metabolism/lower absorption, (ii) increased immuno-active cytokines and (iii) detrimental effects of noncompliance. Based on the literature, dosing of immunosuppression must be aggressive and requires a diligent practitioner. Research has indicated that, despite some success with proven levels of immunosuppression, the African American recipient usually requires a higher 'dose per weight' regimen. However, even with aggressive immunosuppressant dosing, African Americans still have worse outcomes than Caucasian recipients. Additionally, many of the targeted sites of action that immunosuppression exerts its effects on have been found to be amplified in the African American population. Finally, noncompliance is the most discouraging inhibitor of long-term success in organ transplantation. The consequences of noncompliance are biased by ethnicity and affect the African American population more severely. All of these factors

  4. Dual-band pixelless upconversion imaging devices.

    PubMed

    Wu, Le Ke; Hao, Hui Lian; Shen, Wen Zhong; Ariyawansa, Gamini; Perera, A G Unil; Matsik, Steven G

    2007-08-15

    We have proposed a type of mid-infrared (MIR) and far-infrared (FIR) dual-band imaging device, which employs the photon frequency upconversion concept in a GaN/AlGaN MIR and FIR dual-band detector integrated with a GaN/AlGaN violet light emitting diode. On the basis of the photoresponse of single-period GaN/AlGaN dual-band detectors, we present the detailed optimization of multiperiod GaN emitter/AlGaN barrier detectors and their applications to dual-band pixelless upconversion imaging. Satisfying images have been received through the analysis of the modulation transfer function and the upconversion efficiency in the GaN/AlGaN dual-band pixelless upconverters, which exhibit good image resolution, high quantum efficiency, and negligible cross talk. PMID:17700787

  5. Uncoupling the Proinflammatory from the Immunosuppressive Properties of Tumor Necrosis Factor (Tnf) at the P55 TNF Receptor Level

    PubMed Central

    Kassiotis, George; Kollias, George

    2001-01-01

    Multiple sclerosis (MS) is a disabling inflammatory demyelinating disease of the central nervous system, considered to result from self-reactivity to myelin antigens. Tumor necrosis factor (TNF) and the p55 TNF receptor (TNFR) have been strongly implicated in MS pathogenesis. We reveal in this study a dual role for TNF in experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. In addition to its well-established proinflammatory effects, TNF exhibits potent immunosuppressive properties, providing one possible explanation for the immune and disease activating effect of anti-TNF treatment of MS. We show that in TNF-deficient mice, myelin-specific T cell reactivity fails to regress and expansion of activated/memory T cells is abnormally prolonged, leading to exacerbated EAE. Strikingly, immnosuppression by TNF and protection against EAE does not require the p55 TNFR, whereas the same receptor is necessary for the detrimental effects of TNF during the acute phase of the disease. Thus, blocking the function of the p55 TNFR in autoimmune demyelination may inhibit the noxious proinflammatory activities of TNF without compromising its immunosuppressive properties. PMID:11181695

  6. Full-wave receiver architecture for the homodyne motion sensor

    SciTech Connect

    Haugen, Peter C.; Dallum, Gregory E.; Welsh, Patrick A.; Romero, Carlos E.

    2015-09-29

    A homodyne motion sensor or detector based on ultra-wideband radar utilizes the entire received waveform through implementation of a voltage boosting receiver. The receiver includes a receiver input and a receiver output. A first diode is connected to the receiver output. A first charge storage capacitor is connected from between the first diode and the receiver output to ground. A second charge storage capacitor is connected between the receiver input and the first diode. A second diode is connected from between the second charge storage capacitor and the first diode to ground. The dual diode receiver performs voltage boosting of a RF signal received at the receiver input, thereby enhancing receiver sensitivity.

  7. Full-wave receiver architecture for the homodyne motion sensor

    DOEpatents

    Haugen, Peter C; Dallum, Gregory E; Welsh, Patrick A; Romero, Carlos E

    2013-11-19

    A homodyne motion sensor or detector based on ultra-wideband radar utilizes the entire received waveform through implementation of a voltage boosting receiver. The receiver includes a receiver input and a receiver output. A first diode is connected to the receiver output. A first charge storage capacitor is connected from between the first diode and the receiver output to ground. A second charge storage capacitor is connected between the receiver input and the first diode. A second diode is connected from between the second charge storage capacitor and the first diode to ground. The dual diode receiver performs voltage boosting of a RF signal received at the receiver input, thereby enhancing receiver sensitivity.

  8. UV radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide.

    PubMed

    Damian, Diona L; Patterson, Clare R S; Stapelberg, Michael; Park, Joohong; Barnetson, Ross St C; Halliday, Gary M

    2008-02-01

    UV radiation-induced immunosuppression augments cutaneous carcinogenesis. The incidence of skin cancer continues to increase despite increased use of sunscreens, which are less effective at preventing immunosuppression than sunburn. Using the Mantoux reaction as a model of skin immunity, we investigated the effects of solar-simulated (ss) UV and its component UVA and UVB wavebands and tested the ability of topical nicotinamide to protect from UV-induced immunosuppression. Healthy, Mantoux-positive volunteers were UV-irradiated on their backs, with 5% nicotinamide or vehicle applied to different sites in a randomized, double-blinded manner. Subsequent Mantoux testing at irradiated and adjacent unirradiated sites enabled measurement of UV-induced immunosuppression with and without nicotinamide. Suberythemal ssUV caused significant immunosuppression, although component UVB and UVA doses delivered independently did not. Men were immunosuppressed by ssUV doses three times lower than those required to immunosuppress women. This may be an important cause of the higher skin cancer incidence and mortality observed in men. Topical nicotinamide prevented immunosuppression, with gene chip microarrays suggesting that the mechanisms of protection may include alterations in complement, energy metabolism and apoptosis pathways. Nicotinamide is a safe and inexpensive compound that could be added to sunscreens or after-sun lotions to improve protection from immunosuppression. immunosuppression.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://network.nature.com/group/jidclub PMID:17882270

  9. Dual Tank Fuel System

    DOEpatents

    Wagner, Richard William; Burkhard, James Frank; Dauer, Kenneth John

    1999-11-16

    A dual tank fuel system has primary and secondary fuel tanks, with the primary tank including a filler pipe to receive fuel and a discharge line to deliver fuel to an engine, and with a balance pipe interconnecting the primary tank and the secondary tank. The balance pipe opens close to the bottom of each tank to direct fuel from the primary tank to the secondary tank as the primary tank is filled, and to direct fuel from the secondary tank to the primary tank as fuel is discharged from the primary tank through the discharge line. A vent line has branches connected to each tank to direct fuel vapor from the tanks as the tanks are filled, and to admit air to the tanks as fuel is delivered to the engine.

  10. EHF low-noise FET receiver

    NASA Technical Reports Server (NTRS)

    Schellenberg, J. M.; Watkins, E. T.

    1983-01-01

    Extremely high frequency (EHF) receivers for military and NASA programs must be small, lightweight, and highly reliable. In connection with recent advances in the development of mm-wave FET devices and circuits, a basis has been obtained for the eventual replacement of diode mixer front-ends by FET preamplifiers in receivers up to 94 GHz. By placing a low noise amplifier in front of the mixer it is possible to achieve a lower system noise figure than that found in conventional mm-wave receivers. A broader bandwidth can also be provided. Attention is given to the receiver configuration, a low noise FET amplifier, an image rejection filter, a dual-gate FET mixer, a FET local oscillator, and a FET receiver.

  11. Apricot Kernel Oil Ameliorates Cyclophosphamide-Associated Immunosuppression in Rats.

    PubMed

    Tian, Honglei; Yan, Haiyan; Tan, Siwei; Zhan, Ping; Mao, Xiaoying; Wang, Peng; Wang, Zhouping

    2016-08-01

    The effects of dietary apricot kernel oil (AKO), which contains high levels of oleic and linoleic acids and lower levels of α-tocopherol, were evaluated in a rat model of cyclophosphamide-induced immunosuppression. Rats had intraperitoneal injection with cyclophosphamide to induce immunosuppression and were then infused with AKO or normal saline (NS) for 4 weeks. Enzyme-linked immunosorbent assays were used to detect antimicrobial factors in lymphocytes and anti-inflammatory factors in hepatocytes. Hematoxylin & eosin staining was conducted prior to histopathological analysis of the spleen, liver, and thymus. Significant differences were observed between the immune functions of the healthy control group, the normal saline group, and the AKO group. Compared to the normal saline-treated group, lymphocytes isolated from rats administered AKO showed significant improvement in immunoglobulin (Ig)A, IgM, IgG, interleukin (IL)-2, IL-12, and tumor necrosis factor-α (TNF-α) levels (p < 0.01). Liver tissue levels of malondialdehyde and activities of superoxide dismutase and glutathione peroxidase indicated reduced oxidative stress in rats treated with AKO (p < 0.01). Dietary AKO positively affected rat growth and inhibited cyclophosphamide-associated organ degeneration. These results suggested that AKO may enhance the immune system in vivo. These effects may reflect the activities of intermediate oleic and linoleic acid metabolites, which play a vital role in the immune system, and the α-tocopherol in AKO may further enhance this phenomenon. Thus, the use of AKO as a nutritional supplement can be proposed to ameliorate chemotherapy-associated immunosuppression. PMID:27262314

  12. Characterization and Modulation of the Immunosuppressive Phase of Sepsis▿

    PubMed Central

    Muenzer, Jared T.; Davis, Christopher G.; Chang, Kathy; Schmidt, Robert E.; Dunne, W. Michael; Coopersmith, Craig M.; Hotchkiss, Richard S.

    2010-01-01

    Sepsis continues to cause significant morbidity and mortality in critically ill patients. Studies of patients and animal models have revealed that changes in the immune response during sepsis play a decisive role in the outcome. Using a clinically relevant two-hit model of sepsis, i.e., cecal ligation and puncture (CLP) followed by the induction of Pseudomonas aeruginosa pneumonia, we characterized the host immune response. Second, AS101 [ammonium trichloro(dioxoethylene-o,o′)tellurate], a compound that blocks interleukin 10 (IL-10), a key mediator of immunosuppression in sepsis, was tested for its ability to reverse immunoparalysis and improve survival. Mice subjected to pneumonia following CLP had different survival rates depending upon the timing of the secondary injury. Animals challenged with P. aeruginosa at 4 days post-CLP had ∼40% survival, whereas animals challenged at 7 days had 85% survival. This improvement in survival was associated with decreased lymphocyte apoptosis, restoration of innate cell populations, increased proinflammatory cytokines, and restoration of gamma interferon (IFN-γ) production by stimulated splenocytes. These animals also showed significantly less P. aeruginosa growth from blood and bronchoalveolar lavage fluid. Importantly, AS101 improved survival after secondary injury 4 days following CLP. This increased survival was associated with many of the same findings observed in the 7-day group, i.e., restoration of IFN-γ production, increased proinflammatory cytokines, and decreased bacterial growth. Collectively, these studies demonstrate that immunosuppression following initial septic insult increases susceptibility to secondary infection. However, by 7 days post-CLP, the host's immune system has recovered sufficiently to mount an effective immune response. Modulation of the immunosuppressive phase of sepsis may aid in the development of new therapeutic strategies. PMID:20100863

