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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 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

  7. 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

  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 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

  18. 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

  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. 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

  7. 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

  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. 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.

  1. 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

  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. 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

  5. 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

  6. 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

  7. 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

  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. 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

  11. 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

  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. 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.

  17. 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

  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. 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

  3. 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

  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. 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

  9. 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.

  10. 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.

  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. 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

  18. 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

  19. 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

  20. 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

  1. 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

  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. 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.

  12. 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

  13. [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

  14. 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

  15. 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.

  16. 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

  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. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  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. 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

  16. 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

  17. 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

  18. 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

  19. [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

  20. 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

  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

    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. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  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

    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

  14. 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

  15. 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.

  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. 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.

  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. 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.

  20. 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.

  1. [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

  2. 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

  3. 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

  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. 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

  6. 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

  7. 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

  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. 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

  11. 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

  12. 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

  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. 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).

  17. 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.

  18. 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.

  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. 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

  1. 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

  2. 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

  3. 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

  4. 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.

  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. Effect of Increased Immunosuppression on Developmental Outcome of Opsoclonus Myoclonus Syndrome (OMS).

    PubMed

    Mitchell, Wendy G; Wooten, Amelia A; O'Neil, Sharon H; Rodriguez, Jenny G; Cruz, Rosa E; Wittern, Rachael

    2015-07-01

    Opsoclonus myoclonus syndrome (OMS) produces long-term cognitive, behavioral, and motor deficits. Objective was to see if more aggressive treatment improved outcome. Assessment included opsoclonus myoclonus syndrome rating, developmental/cognitive and motor assessment, and adaptive behavior. Fourteen subjects completed testing. Nine had neuroblastoma. Onset was at 10 to 35 months; onset to diagnosis: 2 days to 14 months, and onset to first treatment: 5 days to 15 months. Initial treatment was corticotropin (12), oral steroids (3), plus intravenous immunoglobulin in all. Ten received rituximab, 5 cyclophosphamide. Age at testing ranged from 2.5 to 10.3 years. Adaptive Behavior Score (11 subjects), mean 93.5; estimated Intelligence Quotient/Developmental Quotient mean 93.5; Motor: mean 92.8. Residual opsoclonus myoclonus syndrome symptoms at the time of the evaluation were generally minor; opsoclonus myoclonus syndrome scores ranged from 0 to 6. Comparison to previously reported opsoclonus myoclonus syndrome subjects showed improved outcomes: Adaptive behavior, cognitive and motor scores were significantly higher (P < .001) in new subjects. Outcomes have improved with more aggressive immunosuppression, with most opsoclonus myoclonus syndrome survivors now functioning at or near normal. PMID:25342308

  9. 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

  10. 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

  11. 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

  12. Data-fusion receiver

    DOEpatents

    Gabelmann, Jeffrey M.; Kattner, J. Stephen; Houston, Robert A.

    2006-12-19

    This invention is an ultra-low frequency electromagnetic telemetry receiver which fuses multiple input receive sources to synthesize a decodable message packet from a noise corrupted telemetry message string. Each block of telemetry data to be sent to the surface receiver from a borehole tool is digitally encoded into a data packet prior to transmission. The data packet is modulated onto the ULF EM carrier wave and transmitted from the borehole to the surface and then are simultaneously detected by multiple receive sensors disbursed within the rig environment. The receive sensors include, but are not limited to, electric field and magnetic field sensors. The spacing of the surface receive elements is such that noise generators are unequally coupled to each receive element due to proximity and/or noise generator type (i.e. electric or magnetic field generators). The receiver utilizes a suite of decision metrics to reconstruct the original, non noise-corrupted data packet from the observation matrix via the estimation of individual data frames. The receiver will continue this estimation process until: 1) the message validates, or 2) a preset "confidence threshold" is reached whereby frames within the observation matrix are no longer "trusted".

  13. Hybrid receiver study

    NASA Technical Reports Server (NTRS)

    Stone, M. S.; Mcadam, P. L.; Saunders, O. W.

    1977-01-01

    The results are presented of a 4 month study to design a hybrid analog/digital receiver for outer planet mission probe communication links. The scope of this study includes functional design of the receiver; comparisons between analog and digital processing; hardware tradeoffs for key components including frequency generators, A/D converters, and digital processors; development and simulation of the processing algorithms for acquisition, tracking, and demodulation; and detailed design of the receiver in order to determine its size, weight, power, reliability, and radiation hardness. In addition, an evaluation was made of the receiver's capabilities to perform accurate measurement of signal strength and frequency for radio science missions.

  14. Optical superheterodyne receiver.

    NASA Technical Reports Server (NTRS)

    Duval, K.; Lang, K.; Lucy, R. F.; Peters, C. J.

    1967-01-01

    Optical communication experiments to compare coherent and noncoherent optical detection fading characteristics in different weather conditions, using laser transmitter and optical superheterodyne receiver

  15. Potency of Massoia Bark in Combating Immunosuppressed-related Infection

    PubMed Central

    Hertiani, Triana; Pratiwi, Sylvia Utami Tunjung; Yuswanto, Agustinus; Permanasari, Prisci

    2016-01-01

    Background: As part of our search for new potential natural resources to eradicate infection, we have revealed the prominent potency of massoia bark (Massoia aromatica Becc, Lauraceae) in combating immunosuppressed-related infection. Materials and Methods: The extract was prepared by macerating the pulverized dried bark in ethanol 95%, followed by solvent evaporation. The oil was extracted from the dried bark by steam-hydrodistillation of which preparative thin-layer chromatography was performed on the oil to isolate the active constituent, C-10 massoia lactone (ML). Anti-biofilm assay against Candida albicans was conducted on polystyrene 96 wells microtiter plates, followed by a confocal laser scanning microscope observation to get three-dimensional profiles of the affected biofilms. Effects on the hyphae development inoculated on RPMI-1640 agar plates were observed for 7 days. Influences of samples on mice macrophage phagocytosis were examined by an in vitro technique. Samples concentration tested were in the range of 2.0–0.0625 mg/mL and done in triplicate. Results: Massoia bark extracts (oil and solid phase) and ML exhibited promising activities as anti-biofilm against C. albicans at IC50 0.074% v/v, 271 μg/mL and 0.026 μg/mL, respectively. The ML did not inhibit the hyphae development at the concentration tested; however, the extracts showed inhibition at 62.5 μg/mL. Macrophage phagocytosis stimulation was correlated to the ML content. Conclusion: Massoia bark is potential to be developed as anti-infective in immunosuppressed condition of which the C10 ML (C10H16O2) plays a major role in exerting activity. SUMMARY Massoia bark extracts (oily and solid phase) and C-10 Massoia lactone exhibited promising activities as antibiofilm against Candida albicans at IC50 are 0.074 %v/v, 271 μg/mL and 0.026 μg/mL respectively. The major constituent, C-10 Massoia lactone (C10H16O2) plays major role in exerting anticandida activity and potentially acts as an

  16. High-dose immunosuppression and hematopoietic stem cell transplantation in autoimmune disease: clinical review.

    PubMed

    Openshaw, Harry; Nash, Richard A; McSweeney, Peter A

    2002-01-01

    Since 1996, a number of investigators have carried out phase I-II studies of high-dose immunosuppression with autologous hematopoietic stem cell transplantation (HSCT) in autoimmune diseases. Most of this activity has been in studies of multiple sclerosis (MS), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and juvenile idiopathic arthritis (JIA). Supported by animal models of antigen-induced autoimmunity, the rationale of HSCT is to time-shift the clinical autoimmunity to an earlier period, restoring self-tolerance. Even with the considerable experience of more than 200 transplantations since 1996, it is difficult to judge the optimal approach. This difficulty is in part because of the multiplicity of centers and protocols and the variability in patient eligibility and assessment, the extent of T-cell depletion, and the intensity of the preparatory regimens used. Other than that found in RA, treatment-related mortality has been higher than expected: 17% in SSc (with an additional 10% mortality from progressive disease), 13% in SLE, 13% in JIA, and 8% in MS. Protocol changes to improve safety have been instituted. These changes include the avoidance of high-dose rabbit antithymocyte serum in patients who received T-cell-depleted grafts, use of corticosteroids with granulocyte colony-stimulating factor during stem cell mobilization and as prophylaxis for the engraftment syndrome in MS, lung radiation shielding in SSc, and multiple precautions against the macrophage activation syndrome in JIA. Responses to primary and secondary endpoints have been seen, and there is a consensus among investigators and regulatory bodies that the time has come for randomized phase II-III studies. Each disease presents distinct difficulties: in MS, restriction of eligibility to patients with active inflammatory disease; in SSc, formulation of cardiopulmonary eligibility criteria to decrease risk; in SLE, judgment of whether HSCT adds any

  17. Right to Receive.

    ERIC Educational Resources Information Center

    Oborn, Richard

    The concept of a United States citizen's right to receive information is acquiring increased judicial recognition. This report traces the evolution of that right from its philosophical basis in the United States Consitution, through its interpretation by the Supreme Court, up to the current concern that the public receive certain economic…

  18. Immunosuppressive therapy in allograft transplantation: from novel insights and strategies to tolerance and challenges

    PubMed Central

    Ebrahimi, Ammar; Hosseini, Seyed Ahmad

    2014-01-01

    Immunosuppression therapy is the key to successful post-transplantation outcomes. The need for ideal immunosuppression became durable maintenance of long-term graft survival. In spite of current immunosuppressive therapy regimens advances, surgical procedures, and preservation methods, organ transplantation is associated with a long-term poor survival and significant mortality. This has led to an increased interest to optimize outcomes while minimizing associated toxicity by using alternative methods for maintenance immunosuppression, organ rejection treatment, and monitoring of immunosuppression. T regulatory (Treg) cells, which have immunosuppressive functions and cytokine profiles, have been studied during the last decades. Treg cells are able to inhibit the development of allergen-specific cell responses and consequently play a key role in a healthy immune response to allergens. Mature dendritic cells (DCs) play a crucial role in the differentiation of Tregs, which are known to regulate allergic inflammatory responses. Advance in long-standing allograft outcomes may depend on new drugs with novel mechanisms of action with minimal toxicity. Newer treatment techniques have been developed, including using novel stem cell-based therapies such as mesenchymal stem cells, phagosomes and exosomes. Immunoisolation techniques and salvage therapies, including photopheresis and total lymphoid irradiation have emerged as alternative therapeutic choices. The present review evaluates the recent clinical advances in immunosuppressive therapies for organ transplantation. PMID:26155155

  19. Immunosuppressive treatment for pure membranous lupus nephropathy in a Hispanic population.

    PubMed

    Mejía-Vilet, Juan Manuel; Córdova-Sánchez, Bertha M; Uribe-Uribe, Norma O; Correa-Rotter, Ricardo

    2016-09-01

    Optimal treatment for pure membranous lupus nephritis (MLN) remains unknown. The aim of this study was to evaluate the response to immunosuppressive treatment of Hispanics with pure MLN. This was a retrospective cohort analysis from a tertiary care center. Pure MLN patients were segregated into three groups according to the received induction treatment. All patients received adjunctive steroids. Outcomes included complete remission (CR), partial remission (PR), flare incidence, adverse events, and renal and patient survival. All outcomes were analyzed by Cox regression analysis. A total of 60 patients diagnosed with pure MLN between 2004 and 2014 were segregated into mycophenolate mofetil (MMF) (n = 18), intravenous cyclophosphamide (IVC) (n = 16), or azathioprine (AZA) (n = 26) groups. Complete remission rates at 6, 12, and 24 months were 33.3, 52.9, and 76.4 %, respectively, for MMF; 26.9, 42.3, and 54.6 %, respectively, for AZA; and 6.2, 14.8, and 26.9 %, respectively, for IVC. Based on Cox-adjusted analysis, treatment with MMF was associated with higher CR rates (hazard ratio (HR) 4.43, 1.19-16.4, p = 0.026) compared to IVC. There were no differences in CR rates between MMF and AZA groups. Patients treated with adjunctive antimalarial drugs were more likely to achieve CR (HR 2.46, 1.08-5.64, p = 0.032) and had a non-significant trend to lower incidence of thrombotic events (odds ratio (OR) 0.10, 0.010-1.14, p = 0.064). There were no differences in adverse events, renal flares, and renal or patient survival between groups. MMF might be superior to IVC as induction treatment for pure MLN in Hispanics, while AZA might remain as a valid alternative for treatment. Adjunctive treatment with an antimalarial drug may enhance renal response to therapy. PMID:27475791

  20. Galactosaminogalactan, a New Immunosuppressive Polysaccharide of Aspergillus fumigatus

    PubMed Central

    Simenel, Catherine; Coddeville, Bernadette; van Vliet, Sandra J.; van Kooyk, Yvette; Bozza, Silvia; Moretti, Silvia; Schwarz, Flavio; Trichot, Coline; Aebi, Markus; Delepierre, Muriel; Elbim, Carole; Romani, Luigina; Latgé, Jean-Paul

    2011-01-01

    A new polysaccharide secreted by the human opportunistic fungal pathogen Aspergillus fumigatus has been characterized. Carbohydrate analysis using specific chemical degradations, mass spectrometry, 1H and 13C nuclear magnetic resonance showed that this polysaccharide is a linear heterogeneous galactosaminogalactan composed of α1-4 linked galactose and α1-4 linked N-acetylgalactosamine residues where both monosacharides are randomly distributed and where the percentage of galactose per chain varied from 15 to 60%. This polysaccharide is antigenic and is recognized by a majority of the human population irrespectively of the occurrence of an Aspergillus infection. GalNAc oligosaccharides are an essential epitope of the galactosaminogalactan that explains the universal antibody reaction due to cross reactivity with other antigenic molecules containing GalNAc stretches such as the N-glycans of Campylobacter jejuni. The galactosaminogalactan has no protective effect during Aspergillus infections. Most importantly, the polysaccharide promotes fungal development in immunocompetent mice due to its immunosuppressive activity associated with disminished neutrophil infiltrates. PMID:22102815

  1. Immunosuppression in Solid-Organ Transplantation: Essentials and Practical Tips.

    PubMed

    Jasiak, Natalia M; Park, Jeong M

    2016-01-01

    A multidisciplinary team approach is essential for successful management of patients with solid-organ transplant. Transplant nursing encompasses care and support of transplant recipients as well as caregivers and organ donors through all phases of transplantation, from pretransplant evaluation to posttransplant recovery and maintenance. The field of solid-organ transplantation has advanced rapidly, and new treatments continue to emerge. Nurses who are responsible for the care of transplant recipients should have a knowledge base in transplant immunology and pharmacology. This review discusses mechanism of action, indication, side effects, and drug interactions of commonly used immunosuppressive medications in solid-organ transplantation. Nonoral routes of drug administration, therapeutic drug monitoring, and patient monitoring strategies are also included as practical tips for bedside nurses who are responsible for delivery of direct patient care and education of patients and their caregivers. This review focuses on the following medications: antithymocyte globulins, basiliximab, alemtuzumab, corticosteroids, tacrolimus, cyclosporine, azathioprine, mycophenolate mofetil/mycophenolate sodium, sirolimus, everolimus, belatacept, intravenous immunoglobulin, and rituximab. PMID:27254639

  2. Immunosuppressive plasma cells impede T cell-dependent immunogenic chemotherapy

    PubMed Central

    Shalapour, Shabnam; Font-Burgada, Joan; Di Caro, Giuseppe; Zhong, Zhenyu; Sanchez-Lopez, Elsa; Dhar, Debanjan; Willimsky, Gerald; Ammirante, Massimo; Strasner, Amy; Hansel, Donna E.; Jamieson, Christina; Kane, Christopher J.; Klatte, Tobias; Birner, Peter; Kenner, Lukas; Karin, Michael

    2015-01-01

    Cancer-associated genetic alterations induce expression of tumor antigens which can activate CD8+ cytotoxic T cells (CTL), but the microenvironment of established tumors promotes immune tolerance through poorly understood mechanisms1,2. Recently developed therapeutics that overcome tolerogenic mechanisms activate tumor-directed CTL and are effective in some human cancers1. Immune mechanisms also affect treatment outcome and certain chemotherapeutic drugs stimulate cancer-specific immune responses by inducing immunogenic cell death (ICD) and other effector mechanisms3,4. Our previous studies revealed that B lymphocytes recruited by CXCL13 into prostate cancer (PC) promote castrate-resistant PC (CRPC) by producing lymphotoxin (LT) which activates an IKKα-Bmi1 module in PC stem cells5,6. Since CRPC is refractory to most therapies, we examined B cell involvement in acquisition of chemotherapy resistance. We focused this study on oxaliplatin, an immunogenic chemotherapeutic3,4 that is effective in aggressive PC7. We found that B cells modulate the response to low dose oxaliplatin, which by inducing ICD promotes tumor-directed CTL activation. Three different mouse PC models were refractory to oxaliplatin unless genetically or pharmacologically depleted of B cells. The critical immunosuppressive B cells are plasmocytes that express IgA, IL-10 and PD-L1, whose appearance depends on TGFβ-receptor (TGFβR) signaling. Elimination of these cells, which also infiltrate human therapy-resistant PC, allows CTL-dependent eradication of oxaliplatin-treated tumors. PMID:25924065

  3. Contaminant-induced immunosuppression and mass mortalities among harbor seals.

    PubMed

    Van Loveren, H; Ross, P S; Osterhaus, A D; Vos, J G

    2000-03-15

    Virus-associated mass mortalities among seals inhabiting northwestern Europe have generated an interest in immunotoxicology in this species. A morbillivirus has been isolated from victims, but a contribution of immunotoxic contaminants to the severity of the outbreaks could not be ruled out. Fish-eating seals occupy high trophic levels in the aquatic food chain, and accumulate high levels of contaminants including polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs). Such chemicals have been found to be immunotoxic at low doses in studies of laboratory animals. We carried out an immunotoxicological study, in which captive harbor seals (Phoca vitulina) were fed herring from either relatively uncontaminated sites of the Atlantic Ocean, or from the highly contaminated Baltic Sea. In this report we summarize the contaminant-related immunosuppression observed in the captive group of seals fed herring from the Baltic Sea. In addition, we describe two parallel studies, in which laboratory rats are exposed as adults or perinatally to the contaminants in the Baltic Sea herring, exhibiting immunotoxicity. On the basis of these studies we conclude that complex mixtures of environmental contaminants including PCBs, PCDFs, and PCDDs may represent a real immunotoxic risk to free-ranging seals. PMID:10720747

  4. Chemical synthesis and immunosuppressive activity of dipalmitoyl phosphatidylinositol hexamannoside.

    PubMed

    Ainge, Gary D; Compton, Benjamin J; Hayman, Colin M; Martin, William John; Toms, Steven M; Larsen, David S; Harper, Jacquie L; Painter, Gavin F

    2011-06-17

    Phosphatidylinositol mannosides (PIMs) isolated from mycobacteria have been identified as an important class of phosphoglycolipids with significant immune-modulating properties. We present here the synthesis of dipalmitoyl phosphatidylinositol hexamannoside (PIM(6)) 1 and the first reported functional biology of a synthetic PIM(6). Key steps in the synthetic protocol included the selective glycosylation of an inositol 2,6-diol with a suitably protected mannosyl donor and construction of the glycan core utilizing a [3 + 4] thio-glycosylation strategy. The target 1 was purified by reverse phase chromatography and characterized by standard spectroscopic methods, HPLC, and chemical modification by deacylation to dPIM(6). The (1)H NMR spectrum of synthetic dPIM(6) obtained from 1 matched that of dPIM(6) obtained from nature. PIM(6) (1) exhibited dendritic cell-dependent suppression of CD8(+) T cell expansion in a human mixed lymphocyte reaction consistent with the well established immunosuppressive activity of whole mycobacteria. PMID:21574597

  5. Challenging immunosuppression treatment in lung transplant recipients with kidney failure.

    PubMed

    Högerle, Benjamin A; Kohli, Neeraj; Habibi-Parker, Kirsty; Lyster, Haifa; Reed, Anna; Carby, Martin; Zeriouh, Mohamed; Weymann, Alexander; Simon, André R; Sabashnikov, Anton; Popov, Aron-Frederik; Soresi, Simona

    2016-03-01

    Kidney failure after lung transplantation is a risk factor for chronic kidney disease. Calcineurin inhibitors are immunosuppressants which play a major role in terms of postoperative kidney failure after lung transplantation. We report our preliminary experience with the anti-interleukin-2 monoclonal antibody Basiliximab utilized as a "calcineurin inhibitor-free window" in the setting of early postoperative kidney failure after lung transplantation. Between 2012 and 2015 nine lung transplant patients who developed kidney failure for more than 14 days were included. Basiliximab was administrated in three doses (Day 0, 4, and 20) whilst Tacrolimus was discontinued or reduced to maintain a serum level between 2 and 4 ng/mL. Baseline glomerular filtration rate pre transplant was normal for all patients. Seven patients completely recovered from kidney failure (67%, mean eGFR pre and post Basiliximab: 42.3 mL/min/1.73 m(2) and 69 mL/min/1.73 m(2)) and were switched back on Tacrolimus. Only one of these patients still needs ongoing renal replacement therapy. Two patients showed no recovery from kidney failure and did not survive. Basiliximab might be a safe and feasible therapeutical option in patients which are affected by calcineurin inhibitor-related kidney failure in the early post lung transplant period. Further studies are necessary to confirm our preliminary results. PMID:26892232

  6. The use of novel diagnostics to individualize immunosuppression following transplantation.

    PubMed

    Schlickeiser, Stephan; Boës, David; Streitz, Mathias; Sawitzki, Birgit

    2015-08-01

    Despite major improvements in short-term survival of organ allografts, long-term graft survival has not changed significantly. It is also known that toxic side effects of current immunosuppressive drugs (IS) especially calcineurin inhibitors (CNI) contribute to the unsatisfactory graft and patient survival following transplantation. Thus, clinicians strive to reduce or wean IS in potentially eligible patients. Research in the last 10 years has focussed on identification of biomarkers suitable for patient stratification in minimization or weaning trials. Most of the described biomarkers have been run retrospectively on samples collected within single-centre trials. Thus, often their performance has not been validated in other potentially multicentre clinical trials. Ultimately, the utility of biomarkers to identify potential weaning candidates should be investigated in large randomized prospective trials. In particular, for testing in such trials, we need more information about the accuracy, reproducibility, stability and limitations of the described biomarkers. Also, data repositories summarizing crucial information on biomarker performance in age- and gender-matched healthy individuals of different ethnicity are missing. This together with improved bioinformatics tools might help in developing better scores for patient stratification. Here, we will summarize the current results, knowledge and limitations on biomarkers for drug minimization or weaning trials. PMID:25611562

  7. Immunosuppression Related to Collagen-Vascular Disease or Its Treatment

    PubMed Central

    Hamilton, Carol Dukes

    2005-01-01

    Collagen-vascular diseases are associated with immune dysregulation and inflammation, leading to tissue destruction or compromise. Immunosuppression is more commonly associated with the drugs used to treat these disorders than with the diseases themselves. The newest agents being used to treat collagen-vascular diseases are the tumor necrosis factor (TNF)-α inhibitors. U.S. Food and Drug Administration–approved TNF-α inhibitors have differing effects on the immune system, reflecting their potency and mechanisms of action. They are particularly effective in breaking down granulomatous inflammation, which makes them effective treatment for sarcoidosis and Wegener's granulomatosis. This same property makes them likely to break down the host defense mechanism that normally contains pathogens such as mycobacteria and fungi in a dormant state, namely the physical and immunologic barrier formed by granulomas in the lung and elsewhere. The most common infection reported with the TNF-α inhibitors has been tuberculosis, which may manifest as pulmonary and/or extrapulmonary disease, with the latter being more common and severe than usual. Histoplasma capsulatum, Aspergillus, Cryptococcus neoformans, and Listeria monocytogenes have also been described in a number of cases, and their frequency is discussed. PMID:16322600

  8. Early-Life Exposure to Clostridium leptum Causes Pulmonary Immunosuppression

    PubMed Central

    Huang, Fei; Qiao, Hong-mei; Yin, Jia-ning; Gao, Yang; Ju, Yang-hua; Li, Ya-nan

    2015-01-01

    Introduction Low Clostridium leptum levels are a risk factor for the development of asthma. C. leptum deficiency exacerbates asthma; however, the impact of early-life C. leptum exposure on cesarean-delivered mice remains unclear. This study is to determine the effects of early-life C. leptum exposure on asthma development in infant mice. Methods We exposed infant mice to C. leptum (fed-CL) and then induced asthma using the allergen ovalbumin (OVA). Results Fed-CL increased regulatory T (Treg) cells in cesarean-delivered mice compared with vaginally delivered mice. Compared with OVA-exposed mice, mice exposed to C. leptum + OVA did not develop the typical asthma phenotype, which includes airway hyper-responsiveness, cell infiltration, and T helper cell subset (Th1, Th2, Th9, Th17) inflammation. Early-life C. leptum exposure induced an immunosuppressive environment in the lung concurrent with increased Treg cells, resulting in the inhibition of Th1, Th2, Th9, and Th17 cell responses. Conclusion These findings demonstrate a mechanism whereby C. leptum exposure modulates adaptive immunity and leads to failure to develop asthma upon OVA sensitization later in life. PMID:26565810

  9. Steroid- and calcineurin inhibitor free immunosuppression in kidney transplantation: state of the art and future developments.

    PubMed

    Giessing, Markus; Fuller, Tom Florian; Tuellmann, Max; Slowinski, Torsten; Budde, Klemens; Liefeldt, Lutz

    2007-06-01

    Owing to the increasing disparity of organ demand and organ supply the search for optimal immunosuppressive strategies has become a central issue in kidney transplantation (KTX). In the focus today are modifications of the use of calcineurin-inhibitors (CNIs, Cyclosporine A/Tacrolimus) and steroids, as they are nephrotoxic and promote cardiovascular risk factors like arterial hypertension, hyperlipidemia and diabetes mellitus. These modifications can either be withdrawal or avoidance of these substances in combination with new and/or established immunosuppressants. Because about half of all KTXs are performed by or with the help of urologists' knowledge of modern immunosuppressive regimens is crucial also for urologists. We performed a literature research (PubMed, DIMDI, medline) for CNI- and steroid-sparing protocols and studies to elucidate their influence on graft-function and graft- and patient-survival. New substances and actual studies were also evaluated. Several published reports on CNI- and steroid-sparing protocols after KTX exist, including withdrawal, reduction or avoidance. The time of reduction seems to be crucial: an initially increased immune response should be counterbalanced by an initially intensified immunosuppression. Therefore, late steroid withdrawal seems to be safer than early withdrawal especially in Cyclosporine-based immunosuppression. Steroid avoidance also seems feasible on a CNI based regimen, especially in context with induction therapy. Withdrawal or avoidance of CNIs seems feasible with mycophenolate acid and/or induction therapy with IL 2-receptor antibodies as co-immunosuppressants. This is of interest in grafts with deteriorating function or from donors with extended criteria. Also, CNI- and steroid-free immunosuppression can be successfully performed with new immunosuppressants but results are yet premature. CNI- and/or steroid reduction, withdrawal or even avoidance is feasible. As long-term graft function is the goal of KTX

  10. Overcoming the force and power of immunity: a history of immunosuppression in kidney transplantation.

    PubMed

    Patel, Paul S

    2006-01-01

    Immunosuppression for organ transplantation is a modern concept. The earliest reports of organ replacement have their roots in mythology and human fantasy. The primacy of overcoming the immunologic barrier for successful transplantation of organs has been influenced by geopolitical conflict, unorthodox ideas, application of knowledge across medical disciplines, and serendipity. The earliest form of chemical immunosuppression had its origin in chemical gas in warfare. Further developments in immunology, cancer therapy and biochemistry helped shape the intellectual basis for the introduction of chemical immunosuppression. PMID:16874728

  11. Bordetella Bronchiseptica in the Immunosuppressed Population – A Case Series and Review

    PubMed Central

    Yacoub, Abraham T.; Katayama, Mitsuya; Tran, JoAnn; Zadikany, Ronit; Kandula, Manasa; Greene, John

    2014-01-01

    Organisms that are not known to cause serious infection in the immunocompetent population can, in fact, cause devastating illness in immunosuppressed neutropenic populations especially those who are undergoing hematopoietic stem cell transplantation (HSCT), and solid organ transplantation or a history of malignancy. One organism of interest isolated from immunosuppressed patients at our institution was Bordetella bronchiseptica. It is known to cause respiratory tract disease in the animal population which includes dogs, cats, and rabbits. This organism rarely causes serious infection in the immunocompetent population. However; in immunosuppressed patients, it can cause serious pulmonary disease. We present three cases of B. bronchiseptica pneumonia in patients with a history of malignancy. PMID:24804004

  12. Immunosuppressive Treatment for Retinal Degeneration in Juvenile Neuronal Ceroid Lipofuscinosis (Juvenile Batten Disease).

    PubMed

    Drack, Arlene V; Mullins, Robert F; Pfeifer, Wanda L; Augustine, Erika F; Stasheff, Steven F; Hong, Sandy D

    2015-01-01

    Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) presents with progressive vision loss at 4-7 years of age. Blindness results within 2 years, followed by inexorable neurologic decline and death. There is no treatment or cure. Neuroinflammation is postulated to play a role in the neurodegeneration. The JNCL mouse model demonstrated decreased neuroinflammation and improved motor skills with immunosuppression. Based on this work, a short-term human clinical trial of mycophenolate mofetil has begun, however longer term effects, and whether immunosuppression modulates vision loss, have not been studied. We report a JNCL patient treated with immunosuppressive therapy in whom visual function was comprehensively characterized over 2 years. PMID:24547931

  13. Long-term genotoxic effects of immunosuppressive drugs on lymphocytes of kidney transplant recipients.

    PubMed

    Lizotti Cilião, Heloísa; Batista de Oliveira Camargo-Godoy, Rossana; Mazzaron Barcelos, Gustavo Rafael; Zanuto, Amanda; Daher Alvares Delfino, Vinicius; de Syllos Cólus, Ilce Mara

    2016-08-01

    Immunosuppressive therapy can prevent rejection after organ transplantation. However, increased cancer risk is a serious complication among patients undergoing such therapy. We have evaluated whether prolonged use of immunosuppressive drugs is genotoxic. DNA instability was assessed, using the comet and micronucleus assays, in blood lymphocytes of 76 kidney transplant patients. DNA damage detected by the comet assay increased with time after transplantation. The estimated glomerular filtration rate of the patients did not influence the incidence of DNA damage. No association between micronucleated mononucleated cells and time elapsed after transplantation was observed. Our results suggest that prolonged use of immunosuppressive drugs in kidney transplant patients can induce genetic instability. PMID:27476335

  14. [Renal transplantation without maintenance immunosuppression. Identical twins and kidney transplantation following a successful bone marrow graft].

    PubMed

    Hadi, Riad Abdel; Thomé, Gustavo Gomes; Ribeiro, Adriana Reginato; Manfro, Roberto Ceratti

    2015-01-01

    Renal transplantation without maintenance immunosuppression has been sporadically reported in the literature. The cases include non-adherent patients who discontinued their immunosuppressive medications, transplantation between identical twins, kidney transplantation after a successful bone marrow graft from the same donor and simultaneous bone marrow and kidney transplantation for the treatment of multiple myeloma with associated renal failure. There are also ongoing clinical trials designed to induce donor specific transplant tolerance with infusion of hematopoietic cells from the same kidney donor. Here we describe two cases of renal transplantation without immunosuppression as examples of situations described above. PMID:26154652

  15. Multilevel Correlates of Non-Adherence in Kidney Transplant Patients Benefitting from Full Cost Coverage for Immunosuppressives: A Cross-Sectional Study

    PubMed Central

    Marsicano, Elisa Oliveira; Fernandes, Neimar Silva; Colugnati, Fernando Antônio Basile; Fernandes, Natalia Maria Silva; De Geest, Sabina; Sanders-Pinheiro, Helady

    2015-01-01

    Background Adherence is the result of the interaction of the macro, meso, micro, and patient level factors. The macro level includes full coverage of immunosuppressive medications as is the case in Brazil. We studied the correlates of immunosuppressive non-adherence in post kidney transplant patients in the Brazilian health care system. Methods Using a cross-sectional design, adherence to immunosuppressives was assessed in a sample of 100 kidney transplant patients using a composite non-adherence score consisting of three methods (self-report [i.e., The Basel Adherence Scale for Assessment of Immunossupressives–BAASIS], collateral report, and immunosuppressive blood levels). Multilevel correlations of non-adherence were assessed (macro, meso, micro and patient level). Univariate and multivariate logistic regression was applied to assess the correlates of non-adherence. Results Our sample consisted primarily of male (65%), Caucasians (72%) with a mean age of 45.0 ± 13.5 years old, who received grafts from a living donor (89%), with a mean time after transplantation of 72.3 ± 44.4 months. Prevalence of non-adherence was 51%. Family income higher than five reference wages (21.6 vs. 4%; OR 6.46 [1.35–30.89], p = 0.009; patient level), and having access to private health insurance (35.3% vs. 18.4%; OR 2.42 [0.96–6.10], p = 0.04; meso level) were associated with non-adherence in univariate analysis. Only the higher family income variable was retained in the multiple logistic regression model (OR 5.0; IC: 1.01–25.14; p = 0.04). Conclusions Higher family income was the only factor that was associated with immunosuppressive non-adherence. In Brazil, lower income recipients benefit from better access to care and coverage of health care costs after transplantation. This is supposed to result in a better immunosuppressive adherence compared to high-income patients who have experienced these benefits continuously. PMID:26619070

  16. CALUTRON RECEIVER STRUCTURE

    DOEpatents

    Roush, J.L.

    1959-09-01

    A receiver is described for collecting isotopes in a calutron The receiver has several compartments, formed by a sertes of parallel metal plates and an open front. Each plate has flanges which space it from the other plates and a flexible extension pressing against a common supporting red to maintain the plate in assembled relation when all but the last rod is removed. The plates may be removed individualy from the front of the receiver, cleaned ard replaced without disturbing the alignment of the other plates.

  17. The 30-GHz monolithic receive module

    NASA Technical Reports Server (NTRS)

    Bauhahn, P.; Geddes, J.; Sokolov, V.; Contolatis, T.

    1988-01-01

    The fourth year progress is described on a program to develop a 27.5 to 30 GHz GaAs monolithic receive module for spaceborne-communication antenna feed array applications, and to deliver submodules for experimental evaluation. Program goals include an overall receive module noise figure of 5 dB, a 30 dB RF to IF gain with six levels of intermediate gain control, a five bit phase shifter, and a maximum power consumption of 250 mW. Submicron gate length single and dual gate FETs are described and applied in the development of monolithic gain control amplifiers and low noise amplifiers. A two-stage monolithic gain control amplifier based on ion implanted dual gate MESFETs was designed and fabricated. The gain control amplifier has a gain of 12 dB at 29 GHz with a gain control range of over 13 dB. A two-stage monolithic low noise amplifier based on ion implanted MESFETs which provides 7 dB gain with 6.2 dB noise figure at 29 GHz was also developed. An interconnected receive module containing LNA, gain control, and phase shifter submodules was built using the LNA and gain control ICs as well as a monolithic phase shifter developed previously under this program. The design, fabrication, and evaluation of this interconnected receiver is presented. Progress in the development of an RF/IF submodule containing a unique ion implanted diode mixer diode and a broadband balanced mixer monolithic IC with on-chip IF amplifier and the initial design of circuits for the RF portion of a two submodule receiver are also discussed.

  18. Ceramic Solar Receiver

    NASA Technical Reports Server (NTRS)

    Robertson, C., Jr.

    1984-01-01

    Solar receiver uses ceramic honeycomb matrix to absorb heat from Sun and transfer it to working fluid at temperatures of 1,095 degrees and 1,650 degrees C. Drives gas turbine engine or provides heat for industrial processes.

  19. Ultrasonic pulser-receiver

    SciTech Connect

    Taylor, Steven C.

    2006-09-12

    Ultrasonic pulser-receiver circuitry, for use with an ultrasonic transducer, the circuitry comprising a circuit board; ultrasonic pulser circuitry supported by the circuit board and configured to be coupled to an ultrasonic transducer and to cause the ultrasonic transducer to emit an ultrasonic output pulse; receiver circuitry supported by the circuit board, coupled to the pulser circuitry, including protection circuitry configured to protect against the ultrasonic pulse and including amplifier circuitry configured to amplify an echo, received back by the transducer, of the output pulse; and a connector configured to couple the ultrasonic transducer directly to the circuit board, to the pulser circuitry and receiver circuitry, wherein impedance mismatches that would result if the transducer was coupled to the circuit board via a cable can be avoided.

  20. Solar energy receiver

    DOEpatents

    Schwartz, Jacob

    1978-01-01

    An improved long-life design for solar energy receivers provides for greatly reduced thermally induced stress and permits the utilization of less expensive heat exchanger materials while maintaining receiver efficiencies in excess of 85% without undue expenditure of energy to circulate the working fluid. In one embodiment, the flow index for the receiver is first set as close as practical to a value such that the Graetz number yields the optimal heat transfer coefficient per unit of pumping energy, in this case, 6. The convective index for the receiver is then set as closely as practical to two times the flow index so as to obtain optimal efficiency per unit mass of material.

  1. Receiver Gain Modulation Circuit

    NASA Technical Reports Server (NTRS)

    Jones, Hollis; Racette, Paul; Walker, David; Gu, Dazhen

    2011-01-01

    A receiver gain modulation circuit (RGMC) was developed that modulates the power gain of the output of a radiometer receiver with a test signal. As the radiometer receiver switches between calibration noise references, the test signal is mixed with the calibrated noise and thus produces an ensemble set of measurements from which ensemble statistical analysis can be used to extract statistical information about the test signal. The RGMC is an enabling technology of the ensemble detector. As a key component for achieving ensemble detection and analysis, the RGMC has broad aeronautical and space applications. The RGMC can be used to test and develop new calibration algorithms, for example, to detect gain anomalies, and/or correct for slow drifts that affect climate-quality measurements over an accelerated time scale. A generalized approach to analyzing radiometer system designs yields a mathematical treatment of noise reference measurements in calibration algorithms. By treating the measurements from the different noise references as ensemble samples of the receiver state, i.e. receiver gain, a quantitative description of the non-stationary properties of the underlying receiver fluctuations can be derived. Excellent agreement has been obtained between model calculations and radiometric measurements. The mathematical formulation is equivalent to modulating the gain of a stable receiver with an externally generated signal and is the basis for ensemble detection and analysis (EDA). The concept of generating ensemble data sets using an ensemble detector is similar to the ensemble data sets generated as part of ensemble empirical mode decomposition (EEMD) with exception of a key distinguishing factor. EEMD adds noise to the signal under study whereas EDA mixes the signal with calibrated noise. It is mixing with calibrated noise that permits the measurement of temporal-functional variability of uncertainty in the underlying process. The RGMC permits the evaluation of EDA by

  2. Periodontitis treatment improves systemic lupus erythematosus response to immunosuppressive therapy.

    PubMed

    Fabbri, Cristiana; Fuller, Ricardo; Bonfá, Eloisa; Guedes, Lissiane K N; D'Alleva, Paulo Sergio R; Borba, Eduardo F

    2014-04-01

    Periodontal disease (POD) may affect rheumatic diseases severity, but there are no data regarding the effect of its treatment on disease activity in SLE patients under immunosuppressive therapy. Forty-nine consecutive SLE patients (SLEDAI ≥ 2) with POD and under corticosteroid and cyclophosphamide pulse therapy (IVCYC) were selected. Periodontal assessment included bleeding gingival index (BGI), probing depth (PD), and probing attachment level (PAL). At entry, POD was defined as BGI > 1 and patients were assigned to groups according to the availability of odontological intervention in TREATED (n = 32) and NOT TREATED (n = 17). SLEDAI and POD parameters were determined at entry and after 3 months. Age, female gender, and race were alike among TREATED and NOT TREATED (p > 0.05). Both groups had also comparable disease duration (10.7 ± 6.8 vs. 11.0 ± 6.6, p = 0.83), IVCYC number (5.8 ± 4.8 vs. 4.5 ± 4.8, p = 0.17), and SLEDAI (5.9 ± 4.2 vs. 6.3 ± 4.3, p = 0.73) as well as POD parameters [BGI (40.8 ± 31.0 vs. 40.7 ± 36.2 %, p = 0.89), PD (1.7 ± 1.8 vs. 1.5 ± 0.60 mm, p = 0.80), and PAL (2.5 ± 1.9 vs. 1.9 ± 1.1 mm, p = 0.18)]. At the end of the study, TREATED group had a significant improvement in SLEDAI (5.9 ± 4.2 vs. 3.4 ± 3.3, p = 0.04) with a paralleled reduction in BGI (40.8 ± 31.0 vs. 15.2 ± 17.2 %, p < 0.01), PD (1.7 ± 1.8 vs. 1.1 ± 0.3 mm, p < 0.01), and PAL (2.5 ± 1.9 vs. 1.7 ± 0.9 mm, p < 0.01). In contrast, SLEDAI (6.3 ± 4.3 vs. 6.0 ± 5.5, p = 0.40) and POD parameters [BGI (p = 0.33), PD (p = 0.91), and PAL (p = 0.39)] remained largely unchanged in NOT TREATED group. Periodontal disease treatment seems to have a beneficial effect in controlling disease activity in SLE patients under immunosuppressive therapy. Therefore, management of this modifiable risk factor is

  3. Severe gastrointestinal cytomegalovirus disease in two patients with renal vasculitis after immunosuppression.

    PubMed

    Lee, Kian-Guan; Teo, Su-Hooi; Lim, Cynthia; Loh, Alwin; Chidambaram, Viswanath; Choo, Jason

    2016-09-01

    Although the use of current immunosuppressive regimens has significantly improved the outcomes of autoimmune renal diseases, infectious complications remain an important clinical concern. Cytomegalovirus (CMV) infection has been shown to be one of the major causes of mortality in this group of patients. We report two cases of renal vasculitis (Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA)) that developed into severe gastrointestinal CMV disease and manifested with massive small bowel bleeding, resulting in an eventual fatal outcome for one of the patients. Risk factors, pathogenesis, role of immunosuppression in the development of CMV infection, and antiviral treatment are discussed in this review. These cases highlight the need for further research to evaluate the complex mechanisms between immunosuppression and CMV occurrence as well as the role of antiviral prophylaxis in high-risk patients undergoing immunosuppressive therapies.
. PMID:27443566

  4. Epigenetic regulation of immune cell functions during post-septic immunosuppression

    PubMed Central

    Cavassani, Karen A; Dou, Yali; Kunkel, Steven L

    2011-01-01

    Studies in humans and animal models indicate that profound immunosuppression is one of the chronic consequences of severe sepsis. This immune dysfunction encompasses deficiencies in activation of cells in both the myeloid and lymphoid cell lineages. As a result, survivors of severe sepsis are at risk of succumbing to infections perpetrated by opportunistic pathogens that are normally controlled by a fully functioning immune system. Recent studies have indicated that epigenetic mechanisms may be one driving force behind this immunosuppression, through suppression of proinflammatory gene production and subsequent immune cell activation, proliferation and effector function. A better understanding of epigenetics and post-septic immunosuppression can improve our diagnostic tools and may be an important potential source of novel molecular targets for new therapies. This review will discuss important pathways of immune cell activation affected by severe sepsis, and highlight pathways of epigenetic regulation that may be involved in post-septic immunosuppression. PMID:21048427

  5. Costimulation-Adhesion Blockade is Superior to Cyclosporine A and Prednisone Immunosuppressive Therapy for Preventing Rejection of Differentiated Human Embryonic Stem Cells Following Transplantation

    PubMed Central

    Huber, Bruno C.; Ransohoff, Julia D.; Ransohoff, Katherine J.; Riegler, Johannes; Ebert, Antje; Kodo, Kazuki; Gong, Yongquan; Sanchez-Freire, Veronica; Dey, Devaveena; Kooreman, Nigel G.; Diecke, Sebastian; Zhang, Wendy Y.; Odegaard, Justin; Hu, Shijun; Gold, Joseph D.; Robbins, Robert C.; Wu, Joseph C.

    2014-01-01

    Rationale Human embryonic stem cell (hESC) derivatives are attractive candidates for therapeutic use. The engraftment and survival of hESC derivatives as xenografts or allografts require effective immunosuppression to prevent immune cell infiltration and graft destruction. Objective To test the hypothesis that a short-course, dual-agent regimen of two costimulation-adhesion blockade agents can induce better engraftment of hESC derivatives compared to current immunosuppressive agents. Methods and Results We transduced hESCs with a double fusion reporter gene construct expressing firefly luciferase (Fluc) and enhanced green fluorescent protein (eGFP), and differentiated these cells to endothelial cells (hESC-ECs). Reporter gene expression enabled longitudinal assessment of cell engraftment by bioluminescence imaging (BLI). Costimulation-adhesion therapy resulted in superior hESC-EC and mouse EC engraftment compared to cyclosporine therapy in a hindlimb model. Costimulation-adhesion therapy also promoted robust hESC-EC and hESC-derived cardiomyocyte (hESC-CM) survival in an ischemic myocardial injury model. Improved hESC-EC engraftment had a cardioprotective effect after myocardial injury, as assessed by magnetic resonance imaging (MRI). Mechanistically, costimulation-adhesion therapy is associated with systemic and intra-graft upregulation of T cell immunoglobulin and mucin domain 3 (TIM3) and a reduced pro-inflammatory cytokine profile. Conclusions Costimulation-adhesion therapy is a superior alternative to current clinical immunosuppressive strategies for preventing the post-transplant rejection of hESC derivatives. By extending the window for cellular engraftment, costimulation-adhesion therapy enhances functional preservation following ischemic injury. This regimen may function through a TIM3-dependent mechanism. PMID:24038578

  6. Pharmacokinetics, Pharmacodynamics and Pharmacogenomics of Immunosuppressants in Allogeneic Haematopoietic Cell Transplantation: Part I.

    PubMed

    McCune, Jeannine S; Bemer, Meagan J

    2016-05-01

    Although immunosuppressive treatments and target concentration intervention (TCI) have significantly contributed to the success of allogeneic haematopoietic cell transplantation (alloHCT), there is currently no consensus on the best immunosuppressive strategies. Compared with solid organ transplantation, alloHCT is unique because of the potential for bidirectional reactions (i.e. host-versus-graft and graft-versus-host). Postgraft immunosuppression typically includes a calcineurin inhibitor (cyclosporine or tacrolimus) and a short course of methotrexate after high-dose myeloablative conditioning, or a calcineurin inhibitor and mycophenolate mofetil after reduced-intensity conditioning. There are evolving roles for the antithymyocyte globulins (ATGs) and sirolimus as postgraft immunosuppression. A review of the pharmacokinetics and TCI of the main postgraft immunosuppressants is presented in this two-part review. All immunosuppressants are characterized by large intra- and interindividual pharmacokinetic variability and by narrow therapeutic indices. It is essential to understand immunosuppressants' pharmacokinetic properties and how to use them for individualized treatment incorporating TCI to improve outcomes. TCI, which is mandatory for the calcineurin inhibitors and sirolimus, has become an integral part of postgraft immunosuppression. TCI is usually based on trough concentration monitoring, but other approaches include measurement of the area under the concentration-time curve (AUC) over the dosing interval or limited sampling schedules with maximum a posteriori Bayesian personalization approaches. Interpretation of pharmacodynamic results is hindered by the prevalence of studies enrolling only a small number of patients, variability in the allogeneic graft source and variability in postgraft immunosuppression. Given the curative potential of alloHCT, the pharmacodynamics of these immunosuppressants deserves to be explored in depth. Development of

  7. Immunosuppressive Therapy in Immune-Mediated Liver Disease in the Non-Transplanted Patient

    PubMed Central

    Abhyankar, Anita; Tapper, Elliot; Bonder, Alan

    2013-01-01

    Autoimmune liver disease management goals are primarily slowing disease progression and symptomatic treatment. There are few options for curative medical management other than transplant for a spectrum of autoimmune liver disease that encompasses autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis as well as their overlap syndromes. These diseases are managed primarily with immunosuppressive therapy. Herein, we review the current literature, detailing the promise and pitfalls of the recommended immunosuppressive therapy for these challenging diseases. PMID:24380894

  8. Immunosuppressive therapy in immune-mediated liver disease in the non-transplanted patient.

    PubMed

    Abhyankar, Anita; Tapper, Elliot; Bonder, Alan

    2013-01-01

    Autoimmune liver disease management goals are primarily slowing disease progression and symptomatic treatment. There are few options for curative medical management other than transplant for a spectrum of autoimmune liver disease that encompasses autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis as well as their overlap syndromes. These diseases are managed primarily with immunosuppressive therapy. Herein, we review the current literature, detailing the promise and pitfalls of the recommended immunosuppressive therapy for these challenging diseases. PMID:24380894

  9. Single-Receiver GPS Phase Bias Resolution

    NASA Technical Reports Server (NTRS)

    Bertiger, William I.; Haines, Bruce J.; Weiss, Jan P.; Harvey, Nathaniel E.

    2010-01-01

    Existing software has been modified to yield the benefits of integer fixed double-differenced GPS-phased ambiguities when processing data from a single GPS receiver with no access to any other GPS receiver data. When the double-differenced combination of phase biases can be fixed reliably, a significant improvement in solution accuracy is obtained. This innovation uses a large global set of GPS receivers (40 to 80 receivers) to solve for the GPS satellite orbits and clocks (along with any other parameters). In this process, integer ambiguities are fixed and information on the ambiguity constraints is saved. For each GPS transmitter/receiver pair, the process saves the arc start and stop times, the wide-lane average value for the arc, the standard deviation of the wide lane, and the dual-frequency phase bias after bias fixing for the arc. The second step of the process uses the orbit and clock information, the bias information from the global solution, and only data from the single receiver to resolve double-differenced phase combinations. It is called "resolved" instead of "fixed" because constraints are introduced into the problem with a finite data weight to better account for possible errors. A receiver in orbit has much shorter continuous passes of data than a receiver fixed to the Earth. The method has parameters to account for this. In particular, differences in drifting wide-lane values must be handled differently. The first step of the process is automated, using two JPL software sets, Longarc and Gipsy-Oasis. The resulting orbit/clock and bias information files are posted on anonymous ftp for use by any licensed Gipsy-Oasis user. The second step is implemented in the Gipsy-Oasis executable, gd2p.pl, which automates the entire process, including fetching the information from anonymous ftp

  10. Dual-Income Families.

    ERIC Educational Resources Information Center

    McKitric, Eloise J.

    The impact of economic conditions on two-earner families was examined. Three family types were studied: (1) dual-career family--both the husband and wife are in the labor force but in occupations classified as professional-technical or managerial; (2) dual-earner--both the husband and wife are in the labor force; and (3) traditional family--the…

  11. The Dual Career Family.

    ERIC Educational Resources Information Center

    Gurtin, Lee

    1980-01-01

    The dual career couple is forced to make a series of choices and compromises that impact the realms of marriage and career. The dilemmas that confront dual career marriages can be overcome only by compromise, accommodation, and mutual understanding on the part of the individuals involved. A revamping of human resources and recruitment programs is…

  12. Dual drive actuators

    NASA Technical Reports Server (NTRS)

    Packard, D. T.

    1982-01-01

    A new class of electromechanical actuators is described. These dual drive actuators were developed for the NASA-JPL Galileo Spacecraft. The dual drive actuators are fully redundant and therefore have high inherent reliability. They can be used for a variety of tasks, and they can be fabricated quickly and economically.

  13. Dual Enrollment Academy Programs

    ERIC Educational Resources Information Center

    Gonzalez, Nicolas; Chavez, Guadalupe

    2009-01-01

    Dual Enrollment Engineering (DEEA) and Medical Science (DEMSA) Academies are two-year dual enrollment programs for high school students. Students explore engineering and medical careers through college coursework. Students prepare for higher education in engineering and medical fields while completing associate degrees in biology or engineering…

  14. Current methods of the analysis of immunosuppressive agents in clinical materials: A review.

    PubMed

    Mika, Adriana; Stepnowski, Piotr

    2016-08-01

    More than 100000 solid organ transplantations are performed every year worldwide. Calcineurin (cyclosporine A, tacrolimus), serine/threonine kinase (sirolimus, everolimus) and inosine monophosphate dehydrogenase inhibitor (mycophenolate mofetil), are the most common drugs used as immunosuppressive agents after solid organ transplantation. Immunosuppressive therapy, although necessary after transplantation, is associated with many adverse consequences, including the formation of secondary metabolites of drugs and the induction of their side effects. Calcineurin inhibitors are associated with nephrotoxicity, cardiotoxicity and neurotoxicity; moreover, they increase the risk of many diseases after transplantation. The review presents a study of the movement of drugs in the body, including the processes of absorption, distribution, localisation in tissues, biotransformation and excretion, and also their accompanying side effects. Therefore, there is a necessity to monitor immunosuppressants, especially because these drugs are characterised by narrow therapeutic ranges. Their incorrect concentrations in a patient's blood could result in transplant rejection or in the accumulation of toxic effects. Immunosuppressive pharmaceuticals are macrolide lactones, peptides, and high molecular weight molecules that can be metabolised to several metabolites. Therefore the two main analytical methods used for their determination are high performance liquid chromatography with various detection methods and immunoassay methods. Despite the rapid development of new analytical methods of analysing immunosuppressive agents, the application of the latest generation of detectors and increasing sensitivity of such methods, there is still a great demand for the development of highly selective, sensitive, specific, rapid and relatively simple methods of immunosuppressive drugs analysis. PMID:26874932

  15. Literature-based immunization recommendations for patients requiring immunosuppressive medications for autoimmune bullous dermatoses.

    PubMed

    Laniosz, Valerie; Lehman, Julia S; Poland, Gregory A; Wetter, David A

    2016-06-01

    Autoimmune bullous diseases, such as pemphigus, pemphigoid, and dermatitis herpetiformis, are uniquely associated with vulnerability in the mucocutaneous barrier against infection. The management of immunobullous diseases is complex and may at times require immunosuppressive medications. Iatrogenic immunosuppression may increase susceptibility to vaccine-preventable illnesses. Currently, there are no guidelines to assist the clinician treating patients with immunobullous disease regarding the delivery of various vaccinations. The aim of this review is to provide recommendations for immunization in the unique setting of immunobullous disease. Recommendations are based on careful review of the literature in other conditions requiring iatrogenic immunosuppression, as well as the most recent Centers for Disease Control and Prevention guidelines. Immunization with nonlive vaccines appears to be a safe and effective strategy for preventing infection in the particularly susceptible patient with immunobullous disease. Opportunities for live vaccine administration may become available at lower levels of immune suppression or during clinical remission when immunosuppressive regimens can be reduced. Anticipatory vaccination before the initiation of iatrogenic immunosuppression is ideal. Although immunologic response to vaccination may be suboptimal during immunosuppression, nonlive vaccination is strongly recommended for this patient population. PMID:26711431

  16. Relationship Between Pneumocystis carinii Burden and the Degree of Host Immunosuppression in an Airborne Transmission Experimental Model.

    PubMed

    Khalife, Sara; Chabé, Magali; Gantois, Nausicaa; Audebert, Christophe; Pottier, Muriel; Hlais, Sani; Pinçon, Claire; Chassat, Thierry; Pierrot, Christine; Khalife, Jamal; Aliouat-Denis, Cécile-Marie; Aliouat, El Moukhtar

    2016-05-01

    To quantitatively assess the risk of contamination by Pneumocystis depending on the degree of immunosuppression (ID) of the exposed rat hosts, we developed an animal model, where rats went through different doses of dexamethasone. Then, natural and aerial transmission of Pneumocystis carinii occurred during cohousing of the rats undergoing gradual ID levels (receivers) with nude rats developing pneumocystosis (seeders). Following contact between receiver and seeder rats, the P. carinii burden of receiver rats was determined by toluidine blue ortho staining and by qPCR targeting the dhfr monocopy gene of this fungus. In this rat model, the level of circulating CD4(+) and CD8(+) T lymphocytes remained significantly stable and different for each dose of dexamethasone tested, thus reaching the goal of a new stable and gradual ID rat model. In addition, an inverse relationship between the P. carinii burden and the level of circulating CD4(+) or CD8(+) T lymphocytes was evidenced. This rat model may be used to study other opportunistic pathogens or even co-infections in a context of gradual ID. PMID:26509699

  17. An auroral scintillation observation using precise, collocated GPS receivers

    NASA Astrophysics Data System (ADS)

    Garner, T. W.; Harris, R. B.; York, J. A.; Herbster, C. S.; Minter, C. F., III; Hampton, D. L.

    2011-02-01

    On 10 January 2009, an unusual ionospheric scintillation event was observed by a Global Positioning System (GPS) receiver station in Fairbanks, Alaska. The receiver station is part of the National Geospatial-Intelligence Agency's (NGA) Monitoring Station Network (MSN). Each MSN station runs two identical geodetic-grade, dual-frequency, full-code tracking GPS receivers that share a common antenna. At the Fairbanks station, a third separate receiver with a separate antenna is located nearby. During the 10 January event, ionospheric conditions caused two of the receivers to loose lock on a single satellite. The third receiver tracked through the scintillation. The region of scintillation was collocated with an auroral arc and a slant total electron content (TEC) increase of 5.71 TECu (TECu = 1016/m2). The response of the full-code tracking receivers to the scintillation is intriguing. One of these receivers lost lock, but the other receiver did not. This fact argues that a receiver's internal state dictates its reaction to scintillation. Additionally, the scintillation only affected the L2 signal. While this causes the L1 signal to be lost on the semicodelessly receiver, the full-code tracking receiver only lost the L1 signal when the receiver attempted to reacquire the satellite link.

  18. Highly directional acoustic receivers.

    PubMed

    Cray, Benjamin A; Evora, Victor M; Nuttall, Albert H

    2003-03-01

    The theoretical directivity of a single combined acoustic receiver, a device that can measure many quantities of an acoustic field at a collocated point, is presented here. The formulation is developed using a Taylor series expansion of acoustic pressure about the origin of a Cartesian coordinate system. For example, the quantities measured by a second-order combined receiver, denoted a dyadic sensor, are acoustic pressure, the three orthogonal components of acoustic particle velocity, and the nine spatial gradients of the velocity vector. The power series expansion, which can be of any order, is cast into an expression that defines the directivity of a single receiving element. It is shown that a single highly directional dyadic sensor can have a directivity index of up to 9.5 dB. However, there is a price to pay with highly directive sensors; these sensors can be significantly more sensitive to nonacoustic noise sources. PMID:12656387

  19. Central solar energy receiver

    DOEpatents

    Drost, M. Kevin

    1983-01-01

    An improved tower-mounted central solar energy receiver for heating air drawn through the receiver by an induced draft fan. A number of vertically oriented, energy absorbing, fin-shaped slats are radially arranged in a number of concentric cylindrical arrays on top of the tower coaxially surrounding a pipe having air holes through which the fan draws air which is heated by the slats which receive the solar radiation from a heliostat field. A number of vertically oriented and wedge-shaped columns are radially arranged in a number of concentric cylindrical clusters surrounding the slat arrays. The columns have two mirror-reflecting sides to reflect radiation into the slat arrays and one energy absorbing side to reduce reradiation and reflection from the slat arrays.

  20. Depression in older patients with advanced colorectal cancer is closely connected with immunosuppressive acidic protein.

    PubMed

    Li, Rong; Yang, Jie; Yang, Jihua; Fu, Weijun; Jiang, Hua; Du, Juan; Zhang, Chunyang; Xi, Hao; Hou, Jian

    2014-03-01

    Colorectal cancer (CRC) is one of the most common tumors. CRC patients are susceptible to suffering from depression. Whether the immune system of CRC patients with depression is impaired or stimulated is controversial. Possible reasons for this conflict are the involvement of confounding factors, such as the age of the patient, the stage of the CRC and the types of treatment in previous studies. To demonstrate clearly the relationship between depression and the immune system in the context of CRC, the present study included only older patients with advanced CRC who received only chemotherapy, and the study adopted immunosuppressive acidic protein (IAP) as an immune parameter for the first time. A total of 56 older patients with advanced CRC completed the Zung Self-Rating Depression Scale (SDS) and were divided into two groups according to SDS scores. The patients exhibiting depression were treated with fluoxetine until their symptoms remitted. The serum levels of IAP and the percentages of CD3-positive (CD3+), CD4+, CD8+ T lymphocytes and CD56+ natural killer (NK) cells and Neutrophil-lymphocyte ratio (NLR) were calculated at the time of enrollment and once the symptoms remitted. Correlation analyses revealed that the SDS score was positively associated with serum IAP levels but negatively associated with CD3 and CD4 levels. Among the depressed and non-depressed patients, serum IAP levels and the percentages of CD3 and CD4 cells were dramatically different. After the depression symptoms were treated, the IAP levels dramatically decreased, while the levels of CD3, CD4, CD8 and CD56 were unchanged. All of above suggested that IAP was closely correlated with depression and might be a relatively objective parameter for predicting depression. PMID:23975537

  1. Simplified OMEGA receivers

    NASA Technical Reports Server (NTRS)

    Burhans, R. W.

    1974-01-01

    The details are presented of methods for providing OMEGA navigational information including the receiver problem at the antenna and informational display and housekeeping systems based on some 4 bit data processing concepts. Topics discussed include the problem of limiters, zero crossing detectors, signal envelopes, internal timing circuits, phase counters, lane position displays, signal integrators, and software mapping problems.

  2. Submillimeter wave heterodyne receiver

    NASA Technical Reports Server (NTRS)

    Chattopadhyay, Goutam (Inventor); Manohara, Harish (Inventor); Siegel, Peter H. (Inventor); Ward, John (Inventor)

    2011-01-01

    In an embodiment, a submillimeter wave heterodyne receiver includes a finline ortho-mode transducer comprising thin tapered metallic fins deposited on a thin dielectric substrate to separate a vertically polarized electromagnetic mode from a horizontally polarized electromagnetic mode. Other embodiments are described and claimed.

  3. Olympus beacon receiver

    NASA Technical Reports Server (NTRS)

    Ostergaard, Jens

    1988-01-01

    A medium-size Beacon Receiving System for reception and processing of the B1 (20 GHz) and B2 (30 GHz) beacons from Olympus has been developed. Integration of B1 and B2 receiving equipment into one system using one antenna and a common computer for control and data processing provides the advantages of a compact configuration and synchronization of the two receiver chains. Range for co-polar signal attenuation meaurement is about 30 dB for both beacons, increasing to 40 dB for B2 if the receivers are synchronized to B1. The accuracy is better than 0.5 dB. Cross-polarization discriminations of the order of 10 to 30 dB may be determined with an accuracy of 1 to 2 dB. A number of radiometers for complementary measurements of atmospheric attenuation of 13 to 30 GHz has also been constructed. A small multi-frequency system for operation around 22 GHz and 31 GHz is presently under development.

  4. Low-Profile, Dual-Wavelength, Dual-Polarized Antenna

    NASA Technical Reports Server (NTRS)

    Carswell, James R.

    2010-01-01

    A single-aperture, low-profile antenna design has been developed that supports dual-polarization and simultaneous operation at two wavelengths. It realizes multiple beams in the elevation plane, and supports radiometric, radar, and conical scanning applications. This antenna consists of multiple azimuth sticks, with each stick being a multilayer, hybrid design. Each stick forms the h-plane pattern of the C and Ku-band vertically and horizontally polarized antenna beams. By combining several azimuth sticks together, the elevation beam is formed. With a separate transceiver for each stick, the transmit phase and amplitude of each stick can be controlled to synthesize a beam at a specific incidence angle and to realize a particular side-lobe pattern. By changing the transmit phase distribution through the transceivers, the transmit antenna beam can be steered to different incidence angles. By controlling the amplitude distribution, different side lobe patterns and efficiencies can be realized. The receive beams are formed using digital beam synthesis techniques, resulting in very little loss in the receive path, thus enabling a very-low loss receive antenna to support passive measurements.

  5. Dual Credit/Dual Enrollment and Data Driven Policy Implementation

    ERIC Educational Resources Information Center

    Lichtenberger, Eric; Witt, M. Allison; Blankenberger, Bob; Franklin, Doug

    2014-01-01

    The use of dual credit has been expanding rapidly. Dual credit is a college course taken by a high school student for which both college and high school credit is given. Previous studies provided limited quantitative evidence that dual credit/dual enrollment is directly connected to positive student outcomes. In this study, predictive statistics…

  6. Cutaneous Legionella longbeachae Infection in Immunosuppressed Woman, United Kingdom

    PubMed Central

    Tucker, David; Harris, Kathryn; Turner, Deborah

    2015-01-01

    We report a rare case of cutaneous Legionella longbeachae infection in a patient receiving long-term corticosteroids for immune thrombocytopenia. Such infections cannot be identified by using Legionella urinary antigen testing but are commonly seen after exposure to commercial potting compost, particularly in immunocompromised patients. PMID:26197048

  7. Cutaneous Legionella longbeachae Infection in Immunosuppressed Woman, United Kingdom.

    PubMed

    Grimstead, Daniel; Tucker, David; Harris, Kathryn; Turner, Deborah

    2015-08-01

    We report a rare case of cutaneous Legionella longbeachae infection in a patient receiving long-term corticosteroids for immune thrombocytopenia. Such infections cannot be identified by using Legionella urinary antigen testing but are commonly seen after exposure to commercial potting compost, particularly in immunocompromised patients. PMID:26197048

  8. Improved Dual-Polarized Microstrip Antenna

    NASA Technical Reports Server (NTRS)

    Huang, John

    1993-01-01

    Dual-polarized microstrip antenna features microstrip transmission-line feeds arranged in such configuration that cross-polarized components of radiation relatively low and degree of isolation between feed ports relatively high. V and H feed ports offset from midpoints of feed lines to obtain required opposite phases at feed-point connections to microstrip patches. Two independent beams of same frequency with electric fields polarized orthogonally to each other transmitted or received via antenna. Improved design saves space.

  9. A digital beacon receiver

    NASA Technical Reports Server (NTRS)

    Ransome, Peter D.

    1988-01-01

    A digital satellite beacon receiver is described which provides measurement information down to a carrier/noise density ratio approximately 15 dB below that required by a conventional (phase locked loop) design. When the beacon signal fades, accuracy degrades gracefully, and is restored immediately (without hysteresis) on signal recovery, even if the signal has faded into the noise. Benefits of the digital processing approach used include the minimization of operator adjustments, stability of the phase measuring circuits with time, repeatability between units, and compatibility with equipment not specifically designed for propagation measuring. The receiver has been developed for the European Olympus satellite which has continuous wave (CW) beacons at 12.5 and 29.7 GHz, and a switched polarization beacon at 19.8 GHz approximately, but the system can be reconfigured for CW and polarization-switched beacons at other frequencies.

  10. Multichannel homodyne receiver

    DOEpatents

    Landt, Jeremy A.

    1982-01-01

    A homodyne radar transmitter/receiver device which produces a single combined output which contains modulated backscatter information for all phase conditions of both modulated and unmodulated backscatter signals. The device utilizes taps along coaxial transmission lines, strip transmission line, and waveguides which are spaced by 1/8 wavelength or 1/6 wavelength, etc. This greatly reduces costs by eliminating separate transmission and reception antennas and an expensive arrangement of power splitters and mixers utilized in the prior art.

  11. Multichannel homodyne receiver

    DOEpatents

    Landt, J.A.

    1981-01-19

    A homodyne radar transmitter/receiver device which produces a single combined output which contains modulated backscatter information for all phase conditions of both modulated and unmodulated backscatter signals is described. The device utilizes taps along coaxial transmission lines, strip transmission line, and waveguides which are spaced by 1/8 wavelength or 1/6 wavelength, etc. This greatly reduces costs by eliminating separate transmission and reception antennas and an expensive arrangement of power splitters and mixers utilized in the prior art.

  12. Galileo probe relay receiver

    NASA Technical Reports Server (NTRS)

    Prouty, D. A.; Von Der Embse, U. A.

    1982-01-01

    For the Jovian mission, the data link from the Galileo probe to the orbiter uses suppressed-carrier Manchester encoded BPSK modulation and is protected with R = 1/2, K = 7 convolutional coding. The receiver closes the link by acquiring, tracking, and demodulating the data. It has to operate in a highly stressed environment with severe frequency offset, frequency rate, wind gust, and antenna spin conditions. Salient features are described and breadboard test data presented.

  13. Comparison of Neoral and Sandimmun for induction and maintenance immunosuppression after kidney transplantation.

    PubMed

    Senel, F M; Yildirim, S; Karakayali, H; Moray, G; Haberal, M

    1997-01-01

    We compared the mean trough level/dose (L/D) ratio, mean coefficient of variation (CV) of individual patients, and graft, patient, and rejection-free survival rates of 40 renal transplant recipients receiving Neoral (CyE) with 103 consecutive renal transplant recipients receiving Sandimmun (CyA). The mean L/D ratio on the 3rd post-transplant day (16.2 vs 11.8, P < 0.04), in the 1st week (24.6 vs 16.1; P < 0.03), and 1st month (39.1 vs 28.7; P < 0.05) were higher in the CyE group. In both groups the L/D ratio improved in proportion to the duration of time post-transplant and reached a maximum in the 3rd post-transplant month. In the early post-transplant period in particular, the number of patients achieving target levels was significantly higher, and the mean dose needed to achieve target levels lower, in the CyE group. The variation in trough levels, demonstrated by the CV, was lower in the CyE group (0.41 +/- 0.14) than in the CyA group (0.62 +/- 0.21; P < 0.005). Actuarial 1-year patient and graft survival rates in the CyE group were 100% and 96%, respectively; these were similar to the 100% and 95% in the CyA group. The 1-year rejection-free survival rate in the CyE group was 61% compared to 43% in the CyA group (P < 0.02). We conclude that it is possible to obtain higher blood trough levels at lower doses by administering CyE, particularly in the early post-transplant period. The lower variability of trough levels and the higher L/D ratio in the CyE group, which are related ti improved bioavailability of CyE, may explain the lower rejection rate among these patients. In this study, the microemulsion formulation of cyclosporin (CyE) was found to be more beneficial and cost-effective as induction and maintenance immunosuppression than the conventional formulation (CyA). PMID:9287400

  14. Dynamic Immune Cell Recruitment After Murine Pulmonary Aspergillus fumigatus Infection under Different Immunosuppressive Regimens

    PubMed Central

    Kalleda, Natarajaswamy; Amich, Jorge; Arslan, Berkan; Poreddy, Spoorthi; Mattenheimer, Katharina; Mokhtari, Zeinab; Einsele, Hermann; Brock, Matthias; Heinze, Katrin Gertrud; Beilhack, Andreas

    2016-01-01

    Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonary immune response after A. fumigatus infection to reveal basic immunological events that fail to effectively control invasive fungal disease. In different immunocompromised murine models, myeloid, notably neutrophils, and macrophages, but not lymphoid cells were strongly recruited to the lungs upon infection. Other myeloid cells, particularly dendritic cells and monocytes, were only recruited to lungs of corticosteroid treated mice, which developed a strong pulmonary inflammation after infection. Lymphoid cells, particularly CD4+ or CD8+ T-cells and NK cells were highly reduced upon immunosuppression and not recruited after A. fumigatus infection. Moreover, adoptive CD11b+ myeloid cell transfer rescued cyclophosphamide immunosuppressed mice from lethal A. fumigatus infection but not cortisone and cyclophosphamide immunosuppressed mice. Our findings illustrate that CD11b+ myeloid cells are critical for anti-A. fumigatus defense under cyclophosphamide immunosuppressed conditions. PMID:27468286

  15. Dramatic improvement of anti-SS-A/Ro-associated interstitial lung disease after immunosuppressive treatment.

    PubMed

    Paola, Caramaschi; Giuliana, Festi; Giovanni, Orsolini; Cristian, Caimmi; Domenico, Biasi

    2016-07-01

    The aim of the study was to report three patients affected by interstitial lung disease associated with positive anti-SS-A/Ro autoantibody who showed a dramatic improvement after immunosuppressive treatment. Medical charts were reviewed to obtain clinical data, laboratory parameters, lung function tests, high-resolution computed tomography results and response to immunosuppressive treatment. The three patients showed a clinical picture of a lung-dominant connective tissue disease characterized by a sudden onset with dyspnea, cough and subtle extrathoracic features together with positive anti-SS-A/Ro antibody and weak titer antinuclear antibodies. All three patients responded favorably to immunosuppressive therapy: Two cases were treated with a combination of corticosteroid and cyclophosphamide followed by mycophenolate mofetil; in the third patient, clinical benefit was obtained after rituximab was added to corticosteroid and immunosuppressant drug. In spite of an abrupt onset with significant lung function impairment, all three patients had a favorable clinical response to immunosuppressive therapy. This report may be useful in making therapeutic decisions in case of interstitial lung disease associated with anti-SS-A antibody. PMID:27021338

  16. Cancer-induced heterogeneous immunosuppressive tumor microenvironments and their personalized modulation.

    PubMed

    Yaguchi, Tomonori; Kawakami, Yutaka

    2016-08-01

    Although recent cancer immunotherapy strategies, including immune-checkpoint blockade (i.e. blocking PD-1, PD-L1 or CTLA-4), have shown durable clinical effects in some (but not all) patients with various advanced cancers, further understanding of human immunopathology, particularly in tumor microenvironments, is essential to improve this type of therapy. The major hurdle for immunotherapy is the immunosuppression that is found in cancer patients. There are two types of immunosuppression: one is induced by gene alterations in cancer; the other is local adaptive immunosuppression, triggered by tumor-specific T cells in tumors. The former is caused by multiple mechanisms via various immunosuppressive molecules and via cells triggered by gene alterations, including activated oncogenes, in cancer cells. The various immunosuppressive mechanisms involve signaling cascades that vary among cancer types, subsets within cancer types and individual cancers. Therefore, personalized immune-interventions are necessary to appropriately target oncogene-induced signaling that modulates anti-cancer immune responses, on the basis of genetic and immunological analysis of each patient. Further understanding of human cancer immunopathology may lead to real improvement of current cancer immunotherapies. PMID:27401477

  17. Dynamic Immune Cell Recruitment After Murine Pulmonary Aspergillus fumigatus Infection under Different Immunosuppressive Regimens.