  13. Characterization and modulation of the immunosuppressive phase of sepsis.

    PubMed

    Muenzer, Jared T; Davis, Christopher G; Chang, Kathy; Schmidt, Robert E; Dunne, W Michael; Coopersmith, Craig M; Hotchkiss, Richard S

    2010-04-01

    Sepsis continues to cause significant morbidity and mortality in critically ill patients. Studies of patients and animal models have revealed that changes in the immune response during sepsis play a decisive role in the outcome. Using a clinically relevant two-hit model of sepsis, i.e., cecal ligation and puncture (CLP) followed by the induction of Pseudomonas aeruginosa pneumonia, we characterized the host immune response. Second, AS101 [ammonium trichloro(dioxoethylene-o,o')tellurate], a compound that blocks interleukin 10 (IL-10), a key mediator of immunosuppression in sepsis, was tested for its ability to reverse immunoparalysis and improve survival. Mice subjected to pneumonia following CLP had different survival rates depending upon the timing of the secondary injury. Animals challenged with P. aeruginosa at 4 days post-CLP had approximately 40% survival, whereas animals challenged at 7 days had 85% survival. This improvement in survival was associated with decreased lymphocyte apoptosis, restoration of innate cell populations, increased proinflammatory cytokines, and restoration of gamma interferon (IFN-gamma) production by stimulated splenocytes. These animals also showed significantly less P. aeruginosa growth from blood and bronchoalveolar lavage fluid. Importantly, AS101 improved survival after secondary injury 4 days following CLP. This increased survival was associated with many of the same findings observed in the 7-day group, i.e., restoration of IFN-gamma production, increased proinflammatory cytokines, and decreased bacterial growth. Collectively, these studies demonstrate that immunosuppression following initial septic insult increases susceptibility to secondary infection. However, by 7 days post-CLP, the host's immune system has recovered sufficiently to mount an effective immune response. Modulation of the immunosuppressive phase of sepsis may aid in the development of new therapeutic strategies. PMID:20100863

  14. Fixed-Angle Volar Plate Fixation for Distal Radius Fractures in Immunosuppressed Patients

    PubMed Central

    Peterson, Erik D.

    2008-01-01

    The aim of this study was to define the outcome and complications following open reduction and internal fixed-angle plating of distal radius fractures for patients on chronic immunosuppression medications. A retrospective study identified 11 patients with distal radius fractures that had been on chronic immunosuppressive medication. The mean patient age was 59.9 years (40–82 years). According to the Orthopedic Trauma Association classification, there was one 23A3, one 23B3, and nine 23C type fractures. There were two open fractures. All patients received preoperative antibiotics and underwent reduction and fixation with a volar, fixed-angle plate. Postoperative measurements included postoperative and final radiographic indices, wrist flexion and extension, forearm rotation, and grip strength. Clinical follow-up averaged 13 months, and radiographic follow-up averaged 14.9 months. Statistical analysis was performed comparing means of various parameters with a two-sided t test with an alpha value ≤0.05. All fractures healed, and there were no infections. The final mean ulnar variance, volar tilt, and radial inclination were −0.1 mm (ulnar negative; −2.0 to +2.5 mm), 13° (5–23°), and 21° (15–27°), respectively. The mean articular gap or step was 0.4 mm. There was a small but significant decrease between the final and postoperative mean ulnar variance (p = 0.03). Mean wrist flexion was 47°, extension 47°, pronation 77°, and supination was 76°. Grip strength averaged 16.3 kg versus 25.1 kg for the opposite extremity. The one major complication included a postoperative carpal tunnel syndrome. Fixed-angle volar plate fixation for distal radius fractures in patients with chronic immunosuppression was associated with union (with acceptable radiographic alignment), no wound-healing problems or infections, and with functional wrist and forearm motion and grip strength. PMID:18780023

  15. Anti-inflammatory and immunosuppressive drugs and reproduction

    PubMed Central

    Østensen, Monika; Khamashta, Munther; Lockshin, Michael; Parke, Ann; Brucato, Antonio; Carp, Howard; Doria, Andrea; Rai, Raj; Meroni, Pierluigi; Cetin, Irene; Derksen, Ronald; Branch, Ware; Motta, Mario; Gordon, Caroline; Ruiz-Irastorza, Guillermo; Spinillo, Arsenio; Friedman, Deborah; Cimaz, Rolando; Czeizel, Andrew; Piette, Jean Charles; Cervera, Ricard; Levy, Roger A; Clementi, Maurizio; De Carolis, Sara; Petri, Michelle; Shoenfeld, Yehuda; Faden, David; Valesini, Guido; Tincani, Angela

    2006-01-01

    Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given. PMID:16712713

  16. Eruptive disseminated porokeratosis associated with corticosteroid-induced immunosuppression.

    PubMed

    Bednarek, R; Ezra, N; Toubin, Y; Linos, K; Mousdicas, N

    2015-10-01

    Eruptive disseminated porokeratosis (EDP) is a disease that presents clinically with sudden onset of erythematous papules and plaques, with a ridge-like border histologically represented by a cornoid lamella. We report a case of EDP occurring in a 39-year-old woman 3 days after completion of a 2-week course of oral corticosteroid therapy for an acute asthma exacerbation. The patient was treated with emollients and sun protection. Unlike the more chronic disseminated superficial (actinic) porokeratosis, EDP secondary to immunosuppression from corticosteroid therapy has very rarely been reported in the dermatological literature. PMID:25800103

  17. Research on the immunosuppressive activity of ingredients contained in sunscreens.

    PubMed

    Frikeche, Jihane; Couteau, Céline; Roussakis, Christos; Coiffard, Laurence J M

    2015-04-01

    The immunosuppressive properties of Benzophenone-4, an UV-filter and three ingredients, Allantoin, Bisabolol and Enoxolon used in sunscreen formulation, previously characterized as anti-inflammatory compounds, are studied. The results of this study demonstrate that four tested molecules have effects on DCs and T cells which are the most important cells of the immune system. The impact is also visible on keratinocyte cells which are in the direct contact with skin sunscreens. Each ingredient should be used with caution at reduced doses or even removed from some cosmetic preparations, such as sunscreens. PMID:25556843

  18. Maintenance immunosuppression regimens: conversion, minimization, withdrawal, and avoidance.

    PubMed

    Yang, Harold

    2006-04-01

    A wide choice of drug combinations is available to clinicians for immunosuppression regimens for their kidney transplant patients. Although many protocols have minimized early graft loss, the optimal long-term regimen is unknown. Recent studies clearly showed that cardiovascular death is now the leading cause of graft loss. Strategies must be developed that address this risk while keeping immunologic events low. Transplant physicians have focused on exploring regimens that minimize or avoid the use of corticosteroids. Studies also have started to explore protocols that minimize calcineurin inhibitor therapy. PMID:16567240

  19. Cryptococcal cellulitis on the shin of an immunosuppressed patient.

    PubMed

    Zhu, Tian Hao; Rodriguez, Paola G; Behan, James W; Declerck, Brittney; Kim, Gene H

    2016-01-01

    Cryptococcus neoformans is a common fungus found throughout the environment that causes opportunistic disease in immunocompromised individuals. Infection of humans with C neoformans usually manifests as lung disease through inhalation of spores or meningoencephalitis by involvement of the central nervous system. Rarely, dissemination in the form of cutaneous lesions can occur in individuals with long term immunosuppression. We present a patient with C. neoformans manifesting as cellulitis with focal segmental glomerulosclerosis treated with corticosteroids. Because of the mortality associated with disseminated cryptococcosis, early identification, especially of atypical cutaneous presentations is critical from a dermatological perspective. PMID:27617599

  20. [Polyarteritis nodosa with renal agenesis and immunosuppressive treatment].

    PubMed

    Alcocer, J; Fraga, A; Gudiño, J; Lavalle, C

    1976-01-01

    A case of a 44 years old man with the unique combination of polyarteritis nodosa (PAN) and the congenital absence of a kidney is presented. The clinical picture consisted of fever, general symptoms, hypertermia, peripheric neuropathy, subcutaneous nodules and renal damage. Laboratory findings included increased WBC, telescoped urinary sediment, renal insufficiency, positive rheumatoid factor, policlonal gammopathy and positive Australia antigen. A review of the pertinent literature and the etiopathogenic role of Australia antigen in PAN is discussed. Efficacy of immunosuppressive therapy was evident in this case. PMID:13359

  1. Association of Extrarenal Adverse Effects of Posttransplant Immunosuppression With Sex and ABCB1 Haplotypes

    PubMed Central

    Venuto, Rocco C.; Meaney, Calvin J.; Chang, Shirley; Leca, Nicolae; Consiglio, Joseph D.; Wilding, Gregory E.; Brazeau, Daniel; Gundroo, Aijaz; Nainani, Neha; Morse, Sarah E.; Cooper, Louise M.; Tornatore, Kathleen M.

    2015-01-01

    Abstract Extrarenal adverse effects (AEs) associated with calcineurin inhibitor (CNI) and mycophenolic acid (MPA) occur frequently but are unpredictable posttransplant complications. AEs may result from intracellular CNI accumulation and low activity of P-glycoprotein, encoded by the ABCB1 gene. Since ABCB1 single nucleotide polymorphisms (SNPs) and sex influence P-glycoprotein, we investigated haplotypes and extrarenal AEs. A prospective, cross-sectional study evaluated 149 patients receiving tacrolimus and enteric coated mycophenolate sodium or cyclosporine and mycophenolate mofetil. Immunosuppressive AE assessment determined individual and composite gastrointestinal, neurologic, aesthetic, and cumulative AEs. Lipids were quantitated after 12-hour fast. ABCB1 SNPs: c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642) were determined with haplotype associations computed using the THESIAS program, and evaluated by immunosuppression, sex and race using multivariate general linear models. Tacrolimus patients exhibited more frequent and higher gastrointestinal AE scores compared with cyclosporine with association to CTT (P = 0.018) and sex (P = 0.01). Aesthetic AE score was 3 times greater for cyclosporine with TTC haplotype (P = 0.005). Females had higher gastrointestinal (P = 0.022), aesthetic (P < 0.001), neurologic (P = 0.022), and cumulative AE ratios (P < 0.001). Total cholesterol (TCHOL), low-density lipoproteins (LDL), and triglycerides were higher with cyclosporine. The TTC haplotype had higher TCHOL (P < 0.001) and LDL (P = 0.005). Higher triglyceride (P = 0.034) and lower high-density lipoproteins (P = 0.057) were associated with TTT with sex-adjusted analysis. ABCB1 haplotypes and sex were associated with extrarenal AEs. Using haplotypes, certain female patients manifested more AEs regardless of CNI. Haplotype testing may identify patients with greater susceptibility to AEs and facilitate CNI

  2. Longitudinal Outcomes for Preschool Dual Language Learners Receiving Writing Instruction

    ERIC Educational Resources Information Center

    Matera, Carola

    2011-01-01

    This article analyzed data from a randomized, longitudinal study (Matera & Gerber, 2008) to measure the effectiveness of a writing intervention that provided clearly defined opportunities for Spanish-speaking preschool children in a Head Start program to develop their writing abilities in English. Results from this study indicate that children…