    PubMed

    Kalleda, Natarajaswamy; Amich, Jorge; Arslan, Berkan; Poreddy, Spoorthi; Mattenheimer, Katharina; Mokhtari, Zeinab; Einsele, Hermann; Brock, Matthias; Heinze, Katrin Gertrud; Beilhack, Andreas

    2016-01-01

    Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonary immune response after A. fumigatus infection to reveal basic immunological events that fail to effectively control invasive fungal disease. In different immunocompromised murine models, myeloid, notably neutrophils, and macrophages, but not lymphoid cells were strongly recruited to the lungs upon infection. Other myeloid cells, particularly dendritic cells and monocytes, were only recruited to lungs of corticosteroid treated mice, which developed a strong pulmonary inflammation after infection. Lymphoid cells, particularly CD4(+) or CD8(+) T-cells and NK cells were highly reduced upon immunosuppression and not recruited after A. fumigatus infection. Moreover, adoptive CD11b(+) myeloid cell transfer rescued cyclophosphamide immunosuppressed mice from lethal A. fumigatus infection but not cortisone and cyclophosphamide immunosuppressed mice. Our findings illustrate that CD11b(+) myeloid cells are critical for anti-A. fumigatus defense under cyclophosphamide immunosuppressed conditions. PMID:27468286

  18. Immunosuppressive, anti-inflammatory and anti-cancer properties of triptolide: A mini review

    PubMed Central

    Ziaei, Samira; Halaby, Reginald

    2016-01-01

    Objective: Triptolide, the active component of Tripterygium wilfordii Hook F has been used to treat autoimmune and inflammatory conditions for over two hundred years in traditional Chinese medicine. However, the processes through which triptolide exerts immunosuppression and anti-inflammation are not understood well. In this review, we discuss the autoimmune disorders and inflammatory conditions that are currently treated with triptolide. Triptolide also possesses anti-tumorigenic effects. We discuss the toxicity of various triptolide derivatives and offer suggestions to improve its safety. This study also examines the clinical trials that have investigated the efficacy of triptolide. Our aim is to examine the mechanisms that are responsible for the immunosuppressive, anti-inflammatory, and anti-cancer effects of triptolide. Materials and Methods: The present review provides a comprehensive summary of the literature with respect to the immunosuppressive, anti-inflammatory, and anti-cancer properties of triptolide. Results: Triptolide possesses immunosuppressive, anti-inflammatory, and anti-cancer effects. Conclusion: Triptolide can be used alone or in combination with existing therapeutic modalities as novel treatments for autoimmune disorders, cancers, and for immunosuppression. PMID:27222828

  19. Dietary recommendations for immunosuppressed patients of 17 hematopoietic stem cell transplantation centers in Brazil

    PubMed Central

    Vicenski, Paola Pasini; Alberti, Paloma; do Amaral, Denise Johnsson Campos

    2012-01-01

    Introduction Low-microbial diets are recommended to reduce the risk of foodborne infections when hematopoietic stem cell transplantation patients have neutropenia. However there is no pattern concerning the composition of such a diet. Objective To collect information concerning the structure of nutrition departments and the diets recommended for immunosuppressed patients in transplant centers in Brazil. Methods Questionnaires were sent to the 45 Bone Marrow Transplantation Centers listed by the Sociedade Brasileira de Transplante de Medula Óssea (SBTMO). Completed questionnaires were returned by 17 centers. The questions were related to the profile and the structure of the nutrition department, at what point a general diet is allowed after transplantation, and which food is allowed during the critical period of immunosuppression and soon after transplantation. Results Of the 17 centers that participated, 82% have a professional nutritionist exclusively for the Transplant Department but only 41% have an area specifically for the preparation of diets for immunosuppressed patients. The patients are released from the low-microbial diet to general diets 90-100 days after allogeneic hematopoietic stem cell transplantation by 29% of the centers and only after suspension of immunosuppressive drugs in 24%. Most centers (88%) restrict the consumption of raw fruits, all restrict the consumption of raw vegetables and 88% forbid the consumption of yogurt in the critical period of immunosuppression. There was no consensus on forbidden foods soon after transplantation. Conclusion Major differences in diets recommended to hematopoietic stem cell transplantation patients were observed between the different centers. PMID:23049398

  20. Hair Follicle Dermal Sheath Derived Cells Improve Islet Allograft Survival without Systemic Immunosuppression

    PubMed Central

    Wang, Xiaojie; Hao, Jianqiang; Leung, Gigi; Breitkopf, Trisia; Wang, Eddy; Kwong, Nicole; Akhoundsadegh, Noushin; Warnock, Garth L.; Shapiro, Jerry; McElwee, Kevin J.

    2015-01-01

    Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1) or fibroblasts (FB, group 2) under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P < 0.001) without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation. PMID:26000314

  1. Mycobacterium lentiflavum, a recently identified slow-growing mycobacterial species: clinical significance in immunosuppressed cancer patients and summary of reported cases of infection.

    PubMed

    Safdar, A; Han, X Y

    2005-08-01

    The clinical significance of Mycobacterium lentiflavum, a recently identified nontuberculous mycobacterium, remains uncertain, especially in immunosuppressed cancer patients. The records of all patients in whom M. lentiflavum was identified using a gene sequencing technique between January 2001 and December 2003 were reviewed. The mean age among 12 patients was 51+/-20 years, and 11 (92%) patients had a hematologic malignancy. Six of seven (86%) hematopoietic stem cell transplant recipients had received allogeneic donor grafts. Nine (75%) patients had predisposing risk factors for infection, seven (58%) had severe lymphocytopenia (<400 cells/microl), five (42%) were receiving systemic corticosteroid therapy, and three (25%) had acute graft-versus-host disease. Only 1 of the 12 (8%) patients had evidence of probable pulmonary M. lentiflavum infection. Six M. lentiflavum strains were initially misidentified as Mycobacterium simiae and Mycobacterium avium-intracellulare complex using traditional biochemical tests. Four M. lentiflavum isolates were tested for antimicrobial susceptibility; they were susceptible to isoniazid, ethambutol, clarithromycin, and amikacin, and resistant to rifampin. M. lentiflavum was not clinically significant, even in these severely immunosuppressed cancer patients. PMID:16133412

  2. LANL receiver system development

    SciTech Connect

    Laubscher, B.; Cooke, B.; Cafferty, M.; Olivas, N.

    1997-08-01

    The CALIOPE receiver system development at LANL is the story of two technologies. The first of these technologies consists of off-the-shelf mercury-cadmium-telluride (MCT) detectors and amplifiers. The vendor for this system is Kolmar Technologies. This system was fielded in the Tan Trailer I (TTI) in 1995 and will be referred to in this paper as GEN I. The second system consists of a MCT detector procured from Santa Barbara Research Center (SBRC) and an amplifier designed and built by LANL. This system was fielded in the Tan Trailer II (TTII) system at the NTS tests in 1996 and will be referred to as GEN II. The LANL CALIOPE experimental plan for 1996 was to improve the lidar system by progressing to a higher rep rate laser to perform many shots in a much shorter period of time. In keeping with this plan, the receiver team set a goal of developing a detector system that was background limited for the projected 100 nanosecond (ns) laser pulse. A set of detailed simulations of the DIAL lidar experiment was performed. From these runs, parameters such as optimal detector size, field of view of the receiver system, nominal laser return power, etc. were extracted. With this information, detector physics and amplifier electronic models were developed to obtain the required specifications for each of these components. These derived specs indicated that a substantial improvement over commercially available, off-the-shelf, amplifier and detector technologies would be needed to obtain the goals. To determine if the original GEN I detector was usable, the authors performed tests on a 100 micron square detector at cryogenic temperatures. The results of this test and others convinced them that an advanced detector was required. Eventually, a suitable detector was identified and a number of these single element detectors were procured from SBRC. These single element detectors were witness for the detector arrays built for another DOE project.

  3. Ultra-wideband receiver

    DOEpatents

    McEwan, Thomas E.

    1994-01-01

    An ultra-wideband (UWB) receiver utilizes a strobed input line with a sampler connected to an amplifier. In a differential configuration, .+-.UWB inputs are connected to separate antennas or to two halves of a dipole antenna. The two input lines include samplers which are commonly strobed by a gating pulse with a very low duty cycle. In a single ended configuration, only a single strobed input line and sampler is utilized. The samplers integrate, or average, up to 10,000 pulses to achieve high sensitivity and good rejection of uncorrelated signals.

  4. Ultra-wideband receiver

    DOEpatents

    McEwan, Thomas E.

    1996-01-01

    An ultra-wideband (UWB) receiver utilizes a strobed input line with a sampler connected to an amplifier. In a differential configuration, .+-.UWB inputs are connected to separate antennas or to two halves of a dipole antenna. The two input lines include samplers which are commonly strobed by a gating pulse with a very low duty cycle. In a single ended configuration, only a single strobed input line and sampler is utilized. The samplers integrate, or average, up to 10,000 pulses to achieve high sensitivity and good rejection of uncorrelated signals.

  5. Ultra-wideband receiver

    DOEpatents

    McEwan, T.E.

    1996-06-04

    An ultra-wideband (UWB) receiver utilizes a strobed input line with a sampler connected to an amplifier. In a differential configuration, {+-}UWB inputs are connected to separate antennas or to two halves of a dipole antenna. The two input lines include samplers which are commonly strobed by a gating pulse with a very low duty cycle. In a single ended configuration, only a single strobed input line and sampler is utilized. The samplers integrate, or average, up to 10,000 pulses to achieve high sensitivity and good rejection of uncorrelated signals. 21 figs.

  6. Ultra-wideband receiver

    DOEpatents

    McEwan, T.E.

    1994-09-06

    An ultra-wideband (UWB) receiver utilizes a strobed input line with a sampler connected to an amplifier. In a differential configuration, [+-] UWB inputs are connected to separate antennas or to two halves of a dipole antenna. The two input lines include samplers which are commonly strobed by a gating pulse with a very low duty cycle. In a single ended configuration, only a single strobed input line and sampler is utilized. The samplers integrate, or average, up to 10,000 pulses to achieve high sensitivity and good rejection of uncorrelated signals. 16 figs.

  7. The cellular basis of immunosuppression caused by the radiation leukaemia virus

    PubMed Central

    Peled, A.; Haran-Ghera, N.

    1974-01-01

    Infection of adult C57B1/6 mice with the radiation leukaemia virus resulted in suppression of the ability of the animals to respond to an immunizing inoculum of sheep erythrocytes. Results of the transfer experiments indicated that the immunosuppressive effect was expressed at the immunocompetent cell level, and that the virus affected the thymus-derived population of immunocytes. The immunosuppressive effect of the virus on thymus cells, independent of any contribution by cells of bone marrow origin, was verified with thymus-independent immunogens, polyvinylpyrrolidone (PVP) or pneumococcal polysaccharide SIII (PPS). Mice inoculated with the radiation leukaemia virus produced nearly normal amounts of plaque-forming cells producing antibodies against PVP and PPS, thereby confirming that the immunosuppressive effect of the radiation leukaemia virus was on thymus-derived cells. PMID:4369273

  8. Neurotrophic actions of nonimmunosuppressive analogues of immunosuppressive drugs FK506, rapamycin and cyclosporin A.

    PubMed

    Steiner, J P; Connolly, M A; Valentine, H L; Hamilton, G S; Dawson, T M; Hester, L; Snyder, S H

    1997-04-01

    We show that the nonimmunosuppressive analogues of the immunosuppressive drugs FK506, rapamycin and cyclosporin A promote neurite outgrowth both in PC12 cells and sensory neuronal cultures of dorsal root ganglia with potencies resembling their immunosuppressive homologues. Neurotrophic potencies of the immunophilin ligands resemble their potencies in binding to and inhibiting the rotamase activity of FKBP-12 of cyclophilin. Since nonimmunosuppressive immunophilin ligands, which are devoid of calcineurin inhibitory activity, are equally neurotrophic, inhibition of calcineurin activity is not the mediator of the neurotrophic effects. The immunophilin ligands are neurotrophic in intact animals. FK506 and L-685,818 (the C18-hydroxy, C21-ethyl derivative of FK506) treatment of rats with crushed sciatic nerves enhances both functional and morphologic recovery. The striking potency of these agents, their bioavailability and the dissociation of neurotrophic from immunosuppressant actions argue for their therapeutic relevance in the treatment of neurodegenerative diseases. PMID:9095176

  9. Alternative matrices for therapeutic drug monitoring of immunosuppressive agents using LC–MS/MS

    PubMed Central

    Ghareeb, Mwlod; Akhlaghi, Fatemeh

    2015-01-01

    Immunosuppressive drugs used in solid organ transplants typically have narrow therapeutic windows and high intra- and intersubject variability. To ensure satisfactory exposure, therapeutic drug monitoring (TDM) plays a pivotal role in any successful posttransplant maintenance therapy. Currently, recommendations for optimum immunosuppressant concentrations are based on blood/plasma measurements. However, they introduce many disadvantages, including poor prediction of allograft survival and toxicity, a weak correlation with drug concentrations at the site of action and the invasive nature of the sample collection. Thus, alternative matrices have been investigated. This paper reviews tandem-mass spectrometry (LC–MS/MS) methods used for the quantification of immunosuppressant drugs utilizing nonconventional matrices, namely oral fluids, fingerprick blood and intracellular and intratissue sampling. The advantages, disadvantages and clinical application of such alternative mediums are discussed. Additionally, sample extraction techniques and basic chromatography information regarding these methods are presented in tabulated form. PMID:25966013

  10. Effects of immunosuppression on encephalitis virus infection in the house finch, Carpodacus mexicanus.

    PubMed

    Reisen, William K; Chiles, Robert E; Green, Emily N; Fang, Ying; Mahmood, Farida; Martinez, Vincent M; Laver, Thomas

    2003-03-01

    Immunosuppression of house finches was attempted by blood feeding Culex tarsalis Coquillett mosquitoes or by injecting birds with the corticosteroid dexamethasone or the immunosuppressant drug cyclophosphamide before and after inoculation with western equine encephalomyelitis or St. Louis encephalitis viruses. Mosquito bites (8-37 females blood feeding on each bird over a 3-d period) did not enhance the viremia response or increase the frequency of chronic infection. In contrast, dexamethasone and cyclophosphamide enhanced the amplitude and duration of the viremia response, but had no consistent effect on the antibody responses as measured by enzyme immunoassay or plaque reduction neutralization assay. Elevated viremias were followed by increases in the frequency of chronic infections with St. Louis encephalitis, but not western equine encephalomyelitis. Immunosuppression may provide a useful tool to study the chronic infection process of flaviviruses in vertebrates. PMID:12693850

  11. Reduction of microbleeds by immunosuppression in a patient with Aβ-related vascular inflammation

    PubMed Central

    Traschütz, Andreas; Tzaridis, Theophilos; Penner, Arndt-Hendrik; Kuchelmeister, Klaus; Urbach, Horst; Hattingen, Elke

    2015-01-01

    Objective: To investigate whether the occurrence or clearance of microhemorrhages in cerebral amyloid angiopathy (CAA)-related vascular inflammation can be modified by immunosuppressive treatment. Methods: Clinical and radiologic follow-up for more than 5 years of a patient with histopathologically confirmed CAA-related vascular inflammation treated with a prolonged and tapered regimen of IV cyclophosphamide and oral steroids. Results: Under long-term immunosuppressive treatment, a reduced number of cortical micobleeds was observed on repeat MRIs because of both the prevention of new microbleeds and the clearance of those existing at baseline. Conclusions: Sustained immunosuppression should be considered and systematically investigated as a treatment option for cortical microbleeds in CAA and related inflammatory phenotypes. Classification of evidence: This study provides Class IV evidence. This is a single observational study without controls. PMID:26516630

  12. QPPM receiver for free-space laser communications

    NASA Technical Reports Server (NTRS)

    Budinger, J. M.; Mohamed, J. H.; Nagy, L. A.; Lizanich, P. J.; Mortensen, D. J.

    1994-01-01

    A prototype receiver developed at NASA Lewis Research Center for direct detection and demodulation of quaternary pulse position modulated (QPPM) optical carriers is described. The receiver enables dual-channel communications at 325-Megabits per second (Mbps) per channel. The optical components of the prototype receiver are briefly described. The electronic components, comprising the analog signal conditioning, slot clock recovery, matched filter and maximum likelihood data recovery circuits are described in more detail. A novel digital symbol clock recovery technique is presented as an alternative to conventional analog methods. Simulated link degradations including noise and pointing-error induced amplitude variations are applied. The bit-error-rate performance of the electronic portion of the prototype receiver under varying optical signal-to-noise power ratios is found to be within 1.5-dB of theory. Implementation of the receiver as a hybrid of analog and digital application specific integrated circuits is planned.

  13. Weather Data Receiver

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Northern Video Graphics, Inc. developed a low-cost satellite receiving system for users such as independent meteorologists, agribusiness firms, small airports or flying clubs, marine vessels and small TV stations. Called Video Fax, it is designed for use with certain satellites; the GOES (Geostationary Operational Environmental Satellite) spacecraft operated by the National Oceanic and Atmospheric Administration, the European Space Agency's Meteosat and Japan's Geostationary Meteorological Satellite. By dictum of the World Meteorological Organization, signals from satellites are available to anyone without cost so the Video Fax user can acquire signals directly from the satellite and cut out the middle man, enabling savings. Unit sells for about one-fifth the cost of the equipment used by TV stations. It consists of a two-meter antenna; a receiver; a microprocessor-controlled display computer; and a video monitor. Computer stores data from the satellites and converts it to an image which is displayed on the monitor. Weather map can be preserved as signal data on tape, or it can be stored in a video cassette as a permanent image.

  14. Acquisition of heroin conditioned immunosuppression requires IL-1 signaling in the dorsal hippocampus.

    PubMed

    Lebonville, Christina L; Jones, Meghan E; Hutson, Lee W; Cooper, Letty B; Fuchs, Rita A; Lysle, Donald T

    2016-08-01

    Opioid users experience increased incidence of infection, which may be partially attributable to both direct opiate-immune interactions and conditioned immune responses. Previous studies have investigated the neural circuitry governing opioid conditioned immune responses, but work remains to elucidate the mechanisms mediating this effect. Our laboratory has previously shown that hippocampal IL-1 signaling, specifically, is required for the expression of heroin conditioned immunosuppression following learning. The current studies were designed to further characterize the role of hippocampal IL-1 in this phenomenon by manipulating IL-1 during learning. Experiment 1 tested whether hippocampal IL-1 is also required for the acquisition of heroin conditioned immunosuppression, while Experiment 2 tested whether hippocampal IL-1 is required for the expression of unconditioned heroin immunosuppression. We found that blocking IL-1 signaling in the dorsal hippocampus with IL-1RA during each conditioning session, but not on interspersed non-conditioning days, significantly attenuated the acquisition of heroin conditioned immunosuppression. Strikingly, we found that the same IL-1RA treatment did not alter unconditioned immunosuppression to a single dose of heroin. Thus, IL-1 signaling is not a critical component of the response to heroin but rather may play a role in the formation of the association between heroin and the context. Collectively, these studies suggest that IL-1 signaling, in addition to being involved in the expression of a heroin conditioned immune response, is also involved in the acquisition of this effect. Importantly, this effect is likely not due to blocking the response to the unconditioned stimulus since IL-1RA did not affect heroin's immunosuppressive effects. PMID:27072068

  15. Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia

    PubMed Central

    Narita, Atsushi; Muramatsu, Hideki; Sekiya, Yuko; Okuno, Yusuke; Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Yoshida, Nao; Wang, Xinan; Xu, Yinyan; Kawashima, Nozomu; Doisaki, Sayoko; Hama, Asahito; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Kobayashi, Masao; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

    2015-01-01

    Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was −0.99 standard deviation (SD) (range −4.01–+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972. PMID:26315930

  16. Immunosuppressive activity induced by nitric oxide in culture supernatant of activated rat alveolar macrophages.

    PubMed Central

    Kawabe, T; Isobe, K I; Hasegawa, Y; Nakashima, I; Shimokata, K

    1992-01-01

    Alveolar macrophages (AM) from normal rats had immunosuppressive activity to mitogen-induced proliferative responses of splenic lymphocytes. We studied the mechanism and the implication of the nitric oxide synthetase pathway in AM-mediated suppression of concanavalin A (Con A)-induced lymphocyte proliferation. The culture supernatant from AM cultures alone did not have immunosuppressive activity to Con A-induced proliferative responses of non-adherent spleen cells (n-ad SC), but the culture supernatant from co-culture of AM and autologous n-ad SC had this activity. Con A-pulsed AM also liberated the immunosuppressive factor. When AM and autologous n-ad SC were cultured separately under the condition that medium could freely communicate, the culture supernatant did not suppress the Con A-induced proliferative response of n-ad SC. This indicated that the immunosuppressive factor was liberated when AM was activated by cell-to-cell contact with n-ad SC. Further, we examined the immunosuppressive activity of the culture supernatant of co-culture of AM and autologous n-ad SC to Con A-induced responses of allogeneic n-ad SC and xenogeneic murine n-ad SC, and allogeneic mixed leucocyte reaction, and found that this culture supernatant could suppress all these proliferative responses. Nitrate (NO2-) synthesis was markedly augmented in the culture supernatants of Con A-pulsed AM and co-culture of AM and n-ad SC. NG-monomethyl-L-arginine (MMA), a specific competitive inhibitor of the nitric oxide synthetase pathway (NOSP), extinguished both NO2- synthesis by AM and AM-mediated immunosuppressive activity. These data suggest that NOSP was important in AM-mediated suppression of Con A-induced lymphocyte proliferation. PMID:1385798

  17. Dual-Band Optical Bench for Terahertz Radiometer for Outer Planet Atmospheres (TROPA)

    NASA Technical Reports Server (NTRS)

    Schlecht, Erich; Jamnejad, Vahraz

    2012-01-01

    We have developed a wide-band dual frequency spectrometer for use in deep space planetary atmospheric spectroscopy. The instrument uses a dual-band architecture, both to be able to observe spectral lines from a wide range of atmospheric species, and to allow a higher precision retrieval of temperature/pressure/partial pressure and wind profiles. This dual-band approach requires a new design for the optical bench to couple both frequencies into their respective receivers.

  18. Reprogramming the tumor microenvironment: tumor-induced immunosuppressive factors paralyze T cells

    PubMed Central

    Wu, Annie A; Drake, Virginia; Huang, Huai-Shiuan; Chiu, ShihChi; Zheng, Lei

    2015-01-01

    It has become evident that tumor-induced immuno-suppressive factors in the tumor microenvironment play a major role in suppressing normal functions of effector T cells. These factors serve as hurdles that limit the therapeutic potential of cancer immunotherapies. This review focuses on illustrating the molecular mechanisms of immunosuppression in the tumor microenvironment, including evasion of T-cell recognition, interference with T-cell trafficking, metabolism, and functions, induction of resistance to T-cell killing, and apoptosis of T cells. A better understanding of these mechanisms may help in the development of strategies to enhance the effectiveness of cancer immunotherapies. PMID:26140242

  19. Digital Receiver Phase Meter

    NASA Technical Reports Server (NTRS)

    Marcin, Martin; Abramovici, Alexander

    2008-01-01

    The software of a commercially available digital radio receiver has been modified to make the receiver function as a two-channel low-noise phase meter. This phase meter is a prototype in the continuing development of a phase meter for a system in which radiofrequency (RF) signals in the two channels would be outputs of a spaceborne heterodyne laser interferometer for detecting gravitational waves. The frequencies of the signals could include a common Doppler-shift component of as much as 15 MHz. The phase meter is required to measure the relative phases of the signals in the two channels at a sampling rate of 10 Hz at a root power spectral density <5 microcycle/(Hz)1/2 and to be capable of determining the power spectral density of the phase difference over the frequency range from 1 mHz to 1 Hz. Such a phase meter could also be used on Earth to perform similar measurements in laser metrology of moving bodies. To illustrate part of the principle of operation of the phase meter, the figure includes a simplified block diagram of a basic singlechannel digital receiver. The input RF signal is first fed to the input terminal of an analog-to-digital converter (ADC). To prevent aliasing errors in the ADC, the sampling rate must be at least twice the input signal frequency. The sampling rate of the ADC is governed by a sampling clock, which also drives a digital local oscillator (DLO), which is a direct digital frequency synthesizer. The DLO produces samples of sine and cosine signals at a programmed tuning frequency. The sine and cosine samples are mixed with (that is, multiplied by) the samples from the ADC, then low-pass filtered to obtain in-phase (I) and quadrature (Q) signal components. A digital signal processor (DSP) computes the ratio between the Q and I components, computes the phase of the RF signal (relative to that of the DLO signal) as the arctangent of this ratio, and then averages successive such phase values over a time interval specified by the user.

  20. Radio Astronomy Software Defined Receiver Project

    SciTech Connect

    Vacaliuc, Bogdan; Leech, Marcus; Oxley, Paul; Flagg, Richard; Fields, David

    2011-01-01

    The paper describes a Radio Astronomy Software Defined Receiver (RASDR) that is currently under development. RASDR is targeted for use by amateurs and small institutions where cost is a primary consideration. The receiver will operate from HF thru 2.8 GHz. Front-end components such as preamps, block down-converters and pre-select bandpass filters are outside the scope of this development and will be provided by the user. The receiver includes RF amplifiers and attenuators, synthesized LOs, quadrature down converters, dual 8 bit ADCs and a Signal Processor that provides firmware processing of the digital bit stream. RASDR will interface to a user s PC via a USB or higher speed Ethernet LAN connection. The PC will run software that provides processing of the bit stream, a graphical user interface, as well as data analysis and storage. Software should support MAC OS, Windows and Linux platforms and will focus on such radio astronomy applications as total power measurements, pulsar detection, and spectral line studies.

  1. Solar thermal energy receiver

    NASA Technical Reports Server (NTRS)

    Baker, Karl W. (Inventor); Dustin, Miles O. (Inventor)

    1992-01-01

    A plurality of heat pipes in a shell receive concentrated solar energy and transfer the energy to a heat activated system. To provide for even distribution of the energy despite uneven impingement of solar energy on the heat pipes, absence of solar energy at times, or failure of one or more of the heat pipes, energy storage means are disposed on the heat pipes which extend through a heat pipe thermal coupling means into the heat activated device. To enhance energy transfer to the heat activated device, the heat pipe coupling cavity means may be provided with extensions into the device. For use with a Stirling engine having passages for working gas, heat transfer members may be positioned to contact the gas and the heat pipes. The shell may be divided into sections by transverse walls. To prevent cavity working fluid from collecting in the extensions, a porous body is positioned in the cavity.

  2. Dual spectra well logging system

    SciTech Connect

    Nussbaum, T.W.

    1982-09-07

    A dual spectra well logging system includes a well logging tool which is adapted to pass through a bore hole in an earth formation. The well logging tool includes at least two sensors which sense at least one condition of the earth formation and provides corresponding pulse signals. A circuit connected to the sensors provides a combined pulse signal wherein the pulses of the pulse signal from one sensor has one polarity and the pulses of the pulse signal from the other sensor has pulses of an opposite polarity. A circuit applies the combined pulse signal to a well logging cable which conducts the combined pulse signal to the surface of the earth formation. Surface apparatus includes a network connected to the cable which provides control signals in accordance with the polarity of the pulses in the combined pulse signal. A network connected to the cable inverts the combined pulse signal and provides a combined pulse signal and an inverted combined pulse signal. A first switching network receiving the combined pulse signal passes the pulses derived from the pulses of the one polarity in acccordance with the control signals to provide a first pulse signal while a second switching network receiving the inverted combined pulse signal passes the pulses derived from the pulses of the opposite polarity in accordance with the control signals to provide a second pulse signal. An output network processes the two pulse signals to provide an indication of the earth's condition in accordance with the processed pulse signals.

  3. Curriculum Development and Discursive Practices: Building a Training Culture around Dual Diagnosis.

    ERIC Educational Resources Information Center

    Goldsmith, Steve

    Dual diagnosis of comorbid substance abuse and mental disorder is currently presenting great difficulties across Australia's health and community service sectors. Historically, mental health professionals have received relatively little formal education or training in substance abuse issues. A new curriculum on dual diagnosis was developed and…

  4. Dual-modality imaging

    NASA Astrophysics Data System (ADS)

    Hasegawa, Bruce; Tang, H. Roger; Da Silva, Angela J.; Wong, Kenneth H.; Iwata, Koji; Wu, Max C.

    2001-09-01

    In comparison to conventional medical imaging techniques, dual-modality imaging offers the advantage of correlating anatomical information from X-ray computed tomography (CT) with functional measurements from single-photon emission computed tomography (SPECT) or with positron emission tomography (PET). The combined X-ray/radionuclide images from dual-modality imaging can help the clinician to differentiate disease from normal uptake of radiopharmaceuticals, and to improve diagnosis and staging of disease. In addition, phantom and animal studies have demonstrated that a priori structural information from CT can be used to improve quantification of tissue uptake and organ function by correcting the radionuclide data for errors due to photon attenuation, partial volume effects, scatter radiation, and other physical effects. Dual-modality imaging therefore is emerging as a method of improving the visual quality and the quantitative accuracy of radionuclide imaging for diagnosis of patients with cancer and heart disease.

  5. Advanced space solar dynamic receivers

    NASA Technical Reports Server (NTRS)

    Strumpf, Hal J.; Coombs, Murray G.; Lacy, Dovie E.

    1988-01-01

    A study has been conducted to generate and evaluate advanced solar heat receiver concepts suitable for orbital application with Brayton and Stirling engine cycles in the 7-kW size range. The generated receiver designs have thermal storage capability (to enable power production during the substantial eclipse period which accompanies typical orbits) and are lighter and smaller than state-of-the-art systems, such as the Brayton solar receiver being designed and developed by AiResearch for the NASA Space Station. Two receiver concepts have been developed in detail: a packed bed receiver and a heat pipe receiver. The packed bed receiver is appropriate for a Brayton engine; the heat pipe receiver is applicable for either a Brayton or Stirling engine. The thermal storage for both concepts is provided by the melting and freezing of a salt. Both receiver concepts offer substantial improvements in size and weight compared to baseline receivers.

  6. Fundamental aspects and design of FM upconversion receiver front-end with on-chip SAW filters

    NASA Astrophysics Data System (ADS)

    Vanzeijl, Paulus Thomas Maria

    The characteristics of FM (Frequency Modulation) receivers, including tuned radio frequency and single conversion receivers, are described. The modeling of SAW (Surface Acoustic Wave) delay lines, SAW transversal filters and the behavior of SAW resonators and SAW resonator filters are discussed. The design of the FM upconversion receiver front end is described and a new class of balanced dual loop amplifiers is discussed.

  7. Dual Species NMR Oscillator

    NASA Astrophysics Data System (ADS)

    Weber, Joshua; Korver, Anna; Thrasher, Daniel; Walker, Thad

    2016-05-01

    We present progress towards a dual species nuclear magnetic oscillator using synchronous spin exchange optical pumping. By applying the bias field as a sequence of alkali 2 π pulses, we generate alkali polarization transverse to the bias field. The alkali polarization is then modulated at the noble gas resonance so that through spin exchange collisions the noble gas becomes polarized. This novel method of NMR suppresses the alkali field frequency shift by at least a factor of 2500 as compared to longitudinal NMR. We will present details of the apparatus and measurements of dual species co-magnetometry using this method. Research supported by the NSF and Northrop-Grumman Corp.

  8. Dual-Mode Combustor

    NASA Technical Reports Server (NTRS)

    Trefny, Charles J (Inventor); Dippold, Vance F (Inventor)

    2013-01-01

    A new dual-mode ramjet combustor used for operation over a wide flight Mach number range is described. Subsonic combustion mode is usable to lower flight Mach numbers than current dual-mode scramjets. High speed mode is characterized by supersonic combustion in a free-jet that traverses the subsonic combustion chamber to a variable nozzle throat. Although a variable combustor exit aperture is required, the need for fuel staging to accommodate the combustion process is eliminated. Local heating from shock-boundary-layer interactions on combustor walls is also eliminated.

  9. Dual Funding for Dual Enrollment: An Inducement or an Impediment?

    ERIC Educational Resources Information Center

    Hunt, Erika

    2007-01-01

    While the strategy of funding both systems provides an incentive for both school districts and community colleges to participate with dual enrollment, the current fiscal environment has drawn attention to the inefficient use of the dual funding structure. This article highlights the results of a case study on Florida's dual enrollment program…

  10. FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics.

    PubMed

    Kino, T; Hatanaka, H; Hashimoto, M; Nishiyama, M; Goto, T; Okuhara, M; Kohsaka, M; Aoki, H; Imanaka, H

    1987-09-01

    FK-506, a novel immunosuppressant, has been isolated from the fermentation broth of Streptomyces tsukubaenis No. 9993 as colorless prism and the molecular formula was determined as C44H69NO12.H2O. The compound suppressed immune responses in vitro and in vivo with mice. This immunosuppressive effect was more potent than that of ciclosporin. PMID:2445721

  11. Dual Citizenship Rights: Do they Make More and Richer Citizens?

    PubMed Central

    MAZZOLARI, FRANCESCA

    2009-01-01

    In the 1990s, Colombia, the Dominican Republic, Ecuador, Costa Rica, and Brazil passed dual citizenship laws granting their expatriates the right to naturalize in the receiving country without losing their nationality of origin. I estimate the effects of these new laws on naturalization rates and labor market outcomes in the United States. Based on data from the 1990 and 2000 U.S. censuses, I find that immigrants recently granted dual nationality rights are more likely to naturalize relative to immigrants from other Latin American countries. They also experience relative employment and earnings gains, together with drops in welfare use, suggesting that dual citizenship rights not only increase the propensity to naturalize but may also promote economic assimilation. The effects of dual citizenship on improved economic performance, if mediated through naturalization, are consistent with American citizenship conferring greater economic opportunities. PMID:19348114

  12. Dual citizenship rights: do they make more and richer citizens?

    PubMed

    Mazzolari, Francesca

    2009-02-01

    In the 1990s, Colombia, the Dominican Republic, Ecuador, Costa Rica, and Brazil passed dual citizenship laws granting their expatriates the right to naturalize in the receiving country without losing their nationality of origin. I estimate the effects of these new laws on naturalization rates and labor market outcomes in the United States. Based on data from the 1990 and 2000 U.S. censuses, I find that immigrants recently granted dual nationality rights are more likely to naturalize relative to immigrants from other Latin American countries. They also experience relative employment and earnings gains, together with drops in welfare use, suggesting that dual citizenship rights not only increase the propensity to naturalize but may also promote economic assimilation. The effects of dual citizenship on improved economic performance, if mediated through naturalization, are consistent with American citizenship conferring greater economic opportunities. PMID:19348114

  13. The osmolyte taurine protects against ultraviolet B radiation-induced immunosuppression.

    PubMed

    Rockel, Nicole; Esser, Charlotte; Grether-Beck, Susanne; Warskulat, Ulrich; Flögel, Ulrich; Schwarz, Agatha; Schwarz, Thomas; Yarosh, Daniel; Häussinger, Dieter; Krutmann, Jean

    2007-09-15

    Organic osmolytes, such as taurine, are involved in cell volume homeostasis and cell protection. Epidermal keratinocytes possess an osmolyte strategy, i.e., they take up taurine upon hyperosmotic stress and express the corresponding transporter TAUT. UVB irradiation also triggers taurine uptake and TAUT expression in this cell type. We therefore asked whether taurine plays a role in photoprotection. By using a TAUT-deficient mouse model, lack of taurine in the skin was found to cause a significantly higher sensitivity to UVB-induced immunosuppression. This was not due to an increased generation or decreased repair of UVB-induced DNA photoproducts in the skin of these animals. Instead, decreased skin taurine levels were associated with an increased formation of the soluble immunosuppressive molecule platelet-activating factor (PAF) from the membranes of UVB-irradiated epidermal cells. Blocking PAF activity in taut-deficient mice with a PAF receptor antagonist abrogated their increased sensitivity to UVB-induced immunosuppression. Moreover, taut -/- mice were more sensitive to PAF-mediated immunosuppression than taut +/+ mice. These data suggest that taurine uptake by epidermal cells prevents undue PAF formation, and thereby photoimmunosuppression. Thus, similar to nucleotide excision repair, taurine uptake is critically involved in photoprotection of the skin. PMID:17785795

  14. METHOXYACETALDEHYDE, AN INTERMEDIATE METABOLITE OF 2-METHOXYETHANOL, IS IMMUNOSUPPRESSIVE IN THE RAT

    EPA Science Inventory

    2-Methoxyethanol (ME) is metabolized to 2-methoxyacetic acid (MAA) via the intermediate metabolite methoxyacetaldehyde (MAAD). oth ME and MAA have been shown in this laboratory to be immunosuppressive in rats following oral dosing. n this study, the plaque-forming cell (PFC) resp...