  3. Dual kidney transplantation: case report.

    PubMed

    Vidas, Zeljko; Kocman, Branislav; Knotek, Mladen; Skegro, Dinko

    2010-06-01

    Chronic shortage of kidney transplants worldwide has led to the use of organs from so called marginal or borderline donors, now termed "expanded-criteria donors". There has been an emerging practice of dual kidney transplantation (DKT) to compensate for sub optimal nephron mass of such kidneys. We performed DKT in "Merkur" University Hospital in August 2005. The donor was a 72-year old female with a history of long-term hypertension, aneurysm of the posterior cerebral artery, cerebrovascular insult (CVI), and with normal creatinine values and kidney function at the time of explantation. Initial biopsy of donor kidneys revealed acute tubular damage, with connective changes in 22% and 11% of glomeruli in the left and the right kidney, respectively. The recipient was a 60-year old male diagnosed with the IgA nephropathy on the last biopsy in 1999, and on dialysis since November 2003. Postoperative course was uneventful without any surgical complications. A triple immunosuppressive protocol was used. On follow-up ultrasonography 4 years posttransplantation both kidneys appeared of normal size and parenchymal pattern and with no signs of dilatation of the canal system, and color Doppler examination demonstrated normal flow in both kidneys. In conclusion, the use of DKT ie. donors by the expanded-criteria will continue to increase, and further studies of the results will, with no doubt, support this method. PMID:20698157

  4. An Immunosuppressant Peptide from the Hard Tick Amblyomma variegatum

    PubMed Central

    Tian, Yufeng; Chen, Wenlin; Mo, Guoxiang; Chen, Ran; Fang, Mingqian; Yedid, Gabriel; Yan, Xiuwen

    2016-01-01

    Ixodid ticks are well known for spreading transmitted tick-borne pathogens while being attached to their hosts for almost 1–2 weeks to obtain blood meals. Thus, they must secrete many immunosuppressant factors to combat the hosts’ immune system. In the present work, we investigated an immunosuppressant peptide of the hard tick Amblyomma variegatum. This peptide, named amregulin, is composed of 40 residues with an amino acid sequence of HLHMHGNGATQVFKPRLVLKCPNAAQLIQPGKLQRQLLLQ. A cDNA of the precursor peptide was obtained from the National Center for Biotechnology Information (NCBI, Bethesda, MD, USA). In rat splenocytes, amregulin exerts significant anti-inflammatory effects by inhibiting the secretion of inflammatory factors in vitro, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-8 (IL-8) and interferon-gamma (IFN-γ). In rat splenocytes, treated with amregulin, compared to lipopolysaccharide (LPS) alone, the inhibition of the above inflammatory factors was significant at all tested concentrations (2, 4 and 8 µg/mL). Amregulin shows strong free radical scavenging and antioxidant activities (5, 10 and 20 µg/mL) in vitro. Amregulin also significantly inhibits adjuvant-induced paw inflammation in mouse models in vivo. This peptide may facilitate the ticks’ successful blood feeding and may lead to host immunotolerance of the tick. These findings have important implications for the understanding of tick-host interactions and the co-evolution between ticks and the viruses that they bear. PMID:27153086

  5. Immunosuppressive exosomes: a new approach for treating arthritis.

    PubMed

    Yang, Chenjie; Robbins, Paul D

    2012-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease and one of the leading causes of disability in the USA. Although certain biological therapies, including protein and antibodies targeting inflammatory factors such as the tumor necrosis factor, are effective in reducing symptoms of RA, these treatments do not reverse disease. Also, although novel gene therapy approaches have shown promise in preclinical and clinical studies to treat RA, it is still unclear whether gene therapy can be readily and safely applied to treat the large number of RA patients. Recently, nanosized, endocytic-derived membrane vesicles "exosomes" were demonstrated to function in cell-to-cell communication and to possess potent immunoregulatory properties. In particular, immunosuppressive DC-derived exosomes and blood plasma- or serum-derived exosomes have shown potent therapeutic effects in animal models of inflammatory and autoimmune disease including RA. This paper discusses the current knowledge on the production, efficacy, mechanism of action, and potential therapeutic use of immunosuppressive exosomes for arthritis therapy. PMID:22548070

  6. Cancer-induced immunosuppression: IL-18-elicited immunoablative NK cells.

    PubMed

    Terme, Magali; Ullrich, Evelyn; Aymeric, Laetitia; Meinhardt, Kathrin; Coudert, Jérôme D; Desbois, Mélanie; Ghiringhelli, François; Viaud, Sophie; Ryffel, Bernard; Yagita, Hideo; Chen, Lieping; Mécheri, Salaheddine; Kaplanski, Gilles; Prévost-Blondel, Armelle; Kato, Masashi; Schultze, Joachim L; Tartour, Eric; Kroemer, Guido; Degli-Esposti, Mariapia; Chaput, Nathalie; Zitvogel, Laurence

    2012-06-01

    During cancer development, a number of regulatory cell subsets and immunosuppressive cytokines subvert adaptive immune responses. Although it has been shown that tumor-derived interleukin (IL)-18 participates in the PD-1-dependent tumor progression in NK cell-controlled cancers, the mechanistic cues underlying this immunosuppression remain unknown. Here, we show that IL-18 converts a subset of Kit(-) (CD11b(-)) into Kit(+) natural killer (NK) cells, which accumulate in all lymphoid organs of tumor bearers and mediate immunoablative functions. Kit(+) NK cells overexpressed B7-H1/PD-L1, a ligand for PD-1. The adoptive transfer of Kit(+) NK cells promoted tumor growth in two pulmonary metastases tumor models and significantly reduced the dendritic and NK cell pools residing in lymphoid organs in a B7-H1-dependent manner. Neutralization of IL-18 by RNA interference in tumors or systemically by IL-18-binding protein dramatically reduced the accumulation of Kit(+)CD11b(-) NK cells in tumor bearers. Together, our findings show that IL-18 produced by tumor cells elicits Kit(+)CD11b(-) NK cells endowed with B7-H1-dependent immunoablative functions in mice. PMID:22427351

  7. IL-18 induces PD-1-dependent immunosuppression in cancer.

    PubMed

    Terme, Magali; Ullrich, Evelyn; Aymeric, Laetitia; Meinhardt, Kathrin; Desbois, Mélanie; Delahaye, Nicolas; Viaud, Sophie; Ryffel, Bernard; Yagita, Hideo; Kaplanski, Gilles; Prévost-Blondel, Armelle; Kato, Masashi; Schultze, Joachim L; Tartour, Eric; Kroemer, Guido; Chaput, Nathalie; Zitvogel, Laurence

    2011-08-15

    Immunosuppressive cytokines subvert innate and adaptive immune responses during cancer progression. The inflammatory cytokine interleukin-18 (IL-18) is known to accumulate in cancer patients, but its pathophysiological role remains unclear. In this study, we show that low levels of circulating IL-18, either exogenous or tumor derived, act to suppress the NK cell arm of tumor immunosurveillance. IL-18 produced by tumor cells promotes the development of NK-controlled metastases in a PD-1-dependent manner. Accordingly, PD-1 is expressed by activated mature NK cells in lymphoid organs of tumor bearers and is upregulated by IL-18. RNAi-mediated knockdown of IL-18 in tumors, or its systemic depletion by IL-18-binding protein, are sufficient to stimulate NK cell-dependent immunosurveillance in various tumor models. Together, these results define IL-18 as an immunosuppressive cytokine in cancer. Our findings suggest novel clinical implementations of anti-PD-1 antibodies in human malignancies that produce IL-18. PMID:21724589

  8. Immunosuppressive therapy for transplant-ineligible aplastic anemia patients.

    PubMed

    Schrezenmeier, Hubert; Körper, Sixten; Höchsmann, Britta

    2015-02-01

    Aplastic anemia is a rare life-threatening bone marrow failure that is characterized by bicytopenia or pancytopenia in the peripheral blood and a hypoplastic or aplastic bone marrow. The patients are at risk of infection and hemorrhage due to neutropenia and thrombocytopenia and suffer from symptoms of anemia. The main treatment approaches are allogeneic stem cell transplantation and immunosuppression. Here, we review current standard immunosuppression and the attempts that have been made in the past two decades to improve results: review of recent developments also reveals that sometimes not only the advent of new drugs, good ideas and well-designed clinical trials decide the progress in the field but also marketing considerations of pharmaceutical companies. Aplastic anemia experts unfortunately had to face the situation that efficient drugs were withdrawn simply for marketing considerations. We will discuss the current options and challenges in first-line treatment and management of relapsing and refractory patients with an emphasis on adult patients. Some promising new approaches are currently under investigation in prospective, randomized trials. PMID:25572607

  9. An Immunosuppressant Peptide from the Hard Tick Amblyomma variegatum.

    PubMed

    Tian, Yufeng; Chen, Wenlin; Mo, Guoxiang; Chen, Ran; Fang, Mingqian; Yedid, Gabriel; Yan, Xiuwen

    2016-01-01

    Ixodid ticks are well known for spreading transmitted tick-borne pathogens while being attached to their hosts for almost 1-2 weeks to obtain blood meals. Thus, they must secrete many immunosuppressant factors to combat the hosts' immune system. In the present work, we investigated an immunosuppressant peptide of the hard tick Amblyomma variegatum. This peptide, named amregulin, is composed of 40 residues with an amino acid sequence of HLHMHGNGATQVFKPRLVLKCPNAAQLIQPGKLQRQLLLQ. A cDNA of the precursor peptide was obtained from the National Center for Biotechnology Information (NCBI, Bethesda, MD, USA). In rat splenocytes, amregulin exerts significant anti-inflammatory effects by inhibiting the secretion of inflammatory factors in vitro, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-8 (IL-8) and interferon-gamma (IFN-γ). In rat splenocytes, treated with amregulin, compared to lipopolysaccharide (LPS) alone, the inhibition of the above inflammatory factors was significant at all tested concentrations (2, 4 and 8 µg/mL). Amregulin shows strong free radical scavenging and antioxidant activities (5, 10 and 20 µg/mL) in vitro. Amregulin also significantly inhibits adjuvant-induced paw inflammation in mouse models in vivo. This peptide may facilitate the ticks' successful blood feeding and may lead to host immunotolerance of the tick. These findings have important implications for the understanding of tick-host interactions and the co-evolution between ticks and the viruses that they bear. PMID:27153086

  10. Modified Uterine Allotransplantation and Immunosuppression Procedure in the Sheep Model

    PubMed Central

    Yang, Hong; Zhao, Guang-Yue; Zhang, Geng; Lu, Zhi-Hong; Huang, Yan-Hong; Ma, Xiang-Dong; Liu, Hai-Xia; Liang, Sheng-Ru; Yang, Fang; Chen, Bi-Liang

    2013-01-01

    Objective To develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model. Methods In this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively. Results Viable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe) revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis. Conclusion We have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus) is similar to the human anatomy, making the ovine model excellent for human uterine transplant research. PMID:24278415

  11. Visual loss resulting from immunosuppressive therapy in patients with syphilitic uveitis.

    PubMed

    Afonso, Vivian Cristina Costa; Nascimento, Heloisa; Belfort, Rubens M; Sato, Emilia Inoue; Muccioli, Cristina; Belfort Jr, Rubens

    2015-01-01

    Permanent visual loss can be caused by improper use of immunosuppressive therapy in cases of uveitis without differential diagnosis of syphilitic uveitis. We present four cases of syphilitic uveitis that were incorrectly diagnosed as being secondary to rheumatic diseases and were subsequently treated with immunosuppressive therapy, leading to permanent visual loss. These cases highlight the importance of ruling out syphilis in the differential diagnosis of inflammatory ocular diseases before starting use of immunosuppressive therapy. PMID:26222110

  12. Fatal Myocarditis Associated With HHV-6 Following Immunosuppression in Two Children.

    PubMed

    Stefanski, Heather E; Thibert, Kathryn A; Pritchett, Joshua; Prusty, Bhupesh K; Wagner, John E; Lund, Troy C

    2016-01-01

    Fatal myocarditis is a rare complication in immunosuppressed children. Recent reports have linked human herpesvirus 6 (HHV-6) infection, typically a benign infection in childhood, with myocarditis. HHV-6 can reactivate during periods of immunosuppression. Here, we report 2 cases in which children were immunosuppressed, one for treatment of Evans syndrome and the other post hematopoietic stem cell transplantation, who developed rapid and fatal HHV-6-associated myocarditis. These cases suggest that HHV-6 infection should be considered as an etiology of myocarditis in immunosuppressed patients regardless of correlating blood levels. Early treatment of HHV-6 in patients with myocarditis could improve morbidity and mortality. PMID:26681781

  13. Porcine Reproductive and Respiratory Syndrome Virus–Induced Immunosuppression Exacerbates the Inflammatory Response to Porcine Respiratory Coronavirus in Pigs

    PubMed Central

    Alekseev, Konstantin; Jung, Kwonil; Fang, Ying; Saif, Linda J.