  15. Mycobacterium leprae and Mycobacterium haemophilum co-infection in an iatrogenically immunosuppressed patient.

    PubMed

    SoRelle, Jeffrey A; Beal, Stacy G; Scollard, David M; Gander, Rita M; Cohen, Jack; Nuara, Anthony; Nations, Sharon; Cavuoti, Dominick

    2014-04-01

    We present the case of a native Texan who was diagnosed with tuberculoid leprosy and later developed a cutaneous infection with M. haemophilum following iatrogenic immunosuppression. To our knowledge, there are no such reports of M. haemophilum and M. leprae infection occurring simultaneously in the same host. PMID:24439137

  16. [Thromboerythrocytic immunosuppression and its correction by cell membrane stabilizers during intensive exercise].

    PubMed

    Brovkina, I L; Losenok, S A; Prokopenko, L G

    2008-01-01

    Erythrocytes possessing immunosuppressive properties appear in the blood of animals after intensive physical exercise. These properties of erythrocytes arise during their interaction with platelets and LDL+VLDL fraction. Essenciale increases erythrocyte resistance to the action of platelets modified by lipoproteins while mildronate destroys interaction of lipoproteins and platelets. PMID:18411654

  17. Biomarkers of Immunosuppressant Organ Toxicity after Transplantation - Status, Concepts and Misconceptions

    PubMed Central

    Christians, Uwe; Klawitter, Jost; Klawitter, Jelena; Brunner, Nina; Schmitz, Volker

    2010-01-01

    Introduction A major challenge in transplantation is improving long-term organ transplant and patient survival. Immunosuppressants protect the transplant organ from alloimmune reactions, but they also exhibit sometimes limiting side effects. The key to improving long-term outcome following transplantation is the selection of the correct immunosuppressive regimen for an individual patient to minimize toxicity while maintaining immunosuppressive efficacy. Areas covered Proteomics and metabolomics have the potential to develop sensitive and specific diagnostic tools for monitoring early changes in cell signal transduction, regulation and biochemical pathways. Here we review the steps required for the development of molecular markers from discovery, mechanistic and clinical qualification to regulatory approval, and present a critical discussion of the current status of molecular marker development as relevant for the management and individualization of immunosuppressive drug regimens. Expert opinion Although metabolomics and proteomics-based studies have yielded several candidate molecular markers, most published studies are poorly designed, statistically underpowered and/or often have not gone beyond the discovery stage. Most molecular marker candidates are still at an early stage. Due to the high complexity of and the resources required for diagnostic marker development, initiatives and consortia organized and supported by funding agencies and regulatory agencies will be critical. PMID:21241200

  18. A conserved docking surface on calcineurin mediates interaction with substrates and immunosuppressants

    PubMed Central

    Rodríguez, Antonio; Roy, Jagoree; Martínez-Martínez, Sara; López-Maderuelo, Ma Dolores; Niño-Moreno, Perla; Ortí, Leticia; Pantoja, David; Pineda-Lucena, Antonio; Cyert, Martha S.; Redondo, Juan Miguel

    2009-01-01

    SUMMARY The phosphatase calcineurin, target of the immunosuppressants cyclosporin A and FK506, dephosphorylates NFAT transcription factors to promote immune activation and development of the vascular and nervous systems. NFAT interacts with calcineurin through distinct binding motifs: the PxIXIT and LxVP sites. While many calcineurin substrates contain PxIxIT motifs, the generality of LxVP-mediated interactions is unclear. We define critical residues in the LxVP motif, and demonstrate its binding to a hydrophobic pocket at the interface of the two calcineurin subunits. Mutations in this region disrupt binding of mammalian calcineurin to NFATc1, and interaction of yeast calcineurin with substrates including Rcn1, which contains an LxVP motif. These mutations also interfere with calcineurin-immunosuppressant binding, and an LxVP-based peptide competes with immunosuppressant-immunophilin complexes for binding to calcineurin. These studies suggest that LxVP-type sites are a common feature of calcineurin substrates and that immunosuppressant-immunophilin complexes inhibit calcineurin by interfering with this mode of substrate recognition. PMID:19285944

  19. Factors contributing to immunosuppression in the dairy cow during the periparturient period.

    PubMed

    Ingvartsen, Klaus L; Moyes, Kasey M

    2015-02-01

    The transition from late gestation to early lactation results in dramatic physiological changes including metabolic changes and immunosuppression in the dairy cow. As a result, cows are at a high risk for disease during this time. Evidence supporting a link between metabolic status and naturally occurring immunosuppression is growing. This review focuses on the impacts of metabolic status, and the metabolites that characterize it, on the immune response of cows during the transition period. Glucose is the preferred fuel for immune cells and its low concentration during the transition period may partly explain the naturally occurring immunosuppression at this time. To our knowledge, ketones are not utilized by immune cells and primarily have been shown to inhibit the immune response when concentration is relatively high. The effect of fatty acids on the immune system response remains unclear. Evidence suggests that the type of fatty acid can either stimulate (i.e. saturated fatty acids) or inhibit (i.e. unsaturated fatty acids) the immune response. We have suggested that an index for physiological imbalance (PI), based on circulating metabolites that characterize metabolic status, directly relates to mechanisms associated with the development of disease and is superior to calculated energy balance and therefore is a better predictor of risk of disease. The usefulness of the PI index as a predictor of risk of disease and the mechanisms associated with the links between degree of PI and immunosuppression for dairy cows during the transition period warrants further investigation. PMID:25872323

  20. Impact of immunosuppressant therapy on early recurrence of hepatocellular carcinoma after liver transplantation

    PubMed Central

    Lee, Ju-Yeun; Kim, Yul Hee; Kim, Hyang Sook; Lee, Hye Suk; Lee, Byung Koo; Kim, Hyeyoung; Choi, Young Rok; Hong, Geun; Lee, Kwang-Woong; Suh, Kyung-Suk

    2014-01-01

    Background/Aims The most commonly used immunosuppressant therapy after liver transplantation (LT) is a combination of tacrolimus and steroid. Basiliximab induction has recently been introduced; however, the most appropriate immunosuppression for hepatocellular carcinoma (HCC) patients after LT is still debated. Methods Ninety-three LT recipients with HCC who took tacrolimus and steroids as major immunosuppressants were included. Induction with basiliximab was implemented in 43 patients (46.2%). Mycophenolate mofetil (MMF) was added to reduce the tacrolimus dosage (n=28, 30.1%). The 1-year tacrolimus exposure level was 7.2 ± 1.3 ng/mL (mean ± SD). Results The 1- and 3-year recurrence rates of HCC were 12.9% and 19.4%, respectively. Tacrolimus exposure, cumulative steroid dosages, and MMF dosages had no impact on HCC recurrence. Induction therapy with basiliximab, high alpha fetoprotein (AFP; >400 ng/mL) and protein induced by vitamin K absence/antagonist-II (PIVKA-II; >100 mAU/mL) levels, and microvascular invasion were significant risk factors for 1-year recurrence (P<0.05). High AFP and PIVKA-II levels, and positive 18fluoro-2-deoxy-d-glucose positron-emission tomography findings were significantly associated with 3-year recurrence (P<0.05). Conclusions Induction therapy with basiliximab, a strong immunosuppressant, may have a negative impact with respect to early HCC recurrence (i.e., within 1 year) in high-risk patients. PMID:25032186

  1. Effect of Three Drugs against Encephalitozoon cuniculi Infection in Immunosuppressed Mice

    PubMed Central

    da Costa, Lidiana F. Vidoto; de Castro, João Manoel

    2013-01-01

    Microsporidia comprise a large group of obligate intracellular parasites. The microsporidian Encephalitozoon cuniculi causes disseminated infection in immunosuppressed patients with HIV, cancer, or transplants and in the elderly. In vivo and in vitro studies on the effectiveness of drugs are controversial. Currently, there is no effective treatment. We tested albendazole, albendazole sulfoxide, metronidazole, and cyclosporine in mice immunosuppressed with cyclophosphamide and inoculated by the intraperitoneal route with 107 E. cuniculi spores. One week after experimental inoculation, the mice were treated with albendazole, albendazole sulfoxide, metronidazole, and cyclosporine. Histological and morphometric analyses were performed to compare the treated groups. The state of immunosuppression was evaluated by phenotyping CD4+ and CD8+ T cells by flow cytometry. Nontreated mice showed acute disseminated and fatal encephalitozoonosis. The treatment with benzimidazoles significantly reduced infection until 30 days posttreatment (p.t.), but at 60 days p.t., the infection had recurred. Metronidazole decreased infection by a short time, and cyclosporine was not effective. All animals were immunosuppressed by all the experiments, as demonstrated by the low number of CD4+ and CD8+ T cells. We conclude that no drug was effective against E. cuniculi, but the benzimidazoles controlled the infection transiently. PMID:23612191

  2. Pyrimidine dimers in DNA initiate systemic immunosuppression in UV-irradiated mice.

    PubMed

    Kripke, M L; Cox, P A; Alas, L G; Yarosh, D B

    1992-08-15

    Exposing the skin of mice to UV radiation interferes with the induction of delayed and contact hypersensitivity immune responses initiated at nonirradiated sites. The identity of the molecular target in the skin for these immunosuppressive effects of UV radiation remains controversial. To test the hypothesis that DNA is the target for UV-induced systemic immunosuppression, we exposed C3H mice to UV radiation and then used liposomes to deliver a dimer-specific excision repair enzyme into the epidermis in situ. The application of T4 endonuclease V encapsulated in liposomes to UV-irradiated mouse skin decreased the number of cyclobutane pyrimidine dimers in the epidermis and prevented suppression of both delayed and contact hypersensitivity responses. Moreover, the formation of suppressor lymphoid cells was inhibited. Control, heat-inactivated endonuclease encapsulated in liposomes had no effect. These studies demonstrate that DNA is the major target of UV radiation in the generation of systemic immunosuppression and suggest that the primary molecular event mediating these types of immunosuppression by UV radiation is the formation of pyrimidine dimers. Furthermore, they illustrate that the delivery of lesion-specific DNA repair enzymes to living skin after UV irradiation is an effective tool for restoring immune function and suggest that this approach may be broadly applicable to preventing other alterations caused by DNA damage. PMID:1502162

  3. The effect of infectious bursal disease virus induced immunosuppression on avian influenza virus vaccine efficacy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the field, poultry are exposed to a variety of infectious agents, many of which are immunosuppressive. Co-infections between these agents are common, and these co-infections have effects on disease, immune response, and vaccine efficacy. The effect of co-infections in poultry between immunosupp...

  4. A case of invasive cytomegalovirus duodenitis in an immunosuppressed patient 15 months after renal transplantation.

    PubMed

    Kazanji, N; Davila, F; Manickam, P; Wang, Y; Bossory, L

    2015-06-01

    Cytomegalovirus (CMV) remains one of the most important infections in kidney transplantation. Only a handful of images have been reported in the literature thus far. We present classic pathologic and gross images of CMV duodenitis in an immunosuppressed patient more than one year post-renal transplantation. PMID:25582982

  5. SUSCEPTIBILITY OF THE DEVELOPING IMMUNE SYSTEM OF THE RAT TO IMMUNOSUPPRESSION BY THE PESTICIDE HEPTACHLOR

    EPA Science Inventory

    Determination of the Potential Susceptibility of the Developing Immune System of the Rat to Immunosuppression by the Pesticide Heptachlor
    R.J. Smialowicz1 W.C. Williams1, C.B. Copeland1, and R.A. Matulka2
    1Office of Research and Development, National Health and Environment...

  6. Dexamethasone immunosuppression results in turkey clostridial dermatitis: A retrospective analysis of 7 studies, 1998 - 2009

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have been studying the etiology of turkey osteomyelitis complex (TOC) for the past 20 years and have determined that this syndrome is caused by the inability of some fast-growing male turkeys to cope with production stressors. While immunosuppressive viruses have often been associated with suscep...

  7. Monitoring of Nonsteroidal Immunosuppressive Drugs in Patients With Lung Disease and Lung Transplant Recipients

    PubMed Central

    Meyer, Keith C; Nathanson, Ian; Angel, Luis; Bhorade, Sangeeta M; Chan, Kevin M; Culver, Daniel; Harrod, Christopher G; Hayney, Mary S; Highland, Kristen B; Limper, Andrew H; Patrick, Herbert; Strange, Charlie; Whelan, Timothy

    2012-01-01

    Objectives: Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and inflammatory lung disease and lung transplant recipients are associated with potential risks for adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents. Methods: Committee members developed and refined a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline. Conclusions: It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease. PMID:23131960

  8. DIFFERENCES BETWEEN RATS AND MICE IN THE IMMUNOSUPPRESSIVE ACTIVITY OF 2-METHOXYETHANOL AND 2-METHOXYACETIC ACID

    EPA Science Inventory

    In the present study, the immunosuppressive potential of ME and MAA was evaluated in young adult female Fischer 344 rats and C57BL/6J mice. ats and mice ware dosed by gavage with either ME or in water, at dosages ranging from 90 to 400 mg/kg/d, for 1 consecutive days. ats and mic...

  9. Selection and use of immunosuppressive therapies after liver transplantation: current German practice.

    PubMed

    Herzer, Kerstin; Strassburg, Christian P; Braun, Felix; Engelmann, Cornelius; Guba, Markus; Lehner, Frank; Nadalin, Silvio; Pascher, Andreas; Scherer, Marcus N; Schnitzbauer, Andreas A; Zimmermann, Tim; Nashan, Björn; Sterneck, Martina

    2016-05-01

    In recent years, immunosuppression (IS) after liver transplantation (LT) has become increasingly diversified as the choice of agents has expanded and clinicians seek to optimize the balance of immunosuppressive potency with the risk of adverse events in individual patients. Calcineurin inhibitors (CNIs) are the primary agents used for patients undergoing liver transplantation. Other therapeutic agents like interleukin-2 receptor antagonists are not universally administered, but can be considered for the delay or reduction in CNI exposure. An early addition of mycophenolate mofetil (MMF) or the mTOR inhibitor everolimus also allows for the reduction in the CNI dose. To reduce the risk of malignancy, in particular of skin tumors, as well as to prevent the deterioration of renal function, everolimus-based therapy may be advantageous. Apart from patients with autoimmune hepatitis, steroids are withdrawn within 3-6 months after transplantation. Overall, immunosuppression can only be standardized in a limited proportion of patients due to specific clinical requirements and risk factors. Future studies should attempt to refine accurate individualization of the immunosuppressive regimen in specific difficult-to-treat patient subpopulations. PMID:26855333

  10. Pleurotus nebrodensis polysaccharide (PN-S) enhances the immunity of immunosuppressed mice.

    PubMed

    Cui, Hai-Yan; Wang, Chang-Lu; Wang, Yu-Rong; Li, Zhen-Jing; Chen, Mian-Hua; Li, Feng-Juan; Sun, Yan-Ping

    2015-10-01

    In the present study, the effects of Pleurotus nebrodensis polysaccharide (PN-S) on the immune functions of immunosuppressed mice were determined. The immunosuppressed mouse model was established by treating the mice with cyclophosphamide (40 mg/kg/2d, CY) through intraperitoneal injection. The results showed that PN-S administration significantly reversed the CY-induced weight loss, increased the thymic and splenic indices, and promoted proliferation of T lymphocyte, B lymphocyte, and macrophages. PN-S also enhanced the activity of natural killer cells and increased the immunoglobulin M (IgM) and immunoglobulin G (IgG) levels in the serum. In addition, PN-S treatment significantly increased the phagocytic activity of mouse peritoneal macrophages. PN-S also increased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), and nitric oxide (NOS) in splenocytes. qRT-PCR results also indicated that PN-S increased the mRNA expression of IL-6, TNF-α, INF-γ, and nitric oxide synthase (iNOS) in the splenocytes. These results suggest that PN-S treatment enhances the immune function of immunosuppressed mice. This study may provide a basis for the application of this fungus in adjacent immunopotentiating therapy against cancer and in the treatment of chemotherapy-induced immunosuppression. PMID:26481376

  11. Evolving concepts in the selection of immunosuppression regimen for liver transplant recipients

    PubMed Central

    Locke, Jayme E; Singer, Andrew L

    2011-01-01

    The introduction of calcineurin inhibitor (CNI) based immunosuppression has revolutionized the field of liver transplantation by dramatically reducing the incidence of acute cellular rejection and prolonging patient and allograft survival. However, the introduction of CNIs has also come at the price of increased patient morbidity, particularly with regard to the well-known nephrotoxic effects of the medications. In an effort to minimize the adverse effects, immunosuppression regimen have evolved to include the use of various induction agents and purine synthesis inhibitors to limit the dose of CNI necessary to achieve low acute cellular rejection rates. Careful assessments of risks and benefits are needed as these newer agents have their own side effect profiles. In addition, the impact of newer immunosuppression regimen on hepatitis C (HCV) recurrence has not been completely elucidated. This review will provide an overview of the most common immunosuppression regimen used in liver transplantation and discuss their impact on acute cellular rejection, patient and allograft survival, and HCV recurrence. PMID:24367221

  12. Fludarabine-induced immunosuppression is associated with inhibition of STAT1 signaling.

    PubMed

    Frank, D A; Mahajan, S; Ritz, J

    1999-04-01

    Fludarabine is a nucleoside analog used in the treatment of hematologic malignancies that can induce severe and prolonged immunosuppression. Although it can be incorporated into the DNA of dividing cells, fludarabine is also a potent inhibitor of cells with a low growth fraction, thus it must have other mechanisms of action. STAT1, which is activated in response to many lymphocyte-activating cytokines including the interferons, is essential for cell-mediated immunity, as the absence of this protein is associated with prominent defects in the ability to control viral infections. Here we show that fludarabine, but not the immunosuppressant cyclosporine A, inhibits the cytokine-induced activation of STAT1 and STAT1-dependent gene transcription in normal resting or activated lymphocytes. Fludarabine caused a specific depletion of STAT1 protein (and mRNA) but not of other STATs. This loss of STAT1 was also seen in cells from patients treated with fludarabine in vivo. Brief exposure to fludarabine led to a sustained loss of STAT1, analogous to the prolonged period of immunosuppression induced by exposure to the drug in vivo. Thus, STAT1 may be a useful target in the development of new immunosuppressive and antineoplastic agents. PMID:10202937

  13. Anchorage Receives Record Snowfall

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The forecast called for flurries, but the snow accumulated on the ground in Anchorage, Alaska, at the rate of 2 inches per hour (5 cm per hour) for much of Saturday, March 16, 2002. By the time the winter storm passed on Sunday afternoon, Anchorage had received 28.6 inches (72.6 cm) of snow, surpassing by far the previous record of 15.6 inches (39.6 cm) set on December 29, 1955. Flights were canceled and schools were closed as a result of the storm. This true-color image of Alaska was acquired by the Sea-viewing Wide Field-of-view Sensor (SeaWiFS), flying aboard the OrbView-2 satellite, on March 18. It appears another large, low-pressure system is heading toward the Anchorage region, which could bring substantially more snowfall. The low-pressure system can be identified by the characteristic spiral pattern of clouds located off Alaska's southwestern coast in this scene.

  14. Interferon γ and interleukin 10 responses in immunocompetent and immunosuppressed New Zealand White rabbits naturally infected with Encephalitozoon cuniculi.

    PubMed

    Rodríguez-Tovar, Luis E; Castillo-Velázquez, Uziel; Arce-Mendoza, Alma Y; Nevárez-Garza, Alicia M; Zarate-Ramos, Juan J; Hernández-Vidal, Gustavo; Rodríguez-Ramírez, Heidi G; Trejo-Chávez, Armando

    2016-09-01

    Levels of interferon (IFN)-γ and interleukin (IL)-10 were measured in the serum of immunocompetent and immunosuppressed New Zealand White rabbits naturally infected with Encephalitozoon cuniculi. IFN-γ levels were elevated in infected rabbits, and a synergic effect was observed in animals treated with the immunosuppressive agent dexamethasone (Dex). The role of IL-10 in infected rabbits remains unclear, as IL-10 levels were similar to those of negative controls. Dex appeared to exhibit a proinflammatory effect, as IFN-γ levels were elevated in infected immunosuppressed rabbits. Similarly, Dex exhibited a synergic effect in infected immunosuppressed rabbits, as evidenced by the elevation in IFN-γ production. These data indicate that the immune response to this glucocorticoid should be considered in the design of future animal model studies of immunosuppression. PMID:27156850

  15. [Immunosuppressive treatment of rheumatic diseases. Experimental bases of a rational concept of therapeutic approach (author's transl)].

    PubMed

    Lemmel, E M; Botzenhardt, U

    1976-01-01

    For treatment of diseases such as rheumatoid arthritis or systemic lupus erythematodes, which are initiated or sustained by immune-pathological mechanisms, various "immunosuppressive" drugs are used. There are conflicting data as to the benefit of this type of therapy. In this paper it is attempted to define a base for a more differentiated application of available drugs, since the present therapeutic approach seems rather empiric or is deducted from analogy to selected animal experiments. The investigations presented focus primarily on the behaviour of the small and medium lymphocytes of the organism, the adopted carriers of immunological (as well as autoimmune) reactivity, under conventional conditions (and under the influence of suitable drugs) as a biological supposition for the activity of "immunosuppressives". In rabbits, and mice, number and rate of proliferation of lymphoid cells is determined in untreated controls and animals treated with 6-mercaptopurine (6-MP) and cyclophosphamide (Cy), two immunosuppressive agents representing different types of pharmacological action. The elucidation why in rabbits both substances are equally immunosuppressive, whereas in mice only Cy has significant immunosuppressive activity, yields the base for a therapeutic concept of clinical immunosuppression. This species dependent activity of 6-MP can be explained by different proliferation kinetics of lymphoid cells in mouse and rabbit. Lymphocytes of the rabbit, compared to those of mice, are short-lived and have a distinctly higher proliferation rate. Thus, 6-MP, as an antiproliferative agent, leads, in the rabbit (under long-term as well as single-dose therapy) to a significant reduction of the number of small lymphocytes, whereas it reduces the long-lived lymphocytes of the mouse only marginally, thus explaining the good immunosuppressive potency in the rabbit and failure in the mouse. Cy leads, in both species, to a marked reduction of small lymphocytes and affects the

  16. Efficacy and Safety of a Steroid-Free Immunosuppressive Regimen after Liver Transplantation for Hepatocellular Carcinoma

    PubMed Central

    Wei, Qiang; Xu, Xiao; Wang, Chao; Zhuang, Runzhou; Zhuang, Li; Zhou, Lin; Xie, Haiyang; Wu, Jian; Zhang, Min; Shen, Yan; Wang, Weilin; Zheng, Shusen

    2016-01-01

    Background/Aims We aimed to evaluate the efficacy and safety of an immunosuppressive regimen without steroids after liver transplantation (LT) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods Sixty-six HCC patients who underwent an immunosuppressive regimen without steroids after LT were enrolled in the steroid-free group. The preoperative characteristics and postoperative outcomes of these patients were compared with those of 132 HCC recipients who were placed on an immunosuppressive regimen using steroids (steroid group). The incidence of acute rejection, HBV recurrence, infection, and new-onset diabetes mellitus and the overall and tumor-free survival rates were compared between the two groups. Results Differences were not observed in the 1-year (83.3% vs 97.0%, p=0.067), 3-year (65.4% vs 75.8%, p=0.067) or 5-year (56.3% vs 70.7%, p=0.067) patient survival rates or in the 1-year (62.1% vs 72.7%, p=0.067), 3-year (49.8% vs 63.6%, p=0.067) or 5-year (48.6% vs 63.6%, p=0.067) tumor-free survival rates between the two groups, respectively. In the steroid-free group, the patients who fulfilled the Milan criteria had higher overall and tumor-free survival rates than those in the steroid group (p<0.001). The prevalence of HBV recurrence (3.0% vs 13.6%, p=0.02) was significantly lower in the steroid-free group compared with the steroid group. Conclusions After LT, an immunosuppressive regimen without steroids could be a safe and feasible treatment for HBV-related HCC patients, thus resulting in the reduction of HBV recurrence. Based on the observed survival rates, patients who fulfill the Milan criteria may derive benefits from steroid-free immunosuppression. PMID:27074818

  17. Minimization vs tailoring: Where do we stand with personalized immunosuppression during renal transplantation in 2015?

    PubMed Central

    Zsom, Lajos; Wagner, László; Fülöp, Tibor

    2015-01-01

    The introduction of novel immunosuppressive agents over the last two decades and the improvement of our diagnostic tools for early detection of antibody-mediated injury offer us an opportunity, if not a mandate, to better match the immunosuppression needs of the individual patients with side effects of the therapy. However, immunosuppressive regimens in the majority of programs remain mostly protocol-driven, with relatively little inter-program heterogeneity in certain areas of the world. Emerging data showing different outcomes with a particular immunosuppressive strategy in populations with varying immunological risks underscore a real potential for “personalized medicine” in renal transplantation. Studies demonstrating marked differences in the adverse-effect profiles of individual drugs including the risk for viral infections, malignancy and renal toxicity call for a paradigm shift away from a “one size fits all” approach to an individually tailored immunosuppressive therapy for renal transplant recipients, assisted by both screening for predictors of graft loss and paying close attention to dose or class-related adverse effects. Our paper explores some of the opportunities during the care of these patients. Potential areas of improvements may include: (1) a thorough assessment of immunological and metabolic risk profile of each renal transplant recipient; (2) screening for predictors of graft loss and early signs of antibody-mediated rejection with donor-specific antibodies, protocol biopsies and proteinuria (including close follow up of adverse effects with dose adjustments or conversions as necessary); and (3) increased awareness of the possible link between poor tolerance of a given drug at a given dose and non-adherence with the prescribed regimen. Altogether, these considerations may enable the most effective use of the drugs we already have. PMID:26421259

  18. Histological spectrum of pulmonary manifestations in kidney transplant recipients on sirolimus inclusive immunosuppressive regimens

    PubMed Central

    2012-01-01

    Background After the introduction of novel effective immunosuppressive therapies, kidney transplantation became the treatment of choice for end stage renal disease. While these new therapies lead to better graft survival, they can also cause a variety of complications. Only small series or case reports describe pulmonary pathology in renal allograft recipients on mTOR inhibitor inclusive therapies. The goal of this study was to provide a systematic review of thoracic biopsies in kidney transplant recipients for possible association between a type of immunosuppressive regimen and pulmonary complications. Methods A laboratory database search revealed 28 of 2140 renal allograft recipients (18 males and 10 females, 25 to 77 years old, mean age 53 years) who required a biopsy for respiratory symptoms. The histological features were correlated with clinical findings including immunosuppressive medications. Results The incidence of neoplasia on lung biopsy was 0.4% (9 cases), which included 3 squamous cell carcinomas, 2 adenocarcinomas, 1 diffuse large B-cell lymphoma, 1 lymphomatoid granulomatosis, and 2 post transplant B-cell lymphoproliferative disorders. Diffuse parenchymal lung disease was identified in 0.4% (9 cases), and included 5 cases of pulmonary hemorrhage, 3 cases of organizing pneumonia and 1 case of pulmonary alveolar proteinosis. Five (0.2%) cases showed histological features indicative of a localized infectious process. Patients on sirolimus had neoplasia less frequently than patients on other immunosuppressive combinations (12.5% vs. 58.3%, p = 0.03). Lung biopsies in 4 of 5 patients with clinically suspected sirolimus toxicity revealed pulmonary hemorrhage as the sole histological finding or in combination with other patterns. Conclusions Our study documents a spectrum of neoplastic and non-neoplastic lesions in renal allograft recipients on current immunosuppressive therapies. Sirolimus inclusive regimens are associated with increased risk of pulmonary

  19. Dual Coding in Children.

    ERIC Educational Resources Information Center

    Burton, John K.; Wildman, Terry M.

    The purpose of this study was to test the applicability of the dual coding hypothesis to children's recall performance. The hypothesis predicts that visual interference will have a small effect on the recall of visually presented words or pictures, but that acoustic interference will cause a decline in recall of visually presented words and…

  20. Early Dual Language Learning

    ERIC Educational Resources Information Center

    Genesee, Fred

    2008-01-01

    Parents and child care personnel in English-dominant parts of the world often express misgivings about raising children bilingually. Their concerns are based on the belief that dual language learning during the infant-toddler stage confuses children, delays their development, and perhaps even results in reduced language competence. In this…

  1. Dual Christoffel Transformations

    NASA Astrophysics Data System (ADS)

    Odake, S.; Sasaki, R.

    2011-07-01

    Crum's theorem and its modification à la Krein-Adler are formulated for the discrete quantum mechanics with real shifts, whose eigenfunctions consist of orthogonal polynomials of a discrete variable. The modification produces the associated polynomials with a finite number of degrees deleted. This in turn provides the well known Christoffel transformation for the dual orthogonal polynomials with the corresponding positions deleted.

  2. 26 CFR 1.901-2A - Dual capacity taxpayers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... capacity taxpayers receive, directly or indirectly, a specific economic benefit (as defined in § 1.901-2(a... exchange for a specific economic benefit, and such levy, as applicable in the aggregate to such dual... paid in exchange for a specific economic benefit; and, if the country X income tax is an income...

  3. 26 CFR 1.901-2A - Dual capacity taxpayers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... capacity taxpayers receive, directly or indirectly, a specific economic benefit (as defined in § 1.901-2(a... exchange for a specific economic benefit, and such levy, as applicable in the aggregate to such dual... paid in exchange for a specific economic benefit; and, if the country X income tax is an income...

  4. Two Universities, Two Degrees: A Dual Degree Program for Pharmacists.

    ERIC Educational Resources Information Center

    Milio, Frank

    2001-01-01

    Describes a dual degree program between Towson University and the University of Maryland School of Pharmacy, which allows a student to receive both a B.S. degree in Medicinal Chemistry and a Doctor of Pharmacy degree in a combined 7-year program. It also allows flexibility in pursuing alternate career goals. (EV)

  5. Postgrafting immunosuppression with sirolimus and cyclosporine facilitates stable mixed hematopoietic chimerism in dogs given sublethal total body irradiation before marrow transplantation from DLA-identical littermates.

    PubMed

    Hogan, William J; Little, Marie-Térèse; Zellmer, Eustacia; Friedetzky, Anke; Diaconescu, Razvan; Gisburne, Serina; Lee, Richard; Kuhr, Christian; Storb, Rainer

    2003-08-01

    We studied the value of postgrafting immunosuppression with sirolimus (SRL) and cyclosporine (CSP) in enhancing engraftment of dog leukocyte antigen-identical littermate marrow after nonmyeloablative conditioning in a canine model. Dogs received either 2 Gy (n=7) or 1 Gy (n=5) total body irradiation (TBI), followed by postgrafting immunosuppression with SRL and CSP. In the first cohort, all 7 dogs showed rapid initial engraftment. One engrafted dog died on day 21 due to hemorrhagic pneumonitis. Durable engraftment was seen in 5 of 6 remaining dogs, with a median follow-up of >48 (range, >32 to >56) weeks. The sixth dog rejected the marrow graft (as assessed by variable number of tandem repeats) at 11 weeks; however, a subsequent skin graft from the same marrow donor did not undergo acute cellular rejection, suggesting donor-specific tolerance. In the second cohort, all 5 dogs rejected the marrow graft at a median of 9 weeks (range, 3-11 weeks). We conclude that SRL/CSP is as effective as a previously studied combination of mycophenolate mofetil and CSP at establishing durable marrow engraftment after sublethal conditioning. PMID:12931117

  6. Assessment of the level of vaccine-induced anti-HBs antibodies in children with inflammatory systemic connective tissue diseases treated with immunosuppression

    PubMed Central

    Hernik, Elżbieta; Kwiatkowska, Małgorzata; Rutkowska-Sak, Lidia; Kołodziejczyk, Beata; Gazda, Agnieszka

    2015-01-01

    Objectives Protective vaccinations are the most effective method of prevention of type B virus hepatitis. The aim of the study was to determine whether in children receiving immunosuppressive therapy due to inflammatory systemic connective tissue diseases the protective concentration of the anti-HBs antibodies produced after vaccination against type B virus hepatitis in infancy is maintained. Material and methods The concentration of anti-HBs antibodies was assessed in the sera of 50 children with inflammatory connective tissue diseases – 37 girls (74%) and 13 boys (26%), aged 1.5–17.5 years – during the immunosuppressive treatment, which lasted at least 6 months. The control group consisted of 50 healthy children – 28 girls (56%) and 22 boys (44%) aged 2–17 years. All children were vaccinated in infancy with Engerix B vaccine according to the 0–1–6 months schedule. The antibody concentration of ≥ 10 mIU/ml in patients is regarded as protective. Results No protective antibody concentrations were found in 25 cases (50%) in the group of diseased children and only in 2 children in the control group (4%). Conclusions The concentration of vaccine-induced antibodies should be assessed in children with inflammatory systemic connective tissue diseases and, in case of the absence of a protective concentration, revaccination should be started. The use of glucocorticosteroids, synthetic and biological disease-modifying antirheumatic drugs is no contraindication to vaccination against hepatitis B. PMID:27407228

  7. Everolimus in combination with mycophenolate mofetil as pre- and post-transplantation immunosuppression after nonmyeloablative hematopoietic stem cell transplantation in canine littermates.

    PubMed

    Machka, Christoph; Lange, Sandra; Werner, Juliane; Wacke, Rainer; Killian, Doreen; Knueppel, Anne; Knuebel, Gudrun; Vogel, Heike; Lindner, Iris; Roolf, Catrin; Murua Escobar, Hugo; Junghanss, Christian

    2014-09-01

    The mammalian target of rapamycin inhibitor everolimus (RAD001) is a successfully used immunosuppressant in solid-organ transplantation. Several studies have already used RAD001 in combination with calcineurin inhibitors after hematopoietic stem cell transplantation (HSCT). We investigated calcineurin inhibitor-free pre- and post-transplantation immunosuppression of RAD001 combined with mycophenolate mofetil (MMF) in a nonmyeloablative HSCT setting. After nonmyeloablative conditioning with 2 Gy total body irradiation, 8 dogs received HSCT from dog leukocyte antigen-identical siblings. Immunosuppressives were given at doses of 1.5 mg RAD001 twice daily from day -1 to +49, then tapered until day +56, and 20 mg/kg MMF from day 0 to +28, then tapered until day +42. An historical cyclosporin A (CsA)/MMF regimen was used in the control group. All dogs engrafted. Median platelet nadir amounted in all dogs to 0 × 10(9)/L (median, day +10; duration <50 × 10(9)/L, 22 days) and median leukocyte nadir was 1.0 × 10(9)/L (range, .1 to 2.5 × 10(9)/L; median, day +13). Eventually, 5 of 8 (63%) animals rejected their grafts. Two dogs died of infections on day +19 and +25. Pharmacokinetics of RAD001 and MMF showed median trough levels of 19.1 (range, 10.5 to 43.2) μg/L and .3 (.1 to 1.3) mg/L, respectively. The median area under the curve was 325 (range, 178 to 593) μg/L × hour for RAD001 and 29.6 (range, 7.9 to 40.5) ng/L × hour for MMF. All dogs developed clinically mucosal viral infections during the clinical course. Compared with the control group, the level of toxicities for RAD001/MMF increased in all qualities. Combined immunosuppression of RAD001 and MMF after nonmyeloablative HSCT is associated with significant toxicities, including a prolonged platelet recovery time as well as increased infections compared to the CsA/MMF regimen. PMID:24923538

  8. Real-time software receiver

    NASA Technical Reports Server (NTRS)

    Ledvina, Brent M. (Inventor); Psiaki, Mark L. (Inventor); Powell, Steven P. (Inventor); Kintner, Jr., Paul M. (Inventor)

    2007-01-01

    A real-time software receiver that executes on a general purpose processor. The software receiver includes data acquisition and correlator modules that perform, in place of hardware correlation, baseband mixing and PRN code correlation using bit-wise parallelism.