    2010-01-01

    Abstract We performed a comprehensive analysis of innate and adaptive immune responses in dual-virus infected pigs to understand whether a pre-existing immunomodulatory respiratory viral infection affects the overall immunity to a subsequent porcine respiratory coronavirus (PRCV) infection in pigs. Pigs were either mock-infected or infected with porcine reproductive and respiratory syndrome virus (PRRSV), a virus known to cause immunosuppressive respiratory disease, and then pigs were co-infected with PRCV, which normally causes subclinical respiratory infection. We collected samples for six independent experiments from 178 pigs that were also used for pathological studies. We detected a significant reduction in innate NK-cell-mediated cytotoxic function in PRRSV-infected pigs, which was synergistically further decreased in pigs co-infected with PRCV. Subsequently, in association with clinical signs we observed elevated levels of proinflammatory (IL-6), Th-1 (IL-12), and regulatory (IL-10 and TGF-β) cytokines. Increased frequencies of CD4CD8 double-positive T lymphocytes and myeloid cells, in addition to the elevated Th-1 and proinflammatory cytokines in dual-infected pigs, contributed to the severity of lung disease in pigs. The results of our study clarify how each virus modulates the host innate and adaptive immune responses, leading to inflammatory reactions and lung pathology. Thus measurements of cytokines and frequencies of immune cells may serve as indicators of the progression of respiratory viral co-infections, and provide more definitive approaches for treatment. PMID:20883160

  14. Porcine reproductive and respiratory syndrome virus-induced immunosuppression exacerbates the inflammatory response to porcine respiratory coronavirus in pigs.

    PubMed

    Renukaradhya, Gourapura J; Alekseev, Konstantin; Jung, Kwonil; Fang, Ying; Saif, Linda J

    2010-10-01

    We performed a comprehensive analysis of innate and adaptive immune responses in dual-virus infected pigs to understand whether a pre-existing immunomodulatory respiratory viral infection affects the overall immunity to a subsequent porcine respiratory coronavirus (PRCV) infection in pigs. Pigs were either mock-infected or infected with porcine reproductive and respiratory syndrome virus (PRRSV), a virus known to cause immunosuppressive respiratory disease, and then pigs were co-infected with PRCV, which normally causes subclinical respiratory infection. We collected samples for six independent experiments from 178 pigs that were also used for pathological studies. We detected a significant reduction in innate NK-cell-mediated cytotoxic function in PRRSV-infected pigs, which was synergistically further decreased in pigs co-infected with PRCV. Subsequently, in association with clinical signs we observed elevated levels of proinflammatory (IL-6), Th-1 (IL-12), and regulatory (IL-10 and TGF-β) cytokines. Increased frequencies of CD4CD8 double-positive T lymphocytes and myeloid cells, in addition to the elevated Th-1 and proinflammatory cytokines in dual-infected pigs, contributed to the severity of lung disease in pigs. The results of our study clarify how each virus modulates the host innate and adaptive immune responses, leading to inflammatory reactions and lung pathology. Thus measurements of cytokines and frequencies of immune cells may serve as indicators of the progression of respiratory viral co-infections, and provide more definitive approaches for treatment. PMID:20883160

  15. Immunosuppressive effect of the anti-IL-2-receptor monoclonal antibody, AMT-13, on organ-cultured fetal pancreas allograft survival

    SciTech Connect

    Burkhardt, K.; Loughnan, M.S.; Diamantstein, T.; Mandel, T.E.

    1988-11-01

    Recently, prolongation of cardiac allograft survival in mice was reported using a rat anti-IL-2R mAb (AMT-13). However, its immunosuppressive action in vivo, alone and in combination with other immunosuppressants, and its effect on other organ transplants has not been extensively studied. We grafted cultured fetal pancreas from CBA (H-2k) donors to Balb/c (H-2d) mice. Recipients were treated with 10 consecutive daily injections each of 20 micrograms AMT-13 only, or with an additional mild immunosuppression of 350 rads irradiation. Control groups received rat immunoglobulin or 350 rads irradiation. Graft survival and the phenotype of infiltrating cells were assessed histologically and immunocytochemically on days 12, 17, and 21, and soluble IL-2R levels were measured in the serum with a quantitative ELISA in all recipients. Two of five grafts in the AMT-13-treated group had islets on day 12 posttransplantation despite lymphocytic infiltration in all grafts, while at this time all grafts of rat Ig treated control mice were completely rejected with only scar tissue and a few lymphocytes remaining. Additional immunosuppression with 350 rads irradiation had a marked additive effect with AMT-13. Soluble IL-2R levels in the serum of untreated recipients were not elevated compared with normal serum levels, but recipients injected with AMT-13 had multifold increased soluble IL-2R levels. The percentage of IL-2R+ cells in the grafts of AMT-13-treated animals was either normal (less than 5%) or increased (20%) in the additionally irradiated mice, providing strong evidence that the immunosuppressive effect of AMT-13 is not due to a depletion of activated IL-2R+ lymphocytes.

  16. DSP30 enhances the immunosuppressive properties of mesenchymal stromal cells and protects their suppressive potential from lipopolysaccharide effects: A potential role of adenosine.

    PubMed

    Sangiorgi, Bruno; De Freitas, Helder Teixeira; Schiavinato, Josiane Lilian Dos Santos; Leão, Vitor; Haddad, Rodrigo; Orellana, Maristela Delgado; Faça, Vitor Marcel; Ferreira, Germano Aguiar; Covas, Dimas Tadeu; Zago, Marco Antônio; Panepucci, Rodrigo Alexandre

    2016-07-01

    Multipotent mesenchymal stromal cells (MSC) are imbued with an immunosuppressive phenotype that extends to several immune system cells. In this study, we evaluated how distinct Toll-like receptor (TLR) agonists impact immunosuppressive properties of bone marrow (BM)-MSC and explored the potential mechanisms involved. We show that TLR4 stimulation by lipopolysaccharide (LPS) restricted the ability of MSC to suppress the proliferation of T lymphocytes, increasing the gene expression of interleukin (IL)-1β and IL-6. In contrast, stimulation of TLR9 by DSP30 induced proliferation and the suppressive potential of BM-MSC, coinciding with reducing tumor necrosis factor (TNF)-α expression, increased expression of transforming growth factor (TGF)-β1, increased percentages of BM-MSC double positive for the ectonucleotidases CD39+CD73+ and adenosine levels. Importantly, following simultaneous stimulation with LPS and DSP30, BM-MSC's ability to suppress T lymphocyte proliferation was comparable with that of non-stimulated BM-MSC levels. Moreover, stimulation of BM-MSC with LPS reduced significantly the gene expression levels, on co-cultured T lymphocyte, of IL-10 and interferon (IFN)γ, a cytokine with potential to enhance the immunosuppression mediated by MSC and ameliorate the clinical outcome of patients with graft-versus-host disease (GVHD). Altogether, our findings reiterate the harmful effects of LPS on MSC immunosuppression, besides indicating that DSP30 could provide a protective effect against LPS circulating in the blood of GVHD patients who receive BM-MSC infusions, ensuring a more predictable immunosuppressive effect. The novel effects and potential mechanisms following the stimulation of BM-MSC by DSP30 might impact their clinical use, by allowing the derivation of optimal "licensing" protocols for obtaining therapeutically efficient MSC. PMID:27260206

  17. Similar outcomes for anti-tumor necrosis factor-α antibody and immunosuppressant following seton drainage in patients with Crohn's disease-related anal fistula

    PubMed Central

    Lin, Xutao; Fan, Dejun; Cai, Zerong; Lian, Lei; He, Xiaowen; Zhi, Min; Wu, Xiaojian; He, Xiaosheng; Lan, Ping

    2016-01-01

    Anal fistula is common in patients with Crohn's disease (CD) and leads to significant morbidity. The efficacy of seton drainage combined with anti-tumor necrosis factor-α monoclonal antibody (anti-TNF-α) or immunosuppressant in the treatment of CD-related anal fistula remains unclear. The aim of the present study was to compare the efficacy between seton drainage combined with anti-TNF-α and seton drainage combined with immunosuppressant postoperatively on the treatment of CD-related anal fistula. A total of 65 patients with CD-related anal fistula who had received seton drainage combined with postoperative medication were divided into an antibiotics only group, anti-TNF-α group and immunosuppressant group; all patients were treated with antibiotics. Fistula closure, external orifice exudation rate and recurrence rate were assessed among these patients. The duration of follow-up ranged from 3 to 84 months with an average of 25.3 months. There were 11 (16.9%) cases of recurrence after seton drainage, 9 of which underwent a second seton drainage. In the total study group, 34 (52.3%) cases achieved complete fistula closure, and 10 (15.4%) cases showed external orifice exudation. No significant difference was found among these three groups, regarding fistula closure rate, closure time of fistula and recurrence rate. The external orifice exudation rate was significantly higher in the anti-TNF-α group compared with the antibiotics only group and immunosuppressant group (P=0.004 and P=0.026, respectively). Seton drainage is an effective treatment for CD-related anal fistula. The efficacy is similar whether combined with anti-TNF-α or immunosuppressant.

  18. Spaceborne receivers: Basic principles

    NASA Technical Reports Server (NTRS)

    Stacey, J. M.

    1984-01-01

    The underlying principles of operation of microwave receivers for space observations of planetary surfaces were examined. The design philosophy of the receiver as it is applied to operate functionally as an efficient receiving system, the principle of operation of the key components of the receiver, and the important differences among receiver types are explained. The operating performance and the sensitivity expectations for both the modulated and total power receiver configurations are outlined. The expressions are derived from first principles and are developed through the important intermediate stages to form practicle and easily applied equations. The transfer of thermodynamic energy from point to point within the receiver is illustrated. The language of microwave receivers is applied statistics.

  19. [Pregnancy following liver transplantation and during immunosuppression with cyclosporine].

    PubMed

    Günter, H H; Mauz, S; Ringe, B; Niesert, S

    1990-05-11

    Orthotopic liver transplantation had been performed in 1983 in a now 40-year-old woman in the terminal stage of posthepatitis liver cirrhosis with recurrent oesophageal bleedings and precoma from complete liver-cell failure. She became pregnant in 1988 while under immunosuppression with cyclosporin (2.1-2.7 mg/kg body-weight) and prednisolone (5 or 7.5 mg daily in rotation). Pregnancy proceeded without complication and there were no side effects from cyclosporin. After premature membrane rupture in the 39th week of pregnancy uterine inertia developed during oxytocin stimulation of contractions, and caesarean section was performed. The female infant was normally developed without any malformations. Liver, kidney and adrenal functions were normal, as was haemopoiesis. But possible late sequelae of cyclosporin treatment in the child cannot as yet be assessed because of the short follow-up. PMID:2338057

  20. Primary laryngeal actinomycosis in an immunosuppressed woman: a case report.

    PubMed

    Abed, Tarik; Ahmed, Jay; O'Shea, Niamh; Payne, Simon; Watters, Gavin W

    2013-07-01

    We report a rare case of primary laryngeal actinomycosis, which occurred in a 35-year-old woman with end-stage renal failure secondary to systemic lupus erythematosus with membranous glomerulonephritis. The patient, who had been on long-term immunosuppression therapy, presented with hoarseness. Flexible laryngoscopy detected the presence of a granular glottic mass at the anterior commissure of the larynx. Histology revealed actinomycotic organisms associated with an abscess. The patient was treated with a prolonged course of oral penicillin V and speech therapy, and her dysphonia resolved almost completely. Although actinomycotic infection of the larynx is rare, it should be considered in the differential diagnosis of hoarseness in an immunocompromised patient. PMID:23904305

  1. Solar heat receiver

    DOEpatents

    Hunt, A.J.; Hansen, L.J.; Evans, D.B.

    1982-09-29

    A receiver is described for converting solar energy to heat a gas to temperatures from 700 to 900/sup 0/C. The receiver is formed to minimize impingement of radiation on the walls and to provide maximum heating at and near the entry of the gas exit. Also, the receiver is formed to provide controlled movement of the gas to be heated to minimize wall temperatures. The receiver is designed for use with gas containing fine heat absorbing particles, such as carbon particles.

  2. Immunosuppressive treatment protects against angiotensin II-induced renal damage.

    PubMed

    Muller, Dominik N; Shagdarsuren, Erdenechimeg; Park, Joon-Keun; Dechend, Ralf; Mervaala, Eero; Hampich, Franziska; Fiebeler, Anette; Ju, Xinsheng; Finckenberg, Piet; Theuer, Jürgen; Viedt, Christiane; Kreuzer, Joerg; Heidecke, Harald; Haller, Hermann; Zenke, Martin; Luft, Friedrich C

    2002-11-01

    Angiotensin (Ang) II promotes renal infiltration by immunocompetent cells in double-transgenic rats (dTGRs) harboring both human renin and angiotensinogen genes. To elucidate disease mechanisms, we investigated whether or not dexamethasone (DEXA) immunosuppression ameliorates renal damage. Untreated dTGRs developed hypertension, renal damage, and 50% mortality at 7 weeks. DEXA reduced albuminuria, renal fibrosis, vascular reactive oxygen stress, and prevented mortality, independent of blood pressure. In dTGR kidneys, p22phox immunostaining co-localized with macrophages and partially with T cells. dTGR dendritic cells expressed major histocompatibility complex II and CD86, indicating maturation. DEXA suppressed major histocompatibility complex II+, CD86+, dendritic, and T-cell infiltration. In additional experiments, we treated dTGRs with mycophenolate mofetil to inhibit T- and B-cell proliferation. Reno-protective actions of mycophenolate mofetil and its effect on dendritic and T cells were similar to those obtained with DEXA. We next investigated whether or not Ang II directly promotes dendritic cell maturation in vitro. Ang II did not alter CD80, CD83, and MHC II expression, but increased CCR7 expression and cell migration. To explore the role of tumor necrosis factor (TNF)-alpha on dendritic cell maturation in vivo, we treated dTGRs with the soluble TNF-alpha receptor etanercept. This treatment had no effect on blood pressure, but decreased albuminuria, nuclear factor-kappaB activation, and infiltration of all immunocompetent cells. These data suggest that immunosuppression prevents dendritic cell maturation and T-cell infiltration in a nonimmune model of Ang II-induced renal damage. Ang II induces dendritic migration directly, whereas in vivo TNF-alpha is involved in dendritic cell infiltration and maturation. Thus, Ang II may initiate events leading to innate and acquired immune response. PMID:12414515

  3. Immunosuppressive Treatment Protects Against Angiotensin II-Induced Renal Damage

    PubMed Central

    Muller, Dominik N.; Shagdarsuren, Erdenechimeg; Park, Joon-Keun; Dechend, Ralf; Mervaala, Eero; Hampich, Franziska; Fiebeler, Anette; Ju, Xinsheng; Finckenberg, Piet; Theuer, Jürgen; Viedt, Christiane; Kreuzer, Joerg; Heidecke, Harald; Haller, Hermann; Zenke, Martin; Luft, Friedrich C.

    2002-01-01

    Angiotensin (Ang) II promotes renal infiltration by immunocompetent cells in double-transgenic rats (dTGRs) harboring both human renin and angiotensinogen genes. To elucidate disease mechanisms, we investigated whether or not dexamethasone (DEXA) immunosuppression ameliorates renal damage. Untreated dTGRs developed hypertension, renal damage, and 50% mortality at 7 weeks. DEXA reduced albuminuria, renal fibrosis, vascular reactive oxygen stress, and prevented mortality, independent of blood pressure. In dTGR kidneys, p22phox immunostaining co-localized with macrophages and partially with T cells. dTGR dendritic cells expressed major histocompatibility complex II and CD86, indicating maturation. DEXA suppressed major histocompatibility complex II+, CD86+, dendritic, and T-cell infiltration. In additional experiments, we treated dTGRs with mycophenolate mofetil to inhibit T- and B-cell proliferation. Reno-protective actions of mycophenolate mofetil and its effect on dendritic and T cells were similar to those obtained with DEXA. We next investigated whether or not Ang II directly promotes dendritic cell maturation in vitro. Ang II did not alter CD80, CD83, and MHC II expression, but increased CCR7 expression and cell migration. To explore the role of tumor necrosis factor (TNF)-α on dendritic cell maturation in vivo, we treated dTGRs with the soluble TNF-α receptor etanercept. This treatment had no effect on blood pressure, but decreased albuminuria, nuclear factor-κB activation, and infiltration of all immunocompetent cells. These data suggest that immunosuppression prevents dendritic cell maturation and T-cell infiltration in a nonimmune model of Ang II-induced renal damage. Ang II induces dendritic migration directly, whereas in vivo TNF-α is involved in dendritic cell infiltration and maturation. Thus, Ang II may initiate events leading to innate and acquired immune response. PMID:12414515

  4. Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma

    PubMed Central

    Kopecka, Joanna; Gazzano, Elena; Sara, Orecchia; Ghigo, Dario; Riganti, Chiara

    2015-01-01

    The human malignant mesothelioma (HMM) is characterized by a chemoresistant and immunosuppressive phenotype. An effective strategy to restore chemosensitivity and immune reactivity against HMM is lacking. We investigated whether the use of zoledronic acid is an effective chemo-immunosensitizing strategy. We compared primary HMM samples with non-transformed mesothelial cells. HMM cells had higher rate of cholesterol and isoprenoid synthesis, constitutive activation of Ras/extracellular signal-regulated kinase1/2 (ERK1/2)/hypoxia inducible factor-1α (HIF-1α) pathway and up-regulation of the drug efflux transporter P-glycoprotein (Pgp). By decreasing the isoprenoid supply, zoledronic acid down-regulated the Ras/ERK1/2/HIF-1α/Pgp axis and chemosensitized the HMM cells to Pgp substrates. The HMM cells also produced higher amounts of kynurenine, decreased the proliferation of T-lymphocytes and expanded the number of T-regulatory (Treg) cells. Kynurenine synthesis was due to the transcription of the indoleamine 1,2 dioxygenase (IDO) enzyme, consequent to the activation of the signal transducer and activator of transcription-3 (STAT3). By reducing the activity of the Ras/ERK1/2/STAT3/IDO axis, zoledronic acid lowered the kyurenine synthesis and the expansion of Treg cells, and increased the proliferation of T-lymphocytes. Thanks to its ability to decrease Ras/ERK1/2 activity, which is responsible for both Pgp-mediated chemoresistance and IDO-mediated immunosuppression, zoledronic acid is an effective chemo-immunosensitizing agent in HMM cells. PMID:25544757

  5. Multiple overlapping homologies between two rheumatoid antigens and immunosuppressive viruses.

    PubMed Central

    Douvas, A; Sobelman, S

    1991-01-01

    Amino acid (aa) sequence homologies between viruses and autoimmune nuclear antigens are suggestive of viral involvement in disorders such as systemic lupus erythematosus (SLE) and scleroderma. We analyzed the frequency of exact homologies of greater than or equal to 5 aa between 61 viral proteins (19,827 aa), 8 nuclear antigens (3813 aa), and 41 control proteins (11,743 aa). Both pentamer and hexamer homologies between control proteins and viruses are unexpectedly abundant, with hexamer matches occurring in 1 of 3 control proteins (or once every 769 aa). However, 2 nuclear antigens, the SLE-associated 70-kDa antigen and the scleroderma-associated CENP-B protein, are highly unusual in containing multiple homologies to a group of synergizing immunosuppressive viruses. Two viruses, herpes simplex virus 1 (HSV-1) and human immunodeficiency virus 1 (HIV-1), contain sequences exactly duplicated at 15 sites in the 70-kDa antigen and at 10 sites in CENP-B protein. The immediate-early (IE) protein of HSV-1, which activates HIV-1 regulatory functions, contains three homologies to the 70-kDa antigen (two hexamers and a pentamer) and two to CENP-B (a hexamer and pentamer). There are four homologies (including a hexamer) common to the 70-kDa antigen and Epstein-Barr virus, and three homologies (including two hexamers) common to CENP-B and cytomegalovirus. The majority of homologies in both nuclear antigens are clustered in highly charged C-terminal domains containing epitopes for human autoantibodies. Furthermore, most homologies have a contiguous or overlapping distribution, thereby creating a high density of potential epitopes. In addition to the exact homologies tabulated, motifs of matching sequences are repeated frequently in these domains. Our analysis suggests that coexpression of heterologous viruses having common immunosuppressive functions may generate autoantibodies cross-reacting with certain nuclear proteins. PMID:1712488