  9. Real-time software receiver

    NASA Technical Reports Server (NTRS)

    Ledvina, Brent M. (Inventor); Psiaki, Mark L. (Inventor); Powell, Steven P. (Inventor); Kintner, Jr., Paul M. (Inventor)

    2006-01-01

    A real-time software receiver that executes on a general purpose processor. The software receiver includes data acquisition and correlator modules that perform, in place of hardware correlation, baseband mixing and PRN code correlation using bit-wise parallelism.

  10. High-temperature ceramic receivers

    SciTech Connect

    Jarvinen, P. O.

    1980-01-01

    An advanced ceramic dome cavity receiver is discussed which heats pressurized gas to temperatures above 1800/sup 0/F (1000/sup 0/C) for use in solar Brayton power systems of the dispersed receiver/dish or central receiver type. Optical, heat transfer, structural, and ceramic material design aspects of the receiver are reported and the development and experimental demonstration of a high-temperature seal between the pressurized gas and the high-temperature silicon carbide dome material is described.

  11. High temperature solar thermal receiver

    NASA Technical Reports Server (NTRS)

    1979-01-01

    A design concept for a high temperature solar thermal receiver to operate at 3 atmospheres pressure and 2500 F outlet was developed. The performance and complexity of windowed matrix, tube-header, and extended surface receivers were evaluated. The windowed matrix receiver proved to offer substantial cost and performance benefits. An efficient and cost effective hardware design was evaluated for a receiver which can be readily interfaced to fuel and chemical processes or to heat engines for power generation.

  12. [Investigation of Pneumocystis jirovecii pneumonia and colonization in iatrogenically immunosuppressed and immunocompetent patients].

    PubMed

    Özkoç, Soykan; Bayram Delibaş, Songül

    2015-04-01

    Pneumocystis pneumonia (PCP) is a potentially life-threatening infection for the immunocompromized patients. However, Pneumocystis jirovecii colonization can also be detected in healthy individuals and in patients with various underlying lung diseases. The aim of this study was to evaluate the immunocompetent and iatrogenically immunosuppressed patients in terms of PCP and P.jirovecii colonization. A total of 92 patients (66 male, 26 female; age range: 18-93 years, median: 58.5) who underwent bronchoscopy due to various pulmonary symptoms between January 2011-April 2014, were included in the study. Of these patients, 65 were under immunosuppressive therapy (38 were treated with anti-cancer drugs, 15 with anti-rejection/immunomodulatory drugs and 12 with corticosteroids), while 27 were immunocompetent. Bronchoalveolar lavage (BAL) fluids were evaluated for the presence of P.jirovecii mitochondrial gene coding ribosomal large subunit (mtLSUrRNA) with nested PCR (nPCR) method. All of the samples were also examined by Giemsa and Gomori's methenamine silver (GMG) staining methods. P.jirovecii DNA was detected in 31 (33.7%) out of 92 BAL samples by nPCR. Although six immunosuppressed patients were positive in the first round of amplification, 26 of 65 (40%) immunosuppressed and five of 27 (18.5%) immunocompetent patients were positive with nPCR. P.jirovecii cysts and trophozoites were detected in only five (16.1%) of the 31 nPCR positive samples. The probability of being immunosuppressive among nPCR positive cases was statistically higher than nPCR negative cases (χ²= 3.940; p= 0.047). This difference was more significant in organ transplant recipients and patients under anti-rejection/immunomodulatory treatment (χ²= 6.715, p= 0.01; χ²= 5.550, p= 0.018, respectively). When clinical, laboratory and radiological findings of nPCR positive patients were considered, five patients (2 kidney transplant, 1 bone marrow transplant, 1 interstitial lung disease and 1 lung

  13. Receiving signals of any polarization

    NASA Technical Reports Server (NTRS)

    Ohlson, J. E.; Seidel, B. L.; Stelzried, C. H.

    1981-01-01

    Two-channel detection accomodates linear, circular, and elliptical polarization in one receiving unit. Receiver employs orthomode transducer which breaks any type signal into one left and one right circular component. These are processed in separate receiver channels with equal time-delay, and then recombined for data extraction. System eliminates losses due to polarization mismatch.

  14. A digital-receiver for the MurchisonWidefield Array

    NASA Astrophysics Data System (ADS)

    Prabu, Thiagaraj; Srivani, K. S.; Roshi, D. Anish; Kamini, P. A.; Madhavi, S.; Emrich, David; Crosse, Brian; Williams, Andrew J.; Waterson, Mark; Deshpande, Avinash A.; Shankar, N. Udaya; Subrahmanyan, Ravi; Briggs, Frank H.; Goeke, Robert F.; Tingay, Steven J.; Johnston-Hollitt, Melanie; R, Gopalakrishna M.; Morgan, Edward H.; Pathikulangara, Joseph; Bunton, John D.; Hampson, Grant; Williams, Christopher; Ord, Stephen M.; Wayth, Randall B.; Kumar, Deepak; Morales, Miguel F.; deSouza, Ludi; Kratzenberg, Eric; Pallot, D.; McWhirter, Russell; Hazelton, Bryna J.; Arcus, Wayne; Barnes, David G.; Bernardi, Gianni; Booler, T.; Bowman, Judd D.; Cappallo, Roger J.; Corey, Brian E.; Greenhill, Lincoln J.; Herne, David; Hewitt, Jacqueline N.; Kaplan, David L.; Kasper, Justin C.; Kincaid, Barton B.; Koenig, Ronald; Lonsdale, Colin J.; Lynch, Mervyn J.; Mitchell, Daniel A.; Oberoi, Divya; Remillard, Ronald A.; Rogers, Alan E.; Salah, Joseph E.; Sault, Robert J.; Stevens, Jamie B.; Tremblay, S.; Webster, Rachel L.; Whitney, Alan R.; Wyithe, Stuart B.

    2015-03-01

    An FPGA-based digital-receiver has been developed for a low-frequency imaging radio interferometer, the Murchison Widefield Array (MWA). The MWA, located at the Murchison Radio-astronomy Observatory (MRO) in Western Australia, consists of 128 dual-polarized aperture-array elements (tiles) operating between 80 and 300 MHz, with a total processed bandwidth of 30.72 MHz for each polarization. Radio-frequency signals from the tiles are amplified and band limited using analog signal conditioning units; sampled and channelized by digital-receivers. The signals from eight tiles are processed by a single digital-receiver, thus requiring 16 digital-receivers for the MWA. The main function of the digital-receivers is to digitize the broad-band signals from each tile, channelize them to form the sky-band, and transport it through optical fibers to a centrally located correlator for further processing. The digital-receiver firmware also implements functions to measure the signal power, perform power equalization across the band, detect interference-like events, and invoke diagnostic modes. The digital-receiver is controlled by high-level programs running on a single-board-computer. This paper presents the digital-receiver design, implementation, current status, and plans for future enhancements.

  15. The 30-GHz monolithic receive module

    NASA Technical Reports Server (NTRS)

    Sokolov, V.; Geddes, J.; Bauhahn, P.

    1983-01-01

    Key requirements for a 30 GHz GaAs monolithic receive module for spaceborne communication antenna feed array applications include an overall receive module noise figure of 5 dB, a 30 dB RF to IF gain with six levels of intermediate gain control, a five-bit phase shifter, and a maximum power consumption of 250 mW. The RF designs for each of the four submodules (low noise amplifier, some gain control, phase shifter, and RF to IF sub-module) are presented. Except for the phase shifter, high frequency, low noise FETs with sub-half micron gate lengths are employed in the submodules. For the gain control, a two stage dual gate FET amplifier is used. The phase shifter is of the passive switched line type and consists of 5-bits. It uses relatively large gate width FETs (with zero drain to source bias) as the switching elements. A 20 GHz local oscillator buffer amplifier, a FET compatible balanced mixer, and a 5-8 GHz IF amplifier constitute the RF/IF sub-module. Phase shifter fabrication using ion implantation and a self-aligned gate technique is described. Preliminary RF results obtained on such phase shifters are included.

  16. Steam Rankine Solar Receiver, phase 2

    NASA Technical Reports Server (NTRS)

    Deanda, L. E.; Faust, M.

    1981-01-01

    A steam rankine solar receiver (SRSR) based on a tubular concept was designed and developed. The SRSR is an insulated, cylindrical coiled tube boiler which is mounted at the focal plane of a fully tracking parabolic solar reflector. The concentrated solar energy received at the focal plane is then transformed to thermal energy through steam generation. The steam is used in a small Rankine cycle heat engine to drive a generator for the production of electrical energy. The SRSR was designed to have a dual mode capability, performing as a once through boiler with and without reheat. This was achieved by means of two coils which constitute the boiler. The boiler core size of the SRSR is 17.0 inches in diameter and 21.5 inches long. The tube size is 7/16 inch I.D. by 0.070 inch wall for the primary, and 3/4 inch I.D. by 0.125 inch wall for the reheat section. The materials used were corrosion resistant steel (CRES) type 321 and type 347 stainless steel. The core is insulated with 6 inches of cerablanket insulation wrapped around the outer wall. The aperture end and the reflector back plate at the closed end section are made of silicon carbide. The SRSR accepts 85 kwth and has a design life of 10,000 hrs when producing steam at 1400 F and 2550 psig.

  17. Dual technicolor with hidden local symmetry

    SciTech Connect

    Belitsky, A. V.

    2010-08-15

    We consider a dual description of the technicolor-like gauge theory within the D4/D8-brane configuration with varying confinement and electroweak symmetry breaking scales. Constructing an effective truncated model valid below a certain cutoff, we identify the particle spectrum with Kaluza-Klein modes of the model in a manner consistent with the hidden local symmetry. Integrating out heavy states, we find that the low-energy action receives nontrivial corrections stemming from the mixing between standard model and heavy gauge bosons, which results in reduction of oblique parameters.

  18. Dual RF Astrodynamic GPS Orbital Navigator Satellite

    NASA Technical Reports Server (NTRS)

    Kanipe, David B.; Provence, Robert Steve; Straube, Timothy M.; Reed, Helen; Bishop, Robert; Lightsey, Glenn

    2009-01-01

    Dual RF Astrodynamic GPS Orbital Navigator Satellite (DRAGONSat) will demonstrate autonomous rendezvous and docking (ARD) in low Earth orbit (LEO) and gather flight data with a global positioning system (GPS) receiver strictly designed for space applications. ARD is the capability of two independent spacecraft to rendezvous in orbit and dock without crew intervention. DRAGONSat consists of two picosatellites (one built by the University of Texas and one built by Texas A and M University) and the Space Shuttle Payload Launcher (SSPL); this project will ultimately demonstrate ARD in LEO.

  19. Pharmacodynamic monitoring of immunosuppressive effects indicates reduced cyclosporine activity during telaprevir therapy.

    PubMed

    Roos, Katja; Gotthardt, Daniel; Giese, Thomas; Schnitzler, Paul; Stremmel, Wolfgang; Czock, David; Eisenbach, Christoph

    2014-09-01

    Drug interactions with immunosuppressive drugs are a major problem associated with protease inhibitor-based antiviral triple therapy for hepatitis C virus (HCV) reinfection after liver transplantation. In this retrospective cohort study, we analyzed biomarkers of the immunosuppressive effects of cyclosporine A (CSA) by quantifying nuclear factor of activated T cells (NFAT)-regulated gene expression during telaprevir (TVR) therapy in 5 liver transplant patients. Furthermore, dose adjustments and blood concentrations of CSA as well as the clinical course were analyzed. We observed a clear impact of TVR not only on doses and blood concentrations but also on the immunosuppressive effects of CSA. Despite apparently adequate CSA trough concentrations, the CSA peak concentration decreased to 68% (range = 44%-90%). This was associated with a 1.9-fold (1.6- to 4.1-fold) increase in the residual gene activity of NFAT-regulated genes, which indicated reduced immunosuppressive activity of CSA with TVR co-medication. The median dose of CSA was reduced to 25% (range = 16%-48%) and 31% (range = 22%-64%) after 1 and 2 weeks, respectively. The CSA drug clearance was reduced to 38.7% (range = 31.0%-49.4%). We report excellent antiviral efficacy. At the end of the observation period, all patients were HCV RNA-negative (1 patient at 18 weeks, 1 patient at 12 weeks, and 3 patients at 4 weeks after the end of therapy). Safety was acceptable, with mild acute rejection and reactivation of cytomegalovirus being the most serious adverse events. One patient with histologically proven recurrent cholestatic hepatitis before therapy underwent retransplantation during the course of antiviral therapy. In conclusion, the immunomonitoring of NFAT-regulated gene expression indicated reduced immunosuppressive activity of CSA during antiviral therapy with TVR in our cohort of liver transplant patients. Thus, the immunosuppressive effects of CSA may be overestimated if one is looking

  20. Galectin-9 is Involved in Immunosuppression Mediated by Human Bone Marrow-derived Clonal Mesenchymal Stem Cells.

    PubMed

    Kim, Si-Na; Lee, Hyun-Joo; Jeon, Myung-Shin; Yi, TacGhee; Song, Sun U

    2015-10-01

    Bone marrow-derived mesenchymal stem cells (MSCs) have immunomodulatory properties and can suppress exaggerated pro-inflammatory immune responses. Although the exact mechanisms remain unclear, a variety of soluble factors are known to contribute to MSC-mediated immunosuppression. However, functional redundancy in the immunosuppressive properties of MSCs indicates that other uncharacterized factors could be involved. Galectin-9, a member of the β-galactoside binding galectin family, has emerged as an important regulator of innate and adaptive immunity. We examined whether galectin-9 contributes to MSC-mediated immunosuppression. Galectin-9 was strongly induced and secreted from human MSCs upon stimulation with pro-inflammatory cytokines. An in vitro immunosuppression assay using a knockdown approach revealed that galectin-9-deficient MSCs do not exert immunosuppressive activity. We also provided evidence that galectin-9 may contribute to MSC-mediated immunosuppression by binding to its receptor, TIM-3, expressed on activated lymphocytes, leading to apoptotic cell death of activated lymphocytes. Taken together, our findings demonstrate that galectin-9 is involved in MSC-mediated immunosuppression and represents a potential therapeutic factor for the treatment of inflammatory diseases. PMID:26557808

  1. Reflux solar receiver design considerations

    NASA Astrophysics Data System (ADS)

    Diver, R. B.

    Reflux heat-pipe and pool-boiler receivers are being developed to improve upon the performance and life of directly-illuminated tube receiver technology used in previous successful demonstrations of dish-Stirling systems. The design of a reflux receiver involves engineering tradeoffs. In this paper, on-sun performance measurements of the Sandia pool-boiler receiver are compared with results from the reflux receiver thermal analysis model, AEETES. Flux and performance implications of various design options are analyzed and discussed.

  2. Advanced solar thermal receiver technology

    NASA Technical Reports Server (NTRS)

    Kudirka, A. A.; Leibowitz, L. P.

    1980-01-01

    Development of advanced receiver technology for solar thermal receivers designed for electric power generation or for industrial applications, such as fuels and chemical production or industrial process heat, is described. The development of this technology is focused on receivers that operate from 1000 F to 3000 F and above. Development strategy is mapped in terms of application requirements, and the related system and technical requirements. Receiver performance requirements and current development efforts are covered for five classes of receiver applications: high temperature, advanced Brayton, Stirling, and Rankine cycle engines, and fuels and chemicals.

  3. Bragg-cell receiver study

    NASA Technical Reports Server (NTRS)

    Wilson, Lonnie A.

    1987-01-01

    Bragg-cell receivers are employed in specialized Electronic Warfare (EW) applications for the measurement of frequency. Bragg-cell receiver characteristics are fully characterized for simple RF emitter signals. This receiver is early in its development cycle when compared to the IFM receiver. Functional mathematical models are derived and presented in this report for the Bragg-cell receiver. Theoretical analysis is presented and digital computer signal processing results are presented for the Bragg-cell receiver. Probability density function analysis are performed for output frequency. Probability density function distributions are observed to depart from assumed distributions for wideband and complex RF signals. This analysis is significant for high resolution and fine grain EW Bragg-cell receiver systems.

  4. Performance testing of lidar receivers

    NASA Technical Reports Server (NTRS)

    Shams, M. Y.

    1986-01-01

    In addition to the considerations about the different types of noise sources, dynamic range, and linearity of a lidar receiver, one requires information about the pulse shape retaining capabilities of the receiver. For this purpose, relatively precise information about the height resolution as well as the recovery time of the receiver, due both to large transients and to fast changes in the received signal, is required. As more and more analog receivers using fast analog to digital converters and transient recorders will be used in the future lidar systems, methods to test these devices are essential. The method proposed for this purpose is shown. Tests were carried out using LCW-10, LT-20, and FTVR-2 as optical parts of the optical pulse generator circuits. A commercial optical receiver, LNOR, and a transient recorder, VK 220-4, were parts of the receiver system.

  5. Classification comparisons between dual-pol, compact polarimetric and quad-pol SAR imagery

    NASA Astrophysics Data System (ADS)

    Ainsworth, T. L.; Kelly, J. P.; Lee, J.-S.

    We present a study of the polarimetric information content of dual-pol imaging modes and dual-pol imaging extended by polarimetric scattering models. We compare Wishart classifications both among the partial polarimetric datasets and against the full quad-pol dataset. Our emphasis is the inter-comparisons between the classification results based on dual-pol modes, compact polarimetric modes and scattering model extensions of the compact polarimetric modes. We primarily consider novel dual-pol modes, e.g. transmitting a circular polarization and receiving horizontal and vertical polarizations, and the pseudo-quad-pol data derived from polarimetric scattering models based on dual-pol data. We show that the overall classification accuracy of the pseudo-quad-pol data is essential the same as the classification accuracy obtained directly employing the underlying dual-pol imagery.

  6. Dual double field theory

    NASA Astrophysics Data System (ADS)

    Bergshoeff, Eric A.; Hohm, Olaf; Penas, Victor A.; Riccioni, Fabio

    2016-06-01

    We present the dual formulation of double field theory at the linearized level. This is a classically equivalent theory describing the duals of the dilaton, the Kalb-Ramond field and the graviton in a T-duality or O( D, D) covariant way. In agreement with previous proposals, the resulting theory encodes fields in mixed Young-tableau representations, combining them into an antisymmetric 4-tensor under O( D, D). In contrast to previous proposals, the theory also requires an antisymmetric 2-tensor and a singlet, which are not all pure gauge. The need for these additional fields is analogous to a similar phenomenon for "exotic" dualizations, and we clarify this by comparing with the dualizations of the component fields. We close with some speculative remarks on the significance of these observations for the full non-linear theory yet to be constructed.

  7. Dual-Schemata Model

    NASA Astrophysics Data System (ADS)

    Taniguchi, Tadahiro; Sawaragi, Tetsuo

    In this paper, a new machine-learning method, called Dual-Schemata model, is presented. Dual-Schemata model is a kind of self-organizational machine learning methods for an autonomous robot interacting with an unknown dynamical environment. This is based on Piaget's Schema model, that is a classical psychological model to explain memory and cognitive development of human beings. Our Dual-Schemata model is developed as a computational model of Piaget's Schema model, especially focusing on sensori-motor developing period. This developmental process is characterized by a couple of two mutually-interacting dynamics; one is a dynamics formed by assimilation and accommodation, and the other dynamics is formed by equilibration and differentiation. By these dynamics schema system enables an agent to act well in a real world. This schema's differentiation process corresponds to a symbol formation process occurring within an autonomous agent when it interacts with an unknown, dynamically changing environment. Experiment results obtained from an autonomous facial robot in which our model is embedded are presented; an autonomous facial robot becomes able to chase a ball moving in various ways without any rewards nor teaching signals from outside. Moreover, emergence of concepts on the target movements within a robot is shown and discussed in terms of fuzzy logics on set-subset inclusive relationships.

  8. Development of dog mammary tumor xenograft in immunosuppressed Swiss albino mice.

    PubMed

    Rajmani, R S; Singh, Prafull Kumar; Kumar, Sanjay; Kumar, G Ravi; Sahoo, Aditya P; Santra, Lakshman; Saxena, Shikha; Singh, Lakshya Veer; Chaturvedi, Uttara; Saxena, Lovleen; Desai, G S; Gupta, Shishir Kumar; Kumar, Amit; Jadon, N S; Tiwari, Ashok K

    2014-10-01

    Development and study of dog mammary tumour xenograft in immunosuppressed Swiss Albino Mice adds a new dimension in cancer research as dog tumors have many similarities with human tumors regarding progression, histopathology, molecular mechanism, immune response and therapy. Failure of the immune system to recognize and eliminate cancer cells leads to cancer progression and the fight between immune cells and cancer cells has a great role in understanding the mechanism of cancer progression and elimination. Rejection and acceptance of tumour xenograft depends on efficiency of CD4+, CD8+ and NK cell populations. In the present investigation, dog mammary tumor xenograft in cyclosporine-A and gamma-irradiated, immunosuppressed Swiss Albino mice was developed and the immune cell status of graft accepted and rejected mice was assessed. It was observed that all the major immune cells (CD4+, CD8+ and NK cells) play an equal role in tumour rejection. PMID:25345242

  9. Immunosuppressive drugs prevent a rapid dephosphorylation of transcription factor NFAT1 in stimulated immune cells.

    PubMed Central

    Shaw, K T; Ho, A M; Raghavan, A; Kim, J; Jain, J; Park, J; Sharma, S; Rao, A; Hogan, P G

    1995-01-01

    The immunosuppressive drugs cyclosporin A and FK506 interfere with the inducible transcription of cytokine genes in T cells and in other immune cells, in part by preventing the activation of NF-AT (nuclear factor of activated T cells). We show that transcription factor NFAT1 in T cells is rapidly dephosphorylated on stimulation, that dephosphorylation occurs before translocation of NFAT1 into the cell nucleus, and that dephosphorylation increases the affinity of NFAT1 for its specific sites in DNA. Cyclosporin A prevents the dephosphorylation and the nuclear translocation of NFAT1 in T cells, B cells, macrophages, and mast cells, delineating at least one mechanism that contributes to the profound immunosuppressive effects of this compound. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7479966

  10. Neoplasia in adoptively immunosuppressed rats. A possible model for tumorigenesis in transplant recipients

    SciTech Connect

    Dorsch, S.E.; Cook, E.P.

    1983-07-01

    An extremely high incidence of malignant tumors was observed in groups of rats that had previously been exposed to whole body irradiation, grafted with allogeneic tissue, and injected with lymphocytes capable of specifically suppressing the rejection of the grafted tissue. Neoplasia in these adoptively immunosuppressed rats had features in common with that in therapeutically immunosuppressed transplant recipients. Increased tumor incidence could not be accounted for on the basis of the effects of whole body irradiation or failure of immune surveillance, nor could it be a direct effect of lymphoid tissue stimulation. It is suggested that cell mediated suppressor responses play a critical role in tumorigenesis. The mechanism of this is not simply direct stimulation of lymphoid tissue proliferation.

  11. Immunosuppression and tolerance after total lymphoid irradiation (TLI). [Mice, rats, monkeys, dogs, patients

    SciTech Connect

    Strober, S.; Gottlieb, M.; Slavin, S.; King, D.P.; Hoppe, R.T.; Fuks, Z.; Bieber, C.P.; Kaplan, H.S.

    1980-09-01

    The immunosuppressive effects of total lymphoid irradiation (TLI) in humans and in several species of inbred and outbred laboratory animals have been investigated. A unique property of TLI, the prevention of the graft vs. host disease, was used to induce transplantation tolerance in order to study the mechanism of altered immunity when the celluar basis of the TLI-induced immunosuppression was examined by means of the mixed lymphocyte response (MLR), no suppression of the MLR was observed when spleen cells from unirradiated or whole body-irradiated donors were used instead of donors given TLI. These results indicated that TLI induces a population of cells in the spleen that can nonspecifically suppress the MLR.

  12. First report of Wautersiella falsenii genomovar 2 isolated from the respiratory tract of an immunosuppressed man

    PubMed Central

    Giordano, Cesira; Falleni, Margherita; Capria, Anna-Lisa; Caracciolo, Francesco; Petrini, Mario; Barnini, Simona

    2016-01-01

    Wautersiella falsenii is a Gram-negative, non-motile rod, which grows aerobically on common isolation media and is the only acknowledged species among the genus Wautersiella. Two genomovars, namely 1 and 2, phenotypically indistinguishable but genotypically different, are described. To date, few case reports detailing the clinical disease associated with W. falsenii have been reported, all describing localized infection. To our knowledge, this study reports the first isolation of W. falsenii genomovar 2 from a respiratory sample of an immunosuppressed man. Our hypothesis is that the patient was harboring W. falsenii genomovar 2 and both the immunosuppression and the antimicrobial treatments provided a chance for this organism to emerge. The clinical significance of this result is yet to be evaluated. Although infection with W. falsenii remains rare, this bacterium should not be underestimated mainly because of its natural resistance to many available antimicrobials. PMID:27051582

  13. Longitudinal Analysis of Computerized Alerts for Laboratory Monitoring of Post-liver Transplant Immunosuppressive Care

    PubMed Central

    Jacobs, Jason; Narus, Scott P.; Evans, R. Scott; Staes, Catherine J.

    2015-01-01

    Post-liver transplant patients require lifelong immunosuppressive care and monitoring. Computerized alerts can aid laboratory monitoring, but it is unknown how the distribution of alerts changes over time. We describe the changes over time of the distribution of computerized alerts for laboratory monitoring of post-liver transplant immunosuppressive care. Data were collected for post-liver transplant patients transplanted and managed at Intermountain Healthcare between 2005 and 2012. Alerts were analyzed based on year triggered, time since transplantation, hospitalization status, alert type, action taken (accepted or rejected), reason given for the action taken, and narrative comments. Alerts for overdue laboratory testing became more prevalent as time since transplantation increased. There is an increased need to support monitoring for overdue laboratory testing as the time since transplantation increases. Alerts should support providers as they monitor the evolving needs of post-transplant patients over time. We identify opportunities for improving laboratory monitoring of post-liver transplant patients. PMID:26958291

  14. Effect and Molecular Mechanisms of Traditional Chinese Medicine on Regulating Tumor Immunosuppressive Microenvironment

    PubMed Central

    Guo, Qiujun; Li, Jie; Lin, Hongsheng

    2015-01-01

    Traditional Chinese medicine (TCM) is an important complementary strategy for treating cancer in China. The mechanism is related to regulating the internal environment and remodeling the tumor immunosuppressive microenvironment (TIM). Herein we illustrate how TIM is reformed and its protumor activity on promoting tumor cell proliferation, angiogenesis and lymphangiogenesis, tumor invasion, and the oncogenicity of cancer stem cells. Furthermore we summarize the effects and mechanism of TCM on regulating TIM via enhancing antitumor immune responses (e.g., regulating the expression of MHC molecules and Fas/FasL, attenuating cancerigenic ability of cancer stem cells) and remolding immunosuppressive cells (e.g., reversing immune phenotypes of T lymphocytes and tumor associated macrophages, promoting dendritic cells mature, restraining myeloid derived suppressor cells function, and regulating Th1/Th2 factors). We also reveal the bidirectional and multitargeting functions of TCM on regulating TIM. Hopefully, it provides new theoretical basis for TCM clinical practice in cancer treatment and prevention. PMID:26161392

  15. Response to immunization in children born to renal transplant recipients using immunosuppressive drugs during gestation.

    PubMed

    Dinelli, Maria Isabel Saraiva; Ono, Erika; Viana, Patrícia Oliveira; Spina, Fernanda Garcia; Weckx, Lily Yin; dos Santos, Amélia Miyashiro Nunes; de Moraes-Pinto, Maria Isabel

    2016-01-20

    The use of immunosuppressive drugs can impair vaccination responses. When used during pregnancy, they may interfere with the development of the fetus's immune system. However, little is known regarding their influence on infant's response to vaccinations. Twenty-seven children born to renal transplant mothers (Tx) taking immunosuppressive drugs and 31 healthy children had the humoral immune response and reactogenicity to tetanus, Haemophilus influenzae type b (Hib) and 7 pneumococcal serotypes evaluated. The evolution of BCG vaccine scar was also registered. Antibodies were measured by ELISA. Lymphocyte immunophenotyping was performed on cord blood and at 7-8 months of age. Among Tx neonates, 82.4% had low B lymphocyte numbers at birth, and 29.4% had also low numbers of other lymphocyte subpopulations. Nevertheless, all children developed protective antibodies with similar antibody concentrations to the control group. Vaccine reactogenicity was similar in both groups and BCG healing was uneventful. PMID:26707214

  16. Immunosuppression abrogates resistance of young rabbits to Rabbit Haemorrhagic Disease (RHD)

    PubMed Central

    2014-01-01

    Rabbit Haemorrhagic Disease (RHD) is caused by a calicivirus (RHDV) that kills 90% of infected adult European rabbits within 3 days. Remarkably, young rabbits are resistant to RHD. We induced immunosuppression in young rabbits by treatment with methylprednisolone acetate (MPA) and challenged the animals with RHDV by intramuscular injection. All of these young rabbits died within 3 days of infection due to fulminant hepatitis, presenting a large number of RHDV-positive dead or apoptotic hepatocytes, and a significant seric increase in cytokines, features that are similar to those of naïve adult rabbits infected by RHDV. We conclude that MPA-induced immunosuppression abrogates the resistance of young rabbits to RHD, indicating that there are differences in the innate immune system between young and adult rabbits that contribute to their distinct resistance/susceptibility to RHDV infection. PMID:24490832

  17. Effect of Immunosuppressive Agents on Hepatocyte Apoptosis Post-Liver Transplantation

    PubMed Central

    Lim, Eu Jin; Chin, Ruth; Nachbur, Ueli; Silke, John; Jia, Zhiyuan; Angus, Peter W.; Torresi, Joseph

    2015-01-01

    Introduction Immunosuppressants are used ubiquitously post-liver transplantation to prevent allograft rejection. However their effects on hepatocytes are unknown. Experimental data from non-liver cells indicate that immunosuppressants may promote cell death thereby driving an inflammatory response that promotes fibrosis and raises concerns that a similar effect may occur within the liver. We evaluated apoptosis within the liver tissue of post-liver transplant patients and correlated these findings with in vitro experiments investigating the effects of immunosuppressants on apoptosis in primary hepatocytes. Methods Hepatocyte apoptosis was assessed using immunohistochemistry for M30 CytoDEATH and cleaved PARP in human liver tissue. Primary mouse hepatocytes were treated with various combinations of cyclosporine, tacrolimus, sirolimus, or MMF. Cell viability and apoptosis were evaluated using crystal violet assays and Western immunoblots probed for cleaved PARP and cleaved caspase 3. Results Post-liver transplant patients had a 4.9-fold and 1.7-fold increase in M30 CytoDEATH and cleaved PARP compared to normal subjects. Cyclosporine and tacrolimus at therapeutic concentrations did not affect hepatocyte apoptosis, however when they were combined with MMF, cell death was significantly enhanced. Cell viability was reduced by 46% and 41%, cleaved PARP was increased 2.6-fold and 2.2-fold, and cleaved caspase 3 increased 2.2-fold and 1.8-fold following treatment with Cyclosporine/MMF and Tacrolimus/MMF respectively. By contrast, the sirolimus/MMF combination did not significantly reduce hepatocyte viability or promote apoptosis. Conclusion Commonly used immunosuppressive drug regimens employed after liver transplantation enhance hepatocyte cell death and may thus contribute to the increased liver fibrosis that occurs in a proportion of liver transplant recipients. PMID:26390404

  18. Effect of tolerance versus chronic immunosuppression protocols on the quality of life of kidney transplant recipients

    PubMed Central

    Madariaga, Maria Lucia L.; Spencer, Philip J.; Shanmugarajah, Kumaran; Crisalli, Kerry A.; Chang, David C.; Markmann, James F.; Elias, Nahel; Cosimi, A. Benedict; Sachs, David H.; Kawai, Tatsuo

    2016-01-01

    BACKGROUND Kidney transplant patients on tolerance protocols avoid the morbidity associated with the use of conventional chronic immunosuppressive regimens. However, the impact of tolerance versus conventional regimens on the quality of life (QOL) of kidney transplant patients is unknown. METHODS Five patients who achieved long-term immunosuppression-free renal allograft survival after combined kidney and bone marrow transplantation (tolerant group) were compared with thirty-two comparable kidney transplant recipients on conventional immunosuppression (conventional group). QOL was compared with 16 conventional recipients using the Kidney Disease Quality of Life Short Form 36 (KDQOL SF-36) and the Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD-59R). RESULTS Patients in the tolerant group required significantly less treatment after transplant for hypertension and no medications for diabetes (P < 0.01). There was no incidence of diabetes, dyslipidemia, or malignancies in the tolerant group, while these were observed in 12.5%, 40.6%, and 11.8% of the conventional group, respectively. Tolerant patients experienced better overall health (P < 0.01) and scored higher on kidney transplant-targeted scales and healthy survey scales than patients in the conventional group according to the KDQOL SF-36 (P < 0.05). Tolerant patients were less likely to experience depression, dyspnea, excessive appetite/thirst, flatulence, hearing loss, itching, joint pain, lack of energy, muscle cramps, and lack of libido than conventional patients according to the MTSOSD-59R (P < 0.05). CONCLUSION Kidney transplant recipients who achieved tolerance experience significantly fewer incidences of complications, improved QOL, and fewer comorbid symptoms compared with patients on conventional immunosuppression. These results support the expanded use of tolerance protocols in kidney transplantation. PMID:27336062

  19. CTLA4-Ig immunosuppressive activity at the level of dendritic cell/T cell crosstalk

    PubMed Central

    Mayer, Edda; Hölzl, Markus; Ahmadi, Sarah; Dillinger, Barbara; Pilat, Nina; Fuchs, Dietmar; Wekerle, Thomas; Heitger, Andreas

    2013-01-01

    Immunosuppressive cytotoxic T lymphocyte associated antigen-4 immunoglobulin fusion proteins (CTLA4-Ig) block the CD28:CD80/86 costimulatory pathway. On a cellular level, CTLA4-Ig is understood to dampen T cell responses. As a mechanism, CTLA4-Ig has been reported to affect dendritic cell (DC) function via inducing the immunosuppressive indoleamine 2,3 dioxygenase (IDO) pathway and promoting a DC regulatory phenotype. We here probed cellular mechanisms of CTLA4-Ig immunoregulation in an allogeneic setting using C57BL/6 splenic or bone marrow derived DCs (BMDCs) as stimulators of allogeneic Balb/c derived T cells. To address whether CTLA4-Ig immunosuppression affected DCs, we pre-exposed C57BL/6 splenic or BMDCs to CTLA4-Ig and removed unbound CTLA4-Ig before co-culture with allogeneic T cells. CTLA4-Ig disappeared rapidly (within 4 h) from the cell membrane by combined internalization and dissociation. These CTLA4-Ig pre-exposed DCs were fully capable of stimulating allogeneic T cell proliferation, suggesting that CTLA4-Ig does not impair the DC stimulatory capacity. Only the presence of CTLA4-Ig during DC/T cell co-culture resulted in the expected inhibition of proliferation. C57BL/6 splenic or BMDCs exposed to CTLA4-Ig did not display IDO activity. We conclude that CTLA4-Ig immunosuppressive activity does not depend on a DC regulatory phenotype but on its presence during DC/T cell interaction. PMID:23434857

  20. VT-1161 Protects Immunosuppressed Mice from Rhizopus arrhizus var. arrhizus Infection

    PubMed Central

    Gebremariam, Teclegiorgis; Wiederhold, Nathan P.; Fothergill, Annette W.; Garvey, Edward P.; Hoekstra, William J.; Schotzinger, Robert J.; Patterson, Thomas F.; Filler, Scott G.

    2015-01-01

    We studied the efficacy of the investigational drug VT-1161 against mucormycosis. VT-1161 had more potent in vitro activity against Rhizopus arrhizus var. arrhizus than against R. arrhizus var. delemar. VT-1161 treatment demonstrated dose-dependent plasma drug levels with prolonged survival time and lowered tissue fungal burden in immunosuppressed mice infected with R. arrhizus var. arrhizus and was as effective as high-dose liposomal amphotericin B treatment. These results support further development of VT-1161 against mucormycosis. PMID:26369977

  1. Estradiol and G1 Reduce Infarct Size and Improve Immunosuppression after Experimental Stroke

    PubMed Central

    Zhang, Bing; Subramanian, Sandhya; Dziennis, Suzan; Jia, Jia; Uchida, Masayoshi; Akiyoshi, Kozaburo; Migliati, Elton; Lewis, Anne D.; Vandenbark, Arthur A.; Offner, Halina; Hurn, Patricia D.