  6. Metabolic consequences of modern immunosuppressive agents in solid organ transplantation

    PubMed Central

    Bamgbola, Oluwatoyin

    2016-01-01

    Among other factors, sophistication of immunosuppressive (IS) regimen accounts for the remarkable success attained in the short- and medium-term solid organ transplant (SOT) survival. The use of steroids, mycophenolate mofetil and calcineurin inhibitors (CNI) have led to annual renal graft survival rates exceeding 90% in the last six decades. On the other hand, attrition rates of the allograft beyond the first year have remained unchanged. In addition, there is a persistent high cardiovascular (CV) mortality rate among transplant recipients with functioning grafts. These shortcomings are in part due to the metabolic effects of steroids, CNI and sirolimus (SRL), all of which are implicated in hypertension, new onset diabetes after transplant (NODAT), and dyslipidemia. In a bid to reduce the required amount of harmful maintenance agents, T-cell-depleting antibodies are increasingly used for induction therapy. The downsides to their use are greater incidence of opportunistic viral infections and malignancy. On the other hand, inadequate immunosuppression causes recurrent rejection episodes and therefore early-onset chronic allograft dysfunction. In addition to the adverse metabolic effects of the steroid rescue needed in these settings, the generated proinflammatory milieu may promote accelerated atherosclerotic disorders, thus setting up a vicious cycle. The recent availability of newer agent, belatacept holds a promise in reducing the incidence of metabolic disorders and hopefully its long-term CV consequences. Although therapeutic drug monitoring as applied to CNI may be helpful, pharmacodynamic tools are needed to promote a customized selection of IS agents that offer the most benefit to an individual without jeopardizing the allograft survival. PMID:27293540

  7. Front end for GPS receivers

    NASA Technical Reports Server (NTRS)

    Thomas, Jr., Jess Brooks (Inventor)

    1999-01-01

    The front end in GPS receivers has the functions of amplifying, down-converting, filtering and sampling the received signals. In the preferred embodiment, only two operations, A/D conversion and a sum, bring the signal from RF to filtered quadrature baseband samples. After amplification and filtering at RF, the L1 and L2 signals are each sampled at RF at a high selected subharmonic rate. The subharmonic sample rates are approximately 900 MHz for L1 and 982 MHz for L2. With the selected subharmonic sampling, the A/D conversion effectively down-converts the signal from RF to quadrature components at baseband. The resulting sample streams for L1 and L2 are each reduced to a lower rate with a digital filter, which becomes a straight sum in the simplest embodiment. The frequency subsystem can be very simple, only requiring the generation of a single reference frequency (e.g. 20.46 MHz minus a small offset) and the simple multiplication of this reference up to the subharmonic sample rates for L1 and L2. The small offset in the reference frequency serves the dual purpose of providing an advantageous offset in the down-converted carrier frequency and in the final baseband sample rate.

  8. Does the nature of residual immune function explain the differential risk of non-melanoma skin cancer development in immunosuppressed organ transplant recipients?

    PubMed

    Jung, Ji-Won; Overgaard, Nana H; Burke, Michael T; Isbel, Nicole; Frazer, Ian H; Simpson, Fiona; Wells, James W

    2016-01-15

    Patients receiving immunosuppression to prevent organ transplant rejection are at a greatly increased risk of developing nonmelanoma skin cancer. In recent years a correlation has been identified between the class of immunosuppressant that these patients receive and their subsequent cancer risk; in particular, patients switched from calcineurin inhibitors to mammalian target of rapamycin (mTOR) inhibitors not only displayed a dramatic reduction in new tumor formation but also in some cases a regression of their existing lesions. Studies of cancer models in mice and cell lines in the laboratory have attributed these discrepancies in cancer risk to the ability of immunosuppressants such as mTOR inhibitors to elicit direct anticancer effects, including suppressing angiogenesis and increasing autophagy-mediated DNA repair. Recent evidence from the immunological literature however, suggests a significant alternative contribution of mTOR inhibitors; namely the promotion of memory T-cell function. Recent advances in understanding memory T-cell establishment and the demonstration of their critical role in long-term immunity make it timely to review the available evidence as to whether the improved nonmelanoma skin cancer outcome shown by patients switched to mTOR inhibitor treatment regimens may be associated with the retainment of memory T-cell function. PMID:25612559

  9. Outcome of hepatitis E virus infection in patients with inflammatory arthritides treated with immunosuppressants: a French retrospective multicenter study.

    PubMed

    Bauer, Hélène; Luxembourger, Cécile; Gottenberg, Jacques-Eric; Fournier, Sophie; Abravanel, Florence; Cantagrel, Alain; Chatelus, Emmanuel; Claudepierre, Pascal; Hudry, Christophe; Izopet, Jacques; Fabre, Sylvie; Lefevre, Guillaume; Marguerie, Laurent; Martin, Antoine; Messer, Laurent; Molto, Anna; Pallot-Prades, Béatrice; Pers, Yves-Marie; Roque-Afonso, Anne-Marie; Roux, Christian; Sordet, Christelle; Soubrier, Martin; Veissier, Claire; Wendling, Daniel; Péron, Jean-Marie; Sibilia, Jean

    2015-04-01

    The clinical presentation and outcome of hepatitis E virus (HEV) infection in inflammatory rheumatic diseases are unknown. We aimed to investigate the severity of acute HEV infection and the risk of chronic viral replication in patients with inflammatory arthritides treated with immunosuppressive drugs. All rheumatology and internal medicine practitioners belonging to the Club Rhumatismes et Inflammation in France were sent newsletters asking for reports of HEV infection and inflammatory arthritides. Baseline characteristics of patients and the course of HEV infection were retrospectively assessed by use of a standardized questionnaire. From January 2010 to August 2013, we obtained reports of 23 cases of HEV infection in patients with rheumatoid arthritis (n = 11), axial spondyloarthritis (n = 5), psoriatic arthritis (n = 4), other types of arthritides (n = 3). Patients received methotrexate (n = 16), antitumor necrosis factor α agents (n = 10), rituximab (n = 4), abatacept (n = 2), tocilizumab (n = 2), and corticosteroids (n = 10, median dose 6 mg/d, range 2-20). All had acute hepatitis: median aspartate and alanine aminotransferase levels were 679 and 1300 U/L, respectively. Eleven patients were asymptomatic, 4 had jaundice. The HEV infection diagnosis relied on positive PCR results for HEV RNA (n = 14 patients) or anti-HEV IgM positivity (n = 9). Median follow-up was 29 months (range 3-55). Treatment included discontinuation of immunosuppressants for 20 patients and ribavirin treatment for 5. Liver enzyme levels normalized and immunosuppressant therapy could be reinitiated in all patients. No chronic infection was observed. Acute HEV infection should be considered in patients with inflammatory rheumatism and elevated liver enzyme values. The outcome of HEV infection seems favorable, with no evolution to chronic hepatitis or fulminant liver failure. PMID:25860212

  10. Budget impact analysis of conversion from cyclosporine to sirolimus as immunosuppressive medication in renal transplantation therapy

    PubMed Central

    Foroutan, Naghmeh; Rasekh, Hamid R; Salamzadeh, Jamshid; Jamshidi, Hamid R; Nafar, Mohsen

    2013-01-01

    Objectives The aim of this study was to determine budget impact of conversion from cyclosporine (CsA) to sirolimus (SRL) in renal transplant therapy (RTT) from the perspective of insurance organizations in Iran. Methods An Excel-based model was developed to determine cost of RTT, comparing current CsA based therapy to an mTOR inhibitor-based therapy regimen. Total cost included both cost of immunosuppressive agents and relative adverse events. The inputs were derived from database of Ministry of Health and insurance organizations, hospital and pharmacy based registries, and available literature that were varied through a one-way sensitivity analysis. According to the model, there were almost 17,000 patients receiving RTT in Iran, out of which about 2,200 patients underwent the operation within the study year. The model was constructed based on the results of a local RCT, in which test and control groups received CsA, SRL, and steroids over the first 3 months posttransplantation and, from the fourth month on, CsA, mycophenolate mofetil (MMF), and steroids were used in the CsA group and SRL, MMF, and steroids were administered in the SRL group, respectively. Results The estimated cost of RTT with CsA was US$4,850,000 versus US$4,300,000 receiving SRL. These costs corresponded to the cost saving of almost US$550,000 for the payers. Conclusion To evaluate the financial consequence of adding mTOR inhibitors to the insurers’ formulary, in the present study, a budget impact analysis was conducted on sirolimus. Fewer cases of costly adverse events along with lower required doses of MMF related to SRL based therapies were major reasons for this saving budgetary impact. PMID:24159260

  11. Induction Immunosuppression and Clinical Outcomes in Kidney Transplant Recipients Infected With Human Immunodeficiency Virus.

    PubMed

    Kucirka, L M; Durand, C M; Bae, S; Avery, R K; Locke, J E; Orandi, B J; McAdams-DeMarco, M; Grams, M E; Segev, D L

    2016-08-01

    There is an increased risk of acute rejection (AR) in human immunodeficiency virus-positive (HIV+) kidney transplant (KT) recipients. Induction immunosuppression is standard of care for those at high risk of AR; however, use in HIV+ patients is controversial, given fears of increased infection rates. We sought to compare clinical outcomes between HIV+ KT recipients who were treated with (i) anti-thymocyte globulin (ATG), (ii) IL-2 receptor blocker, and (iii) no induction. We studied 830 HIV+ KT recipients between 2000 and 2014, as captured in the Scientific Registry of Transplant Recipients, and compared rates of delayed graft function (DGF), AR, graft loss and death. Infections and hospitalizations were ascertained by International Classification of Diseases, Ninth Revision codes in a subset of 308 patients with Medicare. Compared with no induction, neither induction agent was associated with an increased risk of infection (weighted hazard ratio [wHR] 0.80, 95% confidence interval [CI] 0.55-1.18). HIV+ recipients who received induction spent fewer days in the hospital (weighted relative risk [wRR] 0.70, 95% CI 0.52-0.95), had lower rates of DGF (wRR 0.66, 95% CI 0.51-0.84), less graft loss (wHR 0.47, 95% CI 0.24-0.89) and a trend toward lower mortality (wHR 0.60, 95% CI 0.24-1.28). Those who received induction with ATG had lower rates of AR (wRR 0.59, 95% CI 0.35-0.99). Induction in HIV+ KT recipients was not associated with increased infections; in fact, those receiving ATG, the most potent agent, had the lowest rates. In light of the high risk of AR in this population, induction therapy should be strongly considered. PMID:27111897

  12. Criteria Used in Clinical Practice to Guide Immunosuppressive Treatment in Patients with Primary Sclerosing Cholangitis

    PubMed Central

    Schulze, Kornelius; Weismüller, Tobias J.; Bubenheim, Michael; Huebener, Peter; Zenouzi, Roman; Lenzen, Henrike; Rupp, Christian; Gotthardt, Daniel; de Leuw, Philipp; Teufel, Andreas; Zimmer, Vincent; Reiter, Florian P.; Rust, Christian; Tharun, Lars; Quaas, Alexander; Weidemann, Sören A.; Lammert, Frank; Sarrazin, Christoph; Manns, Michael P.; Lohse, Ansgar W.; Schramm, Christoph

    2015-01-01

    Background & Aims Current guidelines recommend immunosuppressive treatment (IT) in patients with primary sclerosing cholangitis (PSC) and elevated aminotransferase levels more than five times the upper limit of normal and elevated serum IgG-levels above twice the upper limit of normal. Since there is no evidence to support this recommendation, we aimed to assess the criteria that guided clinicians in clinical practice to initiate IT in patients with previously diagnosed PSC. Methods This is a retrospective analysis of 196 PSC patients from seven German hepatology centers, of whom 36 patients had received IT solely for their liver disease during the course of PSC. Analyses were carried out using methods for competing risks. Results A simplified autoimmune hepatitis (AIH) score >5 (HR of 36, p<0.0001) and a modified histological activity index (mHAI) greater than 3/18 points (HR 3.6, p = 0.0274) were associated with the initiation of IT during the course of PSC. Of note, PSC patients who subsequently received IT differed already at the time of PSC diagnosis from those patients, who did not receive IT during follow-up: they presented with increased levels of IgG (p = 0.004) and more frequently had clinical signs of cirrhosis (p = 0.0002). Conclusions This is the first study which investigates the parameters associated with IT in patients with PSC in clinical practice. A simplified AIH score >5 and a mHAI score >3, suggesting concomitant features of AIH, influenced the decision to introduce IT during the course of PSC. In German clinical practice, the cutoffs used to guide IT may be lower than recommended by current guidelines. PMID:26489083

  13. Tuftsin-derived T-peptide prevents cellular immunosuppression and improves survival rate in septic mice

    PubMed Central

    Gao, Yu-Lei; Chai, Yan-Fen; Dong, Ning; Han, Su; Zhu, Xiao-Mei; Zhang, Qing-Hong; Yao, Yong-Ming

    2015-01-01

    The primary mechanisms of sepsis induced cellular immunesuppression involve immune dysfunction of T lymphocytes and negative immunoregulation of regulatory T cells (Tregs). It has been found that tuftsin is an immune modulating peptide derived from IgG in spleen. T-peptide is one of tuftsin analogs. Herein, we examined the effect of T-peptide on cell-mediated immunity in the presence of lipopolysaccharide (LPS) and the survival rate in septic mice. T-peptide regulated the proliferative ability of CD4+CD25− T cells in dual responses. Meanwhile, 10 and 100 μg/ml T-peptides were able to enhance the apoptotic rate of CD4+CD25− T cells compared with 1 μg/ml T-peptide, but markedly lowered interleukin (IL)-2 levels. When CD4+CD25+ Tregs were treated with T-peptide for 24 hours, and co-cultured with normal CD4+CD25− T cells, the suppressive ability of CD4+CD25+ Tregs on CD4+CD25− T cells was significantly lowered, along with decreased expression in forkhead/winged helix transcription factor p-3 (Foxp-3) as well as cytotoxic T lymphocyte-associated antigen (CTLA)-4, and secretion of transforming growth factor (TGF)-β. Moreover, T-peptide has the ability to improve outcome of septic mice in a dose- and time- dependent manner, and associated with improvement in the microenvironment of cellular immunosuppression in septic mice. PMID:26577833

  14. 42 CFR 410.30 - Prescription drugs used in immunosuppressive therapy.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... therapy. 410.30 Section 410.30 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... Other Health Services § 410.30 Prescription drugs used in immunosuppressive therapy. (a) Scope. Payment may be made for prescription drugs used in immunosuppressive therapy that have been approved...

  15. Lymphoproliferative disorders in inflammatory bowel disease patients on immunosuppression: Lessons from other inflammatory disorders

    PubMed Central

    Lam, Grace Y; Halloran, Brendan P; Peters, Anthea C; Fedorak, Richard N

    2015-01-01

    Immunosuppressive agents, such as thiopurines, methotrexate, and biologics, have revolutionized the treatment of inflammatory bowel disease (IBD). However, a number of case reports, case control studies and retrospective studies over the last decade have identified a concerning link between immunosuppression and lymphoproliferative disorders (LPDs), the oncological phenomenon whereby lymphocytes divide uncontrollably. These LPDs have been associated with Epstein-Barr virus (EBV) infection in which the virus provides the impetus for malignant transformation while immunosuppression hampers the immune system’s ability to detect and clear these malignant cells. As such, the use of immunosuppressive agents may come at the cost of increased risk of developing LPD. While little is known about the LPD risk in IBD, more is known about immunosuppression in the post-transplantation setting and the development of EBV associated post-transplantation lymphoproliferative disorders (PTLD). In review of the PTLD literature, evidence is available to demonstrate that certain immune suppressants such as cyclosporine and T-lymphocyte modulators in particular are associated with an increased risk of PTLD development. As well, high doses of immunosuppressive agents and multiple immunosuppressive agent use are also linked to increased PTLD development. Here, we discuss these findings in context of IBD and what future studies can be taken to understand and reduce the risk of EBV-associated LPD development from immunosuppression use in IBD. PMID:26600976

  16. Dual-Rate Transmission Reduces Weather Effects

    NASA Technical Reports Server (NTRS)

    Posner, E. C.

    1984-01-01

    Scheme ensures maximum data received on average. Dual-rate scheme for maximizing data returned during spacecraft mission, adaptable, as is or with modifications, to high-frequency terrestrial data transmission. Data rate fixed in advance at minimum value guarantees reasonable prospect of success during bad weather. Dualrate strategy yields net data rate 2.5 times best achievable with single transmission rate.

  17. Compact Dual-Mode Microwave Antenna

    NASA Technical Reports Server (NTRS)

    Carr, K. L.

    1982-01-01

    Compact dual-mode antenna, 3.66 cm wide by 1.83 cm thick is used both for heating and thermographic detection of tumors in cancer research. Temperature sensor operates independently or simultaneously with heater. Antenna includes 1.6-GHz transmitter and 4.76-GHz receiver. Strip heater between antennas controls temperature of device. Maximum power output is 25 W.

  18. Precise orbit determination for the shuttle radar topography mission using a new generation of GPS receiver

    NASA Technical Reports Server (NTRS)

    Bertiger, W.; Bar-Sever, Y.; Desai, S.; Duncan, C.; Haines, B.; Kuang, D.; Lough, M.; Reichert, A.; Romans, L.; Srinivasan, J.; Webb, F.; Young, L.; Zumberge, J.

    2000-01-01

    The BlackJack family of GPS receivers has been developed at JPL to satisfy NASA's requirements for high-accuracy, dual-frequency, Y-codeless GPS receivers for NASA's Earth science missions. In this paper we will present the challenges that were overcome to meet this accuracy requirement. We will discuss the various reduced dynamic strategies, Space Shuttle dynamic models, and our tests for accuracy that included a military Y-code dual-frequency receiver (MAGR).

  19. Method and system for dual resolution translation stage

    DOEpatents

    Halpin, John Michael

    2014-04-22

    A dual resolution translation stage includes a stage assembly operable to receive an optical element and a low resolution adjustment device mechanically coupled to the stage assembly. The dual resolution stage also includes an adjustable pivot block mechanically coupled to the stage assembly. The adjustable pivot block includes a pivot shaft. The dual resolution stage further includes a lever arm mechanically coupled to the adjustable pivot block. The lever arm is operable to pivot about the pivot shaft. The dual resolution stage additionally includes a high resolution adjustment device mechanically coupled to the lever arm and the stage assembly.

  20. Regression of advanced melanoma upon withdrawal of immunosuppression: case series and literature review

    PubMed Central

    Thomas, N.; Sharpless, N.; Collichio, F.

    2013-01-01

    We report two cases of stage IV malignant melanoma arising in patients treated with azathioprine for myasthenia gravis. In both cases, the melanoma metastases regressed upon withdrawal of immunosuppression. One patient remains melanoma free at 10 years, and the second patient experienced an 18-month disease free period. There is one prior case report in the medical literature to support full immune reconstitution for treatment in advanced immunosuppression-related melanoma, and one case series suggesting that transplant patients developing melanoma may benefit from a switch to sirolimus. Virtually, no data exist for the medical management of early stage melanoma in the immunosuppressed patients. We review the limited preclinical data in support of immune reconstitution and the data on immunosuppression as a risk factor for melanoma. We conclude that reduction or withdrawal of immunosuppression may be beneficial in patients with advanced stage melanoma and warrants further consideration in patients with early stage melanoma. PMID:19890737

  1. Immunosuppressive Mechanisms of Malignant Gliomas: Parallels at Non-CNS Sites

    PubMed Central

    Perng, Powell; Lim, Michael

    2015-01-01

    The central nervous system (CNS) possesses powerful local and global immunosuppressive capabilities that modulate unwanted inflammatory reactions in nervous tissue. These same immune-modulatory mechanisms are also co-opted by malignant brain tumors and pose a formidable challenge to brain tumor immunotherapy. Routes by which malignant gliomas coordinate immunosuppression include the mechanical and functional barriers of the CNS; immunosuppressive cytokines and catabolites; immune checkpoint molecules; tumor-infiltrating immune cells; and suppressor immune cells. The challenges to overcoming tumor-induced immunosuppression, however, are not unique to the brain, and several analogous immunosuppressive mechanisms also exist for primary tumors outside of the CNS. Ultimately, the immune responses in the CNS are linked and complementary to immune processes in the periphery, and advances in tumor immunotherapy in peripheral sites may therefore illuminate novel approaches to brain tumor immunotherapy, and vice versa. PMID:26217588

  2. Response to primary infection with Herpesvirus saimiri in immunosuppressed juvenile and newborn squirrel monkeys.

    PubMed Central

    Martin, L N; Allen, W P

    1975-01-01

    Immunosuppression of juvenile squirrel monkeys with combined azathioprine, prednisolone, and antilymphocyte globulin resulted in decreased antibody responses to viral antigens after primary infection with Herpesvirus saimiri (HVS). The virus was repeatedly isolated from the oropharynx of immunosuppressed monkeys but not from untreated infected controls. Thus immune factors are important in inhibiting shedding of HVS from the oropharynx. HVS could be isolated from the peripheral blood lymphocytes of infected control monkeys but not from the lymphocytes of immunosuppressed monkeys. Immunosuppressed monkeys also had decreased percentages of lymphocytes capable of forming rosettes with sheep erythrocytes. These results indicate that the immunosuppressive agents had inhibitory effects on lymphocytes (presumably thymus derived) capable of being latently infected with HVS. Antibody responses in newborn monkeys infected with HVS were delayed compared with juvenile monkeys. Treatment of newborn monkeys with antilymphocyte globulin had no suppressive effect on antibody responses to HVS. PMID:170204

  3. Dual Wavelength Lasers

    NASA Technical Reports Server (NTRS)

    Walsh, Brian M.

    2010-01-01

    Dual wavelength lasers are discussed, covering fundamental aspects on the spectroscopy and laser dynamics of these systems. Results on Tm:Ho:Er:YAG dual wavelength laser action (Ho at 2.1 m and Er at 2.9 m) as well as Nd:YAG (1.06 and 1.3 m) are presented as examples of such dual wavelength systems. Dual wavelength lasers are not common, but there are criteria that govern their behavior. Based on experimental studies demonstrating simultaneous dual wavelength lasing, some general conclusions regarding the successful operation of multi-wavelength lasers can be made.

  4. The Submillimeter Array Antennas and Receivers

    NASA Astrophysics Data System (ADS)

    Blundell, R.