    2011-01-01

    Reduced risk and severity of stroke in adult females is thought to depend on normal endogenous levels of estrogen, a well-known neuroprotectant and immunomodulator. In male mice, experimental stroke induces immunosuppression of the peripheral immune system, characterized by a reduction in spleen size and cell numbers and decreased cytokine and chemokine expression. However, stroke-induced immunosuppression has not been evaluated in female mice. To test the hypothesis that estradiol (E2) deficiency exacerbates immunosuppression after focal stroke in females, we evaluated the effect of middle cerebral artery occlusion on infarct size and peripheral and CNS immune responses in ovariectomized mice with or without sustained, controlled levels of 17-β–E2 administered by s.c. implant or the putative membrane estrogen receptor agonist, G1. Both E2- and G1-replacement decreased infarct volume and partially restored splenocyte numbers. Moreover, E2-replacement increased splenocyte proliferation in response to stimulation with anti-CD3/CD28 Abs and normalized aberrant mRNA expression for cytokines, chemokines, and chemokine receptors and percentage of CD4+CD25+FoxP3+ T regulatory cells observed in E2-deficient animals. These beneficial changes in peripheral immunity after E2 replacement were accompanied by a profound reduction in expression of the chemokine, MIP-2, and a 40-fold increased expression of CCR7 in the lesioned brain hemisphere. These results demonstrate for the first time that E2 replacement in ovariectomized female mice improves stroke-induced peripheral immunosuppression. PMID:20304826

  2. Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection.

    PubMed

    Elahi, Shokrollah; Ertelt, James M; Kinder, Jeremy M; Jiang, Tony T; Zhang, Xuzhe; Xin, Lijun; Chaturvedi, Vandana; Strong, Beverly S; Qualls, Joseph E; Steinbrecher, Kris A; Kalfa, Theodosia A; Shaaban, Aimen F; Way, Sing Sing

    2013-12-01

    Newborn infants are highly susceptible to infection. This defect in host defence has generally been ascribed to the immaturity of neonatal immune cells; however, the degree of hyporesponsiveness is highly variable and depends on the stimulation conditions. These discordant responses illustrate the need for a more unified explanation for why immunity is compromised in neonates. Here we show that physiologically enriched CD71(+) erythroid cells in neonatal mice and human cord blood have distinctive immunosuppressive properties. The production of innate immune protective cytokines by adult cells is diminished after transfer to neonatal mice or after co-culture with neonatal splenocytes. Neonatal CD71(+) cells express the enzyme arginase-2, and arginase activity is essential for the immunosuppressive properties of these cells because molecular inhibition of this enzyme or supplementation with L-arginine overrides immunosuppression. In addition, the ablation of CD71(+) cells in neonatal mice, or the decline in number of these cells as postnatal development progresses parallels the loss of suppression, and restored resistance to the perinatal pathogens Listeria monocytogenes and Escherichia coli. However, CD71(+) cell-mediated susceptibility to infection is counterbalanced by CD71(+) cell-mediated protection against aberrant immune cell activation in the intestine, where colonization with commensal microorganisms occurs swiftly after parturition. Conversely, circumventing such colonization by using antimicrobials or gnotobiotic germ-free mice overrides these protective benefits. Thus, CD71(+) cells quench the excessive inflammation induced by abrupt colonization with commensal microorganisms after parturition. This finding challenges the idea that the susceptibility of neonates to infection reflects immune-cell-intrinsic defects and instead highlights processes that are developmentally more essential and inadvertently mitigate innate immune protection. We anticipate that

  3. Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection

    PubMed Central

    Elahi, Shokrollah; Ertelt, James M.; Kinder, Jeremy M.; Jiang, Tony T.; Zhang, Xuzhe; Xin, Lijun; Chaturvedi, Vandana; Strong, Beverly S.; Qualls, Joseph E.; Steinbrecher, Kris A.; Kalfa, Theodosia A.; Shaaban, Aimen F.; Way, Sing Sing

    2014-01-01

    Newborn infants are highly susceptible to infection. This defect in host defence has generally been ascribed to the immaturity of neonatal immune cells; however, the degree of hyporesponsiveness is highly variable and depends on the stimulation conditions1–7. These discordant responses illustrate the need for a more unified explanation for why immunity is compromised in neonates. Here we show that physiologically enriched CD71+ erythroid cells in neonatal mice and human cord blood have distinctive immunosuppressive properties. The production of innate immune protective cytokines by adult cells is diminished after transfer to neonatal mice or after co-culture with neonatal splenocytes. Neonatal CD71+ cells express the enzyme arginase-2, and arginase activity is essential for the immunosuppressive properties of these cells because molecular inhibition of this enzyme or supplementation with l-arginine overrides immunosuppression. In addition, the ablation of CD71+ cells in neonatal mice, or the decline in number of these cells as postnatal development progresses parallels the loss of suppression, and restored resistance to the perinatal pathogens Listeria monocytogenes and Escherichia coli8,9. However, CD71+ cell-mediated susceptibility to infection is counterbalanced by CD71+ cell-mediated protection against aberrant immune cell activation in the intestine, where colonization with commensal microorganisms occurs swiftly after parturition10,11.Conversely, circumventing such colonization by using antimicrobials or gnotobiotic germ-free mice overrides these protective benefits. Thus, CD71+ cells quench the excessive inflammation induced by abrupt colonization with commensal microorganisms after parturition. This finding challenges the idea that the susceptibility of neonates to infection reflects immune-cell-intrinsic defects and instead highlights processes that are developmentally more essential and inadvertently mitigate innate immune protection. We anticipate that

  4. Novel immunosuppressive agent caerulomycin A exerts its effect by depleting cellular iron content

    PubMed Central

    Kaur, Suneet; Srivastava, Gautam; Sharma, Amar Nath; Jolly, Ravinder S

    2015-01-01

    Background and Purpose Recently, we have described the use of caerulomycin A (CaeA) as a potent novel immunosuppressive agent. Immunosuppressive drugs are crucial for long-term graft survival following organ transplantation and treatment of autoimmune diseases, inflammatory disorders, hypersensitivity to allergens, etc. The objective of this study was to identify cellular targets of CaeA and decipher its mechanism of action. Experimental Approach Jurkat cells were treated with CaeA and cellular iron content, iron uptake/release, DNA content and deoxyribonucleoside triphosphate pool determined. Activation of MAPKs; expression level of transferrin receptor 1, ferritin and cell cycle control molecules; reactive oxygen species (ROS) and cell viability were measured using Western blotting, qRT-PCR or flow cytometry. Key Results CaeA caused intracellular iron depletion by reducing its uptake and increasing its release by cells. CaeA caused cell cycle arrest by (i) inhibiting ribonucleotide reductase (RNR) enzyme, which catalyses the rate-limiting step in the synthesis of DNA; (ii) stimulating MAPKs signalling transduction pathways that play an important role in cell growth, proliferation and differentiation; and (iii) by targeting cell cycle control molecules such as cyclin D1, cyclin-dependent kinase 4 and p21CIP1/WAF1. The effect of CaeA on cell proliferation was reversible. Conclusions and Implications CaeA exerts its immunosuppressive effect by targeting iron. The effect is reversible, which makes CaeA an attractive candidate for development as a potent immunosuppressive drug, but also indicates that iron chelation can be used as a rationale approach to selectively suppress the immune system, because compared with normal cells, rapidly proliferating cells require a higher utilization of iron. PMID:25537422

  5. Immunomodulatory effects of Taishan Pinus massoniana pollen polysaccharide and propolis on immunosuppressed chickens.

    PubMed

    Li, Bing; Wei, Kai; Yang, Shifa; Yang, Ya; Zhang, Yongbing; Zhu, Fujie; Wang, Di; Zhu, Ruiliang

    2015-01-01

    Co-infection of reticuloendotheliosis virus (REV) and avian leukosis virus subgroup J (ALV-J), which can cause suppressed immunity and vaccination failure, frequently occurs in chicken flocks in China. Taishan Pinus massoniana pollen polysaccharide (TPPPS) and propolis (PP) have been proven to possess immune modulatory effects and improve the immune effects of vaccines. This study aimed to investigate the immune modulatory ability of TPPPS and PP on chickens co-infected with immunosuppressive viruses. Prior to the study, chickens were artificially established as REV and ALV-J co-infection models. Four randomly assigned groups of these immunosuppressed chickens were successively administered with TPPPS, PP, mixture of TPPPS and PP (TPPPS-PP), or phosphate-buffered saline (PBS) for three days. At nine days old, the four immunosuppressed groups, as well as one normal group, were inoculated with the attenuated Newcastle disease (ND) vaccine. During the monitoring period, the indices of immune organ weight, lymphocyte transformation rates, CD4(+) and CD8(+) T-lymphocyte counts in peripheral blood, IL-2 and IFN-γ secretions, serum antibody titers of ND vaccine, and viral loads in spleens were determined. The results showed that chickens administered with TPPPS, PP, or TPPPS-PP could significantly enhance the levels of the above immune parameters compared to chickens in the PBS group. We observed the strongest immunity in the TPPPS-PP group, which indicates that the combination of TPPPS and PP versus TPPPS or PP alone, could generate better effects on improving the immune system effectiveness of immunosuppressed chickens. PMID:25450885

  6. Barcelona Consensus on Biomarker-Based Immunosuppressive Drugs Management in Solid Organ Transplantation.

    PubMed

    Brunet, Mercè; Shipkova, Maria; van Gelder, Teun; Wieland, Eberhard; Sommerer, Claudia; Budde, Klemens; Haufroid, Vincent; Christians, Uwe; López-Hoyos, Marcos; Barten, Markus J; Bergan, Stein; Picard, Nicolas; Millán López, Olga; Marquet, Pierre; Hesselink, Dennis A; Noceti, Ofelia; Pawinski, Tomasz; Wallemacq, Pierre; Oellerich, Michael

    2016-04-01

    With current treatment regimens, a relatively high proportion of transplant recipients experience underimmunosuppression or overimmunosuppression. Recently, several promising biomarkers have been identified for determining patient alloreactivity, which help in assessing the risk of rejection and personal response to the drug; others correlate with graft dysfunction and clinical outcome, offering a realistic opportunity for personalized immunosuppression. This consensus document aims to help tailor immunosuppression to the needs of the individual patient. It examines current knowledge on biomarkers associated with patient risk stratification and immunosuppression requirements that have been generally accepted as promising. It is based on a comprehensive review of the literature and the expert opinion of the Biomarker Working Group of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. The quality of evidence was systematically weighted, and the strength of recommendations was rated according to the GRADE system. Three types of biomarkers are discussed: (1) those associated with the risk of rejection (alloreactivity/tolerance), (2) those reflecting individual response to immunosuppressants, and (3) those associated with graft dysfunction. Analytical aspects of biomarker measurement and novel pharmacokinetic-pharmacodynamic models accessible to the transplant community are also addressed. Conventional pharmacokinetic biomarkers may be used in combination with those discussed in this article to achieve better outcomes and improve long-term graft survival. Our group of experts has made recommendations for the most appropriate analysis of a proposed panel of preliminary biomarkers, most of which are currently under clinical evaluation in ongoing multicentre clinical trials. A section of Next Steps was also included, in which the Expert Committee is committed to sharing this knowledge with the Transplant Community in the form of triennial

  7. Avirulent Toxoplasma gondii generates therapeutic antitumor immunity by reversing immunosuppression in the ovarian cancer microenvironment.

    PubMed

    Baird, Jason R; Fox, Barbara A; Sanders, Kiah L; Lizotte, Patrick H; Cubillos-Ruiz, Juan R; Scarlett, Uciane K; Rutkowski, Melanie R; Conejo-Garcia, Jose R; Fiering, Steven; Bzik, David J

    2013-07-01

    Reversing tumor-associated immunosuppression seems necessary to stimulate effective therapeutic immunity against lethal epithelial tumors. Here, we show this goal can be addressed using cps, an avirulent, nonreplicating uracil auxotroph strain of the parasite Toxoplasma gondii (T. gondii), which preferentially invades immunosuppressive CD11c(+) antigen-presenting cells in the ovarian carcinoma microenvironment. Tumor-associated CD11c(+) cells invaded by cps were converted to immunostimulatory phenotypes, which expressed increased levels of the T-cell receptor costimulatory molecules CD80 and CD86. In response to cps treatment of the immunosuppressive ovarian tumor environment, CD11c(+) cells regained the ability to efficiently cross-present antigen and prime CD8(+) T-cell responses. Correspondingly, cps treatment markedly increased tumor antigen-specific responses by CD8(+) T cells. Adoptive transfer experiments showed that these antitumor T-cell responses were effective in suppressing solid tumor development. Indeed, intraperitoneal cps treatment triggered rejection of established ID8-VegfA tumors, an aggressive xenograft model of ovarian carcinoma, also conferring a survival benefit in a related aggressive model (ID8-Defb29/Vegf-A). The therapeutic benefit of cps treatment relied on expression of IL-12, but it was unexpectedly independent of MyD88 signaling as well as immune experience with T. gondii. Taken together, our results establish that cps preferentially invades tumor-associated antigen-presenting cells and restores their ability to trigger potent antitumor CD8(+) T-cell responses. Immunochemotherapeutic applications of cps might be broadly useful to reawaken natural immunity in the highly immunosuppressive microenvironment of most solid tumors. PMID:23704211

  8. Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection

    NASA Astrophysics Data System (ADS)

    Elahi, Shokrollah; Ertelt, James M.; Kinder, Jeremy M.; Jiang, Tony T.; Zhang, Xuzhe; Xin, Lijun; Chaturvedi, Vandana; Strong, Beverly S.; Qualls, Joseph E.; Steinbrecher, Kris A.; Kalfa, Theodosia A.; Shaaban, Aimen F.; Way, Sing Sing

    2013-12-01

    Newborn infants are highly susceptible to infection. This defect in host defence has generally been ascribed to the immaturity of neonatal immune cells; however, the degree of hyporesponsiveness is highly variable and depends on the stimulation conditions. These discordant responses illustrate the need for a more unified explanation for why immunity is compromised in neonates. Here we show that physiologically enriched CD71+ erythroid cells in neonatal mice and human cord blood have distinctive immunosuppressive properties. The production of innate immune protective cytokines by adult cells is diminished after transfer to neonatal mice or after co-culture with neonatal splenocytes. Neonatal CD71+ cells express the enzyme arginase-2, and arginase activity is essential for the immunosuppressive properties of these cells because molecular inhibition of this enzyme or supplementation with L-arginine overrides immunosuppression. In addition, the ablation of CD71+ cells in neonatal mice, or the decline in number of these cells as postnatal development progresses parallels the loss of suppression, and restored resistance to the perinatal pathogens Listeria monocytogenes and Escherichia coli. However, CD71+ cell-mediated susceptibility to infection is counterbalanced by CD71+ cell-mediated protection against aberrant immune cell activation in the intestine, where colonization with commensal microorganisms occurs swiftly after parturition. Conversely, circumventing such colonization by using antimicrobials or gnotobiotic germ-free mice overrides these protective benefits. Thus, CD71+ cells quench the excessive inflammation induced by abrupt colonization with commensal microorganisms after parturition. This finding challenges the idea that the susceptibility of neonates to infection reflects immune-cell-intrinsic defects and instead highlights processes that are developmentally more essential and inadvertently mitigate innate immune protection. We anticipate that these

  9. Immune responses against islet allografts during tapering of immunosuppression - A pilot study in 5 subjects.

    PubMed

    Huurman, Volkert A L; van der Torren, Cornelis R; Gillard, Pieter; Hilbrands, Robert; van der Meer-Prins, Ellen P M W; Duinkerken, Gaby; Gorus, Frans K; Claas, Frans H J; Keymeulen, Bart; Roelen, Dave L; Pipeleers, Daniel G; Roep, Bart O

    2012-04-25

    Transplantation of isolated islet of Langerhans cells has great potential as a cure for type 1 diabetes but continuous immune suppressive therapy often causes considerable side effects. Tapering of immunosuppression in successfully transplanted patients would lower patients' health risk. To identify immune biomarkers that may prove informative in monitoring tapering, we studied the effect of tapering on islet auto- and alloimmune reactivity in a pilot study in five transplant recipients in vitro. Cytokine responses to the graft were measured using Luminex technology. Avidity of alloreactive cytotoxic T Lymphocytes (CTL) was determined by CD8 blockade. The influence of immunosuppression was mimicked by in vitro replenishment of tacrolimus and MPA, the active metabolite of mycophenolate mofetil. Tapering of tacrolimus was generally followed by decreased C-peptide production. T-cell autoreactivity increased in four out of five patients during tapering. Overall alloreactive CTL precursor frequencies did not change, but their avidity to donor mismatches increased significantly after tapering (p=0.035). In vitro addition of tacrolimus but not MPA strongly inhibited CTL alloreactivity during tapering and led to a significant shift to anti-inflammatory graft-specific cytokine production. Tapering of immunosuppression is characterized by diverse immune profiles that appear to relate inversely to plasma C-peptide levels. Highly avid allospecific CTLs that are known to associate with rejection increased during tapering, but could be countered by restoring immune suppression in vitro. Immune monitoring studies may help guiding tapering of immunosuppression after islet cell transplantation, even though we do not have formal prove yet that the observed changes reflect direct effects of immune suppression on immunity. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology. PMID:23607493

  10. Immune responses against islet allografts during tapering of immunosuppression--a pilot study in 5 subjects.

    PubMed

    Huurman, V A L; van der Torren, C R; Gillard, P; Hilbrands, R; van der Meer-Prins, E P M W; Duinkerken, G; Gorus, F K; Claas, F H J; Keymeulen, B; Roelen, D L; Pipeleers, D G; Roep, B O

    2012-08-01

    Transplantation of isolated islet of Langerhans cells has great potential as a cure for type 1 diabetes but continuous immune suppressive therapy often causes considerable side effects. Tapering of immunosuppression in successfully transplanted patients would lower patients' health risk. To identify immune biomarkers that may prove informative in monitoring tapering, we studied the effect of tapering on islet auto- and alloimmune reactivity in a pilot study in five transplant recipients in vitro. Cytokine responses to the graft were measured using Luminex technology. Avidity of alloreactive cytotoxic T Lymphocytes (CTL) was determined by CD8 blockade. The influence of immunosuppression was mimicked by in vitro replenishment of tacrolimus and MPA, the active metabolite of mycophenolate mofetil. Tapering of tacrolimus was generally followed by decreased C-peptide production. T-cell autoreactivity increased in four out of five patients during tapering. Overall alloreactive CTL precursor frequencies did not change, but their avidity to donor mismatches increased significantly after tapering (P = 0·035). In vitro addition of tacrolimus but not MPA strongly inhibited CTL alloreactivity during tapering and led to a significant shift to anti-inflammatory graft-specific cytokine production. Tapering of immunosuppression is characterized by diverse immune profiles that appear to relate inversely to plasma C-peptide levels. Highly avid allospecific CTLs that are known to associate with rejection increased during tapering, but could be countered by restoring immune suppression in vitro. Immune monitoring studies may help guiding tapering of immunosuppression after islet cell transplantation, even though we do not have formal prove yet that the observed changes reflect direct effects of immune suppression on immunity. PMID:22774994

  11. Virulent Salmonella typhimurium-induced lymphocyte depletion and immunosuppression in chickens.

    PubMed Central

    Hassan, J O; Curtiss, R

    1994-01-01

    The effect of experimental Salmonella infection on chicken lymphoid organs, immune responses, and fecal shedding of salmonellae were assessed following oral inoculation of 1-day-old chicks or intra-air-sac infection of 4-week-old chickens with virulent S. typhimurium wild-type chi 3761 or avirulent S. typhimurium delta cya delta crp vaccine strain chi 3985. Some 4-week-old chickens infected intra-air-sac with chi 3761 or chi 3985 were challenged with Bordetella avium to determine the effect of Salmonella infection on secondary infection by B. avium. S. typhimurium chi 3761 caused lymphocyte depletion, atrophy of lymphoid organs, and immunosuppression 2 days after infection in 1-day-old chicks and 4-week-old chickens. The observed lymphocyte depletion or atrophy of lymphoid organs was transient and dose dependent. Lymphocyte depletion and immunosuppression were associated with prolonged fecal shedding of S. typhimurium chi 3761. No lymphocyte depletion, immunosuppression, or prolonged Salmonella shedding was observed in groups of chickens infected orally or intra-air-sac with chi 3985. Infection of chickens with salmonellae before challenge with B. avium did not suppress the specific antibody response to B. avium. However, B. avium isolation was higher in visceral organs of chickens infected with chi 3761 and challenged with B. avium than in chickens infected with B. avium only. Infection of chickens with chi 3985 reduced B. avium colonization. We report a new factor in Salmonella pathogenesis and reveal a phenomenon which may play a critical role in the development of Salmonella carrier status in chickens. We also showed that 10(8) CFU of chi 3985, which is our established oral vaccination dose for chickens, did not cause immunosuppression or enhance the development of Salmonella carrier status in chickens. Images PMID:8168969

  12. Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease.

    PubMed

    Dalotto-Moreno, Tomás; Croci, Diego O; Cerliani, Juan P; Martinez-Allo, Verónica C; Dergan-Dylon, Sebastián; Méndez-Huergo, Santiago P; Stupirski, Juan C; Mazal, Daniel; Osinaga, Eduardo; Toscano, Marta A; Sundblad, Victoria; Rabinovich, Gabriel A; Salatino, Mariana

    2013-02-01

    Galectin-1 (Gal1), an evolutionarily conserved glycan-binding protein, contributes to the creation of an immunosuppressed microenvironment at sites of tumor growth. In spite of considerable progress in elucidating its role in tumor-immune escape, the mechanisms underlying the inhibitory functions of Gal1 remain obscure. Here, we investigated the contribution of tumor Gal1 to tumor growth, metastasis, and immunosuppression in breast cancer. We found that the frequency of Gal1(+) cells in human breast cancer biopsies correlated positively with tumor grade, while specimens from patients with benign hyperplasia showed negative or limited Gal1 staining. To examine the pathophysiologic relevance of Gal1 in breast cancer, we used the metastatic mouse mammary tumor 4T1, which expresses and secretes substantial amounts of Gal1. Silencing Gal1 expression in this model induced a marked reduction in both tumor growth and the number of lung metastases. This effect was abrogated when mice were inoculated with wild-type 4T1 tumor cells in their contralateral flank, suggesting involvement of a systemic modulation of the immune response. Gal1 attenuation in 4T1 cells also reduced the frequency of CD4(+)CD25(+) Foxp3(+) regulatory T (T(reg)) cells within the tumor, draining lymph nodes, spleen, and lung metastases. Further, it abrogated the immunosuppressive function of T(reg) cells and selectively lowered the expression of the T-cell regulatory molecule LAT (linker for activation of T cells) on these cells, disarming their suppressive activity. Taken together, our results offer a preclinical proof of concept that therapeutic targeting of Gal1 can overcome breast cancer-associated immunosuppression and can prevent metastatic disease. PMID:23204230

  13. Hepatitis C-induced hepatocyte apoptosis following liver transplantation is enhanced by immunosuppressive agents.

    PubMed

    Lim, E J; Chin, R; Nachbur, U; Silke, J; Jia, Z; Angus, P W; Torresi, J

    2016-09-01

    In recurrent hepatitis C (HCV) post-liver transplantation (OLT), the combination of immunosuppressants and HCV is postulated to increase hepatocyte apoptosis and liver fibrosis. We evaluated hepatocyte apoptosis within the liver tissue of patients with postOLT HCV recurrence compared to HCV-negative individuals and correlated these findings with the effects of immunosuppressants on HCV-induced cell death and its inhibition in primary mouse hepatocytes (PMoH). Liver biopsies from patients with and without HCV were evaluated by immunohistochemistry for markers of apoptosis M30 CytoDEATH (M30) and cleaved PARP (clPARP). PMoH from C57BL/6 mice were infected with recombinant adenoviruses (rAdHCV) that expressed HCV proteins in hepatocytes. Infected cells were treated with cyclosporine, tacrolimus, sirolimus and/or MMF with or without pan-caspase inhibitor Q-VD-Oph. Cell viability and apoptosis were evaluated using crystal violet assays and Western immunoblots probed for cleaved caspase-3 (clCas3) and clPARP. Both M30 and clPARP were increased in the liver biopsies of patients with postOLT HCV recurrence compared to HCV-negative individuals. Treatment of rAdHCV-infected PMoH with cyclosporine, tacrolimus or sirolimus reduced cell viability and increased clCas3 and clPARP compared to rAdHCV infection alone. Addition of MMF to cyclosporine, tacrolimus or sirolimus further reduced cell viability and increased clCas3 and clPARP. Q-VD-Oph improved cell viability in HCV-infected PMoH treated with immunosuppressants alone and in combination and reduced clCas3 and clPARP by approximately 90%. Immunosuppressive agents, especially in combination, enhanced apoptosis in HCV-infected hepatocytes. The finding that Q-VD-Oph reversed hepatocyte death suggests that treatments utilizing apoptosis inhibition might reduce liver injury in postOLT HCV recurrence. PMID:27167351

  14. Avirulent Toxoplasma gondii generates therapeutic antitumor immunity by reversing immunosuppression in the ovarian cancer microenvironment

    PubMed Central

    Baird, Jason R.; Fox, Barbara A.; Sanders, Kiah L.; Lizotte, Patrick H.; Cubillos-Ruiz, Juan R.; Scarlett, Uciane K.; Rutkowski, Melanie R.; Conejo-Garcia, Jose R.; Fiering, Steven; Bzik, David J.

    2013-01-01

    Reversing tumor-associated immunosuppression appears necessary to stimulate effective therapeutic immunity against lethal epithelial tumors. Here, we show this goal can be addressed using cps, an avirulent, nonreplicating uracil auxotroph strain of the parasite Toxoplasma gondii, which preferentially invades immunosuppressive CD11c+ antigen-presenting cells in the ovarian carcinoma microenvironment. Tumor-associated CD11c+ cells invaded by cps were converted to immunostimulatory phenotypes which expressed increased levels of the T cell receptor co-stimulatory molecules CD80 and CD86. In response to cps treatment of the immunosuppressive ovarian tumor environment, CD11c+ cells regained the ability to efficiently cross-present antigen and prime CD8+ T cell responses. Correspondingly, cps treatment markedly increased tumor antigen-specific responses by CD8+ T cells. Adoptive transfer experiments demonstrated that these antitumor T cell responses were effective in suppressing solid tumor development. Indeed, intraperitoneal cps treatment triggered rejection of established ID8-VegfA tumors, an aggressive xenograft model of ovarian carcinoma, also conferring a survival benefit in a related aggressive model (ID8-Defb29/Vegf-A). The therapeutic benefit of cps treatment relied on expression of IL-12, but it was unexpectedly independent of MyD88 signaling as well as immune experience with T. gondii. Taken together, our results establish that cps preferentially invades tumor-associated antigen-presenting cells and restores their ability to trigger potent antitumor CD8+ T cell responses. Immunochemotherapeutic applications of cps might be broadly useful to reawaken natural immunity in the highly immunosuppressive microenvironment of most solid tumors. PMID:23704211

  15. VT-1161 Protects Immunosuppressed Mice from Rhizopus arrhizus var. arrhizus Infection.

    PubMed

    Gebremariam, Teclegiorgis; Wiederhold, Nathan P; Fothergill, Annette W; Garvey, Edward P; Hoekstra, William J; Schotzinger, Robert J; Patterson, Thomas F; Filler, Scott G; Ibrahim, Ashraf S

    2015-12-01

    We studied the efficacy of the investigational drug VT-1161 against mucormycosis. VT-1161 had more potent in vitro activity against Rhizopus arrhizus var. arrhizus than against R. arrhizus var. delemar. VT-1161 treatment demonstrated dose-dependent plasma drug levels with prolonged survival time and lowered tissue fungal burden in immunosuppressed mice infected with R. arrhizus var. arrhizus and was as effective as high-dose liposomal amphotericin B treatment. These results support further development of VT-1161 against mucormycosis. PMID:26369977

  16. Isolation of an immunosuppressive lectin from Phaseolus vulgaris L. cv Cacahuate using stroma.

    PubMed

    Vargas-Albores, F; Hernández, J; Córdoba, F; Zenteno, E

    1993-11-01

    An immunosuppressive lectin was isolated from seed of Phaseolus vulgaris cv Cacahuate using physically entrapped stroma. The lectin was found to be a 94 kDa tetrameric protein. When 50 micrograms, of this lectin were administered intraperitoneally 2 days before the immunization with sheep red blood cells, humoral response against the immunogen was completely inhibited. Other properties of the protein are discussed. PMID:8248029

  17. Viral Dose and Immunosuppression Modulate the Progression of Acute BVDV-1 Infection in Calves: Evidence of Long Term Persistence after Intra-Nasal Infection

    PubMed Central

    Strong, Rebecca; La Rocca, Severina Anna; Paton, David; Bensaude, Emmanuelle; Sandvik, Torstein; Davis, Leanne; Turner, Jane; Drew, Trevor; Raue, Rudiger; Vangeel, Ilse; Steinbach, Falko

    2015-01-01

    Bovine viral diarrhoea virus (BVDV) infection of cattle causes a diverse range of clinical outcomes from being asymptomatic, or a transient mild disease, to producing severe cases of acute disease leading to death. Four groups of calves were challenged with a type 1 BVDV strain, originating from a severe outbreak of BVDV in England, to study the effect of viral dose and immunosuppression on the viral replication and transmission of BVDV. Three groups received increasing amounts of virus: Group A received 102.55TCID50/ml, group B 105.25TCID50/ml and group C 106.7TCID 50/ml. A fourth group (D) was inoculated with a medium dose (105.25TCID50/ml) and concomitantly treated with dexamethasone (DMS) to assess the effects of chemically induced immunosuppression. Naïve calves were added as sentinel animals to assess virus transmission. The outcome of infection was dose dependent with animals given a higher dose developing severe disease and more pronounced viral replication. Despite virus being shed by the low-dose infection group, BVD was not transmitted to sentinel calves. Administration of dexamethasone (DMS) resulted in more severe clinical signs, prolonged viraemia and virus shedding. Using PCR techniques, viral RNA was detected in blood, several weeks after the limit of infectious virus recovery. Finally, a recently developed strand-specific RT-PCR detected negative strand viral RNA, indicative of actively replicating virus, in blood samples from convalescent animals, as late as 85 days post inoculation. This detection of long term replicating virus may indicate the way in which the virus persists and/or is reintroduced within herds. PMID:25955849

  18. Aerosolized Amphotericin B Lipid Complex as Adjunctive Treatment for Fungal Lung Infection in Patients with Cancer-Related Immunosuppression and Recipients of Hematopoietic Stem Cell Transplantation

    PubMed Central

    Safdar, Amar; Rodriguez, Gilhen H.

    2013-01-01

    Aerosolized amphotericin B lipid complex (aeABLC) has been successfully used to prevent fungal disease. Experience with aeABLC as treatment of fungal lung disease is limited. We evaluated the safety and efficacy of aeABLC adjunct therapy for fungal lung disease in a retrospective study of 32 immunosuppressed adults. Acute leukemia (69%) and severe neutropenia (63%) were common. The median duration of aeABLC was 185 ± 424 days in patients who underwent allogeneic stem cell transplantation (56%). High-dose corticosteroids were administered during aeABLC in 28% of patients. Fungal lung disease was proven or probable in 41% of patients. Most patients (78%) received systemic antifungal therapy for a median of 14 ± 18 days before aeABLC. The median cumulative aeABLC dose was 1,050 ± 2,368 mg, and the median duration of aeABLC therapy was 28 ± 130 days. Most patients (78%) received 50 mg aeABLC twice daily. Partial or complete resolution of fungal lung disease was noted in 50% of patients. In 3 patients (9%) modest cough, mild bronchospasm, and transient chest pain with accompanying nausea and vomiting resolved completely after discontinuation of aeABLC. No patient required hospitalization for drug toxicity or had a serious (grade III or IV) drug toxicity. Treatment with aeABLC was tolerated without serious toxicity and may be considered in the setting of severe immunosuppression, cancer, and/or stem cell transplantation in patients with difficult-to-treat fungal lung disease. PMID:23784915

  19. Acute onset of encephalomyelitis with atypical lesions associated with dual infection of Sarcocystis neurona and Toxoplasma gondii in a dog.

    PubMed

    Gerhold, Richard; Newman, Shelley J; Grunenwald, Caroline M; Crews, Amanda; Hodshon, Amy; Su, Chunlei

    2014-10-15

    A two-year-old male, neutered, basset hound-beagle mix with progressive neurological impairment was examined postmortem. Grossly, the dog had multiple raised masses on the spinal cord between nerve roots. Microscopically, the dog had protozoal myeloencephalitis. Toxoplasma gondii and Sarcocystis neurona were detected in the CNS by immunohistochemistry and polymerase chain reaction (PCR). Sarcocysts in formalin-fixed muscle were negative for Sarcocystis by PCR. Banked serum was negative for T. gondii using the modified agglutination test, suggesting an acute case of T. gondii infection or immunosuppression; however, no predisposing immunosuppressive diseases, including canine distemper, were found. To the authors' knowledge, this is the first report of dual T. gondii and S. neurona infection in a dog. PMID:25260332

  20. Systemic increased immune response to Nocardia brasiliensis co-exists with local immunosuppressive microenvironment.

    PubMed

    Salinas-Carmona, Mario Cesar; Rosas-Taraco, Adrian Geovanni; Welsh, Oliverio

    2012-10-01

    Human diseases produced by pathogenic actinomycetes are increasing because they may be present as opportunistic infections. Some of these microbes cause systemic infections associated with immunosuppressive conditions, such as chemotherapy for cancer, immunosuppressive therapy for transplant, autoimmune conditions, and AIDS; while others usually cause localized infection in immunocompetent individuals. Other factors related to this increase in incidence are: antibiotic resistance, not well defined taxonomy, and a delay in isolation and identification of the offending microbe. Examples of these infections are systemic disease and brain abscesses produced by Nocardia asteroides or the located disease by Nocardia brasiliensis, named actinomycetoma. During the Pathogenic Actinomycetes Symposium of the 16th International Symposium on Biology of Actinomycetes (ISBA), held in Puerto Vallarta, Mexico, several authors presented recent research on the mechanisms by which N. brasiliensis modulates the immune system to survive in the host and advances in medical treatment of human actinomycetoma. Antibiotics and antimicrobials that are effective against severe actinomycetoma infections with an excellent therapeutic outcome and experimental studies of drugs that show promising bacterial inhibition in vivo and in vitro were presented. Here we demonstrate a systemic strong acquired immune response in humans and experimental mice at the same time of a local dominance of anti inflammatory cytokines environment. The pathogenic mechanisms of some actinomycetes include generation of an immunosuppressive micro environment to evade the protective immune response. This information will be helpful in understanding pathogenesis and to design new drugs for treatment of actinomycetoma. PMID:22825801

  1. The Financial Impact of Immunosuppressant Expenses on New Kidney Transplant Recipients

    PubMed Central

    Gordon, Elisa J.; Prohaska, Thomas R.; Sehgal, Ashwini R.

    2008-01-01

    Background This study aimed to examine kidney transplant recipients’ ability to afford transplant-related out-of-pocket expenses and the financial impact of these expenses on their lives. Participants and methods This cross-sectional study involved 77 kidney recipients. Variables analyzed were: ability to afford daily necessities; impact of immunosuppressant expenses on patients’ lives; awareness of Medicare support terminating 3 years post-transplant; and strategies used to pay for out-of-pocket transplant expenses. The Economic Strain Scale measured financial strain. Results Twenty-nine percent of kidney recipients experienced financial strain. Poor, less educated, and younger patients were more likely to report financial strain. Out-of-pocket expenses relating to kidney transplantation adversely affected patients’ ability to afford leisure activities (35%), a house (27%), and a car (26%). Thirty-one percent reported that immunosuppressant expenses have had somewhat to great (adverse) impact on their lives. Of those on Medicare and not disabled (n=41), 51% were unaware Medicare coverage will terminate, and 71% did not know how long coverage lasts. Conclusions Financial strain presents a considerable risk to kidney recipients’ ability to purchase immunosuppression. Socioeconomic disparities in recipients’ financial strain may be a source of disparities in graft survival. Transplant professionals should better inform transplant candidates about financial consequences of transplantation. PMID:18673373

  2. Impact of Laboratory Practices on Interlaboratory Variability in Therapeutic Drug Monitoring of Immunosuppressive Drugs.