    The Submillimeter Array (SMA) was conceived at the Smithsonian Astrophysical Observatory in 1984 as a six element interferometer to operate in the major atmospheric windows from about 200 to 900 GHz. In 1996, the Academica Sinica Institute of Astronomy and Astrophysics of Taiwan joined the project and agreed to provide additional hardware to expand the interferometer to eight elements. All eight antennas are now operating at the observatory site on Mauna Kea, and astronomical observations have been made in the 230, 345, and 650 GHz bands. The SMA antennas have a diameter of 6 m, a surface accuracy of better than 25 micron rms, and can be reconfigured to provide spatial resolutions down to about 0.5" at 200 GHz and, eventually, 0.1" at 850 GHz. Coupling to the receiver package within each antenna is achieved via a beam waveguide, in a bent Nasmyth configuration, comprised of a flat tertiary mirror and two ellipsoidal mirrors that form a secondary pupil used for receiver calibration. An additional fixed mirror and a rotating wire grid polarizer are then used for receiver selection. Each antenna houses a single cryostat, with an integrated cryocooler capable of cooling up to eight receivers to 4 K. In the current configuration only three receiver bands are available: 175-255 GHz, 250-350 GHz, and 600-720 GHz, and simultaneous operation of the 650 GHz receiver with either of the lower frequency receivers is possible. Eventually dual polarization will be available from 325-350 GHz, and dual frequency operation will be possible, pairing either of the lower frequency receivers with any of the high frequency units: 325-425 GHz, 425-510 GHz, 600-720 GHz, and 800-900 GHz. Each receiver currently uses a single superconductor-insulator-superconductor junction as the mixing element, and has first stage intermediate frequency amplification at 4 K with an instantaneous bandwidth of 2.5 GHz, centered at 5 GHz. The mixers are of a fixed-tuned waveguide design, are inherently broad

  5. The reconstitution of the thymus in immunosuppressed individuals restores CD4-specific cellular and humoral immune responses

    PubMed Central

    Plana, Montserrat; Garcia, Felipe; Darwich, Laila; Romeu, Joan; López, Anna; Cabrera, Cecilia; Massanella, Marta; Canto, Esther; Ruiz-Hernandez, Raul; Blanco, Julià; Sánchez, Marcelo; Gatell, Josep M; Clotet, Bonaventura; Ruiz, Lidia; Bofill, Margarita

    2011-01-01

    Infection with HIV-1 frequently results in the loss of specific cellular immune responses and an associated lack of antibodies. Recombinant growth hormone (rGH) administration reconstitutes thymic tissue and boosts the levels of peripheral T cells, so rGH therapy may be an effective adjuvant through promoting the recovery of lost cellular and T-cell-dependent humoral immune responses in immunosuppressed individuals. To test this concept, we administered rGH to a clinically defined group of HIV-1-infected subjects with defective cellular and serological immune responses to at least one of three commonly employed vaccines (hepatitis A, hepatitis B or tetanus toxoid). Of the original 278 HIV-1-infected patients entering the trial, only 20 conformed to these immunological criteria and were randomized into three groups: Group A (n = 8) receiving rGH and challenged with the same vaccine to which they were unresponsive and Groups B (n = 5) and C (n = 7) who received either rGH or vaccination alone, respectively. Of the eight subjects in Group A, five recovered CD4 cellular responses to vaccine antigen and four of these produced the corresponding antibodies. In the controls, three of the five in group B recovered cellular responses with two producing antibodies, whereas three of the seven in Group C recovered CD4 responses, with only two producing antibodies. Significantly, whereas seven of ten patients receiving rGH treatment in Group A (six patients) and B (one patient) recovered T-cell responses to HIVp24, only two of six in Group C responded similarly. In conclusion, reconstitution of the thymus in immunosuppressed adults through rGH hormone treatment restored both specific antibody and CD4 T-cell responses. PMID:21501161

  6. The reconstitution of the thymus in immunosuppressed individuals restores CD4-specific cellular and humoral immune responses.

    PubMed

    Plana, Montserrat; Garcia, Felipe; Darwich, Laila; Romeu, Joan; López, Anna; Cabrera, Cecilia; Massanella, Marta; Canto, Esther; Ruiz-Hernandez, Raul; Blanco, Julià; Sánchez, Marcelo; Gatell, Josep M; Clotet, Bonaventura; Ruiz, Lidia; Bofill, Margarita

    2011-07-01

    Infection with HIV-1 frequently results in the loss of specific cellular immune responses and an associated lack of antibodies. Recombinant growth hormone (rGH) administration reconstitutes thymic tissue and boosts the levels of peripheral T cells, so rGH therapy may be an effective adjuvant through promoting the recovery of lost cellular and T-cell-dependent humoral immune responses in immunosuppressed individuals. To test this concept, we administered rGH to a clinically defined group of HIV-1-infected subjects with defective cellular and serological immune responses to at least one of three commonly employed vaccines (hepatitis A, hepatitis B or tetanus toxoid). Of the original 278 HIV-1-infected patients entering the trial, only 20 conformed to these immunological criteria and were randomized into three groups: Group A (n = 8) receiving rGH and challenged with the same vaccine to which they were unresponsive and Groups B (n = 5) and C (n = 7) who received either rGH or vaccination alone, respectively. Of the eight subjects in Group A, five recovered CD4 cellular responses to vaccine antigen and four of these produced the corresponding antibodies. In the controls, three of the five in group B recovered cellular responses with two producing antibodies, whereas three of the seven in Group C recovered CD4 responses, with only two producing antibodies. Significantly, whereas seven of ten patients receiving rGH treatment in Group A (six patients) and B (one patient) recovered T-cell responses to HIVp24, only two of six in Group C responded similarly. In conclusion, reconstitution of the thymus in immunosuppressed adults through rGH hormone treatment restored both specific antibody and CD4 T-cell responses. PMID:21501161

  7. Helper-dependent adenovirus achieve more efficient and persistent liver transgene expression in non-human primates under immunosuppression.

    PubMed

    Unzu, C; Melero, I; Hervás-Stubbs, S; Sampedro, A; Mancheño, U; Morales-Kastresana, A; Serrano-Mendioroz, I; de Salamanca, R E; Benito, A; Fontanellas, A

    2015-11-01

    Helper-dependent adenoviral (HDA) vectors constitute excellent gene therapy tools for metabolic liver diseases. We have previously shown that an HDA vector encoding human porphobilinogen deaminase (PBGD) corrects acute intermittent porphyria mice. Now, six non-human primates were injected in the left hepatic lobe with the PBGD-encoding HDA vector to study levels and persistence of transgene expression. Intrahepatic administration of 5 × 10(12) viral particles kg(-1) (10(10) infective units kg(-1)) of HDA only resulted in transient (≈14 weeks) transgene expression in one out of three individuals. In contrast, a more prolonged 90-day immunosuppressive regimen (tacrolimus, mycophenolate, rituximab and steroids) extended meaningful transgene expression for over 76 weeks in two out of two cases. Transgene expression under immunosuppression (IS) reached maximum levels 6 weeks after HDA administration and gradually declined reaching a stable plateau within the therapeutic range for acute porphyria. The non-injected liver lobes also expressed the transgene because of vector circulation. IS controlled anticapsid T-cell responses and decreased the induction of neutralizing antibodies. Re-administration of HDA-hPBGD at week +78 achieved therapeutically meaningful transgene expression only in those animals receiving IS again at the time of this second vector exposure. Overall, immunity against adenoviral capsids poses serious hurdles for long-term HDA-mediated liver transduction, which can be partially circumvented by pharmacological IS. PMID:26125605

  8. Human mesenchymal stem cells creating an immunosuppressive environment and promote breast cancer in mice.

    PubMed

    Ljujic, Biljana; Milovanovic, Marija; Volarevic, Vladislav; Murray, Bridgid; Bugarski, Diana; Przyborski, Stefan; Arsenijevic, Nebojsa; Lukic, Miodrag L; Stojkovic, Miodrag

    2013-01-01

    Human mesenchymal stem cells (hMSC) can home to tumor sites and promote tumor growth. The effects of hMSC on tumor growth are controversial and involvement of hMSC in tumor immunology has not been adequately addressed. Therefore, we investigated whether injection of hMSC affects tumor appearance, growth and metastasis, and anti-tumor immunity in an experimental animal model of metastatic breast cancer. Injection of hMSC in BALB/c mice bearing mammary carcinoma promoted tumor growth and metastasis, which was accompanied by lower cytotoxic activity of splenocytes, NK cells and CD8⁺ T cells in vitro. Tumor-bearing mice that received hMSC had significantly lower percentages of CD3⁺NKp46⁺ NKT-like, higher percentages of CD4⁺Foxp3⁺ T cells, increased serum levels of Th2 and decreased serum levels of Th1 cytokines, and significantly higher number of CD4⁺ cells expressing IL-10. These results demonstrate that immunosuppressive environment created by hMSC promoted breast tumor growth and metastasis in mice. PMID:23892388

  9. Human mesenchymal stem cells creating an immunosuppressive environment and promote breast cancer in mice

    PubMed Central

    Ljujic, Biljana; Milovanovic, Marija; Volarevic, Vladislav; Murray, Bridgid; Bugarski, Diana; Przyborski, Stefan; Arsenijevic, Nebojsa; Lukic, Miodrag L.; Stojkovic, Miodrag

    2013-01-01

    Human mesenchymal stem cells (hMSC) can home to tumor sites and promote tumor growth. The effects of hMSC on tumor growth are controversial and involvement of hMSC in tumor immunology has not been adequately addressed. Therefore, we investigated whether injection of hMSC affects tumor appearance, growth and metastasis, and anti-tumor immunity in an experimental animal model of metastatic breast cancer. Injection of hMSC in BALB/c mice bearing mammary carcinoma promoted tumor growth and metastasis, which was accompanied by lower cytotoxic activity of splenocytes, NK cells and CD8+ T cells in vitro. Tumor-bearing mice that received hMSC had significantly lower percentages of CD3+NKp46+ NKT-like, higher percentages of CD4+Foxp3+ T cells, increased serum levels of Th2 and decreased serum levels of Th1 cytokines, and significantly higher number of CD4+ cells expressing IL-10. These results demonstrate that immunosuppressive environment created by hMSC promoted breast tumor growth and metastasis in mice. PMID:23892388

  10. Bone marrow transplantation versus immunosuppressive therapy in patients with acquired severe aplastic anemia.

    PubMed

    Bacigalupo, Andrea; Giammarco, Sabrina; Sica, Simona

    2016-08-01

    Standard front-line treatment for acquired aplastic anemia (AA) for patients is either immunosuppressive therapy (IST) or bone marrow transplantation (BMT), usually from an HLA identical sibling. Whereas long-term survival is comparable with either treatment, important differences remain: IST patients may have incomplete or no recovery, are exposed to late clonal disorders and relapse of the original disease. Transplantation is a curative treatment, but patients are exposed to transplant-related complications both acute and chronic, such as chronic graft versus host disease (cGvHD). In the year 2000, a study by the European Group for Blood and Marrow Transplantation (EBMT), looked at failure free survival (FFS), in patients receiving first-line BMT from an HLA identical sibling, or the first-line IST. Young patients with low neutrophil counts benefited of the first-line BMT; the opposite was true for older patients with higher neutrophil counts; and a third intermediate group of patients had comparable survival irrespective of the first-line therapy. We have now studied a more recent cohort of patients to assess whether things have changed over the years. We have found similar results, although overall survival has improved, as a consequence of changes in the IST and BMT protocols. PMID:27278666