    PubMed

    Christians, Uwe; Vinks, Alexander A; Langman, Loralie J; Clarke, William; Wallemacq, Pierre; van Gelder, Teun; Renjen, Varun; Marquet, Pierre; Meyer, Eric J

    2015-12-01

    The immunosuppressants cyclosporine, tacrolimus, sirolimus, everolimus, and probably also mycophenolic acid require therapeutic drug monitoring (TDM)-guided dosing to ensure that blood concentrations are kept within the target range in transplant patients. Reliable, accurate, and precise test methods are therefore essential to effectively monitor levels and to make proper dose adjustments. Data from proficiency testing programs have shown substantial interlaboratory variability. Only few attempts have been made to study the underlying causes. The aim of this study was to systematically document current practices used for immunosuppressant drug TDM in clinical laboratories and identify methodological and practice differences, which may cause the variability observed among laboratories. Data collection was primarily conducted by a structured Web-based survey. Invitations to participate in the survey were distributed to clinical laboratories providing immunosuppressant drug TDM. Surveys were completed by 76 laboratories in 14 countries. The results of our survey suggest that there are 3 main reasons for interlaboratory variability: (1) lack of standardization of laboratory procedures and workflows starting with sample collection and handling, (2) lack of use of appropriate reference materials (eg, isotope-labeled internal standards for liquid chromatography-tandem mass spectroscopy), and (3) poor compliance with internationally accepted good laboratory practice guidelines (eg, related to quality control, quality assurance, validation, training of personnel). The results of the survey also suggest that interlaboratory variability is a multifactorial problem. Technical-level consensus on laboratory operational procedures, quality systems, and personnel training will be of great importance to improve quality and interlaboratory comparability. PMID:26291980

  3. Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer

    PubMed Central

    Birge, R B; Boeltz, S; Kumar, S; Carlson, J; Wanderley, J; Calianese, D; Barcinski, M; Brekken, R A; Huang, X; Hutchins, J T; Freimark, B; Empig, C; Mercer, J; Schroit, A J; Schett, G; Herrmann, M

    2016-01-01

    Apoptosis is an evolutionarily conserved and tightly regulated cell death modality. It serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete cells that have reached advanced age or whose genomes have been irreparably damaged. Apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. Over the past decades, the molecular and cell biological events associated with efferocytosis have been rigorously studied, and many eat-me signals and receptors have been identified. The externalization of phosphatidylserine (PS) is arguably the most emblematic eat-me signal that is in turn bound by a large number of serum proteins and opsonins that facilitate efferocytosis. Under physiological conditions, externalized PS functions as a dominant and evolutionarily conserved immunosuppressive signal that promotes tolerance and prevents local and systemic immune activation. Pathologically, the innate immunosuppressive effect of externalized PS has been hijacked by numerous viruses, microorganisms, and parasites to facilitate infection, and in many cases, establish infection latency. PS is also profoundly dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity. In this review, we discuss the biology of PS with respect to its role as a global immunosuppressive signal and how PS is exploited to drive diverse pathological processes such as infection and cancer. Finally, we outline the rationale that agents targeting PS could have significant value in cancer and infectious disease therapeutics. PMID:26915293

  4. The influence of immunosuppressive drugs on neural stem/progenitor cell fate in vitro

    SciTech Connect

    Skardelly, Marco; Glien, Anja; Groba, Claudia; Schlichting, Nadine; Kamprad, Manja; Meixensberger, Juergen; Milosevic, Javorina

    2013-12-10

    In allogenic and xenogenic transplantation, adequate immunosuppression plays a major role in graft survival, especially over the long term. The effect of immunosuppressive drugs on neural stem/progenitor cell fate has not been sufficiently explored. The focus of this study is to systematically investigate the effects of the following four different immunotherapeutic strategies on human neural progenitor cell survival/death, proliferation, metabolic activity, differentiation and migration in vitro: (1) cyclosporine A (CsA), a calcineurin inhibitor; (2) everolimus (RAD001), an mTOR-inhibitor; (3) mycophenolic acid (MPA, mycophenolate), an inhibitor of inosine monophosphate dehydrogenase and (4) prednisolone, a steroid. At the minimum effective concentration (MEC), we found a prominent decrease in hNPCs' proliferative capacity (BrdU incorporation), especially for CsA and MPA, and an alteration of the NAD(P)H-dependent metabolic activity. Cell death rate, neurogenesis, gliogenesis and cell migration remained mostly unaffected under these conditions for all four immunosuppressants, except for apoptotic cell death, which was significantly increased by MPA treatment. - Highlights: • Four immunosuppresants (ISs) were tested in human neural progenitor cells in vitro. • Cyclosporine A and mycophenolic acid showed a prominent anti-proliferative activity • Mycophenolic acid exhibited a significant pro-apoptotic effect. • NAD(P)H-dependent metabolic activity was occasionally induced by ISs. • Neuronal differentiation and migration potential remained unaffected by ISs treatment.

  5. Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood.

    PubMed

    Yoshimi, Ayami; van den Heuvel-Eibrink, Marry M; Baumann, Irith; Schwarz, Stephan; Simonitsch-Klupp, Ingrid; de Paepe, Pascale; Campr, Vit; Kerndrup, Gitte Birk; O'Sullivan, Maureen; Devito, Rita; Leguit, Roos; Hernandez, Miguel; Dworzak, Michael; de Moerloose, Barbara; Stary, Jan; Hasle, Henrik; Smith, Owen P; Zecca, Marco; Catala, Albert; Schmugge, Markus; Locatelli, Franco; Führer, Monika; Fischer, Alexandra; Guderle, Anne; Nöllke, Peter; Strahm, Brigitte; Niemeyer, Charlotte M

    2014-04-01

    Refractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with refractory cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse antithymocyte globulin and 53% for rabbit antithymocyte globulin (P=0.04). The inferior response in the rabbit antithymocyte globulin group resulted in lower 4-year transplantation-free (69% versus 46%; P=0.003) and failure-free (58% versus 48%; P=0.04) survival rates in this group compared with those in the horse antithymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% versus 85%; P=ns). The cumulative incidence of relapse (15% versus 9%; P=ns) and clonal evolution (12% versus 4%; P=ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit antithymocyte globulin is inferior to that of horse antithymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory cytopenia of childhood, the long-term risk of relapse or clonal evolution remains. (ClinicalTrial.gov identifiers: NCT00662090). PMID:24162791

  6. Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood

    PubMed Central

    Yoshimi, Ayami; van den Heuvel-Eibrink, Marry M.; Baumann, Irith; Schwarz, Stephan; Simonitsch-Klupp, Ingrid; de Paepe, Pascale; Campr, Vit; Kerndrup, Gitte Birk; O’Sullivan, Maureen; Devito, Rita; Leguit, Roos; Hernandez, Miguel; Dworzak, Michael; de Moerloose, Barbara; Starý, Jan; Hasle, Henrik; Smith, Owen P.; Zecca, Marco; Catala, Albert; Schmugge, Markus; Locatelli, Franco; Führer, Monika; Fischer, Alexandra; Guderle, Anne; Nöllke, Peter; Strahm, Brigitte; Niemeyer, Charlotte M.

    2014-01-01

    Refractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with refractory cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse antithymocyte globulin and 53% for rabbit antithymocyte globulin (P=0.04). The inferior response in the rabbit antithymocyte globulin group resulted in lower 4-year transplantation-free (69% versus 46%; P=0.003) and failure-free (58% versus 48%; P=0.04) survival rates in this group compared with those in the horse antithymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% versus 85%; P=ns). The cumulative incidence of relapse (15% versus 9%; P=ns) and clonal evolution (12% versus 4%; P=ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit antithymocyte globulin is inferior to that of horse antithymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory cytopenia of childhood, the long-term risk of relapse or clonal evolution remains. (ClinicalTrial.gov identifiers: NCT00662090) PMID:24162791

  7. Temporal Response of the Human Virome to Immunosuppression and Antiviral Therapy

    PubMed Central

    De Vlaminck, Iwijn; Khush, Kiran K.; Strehl, Calvin; Kohli, Bitika; Neff, Norma F.; Okamoto, Jennifer; Snyder, Thomas M.; Weill, David; Bernstein, Daniel; Valantine, Hannah A.; Quake, Stephen R.

    2014-01-01

    Summary There are few substantive methods to measure the health of the immune system, and the connection between immune strength and the viral component of the microbiome is poorly understood. Organ transplant recipients are treated with a post-transplant therapy that combines immunosuppressive and antiviral drugs, offering a window into the effects of immune modulation on the virome. We used sequencing of cell-free DNA in plasma to investigate drug-virome interactions in a cohort of organ transplant recipients (656 samples, 96 patients), and find that antivirals and immunosuppressants strongly affect the structure of the virome in plasma. We observe marked virome compositional dynamics at the onset of the therapy and find that the total viral load increases with immunosuppression, whereas the bacterial component of the microbiome remains largely unaffected. The data provide insight into the relationship between the human virome, the state of the immune system, and the effects of pharmacological treatment, and offer a potential application of the virome state to predict immunocompetence. PMID:24267896

  8. Effects of cytotoxic immunosuppressants on tuberculin-sensitive lymphocytes in guinea pigs.

    PubMed Central

    Winkelstein, A

    1975-01-01

    The immunosuppressive activities of two phase-specific drugs, 6-mercaptopurine (6-MP) and methotrexate, and a cycle-specific agent, cyclophosphamide, were evaluated on the lymphocytic component of established tuberculin hypersensitivity in guinea pigs. In these animals, purified protein derivative (PPD)-sensitive lymphocytes are in an intermitotic phase of their proliferative cycle. Neither phase-specific drug significantly altered either the number or functional activities of these lymphocytes. By two in vitro criteria, PPD-induced lymphoproliferation and elaboration of migration inhibition factor (MIF), the responses of lymph node cells were equivalent to sensitized controls. In addition, these agents did not deplete pools of T lymphocytes, impair responses to phytohemagglutinin (PHA), nor inhibit cutaneous reactivity if employed before sensitization. In contrast, cyclophosphamide showed broader immunosuppressive effects including significant toxicities for intermitotic lymphocytes. This drug depleted pools of T cells and markedly impaired the in vitro proliferative responses of residual lymphocytes. The latter occurred with both PHA and PPD. Suppression of PHA reactivity was a dose-dependent phenomenon but was evident even with small quantities of this alkylating agent. The suppression of antigen-induced responses was independent of the proliferative status of target lymphocytes in vivo, after a single large dose, it persisted for more than 3 wk. In total, these results indicate that the effective use of cytotoxic drugs as immunosuppressants must include consideration of both the cycle specificities of the agent and the proliferative activities of the target lymphoid population. PMID:1081551

  9. Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics of Immunosuppressants in Allogeneic Hematopoietic Cell Transplantation: Part II.

    PubMed

    McCune, Jeannine S; Bemer, Meagan J; Long-Boyle, Janel

    2016-05-01

    Part I of this article included a pertinent review of allogeneic hematopoietic cell transplantation (alloHCT), the role of postgraft immunosuppression in alloHCT, and the pharmacokinetics, pharmacodynamics, and pharmacogenomics of the calcineurin inhibitors and methotrexate. In this article (Part II), we review the pharmacokinetics, pharmacodynamics, and pharmacogenomics of mycophenolic acid (MPA), sirolimus, and the antithymocyte globulins (ATG). We then discuss target concentration intervention (TCI) of these postgraft immunosuppressants in alloHCT patients, with a focus on current evidence for TCI and on how TCI may improve clinical management in these patients. Currently, TCI using trough concentrations is conducted for sirolimus in alloHCT patients. Several studies demonstrate that MPA plasma exposure is associated with clinical outcomes, with an increasing number of alloHCT patients needing TCI of MPA. Compared with MPA, there are fewer pharmacokinetic/dynamic studies of rabbit ATG and horse ATG in alloHCT patients. Future pharmacokinetic/dynamic research of postgraft immunosuppressants should include '-omics'-based tools: pharmacogenomics may be used to gain an improved understanding of the covariates influencing pharmacokinetics as well as proteomics and metabolomics as novel methods to elucidate pharmacodynamic responses. PMID:26620047

  10. Allogeneic and Xenogeneic Transplantation of Adipose-Derived Stem Cells in Immunocompetent Recipients Without Immunosuppressants

    PubMed Central

    Lin, Guiting; Lue, Tom F.

    2012-01-01

    Mesenchymal stem cells (MSCs) are well known for their immunomodulatory capabilities. In particular, their immunosuppressive property is believed to permit their allogeneic or even xenogeneic transplantation into immunocompetent recipients without the use of immunosuppressants. Adipose-derived stem cell (ADSC), owing to its ease of isolation from an abundant tissue source, is a promising MSC for the treatment of a wide range of diseases. ADSC has been shown to lack major histocompatibility complex-II expression, and its immunosuppressive effects mediated by prostaglandin E2. Both preclinical and clinical studies have shown that allogeneic transplantation of ADSCs was able to control graft-versus-host disease. In regard to xenotransplantation a total of 27 preclinical studies have been published, with 20 of them performed with the investigators' intent. All 27 studies used ADSCs isolated from humans, possibly due to the wide availability of lipoaspirates. On the other hand, the recipients were mouse in 13 studies, rat in 11, rabbit in 2, and dog in 1. The targeted diseases varied greatly but all showed significant improvements after ADSC xenotransplantation. For clinical application in human medicine, ADSC xenotransplantation offers no obvious advantage over autotransplantation. But in veterinary medicine, xenotransplantation with porcine ADSC is a practical alternative to the costly and inconvenient autotransplantation. PMID:22621212

  11. The antigenic and immunosuppressive properties of normal and antilymphocytic equine IgG subfractions

    PubMed Central

    Allardyce, R. A.; Anderson, N. F.; Vaerman, J. P.; James, K.

    1973-01-01

    The antigenic and immunosuppressive properties of normal and antilympho-cytic equine globulin subfractions were investigated in the rat model in an attempt to increase the efficacy of prolonged ALG therapy by limiting the immunogenic stimulus of `inactive' subfractions. Chromatographic separation of equine IgG components yielded an electro-phoretically slow gamma 2 fraction consisting of IgG2a and IgG2b and a more heterogeneous fast gamma 1 subfraction. Immunosuppression resulting from the administration of isolated subfractions was measured by the response to alum-BSA and skin allograft survival. Antigenicity was determined by a variety of immunological procedures. The immunosuppressive character of the ALG was confined to the gamma 2 fraction, however this fraction also proved antigenic in our system. The administration of normal equine IgG subfractions in combination with Freund's complete adjuvant resulted in the demonstration of antigenic differences between the fast and slow IgG components. ImagesFig. 1Fig. 2 PMID:4120853

  12. Rescuing lymphocytes from HLA-G immunosuppressive effects mediated by the tumor microenvironment

    PubMed Central

    Wu, Danli; Kuiaste, Isere; Moreau, Philippe; Carosella, Edgardo; Yotnda, Patricia

    2015-01-01

    Several studies have demonstrated that the antitumor activities of both T and natural killer (NK) effector populations are limited by the immunosuppressive strategies of tumors. In several malignant transformations, the expression of HLA-G by tumor cells rises dramatically, rendering them strongly immunosuppressive. In this study, we postulated that the absence of HLA-G receptors would prevent the immunosuppressive effects of both soluble and membrane-bound HLA-G. Thus, we investigated the therapeutic potential of effector NK cells genetically modified to downregulate the expression of ILT2 (HLA-G receptor) on their cell surfaces. We have shown that the proliferation of modified NK is still dependent on stimulation signals (no malignant transformation). ILT2− NK cells proliferate, migrate, and eliminate HLA-G negative targets cells to the same extent parental NK cells do. However, in the presence of HLA-G positive tumors, ILT2− NK cells exhibit superior proliferation, conjugate formation, degranulation, and killing activities compared to parent NK cells. We tested the effectiveness of ILT2− NK cells in vivo using a xenograft cancer model and found that silencing ILT2 rescued their anti-tumor activity. We believe that combining ILT2− NK cells with existing therapeutic strategies will strengthen the antitumor response in cancer patients. PMID:26460949

  13. [Chemical constituents from stems of Hedyotis hedyotidea and their immunosuppressive activity].

    PubMed

    Zhang, Tian-tian; Gao, Sha-sha; Hou, Jun-jie; Zhou, Yong-qin; Zhou, Jie-wen; Wang, Xiao-gang; Qin, Nan; Chen, Jia-chun; Duan, Hong-quan; Fang, Jin-bo

    2015-06-01

    Hedyotis hedyotidea has been traditionally used for the treatment of arthritis, cold, cough, gastro-enteritis, headstroke, etc. But few studies have screened the active compounds from extracts of H. hedyotidea. In this study, the structure of the chemical constituents from stems of H. hedyotidea were determined and the immunosuppressive activity of the compounds was evaluated. The compounds were separated and purified with silica gel, gel column chromatographies and preparative HPLC, and their structures were identified by spectral methods such as MS and NMR. Eleven compounds were obtained and identified as(6S,9S) -vomifoliol (1), betulonic acid (2), betulinic acid (3), betulin(4), 3-epi-betulinic acid (5), ursolic acid (6), β-sitosterol (7), stigmast-4-en-3-one (8), 7β-hydroxysitosterol (9), (3β,7β) -7-methoxystigmast-5-en-3-ol (10) and morindacin (11). This is the first report of compounds 1, 2, 4, 8, 9, 10 and 11 from H. hedyotidea. Compounds 1, 2 and 8-11 were firstly isolated from the genus Hedyotis, and compounds 9 and 10 were isolated from the family Rubiaceae for the first time. The immunosuppressive activity of these compounds was tested using the lymphocyte transsormationtest. Compounds 4, 6 and 9 showed significant immunosuppressive activity. PMID:26591525

  14. Hyaluronic acid prevents immunosuppressive drug-induced ovarian damage via up-regulating PGRMC1 expression

    PubMed Central

    Zhao, Guangfeng; Yan, Guijun; Cheng, Jie; Zhou, Xue; Fang, Ting; Sun, Haixiang; Hou, Yayi; Hu, Yali

    2015-01-01

    Chemotherapy treatment in women can frequently cause damage to the ovaries, which may lead to primary ovarian insufficiency (POI). In this study, we assessed the preventative effects of hyaluronic acid (HA) in immunosuppressive drug-induced POI-like rat models and investigated the possible mechanisms. We found that HA, which was reduced in primary and immunosuppressant-induced POI patients, could protect the immunosuppressant-induced damage to granulosa cells (GCs) in vitro. Then we found that HA blocked the tripterygium glycosides (TG) induced POI-like presentations in rats, including delayed or irregular estrous cycles, reduced 17 beta-estradiol(E2) concentration, decreased number of follicles, destruction of follicle structure, and damage of reproductive ability. Furthermore, we investigated the mechanisms of HA prevention effects on POI, which was associated with promotion of GC proliferation and PGRMC1 expression. In conclusion, HA prevents chemotherapy-induced ovarian damage by promoting PGRMC1 in GCs. This study may provide a new strategy for prevention and treatment of POI. PMID:25558795

  15. Social networks and immunosuppression during stress: relationship conflict or energy conservation?

    PubMed

    Segerstrom, Suzanne C

    2008-03-01

    Despite the apparent health benefits of social relationships, some studies indicate that larger social networks can be associated with greater vulnerability to infectious disease, particularly if stressors are also present. Two possibilities for such effects are, first, that more social contacts lead to more negative affect and social conflict during stressors, or second, that maintaining more social contacts is an energetically costly activity, and ecologically motivated immunosuppression is one means of providing energy to maintain social resources. First-year law students (N=76) completed questionnaires and had delayed-type hypersensitivity skin tests at five time points during their first 6 months of law school. Both moving away from home and a smaller social network associated with larger DTH responses (both p<0.05) across all time points. However, negative affect, either broadly defined or as specific affects (hostility, sadness, guilt), did not mediate social network effects, suggesting that negative affect and social conflict are less plausible explanations than ecological immunosuppression. Ecological models would predict that temporary immunosuppression is less harmful to health in the long run than loss of social resources. PMID:18055166

  16. Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer.

    PubMed

    Birge, R B; Boeltz, S; Kumar, S; Carlson, J; Wanderley, J; Calianese, D; Barcinski, M; Brekken, R A; Huang, X; Hutchins, J T; Freimark, B; Empig, C; Mercer, J; Schroit, A J; Schett, G; Herrmann, M

    2016-06-01

    Apoptosis is an evolutionarily conserved and tightly regulated cell death modality. It serves important roles in physiology by sculpting complex tissues during embryogenesis and by removing effete cells that have reached advanced age or whose genomes have been irreparably damaged. Apoptosis culminates in the rapid and decisive removal of cell corpses by efferocytosis, a term used to distinguish the engulfment of apoptotic cells from other phagocytic processes. Over the past decades, the molecular and cell biological events associated with efferocytosis have been rigorously studied, and many eat-me signals and receptors have been identified. The externalization of phosphatidylserine (PS) is arguably the most emblematic eat-me signal that is in turn bound by a large number of serum proteins and opsonins that facilitate efferocytosis. Under physiological conditions, externalized PS functions as a dominant and evolutionarily conserved immunosuppressive signal that promotes tolerance and prevents local and systemic immune activation. Pathologically, the innate immunosuppressive effect of externalized PS has been hijacked by numerous viruses, microorganisms, and parasites to facilitate infection, and in many cases, establish infection latency. PS is also profoundly dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity. In this review, we discuss the biology of PS with respect to its role as a global immunosuppressive signal and how PS is exploited to drive diverse pathological processes such as infection and cancer. Finally, we outline the rationale that agents targeting PS could have significant value in cancer and infectious disease therapeutics. PMID:26915293

  17. High immunosuppressive burden in cancer patients: a major hurdle for cancer immunotherapy.

    PubMed

    Kalathil, Suresh Gopi; Thanavala, Yasmin

    2016-07-01

    A bottleneck for immunotherapy of cancer is the immunosuppressive microenvironment in which the tumor cells are located. Regardless of the fact that large numbers of tumor-specific T cells can be generated in patients by active immunization or adoptive transfer, these T cells do not readily translate to tumor cell killing in vivo. The immune regulatory mechanism that prevents autoimmunity may be harnessed by tumor cells for the evasion of immune destruction. Regulatory T cells, myeloid-derived suppressor cells, inhibitory cytokines and immune checkpoint receptors are the major components of the immune system acting in concert with causing the subversion of anti-tumor immunity in the tumor microenvironment. This redundant immunosuppressive network may pose an impediment to efficacious immunotherapy, thus facilitating tumor progression. Cancer progression clearly documents the failure of immune control over relentless growth of tumor cells. Detailed knowledge of each of these factors responsible for creating an immunosuppressive shield to protect tumor cells from immune destruction is essential for the development of novel immune-based therapeutic interventions of cancer. Multipronged targeted depletion of these suppressor cells may restore production of granzyme B by CD8(+) T cells and increase the number of IFN-γ-producing CD4(+) T cells. PMID:26910314

  18. Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells

    PubMed Central

    Gallina, Giovanna; Dolcetti, Luigi; Serafini, Paolo; Santo, Carmela De; Marigo, Ilaria; Colombo, Mario P.; Basso, Giuseppe; Brombacher, Frank; Borrello, Ivan; Zanovello, Paola; Bicciato, Silvio; Bronte, Vincenzo

    2006-01-01

    Active suppression of tumor-specific T lymphocytes can limit the efficacy of immune surveillance and immunotherapy. While tumor-recruited CD11b+ myeloid cells are known mediators of tumor-associated immune dysfunction, the true nature of these suppressive cells and the fine biochemical pathways governing their immunosuppressive activity remain elusive. Here we describe a population of circulating CD11b+IL-4 receptor α+ (CD11b+IL-4Rα+), inflammatory-type monocytes that is elicited by growing tumors and activated by IFN-γ released from T lymphocytes. CD11b+IL-4Rα+ cells produced IL-13 and IFN-γ and integrated the downstream signals of these cytokines to trigger the molecular pathways suppressing antigen-activated CD8+ T lymphocytes. Analogous immunosuppressive circuits were active in CD11b+ cells present within the tumor microenvironment. These suppressor cells challenge the current idea that tumor-conditioned immunosuppressive monocytes/macrophages are alternatively activated. Moreover, our data show how the inflammatory response elicited by tumors had detrimental effects on the adaptive immune system and suggest novel approaches for the treatment of tumor-induced immune dysfunctions. PMID:17016559

  19. Immunosuppressive potency of mechanistic target of rapamycin inhibitors in solid-organ transplantation

    PubMed Central

    Baroja-Mazo, Alberto; Revilla-Nuin, Beatriz; Ramírez, Pablo; Pons, José A

    2016-01-01

    Mammalian target of rapamycin, also known as mechanistic target of rapamycin (mTOR) is a protein kinase that belongs to the PI3K/AKT/mTOR signaling pathway, which is involved in several fundamental cellular functions such as cell growth, proliferation, and survival. This protein and its associated pathway have been implicated in cancer development and the regulation of immune responses, including the rejection response generated following allograft transplantation. Inhibitors of mTOR (mTORi) such as rapamycin and its derivative everolimus are potent immunosuppressive drugs that both maintain similar rates of efficacy and could optimize the renal function and diminish the side effects compared with calcineurin inhibitors. These drugs are used in solid-organ transplantationtoinduceimmunosuppression while also promoting the expansion of CD4+CD25+FOXP3+ regulatory T-cells that could favor a scenery of immunological tolerance. In this review, we describe the mechanisms by which inhibitors of mTOR induce suppression by regulation of these pathways at different levels of the immune response. In addition, we particularly emphasize about the main methods that are used to assess the potency of immunosuppressive drugs, highlighting the studies carried out about immunosuppressive potency of inhibitors of mTOR. PMID:27011916

  20. Multiple myeloma exosomes establish a favourable bone marrow microenvironment with enhanced angiogenesis and immunosuppression.

    PubMed

    Wang, Jinheng; De Veirman, Kim; Faict, Sylvia; Frassanito, Maria Antonia; Ribatti, Domenico; Vacca, Angelo; Menu, Eline

    2016-06-01

    Multiple myeloma (MM) pathogenesis and progression largely rely on the cells and extracellular factors in the bone marrow (BM) microenvironment. Compelling studies have identified tumour exosomes as key regulators in the maintenance and education of the BM microenvironment by targeting stromal cells, immune cells, and vascular cells. However, the role of MM exosomes in the modification of the BM microenvironment and MM progression remains unclear. Here, we explored the functions of MM exosomes in angiogenesis and immunosuppression in vitro and in vivo. Murine MM exosomes carrying multiple angiogenesis-related proteins enhanced angiogenesis and directly promoted endothelial cell growth. Several pathways such as signal transducer and activator of transcription 3 (STAT3), c-Jun N-terminal kinase, and p53 were modulated by the exosomes in endothelial and BM stromal cells. These exosomes promoted the growth of myeloid-derived suppressor cells (MDSCs) in naive mice through activation of the STAT3 pathway and changed their subsets to similar phenotypes to those seen in MM-bearing mice. Moreover, MM exosomes up-regulated inducible nitric oxide synthase and enhanced the immunosuppressive capacity of BM MDSCs in vivo. Our data show that MM exosomes modulate the BM microenvironment through enhancement of angiogenesis and immunosuppression, which will further facilitate MM progression. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26956697

  1. New puzzles for the use of non-invasive ventilation for immunosuppressed patients.

    PubMed

    Barbas, Carmen Sílvia Valente; Serpa Neto, Ary

    2016-01-01

    On October 27, 2015, Lemile and colleagues published an article in JAMA entitled "Effect of Noninvasive Ventilation vs. Oxygen Therapy on Mortality among Immunocompromised Patients with Acute Respiratory Failure: A Randomized Clinical Trial", which investigated the effects of non-invasive ventilation (NIV) in 28-day mortality of 374 critically ill immunosuppressed patients. The authors found that among immunosuppressed patients admitted to the intensive care unit (ICU) with hypoxemic acute respiratory failure, early NIV compared with oxygen therapy alone did not reduce 28-day mortality. Furthermore, different from the previous publications, there were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays. The study power was limited, median oxygen flow used was higher than used before or 9 L/min, NIV settings provided tidal volumes higher than what is considered protective nowadays or from 7 to 10 mL/kg of ideal body weight and the hypoxemic respiratory failure was moderate to severe (median PaO2/FIO2 was around 140), a group prone to failure in noninvasive ventilatory support. Doubts arose regarding the early use of NIV in immunosuppressed critically ill patients with non-hypercapnic hypoxemic respiratory failure that need to be solved in the near future. PMID:26904233

  2. Periostin promotes immunosuppressive premetastatic niche formation to facilitate breast tumour metastasis.

    PubMed

    Wang, Zhe; Xiong, Shanshan; Mao, Yubin; Chen, Mimi; Ma, Xiaohong; Zhou, Xueliang; Ma, Zhenling; Liu, Fan; Huang, Zhengjie; Luo, Qi; Ouyang, Gaoliang

    2016-08-01

    Periostin (POSTN) is a limiting factor in the metastatic colonization of disseminated tumour cells. However, the role of POSTN in regulating the immunosuppressive function of immature myeloid cells in tumour metastasis has not been documented. Here, we demonstrate that POSTN promotes the pulmonary accumulation of myeloid-derived suppressor cells (MDSCs) during the early stage of breast tumour metastasis. Postn deletion decreases neutrophil and monocytic cell populations in the bone marrow of mice and suppresses the accumulation of MDSCs to premetastatic sites. We also found that POSTN-deficient MDSCs display reduced activation of ERK, AKT and STAT3 and that POSTN deficiency decreases the immunosuppressive functions of MDSCs during tumour progression. Moreover, the pro-metastatic role of POSTN is largely limited to ER-negative breast cancer patients. Lysyl oxidase contributes to POSTN-promoted premetastatic niche formation and tumour metastasis. Our findings indicate that POSTN is essential for immunosuppressive premetastatic niche formation in the lungs during breast tumour metastasis and is a potential target for the prevention and treatment of breast tumour metastasis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:27193093

  3. Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques.

    PubMed

    Meyer, C; Walker, J; Dewane, J; Engelmann, F; Laub, W; Pillai, S; Thomas, Charles R; Messaoudi, I

    2015-09-01

    In this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease. PMID:25902927

  4. Immunosuppression and temporary skin transplantation in the treatment of massive third degree burns.

    PubMed Central

    Burke, J F; Quinby, W C; Bondoc, C C; Cosimi, A B; Russell, P S; Szyfelbein, S K

    1975-01-01

    A method of burn treatment (immunosuppression and temporary skin transplantation) for patients suffering from massive third degree burns is evaluated. The method is based on the prompt excision of all dead tissue (burn eschar) and immediate closure of the wound by skin grafts. Total wound closure is achieved before bacterial infection or organ failure takes place by carrying out all initial excision and grafting procedures within the first ten days post burn and supplementing the limited amount of autograft with allograft. Continuous wound closure is maintained for up to 50 days through immunosuppression. Both azathioprine and ATG have been used but ATG is preferred. During the period of immunosuppression, allograft is stepwise excised and replaced with autograft donor sites regenerate for recropping. Bacterial complications are minimized by housing the patient in the protected environment of the Bacteria Controlled Nursing Unit. Intensive protein and calorie alimentation are provided, and 0.5% aqueous AgNO3 dressings are used. A swinging febrile illness has been associated with large areas of allograft rejection. Eleven children have been treated and seven have been returned to normal, productive schooling. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:809014

  5. New puzzles for the use of non-invasive ventilation for immunosuppressed patients

    PubMed Central

    Serpa Neto, Ary

    2016-01-01

    On October 27, 2015, Lemile and colleagues published an article in JAMA entitled “Effect of Noninvasive Ventilation vs. Oxygen Therapy on Mortality among Immunocompromised Patients with Acute Respiratory Failure: A Randomized Clinical Trial”, which investigated the effects of non-invasive ventilation (NIV) in 28-day mortality of 374 critically ill immunosuppressed patients. The authors found that among immunosuppressed patients admitted to the intensive care unit (ICU) with hypoxemic acute respiratory failure, early NIV compared with oxygen therapy alone did not reduce 28-day mortality. Furthermore, different from the previous publications, there were no significant differences in ICU-acquired infections, duration of mechanical ventilation, or lengths of ICU or hospital stays. The study power was limited, median oxygen flow used was higher than used before or 9 L/min, NIV settings provided tidal volumes higher than what is considered protective nowadays or from 7 to 10 mL/kg of ideal body weight and the hypoxemic respiratory failure was moderate to severe (median PaO2/FIO2 was around 140), a group prone to failure in noninvasive ventilatory support. Doubts arose regarding the early use of NIV in immunosuppressed critically ill patients with non-hypercapnic hypoxemic respiratory failure that need to be solved in the near future. PMID:26904233

  6. Social Networks and Immunosuppression During Stress: Relationship Conflict or Energy Conservation?

    PubMed Central

    Segerstrom, Suzanne C.

    2008-01-01

    Despite the apparent health benefits of social relationships, some studies indicate that larger social networks can be associated with greater vulnerability to infectious disease, particularly if stressors are also present. Two possibilities for such effects are, first, that more social contacts lead to more negative affect and social conflict during stressors, or second, that maintaining more social contacts is an energetically costly activity, and ecologically motivated immunosuppression is one means of providing energy to maintain social resources. First-year law students (N = 76) completed questionnaires and had delayed-type hypersensitivity skin tests at five time points during their first 6 months of law school. Both moving away from home and a smaller social network associated with larger DTH responses (both p < .05) across all time points. However, negative affect, either broadly defined or as specific affects (hostility, sadness, guilt), did not mediate social network effects, suggesting that negative affect and social conflict are less plausible explanations than ecological immunosuppression. Ecological models would predict that temporary immunosuppression is less harmful to health in the long run than loss of social resources. PMID:18055166

  7. Immunosuppressive Effects of A-Type Procyanidin Oligomers from Cinnamomum tamala

    PubMed Central

    Chen, Liang; Yang, Yang; Yuan, Pulong; Yang, Yifu; Chen, Kaixian; Jia, Qi; Li, Yiming

    2014-01-01

    Cinnamon barks extracts have been reported to regulate immune function; however, the component(s) in cinnamon barks responsible for this effect is/are not yet clear. The aim of this study is to find out the possible component(s) that can be used as therapeutic agents for immune-related diseases from cinnamon bark. In this study, the immunosuppressive effects of fraction (named CT-F) and five procyanidin oligomers compounds, cinnamtannin B1, cinnamtannin D1 (CTD-1), parameritannin A1, procyanidin B2, and procyanidin C1, from Cinnamomum tamala or Cinnamomum cassia bark were examined on splenocytes proliferation model induced by ConA or LPS. Then, the effects of activated compound CTD-1 on cytokine production and 2,4-dinitrofluorobenzene (DNFB) induced delayed-type hypersensitivity (DTH) response were detected to evaluate the immunosuppressive activity of CTD-1. It was found that CT-F and CTD-1 significantly inhibited the splenocyte proliferation induced by ConA or LPS. CTD-1 dose-dependently reduced the level of IFN-γ and IL-2 and intensively suppressed DNFB-induced DTH responses. These findings suggest that the immunosuppressive activities of cinnamon bark are in part due to procyanidin oligomers. CTD-1 may be a potential therapeutic agent for immune-related diseases. PMID:25530780

  8. Reversal of long-term sepsis-induced immunosuppression by dendritic cells

    PubMed Central

    Benjamim, Claudia F.; Lundy, Steven K.; Lukacs, Nicholas W.; Hogaboam, Cory M.; Kunkel, Steven L.

    2005-01-01

    Severe sepsis leads to long-term systemic and local immunosuppression, which is the cause of a number of complications, including pulmonary infection. A therapeutic strategy that reverses this immunosuppression is required, given the ongoing high mortality rate of patients who have survived a severe sepsis. The present study demonstrates that experimental severe sepsis renders the lung susceptible to a normally innocuous Aspergillus fumigatus fungus challenge, due to a dominant lung type 2 cytokine profile. Dendritic cells (DCs) obtained from the lungs of mice subjected to cecal ligation and puncture (CLP) model were skewed toward type 2 cytokine profile, which occurred with exaggerated expression of Toll-like receptor 2 (TLR2). The intrapulmonary transfer of bone marrow–derived DCs (BMDCs) in postseptic mice prevented fatal Aspergillus infection. This therapy reduced the overall inflammatory response and fungal growth in the lung, and promoted the balance of proinflammatory and suppressive cytokines in the lung. Thus, intrapulmonary DC supplementation appears to restore the pulmonary host response in the postseptic lung in our animal model. These data strongly suggest that lung DCs are profoundly affected as a consequence of the systemic impact of severe sepsis, and the identification of mechanisms that restore their function may serve as a key strategy to reverse sepsis-induced immunosuppression. PMID:15604223

  9. Localization of radiolabeled antibody in SVT2 tumor increases with immunosuppression of the host. [Mice

    SciTech Connect

    Buchsbaum, D.J.; Anderson, J.M.; Bray, B.E.

    1982-10-01

    The localization of radiolabeled tumor-specific antibodies to an SV40-transformed mouse tumor was analyzed in immunosuppressed (X-ray and cortisone) and nonimmunosuppressed mice. (C57B1/6 x Balb/c)F/sub 1/ mice were immunized with the SVT2 tumor of Balb/c origin. Radiolabeled antibody was isolated from /sup 125/I-labeled immune gamma globulin by adsorption onto SVT2 cells, and elution from these cells using citrate buffer. The radiolabeled antibodies were injected into normal (C57B1/6 x Balb/c)F/sub 1/ mice. The purified antibodies present in this serum bound specifically in vitro to SV40-transformed cell lines. In vivo, the /sup 125/I-labeled antibodies localized preferentially in the SVT2 tumor in immunosuppressed mice. Significantly less /sup 125/I-labelled antibody localized in the SVT2 tumor in nonimmunosuppressed mice.The localization of /sup 125/I-labeled antibody in SVT2 tumor in immunosuppressed mice was reduced significantly by passive administration of anti-SVT2 serum.

  10. Quercetin targets the interaction of calcineurin with LxVP-type motifs in immunosuppression.

    PubMed

    Zhao, Yane; Zhang, Jin; Shi, Xiaoyu; Li, Jing; Wang, Rui; Song, Ruiwen; Wei, Qun; Cai, Huaibin; Luo, Jing

    2016-08-01

    Calcineurin (CN) is a unique calcium/calmodulin (CaM)-activated serine/threonine phosphatase. To perform its diverse biological functions, CN communicates with many substrates and other proteins. In the physiological activation of T cells, CN acts through transcriptional factors belonging to the NFAT family and other transcriptional effectors. The classic immunosuppressive drug cyclosporin A (CsA) can bind to cyclophilin (CyP) and compete with CN for the NFAT LxVP motif. CsA has debilitating side effects, including nephrotoxicity, hypertension and tremor. It is desirable to develop alternative immunosuppressive agents. To this end, we first tested the interactions between CN and the LxVP-type substrates, including endogenous regulators of calcineurin (RCAN1) and NFAT. Interestingly, we found that quercetin, the primary dietary flavonol, can inhibit the activity of CN and significantly disrupt the associations between CN and its LxVP-type substrates. We then validated the inhibitory effects of quercetin on the CN-NFAT interactions in cell-based assays. Further, quercetin also shows dose-dependent suppression of cytokine gene expression in mouse spleen cells. These data raise the possibility that the interactions of CN with its LxVP-type substrates are potential targets for immunosuppressive agents. PMID:27109380

  11. Immigration: perspectives from receiving countries.

    PubMed

    Weiner, M

    1990-01-01

    The author examines the issue of international migration from the standpoint of receiving countries. He attempts "to understand how and why migrant-receiving countries respond as they do, and to suggest some of the new issues in international migration that arise in a world in which the supply of would-be migrants and refugees is now greater than receiving countries are willing to accept." PMID:12283227

  12. CHANGES IN MOUSE CIRULATING LEUKOCYTE NUMBERS IN C57BL/6 MICE IMMUNOSUPPRESSED FOR CRYPTOSPORIDIUM PARVUM OOCYST PRODUCTION

    EPA Science Inventory

    The Iowa strain of Cryptosporidium parvum will not propagate in immunocompetent mice, but will successfully infect genetically immunocompromised Nude or SCID mice as well as immunocompetent mice which have been immunosuppressed with glucocorticoids. Using dexamethasone - tetracy...

  13. Self-dual electromagnetic fields

    NASA Astrophysics Data System (ADS)

    Chubykalo, Andrew E.; Espinoza, Augusto; Kosyakov, B. P.

    2010-08-01

    We demonstrate the utility of self-dual fields in electrodynamics. Stable configurations of free electromagnetic fields can be represented as superpositions of standing waves, each possessing zero Poynting vector and zero orbital angular momentum. The standing waves are themselves superpositions of self-dual and anti-self-dual solutions. The idea of self-duality provides additional insights into the geometrical and spectral properties of stable electromagnetic configurations, such as those responsible for the formation of ball lightning.

  14. MiR-582-5p/miR-590-5p targeted CREB1/CREB5–NF-κB signaling and caused opioid-induced immunosuppression in human monocytes

    PubMed Central

    Long, X; Li, Y; Qiu, S; Liu, J; He, L; Peng, Y

    2016-01-01

    Chronic opioid abusers are more susceptible to bacterial and viral infections, but the molecular mechanism underlying opioid-induced immunosuppression is unknown. MicroRNAs (miRNAs) are emerging as key players in the control of biological processes, and may participate in immune regulation. In this study, we investigated the molecular mechanisms in opioid-induced and miRNA-mediated immunosuppression, in the context of miRNA dysregulation in opioid abusers. Blood samples of heroin abusers were collected and analyzed using miRNA microarray analysis and quantitative PCR validation. The purified primary human monocytes were cultured in vitro to explore the underlying mechanism. We found that morphine and its derivative heroin significantly decreased the expression levels of miR-582-5p and miR-590-5p in monocytes. cAMP response element-binding protein 1 (CREB1) and CREB5 were detected as direct target genes of miR-582-5p and miR-590-5p, respectively, by using dual-luciferase assay and western bolt. Functional studies showed that knockdown of CREB1/CREB5 increased tumor necrosis factor alpha (TNF-α) level and enhanced expression of phospho–NF-κB p65 and NF-κB p65. Our results demonstrated that miR-582-5p and miR-590-5p play important roles in opioid-induced immunosuppression in monocytes by targeting CREB1/CREB5–NF-κB signaling pathway. PMID:26978739

  15. Abdominal Dual Energy Imaging

    NASA Astrophysics Data System (ADS)

    Sommer, F. Graham; Brody, William R.; Cassel, Douglas M.; Macovski, Albert

    1981-11-01

    Dual energy scanned projection radiography of the abdomen has been performed using an experimental line-scanned radiographic system. Digital images simultaneously obtained at 85 and 135 kVp are combined, using photoelectric/Compton decomposition algorithms to create images from which selected materials are cancelled. Soft tissue cancellation images have proved most useful in various abdominal imaging applications, largely due to the elimination of obscuring high-contrast bowel gas shadows. These techniques have been successfully applied to intravenous pyelography, oral cholecystography, intravenous abdominal arteriog-raphy and the imaging of renal calculi.

  16. Dual stage check valve

    NASA Technical Reports Server (NTRS)

    Whitten, D. E. (Inventor)

    1973-01-01

    A dual stage seat valve head arrangement is described which consists of a primary sealing point located between a fixed orifice seat and a valve poppet, and a secondary sealing point between an orifice poppet and a valve poppet. Upstream of the valve orifice is a flexible, convoluted metal diaphragm attached to the orifice poppet. Downstream of the valve orifice, a finger spring exerts a force against the valve poppet, tending to keep the valve in a closed position. The series arrangement of a double seat and poppet is able to tolerate small particle contamination while minimizing chatter by controlling throttling or metering across the secondary seat, thus preserving the primary sealing surface.

  17. Dual solvent refining process

    SciTech Connect

    Woodle, R.A.

    1982-04-20

    A dual solvent refining process is claimed for solvent refining petroleum based lubricating oil stocks with n-methyl-2-pyrrolidone as selective solvent for aromatic oils wherein a highly paraffinic oil having a narrow boiling range approximating the boiling point of n-methyl-2-pyrrolidone is employed as a backwash solvent. The process of the invention results in an increased yield of refined lubricating oil stock of a predetermined quality and simplifies separation of the solvents from the extract and raffinate oil fractions.

  18. Dual modification of biomolecules.

    PubMed

    Maruani, Antoine; Richards, Daniel A; Chudasama, Vijay

    2016-07-14

    With the advent of novel bioorthogonal reactions and "click" chemistry, an increasing number of strategies for the single labelling of proteins and oligonucleotides have emerged. Whilst several methods exist for the site-selective introduction of a single chemical moiety, site-selective and bioorthogonal dual modification of biomolecules remains a challenge. The introduction of multiple modules enables a plethora of permutations and combinations and can generate a variety of bioconjuguates with many potential applications. From de novo approaches on oligomers to the post-translational functionalisation of proteins, this review will highlight the main strategies to dually modify biomolecules. PMID:27278999

  19. UWB delay and multiply receiver

    DOEpatents

    Dallum, Gregory E.; Pratt, Garth C.; Haugen, Peter C.; Romero, Carlos E.

    2013-09-10

    An ultra-wideband (UWB) delay and multiply receiver is formed of a receive antenna; a variable gain attenuator connected to the receive antenna; a signal splitter connected to the variable gain attenuator; a multiplier having one input connected to an undelayed signal from the signal splitter and another input connected to a delayed signal from the signal splitter, the delay between the splitter signals being equal to the spacing between pulses from a transmitter whose pulses are being received by the receive antenna; a peak detection circuit connected to the output of the multiplier and connected to the variable gain attenuator to control the variable gain attenuator to maintain a constant amplitude output from the multiplier; and a digital output circuit connected to the output of the multiplier.

  20. An in vitro model to assess the immunosuppressive effect of tick saliva on the mobilization of inflammatory monocyte-derived cells.

    PubMed

    Vachiery, Nathalie; Puech, Carinne; Cavelier, Patricia; Rodrigues, Valérie; Aprelon, Rosalie; Lefrançois, Thierry; Martinez, Dominique; Epardaud, Mathieu

    2015-01-01

    Tick-borne pathogens cause potent infections. These pathogens benefit from molecules contained in tick saliva that have evolved to modulate host innate and adaptive immune responses. This is called "saliva-activated transmission" and enables tick-borne pathogens to evade host immune responses. Ticks feed on their host for relatively long periods; thus, mechanisms counteracting the inflammation-driven recruitment and activation of innate effector cells at the bite site, are an effective strategy to escape the immune response. Here, we developed an original in vitro model to evaluate and to characterize the immunomodulatory effects of tick saliva that prevent the establishment of a local inflammatory immune response. This model mimics the tick bite and enables the assessment of the effect of saliva on the inflammatory-associated dynamic recruitment of cells from the mononuclear phagocyte system. Using this model, we were able to recapitulate the dual effect of tick saliva on the mobilization of inflammatory monocyte-derived cells, i.e. (i) impaired recruitment of monocytes from the blood to the bite wound; and (ii) poor mobilization of monocyte-derived cells from the skin to the draining lymph node. This simple tool reconstitutes the effect of tick saliva in vivo, which we characterized in the mouse, and should enable the identification of important factors facilitating pathogen infection. Furthermore, this model may be applied to the characterization of any pathogen-derived immunosuppressive molecule affecting the establishment of the inflammatory immune response. PMID:26412247

  1. Adverse events in 50 cats with allergic dermatitis receiving ciclosporin.

    PubMed

    Heinrich, Nicole A; McKeever, Patrick J; Eisenschenk, Melissa C

    2011-12-01

    Ciclosporin is an immunosuppressive drug that has been used to treat allergies and other immune-mediated diseases in cats, dogs and humans. Information about the adverse effects of ciclosporin in cats has been limited to smaller studies and case reports. Adverse effects in dogs are mainly gastrointestinal in nature, but humans can also experience hypertension and altered renal function. The aim of this retrospective case series study was to document the occurrence and clinical appearance of adverse events in cats receiving ciclosporin to treat allergic skin disease. The medical records of 50 cats with allergic dermatitis treated with oral ciclosporin (1.9-7.3 mg/kg/day) were reviewed. Adverse events occurred in 66% (33 cats). Adverse events likely to be associated with ciclosporin included the following: vomiting or diarrhoea within 1-8 weeks of receiving ciclosporin (24%), weight loss (16%), anorexia and subsequent hepatic lipidosis (2%) and gingival hyperplasia (2%). Other adverse events less likely to be associated with ciclosporin therapy included the following: weight gain (14%), dental tartar and gingivitis (10%), otitis (4%), chronic diarrhoea (4%), inflammatory bowel disease with indolent gastrointestinal lymphoma (2%), urinary tract infection (2%), cataract (2%), elevated liver enzymes (2%), hyperthyroidism and renal failure (2%) and transient inappropriate urination (2%). Some cats experienced multiple adverse events. Case-control studies are needed to prove cause and effect of ciclosporin with regard to these adverse events. PMID:21545660

  2. Customizable Digital Receivers for Radar

    NASA Technical Reports Server (NTRS)

    Moller, Delwyn; Heavey, Brandon; Sadowy, Gregory

    2008-01-01

    Compact, highly customizable digital receivers are being developed for the system described in 'Radar Interferometer for Topographic Mapping of Glaciers and Ice Sheets' (NPO-43962), NASA Tech Briefs, Vol. 31, No. 7 (August 2007), page 72. The receivers are required to operate in unison, sampling radar returns received by the antenna elements in a digital beam-forming (DBF) mode. The design of these receivers could also be adapted to commercial radar systems. At the time of reporting the information for this article, there were no commercially available digital receivers capable of satisfying all of the operational requirements and compact enough to be mounted directly on the antenna elements. A provided figure depicts the overall system of which the digital receivers are parts. Each digital receiver includes an analog-to-digital converter (ADC), a demultiplexer (DMUX), and a field-programmable gate array (FPGA). The ADC effects 10-bit band-pass sampling of input signals having frequencies up to 3.5 GHz. The input samples are demultiplexed at a user-selectable rate of 1:2 or 1:4, then buffered in part of the FPGA that functions as a first-in/first-out (FIFO) memory. Another part of the FPGA serves as a controller for the ADC, DMUX, and FIFO memory and as an interface between (1) the rest of the receiver and (2) a front-panel data port (FPDP) bus, which is an industry-standard parallel data bus that has a high data-rate capability and multichannel configuration suitable for DBF. Still other parts of the FPGA in each receiver perform signal-processing functions. The digital receivers can be configured to operate in a stand-alone mode, or in a multichannel mode as needed for DBF. The customizability of the receiver makes it applicable to a broad range of system architectures. The capability for operation of receivers in either a stand-alone or a DBF mode enables the use of the receivers in an unprecedentedly wide variety of radar systems.

  3. 92 GHz dual-polarized integrated horn antennas

    NASA Technical Reports Server (NTRS)

    Ali-Ahmad, Walid Y.; Rebeiz, Gabriel M.

    1991-01-01

    A dual-polarized two-dimensional imaging array was designed for millimeter-wave applications. The dual-polarized design consists of two dipoles perpendicular to each other and suspended on the same membrane inside a pyramidal cavity etched in silicon. The dual-polarized antenna is fully monolithic with room available for processing electronics. The IF or video signals are taken out through a novel bias and feeding structure. The measured polarization isolation is better than 20 dB at 92 GHz, and the orthogonal channels show identical far-field patterns. The antenna is well suited for millimeter-wave polarimetric synthetic-aperture radars (SARs) and high-efficiency balanced-mixer receivers.

  4. Freudenthal dual Lagrangians

    NASA Astrophysics Data System (ADS)

    Borsten, L.; Duff, M. J.; Ferrara, S.; Marrani, A.

    2013-12-01

    The global U-dualities of extended supergravity have played a central role in differentiating the distinct classes of extremal black hole solutions. When the U-duality group satisfies certain algebraic conditions, as is the case for a broad class of supergravities, the extremal black holes enjoy a further symmetry known as Freudenthal duality (F-duality), which although distinct from U-duality preserves the Bekenstein-Hawking entropy. Here it is shown that, by adopting the doubled Lagrangian formalism, F-duality, defined on the doubled field strengths, is not only a symmetry of the black hole solutions, but also of the equations of motion themselves. A further role for F-duality is introduced in the context of world-sheet actions. The Nambu-Goto world-sheet action in any (t, s) signature spacetime can be written in terms of the F-dual. The corresponding field equations and Bianchi identities are then related by F-duality allowing for an F-dual formulation of Gaillard-Zumino duality on the world-sheet. An equivalent polynomial ‘Polyakov-type’ action is introduced using the so-called black hole potential. Such a construction allows for actions invariant under all groups of type E7, including E7 itself, although in this case the stringy interpretation is less clear.

  5. Dual-CARS microscopy

    NASA Astrophysics Data System (ADS)

    Enejder, Annika; Brackmann, Christian; Burkacky, Ondrej; Åkeson, Madeleine

    2007-02-01

    We present a new Coherent Anti-Stokes Raman Scattering (CARS) microscopy technique for label-free imaging of biomolecules in living cells; dual-CARS microscopy. The use of three synchronized laser pulses in a dual-pump/dualdetection configuration enables imaging of two species with different molecular vibrations simultaneously, as well as acquisition of images free of non-resonant background. We show the power of the method by imaging deuterated nonadecane slowly diffusing into a suspension of living yeast cells in medium, clearly distinguishing the medium and the lipid droplets in the cells by probing the CH II vibration from the D-nonadecane by probing the CD vibration. In addition, images of lipid stores in living C. elegans nematodes free of non-resonant background are shown. This results in a significant enhancement of the image contrast, allowing the visualization of emerging, low-density lipid stores in a dauer larva, difficult to distinguish in conventional CARS microscopy. The separation of the non-resonant background is shown to be beneficial also when monitoring molecules with weak vibrational modes. The improved sensitivity obtained is illustrated by probing the C=C vibration in polyunsaturated lipids extracted from fish. This enables the monitoring of the degree of unsaturation of lipids, a high value of which is reported in foods known to have positive effects on human health.

  6. The release of transforming growth factor-beta following haemorrhage: its role as a mediator of host immunosuppression.

    PubMed Central

    Ayala, A; Meldrum, D R; Perrin, M M; Chaudry, I H

    1993-01-01

    Haemorrhage in the absence of trauma is reported to induce a profound depression in cell-mediated immunity. Recent studies have drawn attention to the cytokine transforming growth factor-beta (TGF-beta) that, while important in wound healing, also has marked immunosuppressive effects. The aim of this study was to determine whether: (1) haemorrhage induces an increase in circulating TGF-beta and if this is associated with the loss of host immunoresponsiveness; and (2) administration of monoclonal antibody (mAb) to TGF-beta following haemorrhage ablates these changes. To determine this, C3H/HeN mice were bled to and maintained at a mean arterial pressure of 35 mmHg for 1 hr. This required removing approximately 50% of the circulating blood volume. Following this period of hypotension, the mice were adequately resuscitated. Blood samples obtained at 24 and 72 hr, but not at 2 hr, following haemorrhage showed a significant elevation in plasma TGF-beta levels when compared to shams. At 24 hr, the increase of TGF-beta in the plasma was associated with decreases in both concanavalin A (Con A)-induced splenocyte proliferation and splenic macrophage antigen presentation. Treating animals with neutralizing antibody (animals received 200 micrograms mAb against bovine TGF-beta 1,2,3/mouse intraarterially) not only reduced the levels of TGF-beta in the blood at 24 hr, but also restored splenocyte functions, such as Con A-induced proliferation, interleukin-2 (IL-2) release, and the capacity of splenic macrophages to present antigen. However, elevated levels of prostaglandin E2 (PGE2) seen in plasma during haemorrhage were only partially depressed by the antibody treatment. These results indicate that the release of TGF-beta contributes to the protracted (> or = 24 hr) suppression of cell-mediated immunity following haemorrhage. PMID:8406575

  7. Previous cancer and/or lymphoma in patients with refractory IBD--pro: anti-TNF or immunosuppressive treatment.

    PubMed

    Laharie, David

    2014-01-01

    Management of patients with IBD and a past or current malignancy has become more frequent in daily practice. As trends in IBD therapy are moving to more immunomodulators, administered earlier and for longer periods than ever, an increasing number of IBD patients with a prior malignancy may receive conventional immunosuppressants (IS) and/or anti-TNF. However, few data are available for managing this IBD subpopulation due to three main reasons: (1) previous cancer is usually an exclusion criterion from all clinical trials, (2) guidelines do not recommend any immunomodulator use in patients who have had a malignancy within the last 5 years, and (3) physicians are reluctant to use immunomodulators which could reactivate dormant micrometastasis. However, there is a lack of scientific evidence for avoiding immunomodulators in IBD patients with previous cancer. In a recently published cohort of patients with previous cancer, no excess incidence of incident cancer was associated with exposure to IS. Data with anti-TNF are lacking in IBD. Recently in a registry including 79 patients with refractory IBD who started an anti-TNF therapy while having had a prior malignancy within the past 5 years, survival rates without incident cancer were 96 and 72% at 1 and 5 years, respectively. Thus, evidence to not start IS and/or anti-TNF therapy in IBD patients who have had a previous cancer is weak. Pending larger studies, a case-by-case joint decision taken with the oncologist and the patient is recommended, and should take IBD and the cancer risk-benefit ratio for using immunomodulators to treat refractory disease into consideration. PMID:25531363

  8. Dual-Credit in Kentucky

    ERIC Educational Resources Information Center

    Stephenson, Lisa G.

    2013-01-01

    Credit-based transition programs provide high school students with opportunities to jump start their college education. The Kentucky Community and Technical College System (KCTCS) offers college credit through dual-credit programs. While KCTCS dual-credit offerings have been successful in helping high school students start their college education…

  9. Effect of Long-term Care Use on Medicare and Medicaid Expenditures for Dual Eligible and Non-dual Eligible Elderly Beneficiaries

    PubMed Central

    Kane, Robert L; Wysocki, Andrea; Parashuram, Shriram; Shippee, Tetyana; Lum, Terry

    2013-01-01

    Background: Dual eligible Medicare and Medicaid beneficiaries consume disproportionate shares of both programs. Objectives: To compare Medicare and Medicaid expenditures of elderly dual eligible beneficiaries with non-dual eligible beneficiaries based on their long-term care (LTC) use. Research Design: Secondary analysis of linked MAX and Medicare data in seven states. Subjects: Dual eligible adults (65+) receiving LTC in institutions, in the community, or not at all; and Medicare non-dual eligibles. Measures: Medicaid acute medical and LTC expenditures per beneficiary year, Medicare expenditures. Results: Among dual eligibles and non-dual eligibles, the average number of diseases and case mix scores are higher for LTC users. Adjusting for case mix virtually eliminates the difference for medical costs, but not for LTC expenditures. Adjusting for LTC status reduces the difference in LTC costs, but increases the difference in medical costs. Conclusions: Efforts to control costs for dual eligibles should target those in LTC while better coordinating medical and LTC expenditures. PMID:24753971

  10. Coe Receives 2007 Gilbert Award

    NASA Astrophysics Data System (ADS)

    Bogue, Scott W.; Coe, Robert S.

    2008-05-01

    Robert S. Coe received the 2007 William Gilbert Award at the 2007 AGU Fall Meeting in San Francisco, Calif. The award recognizes outstanding and unselfish work in magnetism of Earth materials and of the Earth and planets.

  11. Dual fuel low NOx burner

    SciTech Connect

    Shyhching Yang; Bortz, S.J.

    1993-08-31

    A dual fuel burner is described comprising: a divergent quarl having an entrance, and exit downstream from said entrance, and a plurality of axially extending staging air ports equally spaced around said exit; a wind pipe coaxially connected to said entrance of said quarl; a swirl generator coaxially received in said wind pipe, said swirl generator having a plurality of vanes and a center hole; a gas gun including a tube and a gas nozzle, said tube having an upstream end and a downstream end and being coaxially positioned within said center hole of said swirl generator said gas nozzle being mounted to said downstream end of said tube and positioned in the vicinity of said entrance of said quarl, said gas nozzle having a plurality of passageways having center lines that diverge in the downstream direction and are inclined at an angle of about 15 to 40 degrees with respect to the centerline of said quarl; an oil gun including an oil tube, an oil nozzle, and a high pressure air tube, said oil gun tube having an upstream end and a downstream end, said oil gun tube being coaxially positioned within said gas gun tube, said oil nozzle being mounted to said downstream end of said oil gun tube and positioned in the vicinity of said entrance of said quarl, said oil nozzle including a plurality of passageways having center lines that diverge in the downstream direction and are inclined at an angle of about 15 to 40 degrees with respect to the centerline of said quarl; said high pressure tube provided within said oil gun tube, said high pressure tube being in fluid communication with said oil nozzle passageways.

  12. CD14{sup +} monocytes promote the immunosuppressive effect of human umbilical cord matrix stem cells

    SciTech Connect

    Wang, Ding; TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin ; Chen, Ke; TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin ; Du, Wei Ting; Han, Zhi-Bo; TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin ; Ren, He; Chi, Ying; TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin ; and others

    2010-09-10

    Here, the effect of CD14{sup +} monocytes on human umbilical cord matrix stem cell (hUC-MSC)-mediated immunosuppression was studied in vitro. hUC-MSCs exerted a potent inhibitory effect on the proliferation and interferon-{gamma} (IFN-{gamma}) secretion capacities of CD4{sup +} and CD8{sup +} T cells in response to anti-CD3/CD28 stimulation. Transwell co-culture system revealed that the suppressive effect was primarily mediated by soluble factors. Addition of prostaglandin synthesis inhibitors (indomethacin or NS-398) almost completely abrogated the immunosuppression activity of hUC-MSCs, identifying prostaglandin E{sub 2} (PGE{sub 2}) as an important soluble mediator. CD14{sup +} monocytes were found to be able to enhance significantly the immunosuppressive effect of hUC-MSCs in a dose-dependent fashion. Moreover, the inflammatory cytokine IL-1{beta}, either exogenously added or produced by CD14{sup +} monocytes in culture, could trigger expression of high levels of PGE{sub 2} by hUC-MSCs, whereas inclusion of the IL-1 receptor antagonist (IL-1RA) in the culture down-regulated not only PGE{sub 2} expression, but also reversed the promotional effect of CD14{sup +} monocytes and partially restored CD4{sup +} and CD8{sup +} T cell proliferation and IFN-{gamma} secretion. Our data demonstrate an important role of monocytes in the hUC-MSC-induced immunomodulation, which may have important implications in future efforts to explore the clinical potentials of hUC-MSCs.

  13. Immunological risk assessment: The key to individualized immunosuppression after kidney transplantation.

    PubMed

    Pratschke, Johann; Dragun, Duska; Hauser, Ingeborg A; Horn, Sabine; Mueller, Thomas F; Schemmer, Peter; Thaiss, Friedrich

    2016-04-01

    The wide range of immunosuppressive therapies and protocols permits tailored planning of the initial regimen according to the immunological risk status of individual patients. Pre-transplant risk assessment can include many factors, but there is no clear consensus on which parameters to take into account, and their relative importance. In general younger patients are known to be at higher risk for acute rejection, compounded by higher rates of non-adherence in adolescents. Donor age and recipient gender do not appear to exert a meaningful effect on risk of rejection per se, but black recipient ethnicity remains a well-established risk factor even under modern immunosuppression regimens. Little difference in risk is now observed between deceased- and living-donor recipients. Immunological risk assessment has developed substantially in recent years. Cross-match testing with cytotoxic analysis has long been supplemented by flow cytometry, but development of solid-phase single-bead antigen testing of solubilized human leukocyte antigens (HLA) to detect donor-specific antibodies (DSA) permits a far more nuanced stratification of immunological risk status, including the different classes and intensities of HLA antibodies Class I and/or II, including HLA-DSA. Immunologic risk evaluation is now often based on a combination of these tests, but other assessments are becoming more widely introduced, such as measurement of non-HLA antibodies against angiotensin type 1 (AT1) receptors or T-cell ELISPOT assay of alloantigen-specific donor. Targeted densensitization protocols can improve immunological risk, notably for DSA-positive patients with negative cytotoxicity and flow cross-match. HLA mismatch remains an important and undisputed risk factor for rejection. Delayed graft function also increases the risk of subsequent acute rejection, and the early regimen can be modified in such cases. Overall, there is a shift towards planning the immunosuppressive regimen based on pre

  14. Deletion of the meq gene significantly decreases immunosuppression in chickens caused by pathogenic marek's disease virus

    PubMed Central

    2011-01-01

    Background Marek's disease virus (MDV) causes an acute lymphoproliferative disease in chickens, resulting in immunosuppression, which is considered to be an integral aspect of the pathogenesis of Marek's disease (MD). A recent study showed that deletion of the Meq gene resulted in loss of transformation of T-cells in chickens and a Meq-null virus, rMd5ΔMeq, could provide protection superior to CVI988/Rispens. Results In the present study, to investigate whether the Meq-null virus could be a safe vaccine candidate, we constructed a Meq deletion strain, GX0101ΔMeq, by deleting both copies of the Meq gene from a pathogenic MDV, GX0101 strain, which was isolated in China. Pathogenesis experiments showed that the GX0101ΔMeq virus was fully attenuated in specific pathogen-free chickens because none of the infected chickens developed Marek's disease-associated lymphomas. The study also evaluated the effects of GX0101ΔMeq on the immune system in chickens after infection with GX0101ΔMeq virus. Immune system variables, including relative lymphoid organ weight, blood lymphocytes and antibody production following vaccination against AIV and NDV were used to assess the immune status of chickens. Experimental infection with GX0101ΔMeq showed that deletion of the Meq gene significantly decreased immunosuppression in chickens caused by pathogenic MDV. Conclusion These findings suggested that the Meq gene played an important role not only in tumor formation but also in inducing immunosuppressive effects in MDV-infected chickens. PMID:21205328

  15. Clinical impact of occult hepatitis B virus infection in immunosuppressed patients

    PubMed Central

    Sagnelli, Evangelista; Pisaturo, Mariantonietta; Martini, Salvatore; Filippini, Pietro; Sagnelli, Caterina; Coppola, Nicola

    2014-01-01

    Occult hepatitis B infection (OBI), is characterized by low level hepatitis B virus (HBV) DNA in circulating blood and/or liver tissue. In clinical practice the presence of antibody to hepatitis B core antigen in hepatitis B surface antigen (HBsAg)-/anti-HBs-negative subjects is considered indicative of OBI. OBI is mostly observed in the window period of acute HBV infection in blood donors and in recipients of blood and blood products, in hepatitis C virus chronic carriers, in patients under pharmacological immunosuppression, and in those with immunodepression due to HIV infection or cancer. Reactivation of OBI mostly occurs in anti-HIV-positive subjects, in patients treated with immunosuppressive therapy in onco-hematological settings, in patients who undergo hematopoietic stem cell transplantation, in those treated with anti-CD20 or anti-CD52 monoclonal antibody, or anti-tumor necrosis factors antibody for rheumatological diseases, or chemotherapy for solid tumors. Under these conditions the mortality rate for hepatic failure or progression of the underlying disease due to discontinuation of specific treatment can reach 20%. For patients with OBI, prophylaxis with nucleot(s)ide analogues should be based on the HBV serological markers, the underlying diseases and the type of immunosuppressive treatment. Lamivudine prophylaxis is indicated in hemopoietic stem cell transplantation and in onco-hematological diseases when high dose corticosteroids and rituximab are used; monitoring may be indicated when rituximab-sparing schedules are used, but early treatment should be applied as soon as HBsAg becomes detectable. This review article presents an up-to-date evaluation of the current knowledge on OBI. PMID:25018849

  16. Pneumococcal Surface Protein A Plays a Major Role in Streptococcus pneumoniae-Induced Immunosuppression.

    PubMed

    Saumyaa; Pujanauski, Lindsey; Colino, Jesus; Flora, Michael; Torres, Raul M; Tuomanen, Elaine; Snapper, Clifford M

    2016-05-01

    Intact, inactivated Streptococcus pneumoniae [including the unencapsulated S. pneumoniae, serotype 2 strain (R36A)] markedly inhibits the humoral immune response to coimmunized heterologous proteins, a property not observed with several other intact Gram-positive or Gram-negative bacteria. In this study, we determined the nature of this immunosuppressive property. Because phosphorylcholine (PC), a major haptenic component of teichoic acid in the S. pneumoniae cell wall, and lipoteichoic acid in the S. pneumoniae membrane were previously reported to be immunosuppressive when derived from filarial parasites, we determined whether R36A lacking PC (R36A(pc-)) was inhibitory. Indeed, although R36A(pc-) exhibited a markedly reduced level of inhibition of the IgG response to coimmunized chicken OVA (cOVA), no inhibition was observed when using several other distinct PC-expressing bacteria or a soluble, protein-PC conjugate. Further, treatment of R36A with periodate, which selectively destroys PC residues, had no effect on R36A-mediated inhibition. Because R36A(pc-) also lacks choline-binding proteins (CBPs) that require PC for cell wall attachment, and because treatment of R36A with trypsin eliminated its inhibitory activity, we incubated R36A in choline chloride, which selectively strips CBPs from its surface. R36A lacking CBPs lost most of its inhibitory property, whereas the supernatant of choline chloride-treated R36A, containing CBPs, was markedly inhibitory. Coimmunization studies using cOVA and various S. pneumoniae mutants, each genetically deficient in one of the CBPs, demonstrated that only S. pneumoniae lacking the CBP pneumococcal surface protein A lost its ability to inhibit the IgG anti-cOVA response. These results strongly suggest that PspA plays a major role in mediating the immunosuppressive property of S. pneumoniae. PMID:27029587

  17. Global LC/MS Metabolomics Profiling of Calcium Stressed and Immunosuppressant Drug Treated Saccharomyces cerevisiae

    PubMed Central

    Jenkins, Stefan; Fischer, Steven M.; Chen, Lily; Sana, Theodore R.

    2013-01-01

    Previous studies have shown that calcium stressed Saccharomyces cerevisiae, challenged with immunosuppressant drugs FK506 and Cyclosporin A, responds with comprehensive gene expression changes and attenuation of the generalized calcium stress response. Here, we describe a global metabolomics workflow for investigating the utility of tracking corresponding phenotypic changes. This was achieved by efficiently analyzing relative abundance differences between intracellular metabolite pools from wild-type and calcium stressed cultures, with and without prior immunosuppressant drugs exposure. We used pathway database content from WikiPathways and YeastCyc to facilitate the projection of our metabolomics profiling results onto biological pathways. A key challenge was to increase the coverage of the detected metabolites. This was achieved by applying both reverse phase (RP) and aqueous normal phase (ANP) chromatographic separations, as well as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources for detection in both ion polarities. Unsupervised principle component analysis (PCA) and ANOVA results revealed differentiation between wild-type controls, calcium stressed and immunosuppressant/calcium challenged cells. Untargeted data mining resulted in 247 differentially expressed, annotated metabolites, across at least one pair of conditions. A separate, targeted data mining strategy identified 187 differential, annotated metabolites. All annotated metabolites were subsequently mapped onto curated pathways from YeastCyc and WikiPathways for interactive pathway analysis and visualization. Dozens of pathways showed differential responses to stress conditions based on one or more matches to the list of annotated metabolites or to metabolites that had been identified further by MS/MS. The purine salvage, pantothenate and sulfur amino acid pathways were flagged as being enriched, which is consistent with previously published literature for

  18. Global LC/MS Metabolomics Profiling of Calcium Stressed and Immunosuppressant Drug Treated Saccharomyces cerevisiae.

    PubMed

    Jenkins, Stefan; Fischer, Steven M; Chen, Lily; Sana, Theodore R

    2013-01-01

    Previous studies have shown that calcium stressed Saccharomyces cerevisiae, challenged with immunosuppressant drugs FK506 and Cyclosporin A, responds with comprehensive gene expression changes and attenuation of the generalized calcium stress response. Here, we describe a global metabolomics workflow for investigating the utility of tracking corresponding phenotypic changes. This was achieved by efficiently analyzing relative abundance differences between intracellular metabolite pools from wild-type and calcium stressed cultures, with and without prior immunosuppressant drugs exposure. We used pathway database content from WikiPathways and YeastCyc to facilitate the projection of our metabolomics profiling results onto biological pathways. A key challenge was to increase the coverage of the detected metabolites. This was achieved by applying both reverse phase (RP) and aqueous normal phase (ANP) chromatographic separations, as well as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources for detection in both ion polarities. Unsupervised principle component analysis (PCA) and ANOVA results revealed differentiation between wild-type controls, calcium stressed and immunosuppressant/calcium challenged cells. Untargeted data mining resulted in 247 differentially expressed, annotated metabolites, across at least one pair of conditions. A separate, targeted data mining strategy identified 187 differential, annotated metabolites. All annotated metabolites were subsequently mapped onto curated pathways from YeastCyc and WikiPathways for interactive pathway analysis and visualization. Dozens of pathways showed differential responses to stress conditions based on one or more matches to the list of annotated metabolites or to metabolites that had been identified further by MS/MS. The purine salvage, pantothenate and sulfur amino acid pathways were flagged as being enriched, which is consistent with previously published literature for

  19. Licensing by Inflammatory Cytokines Abolishes Heterogeneity of Immunosuppressive Function of Mesenchymal Stem Cell Population.

    PubMed

    Szabó, Enikő; Fajka-Boja, Roberta; Kriston-Pál, Éva; Hornung, Ákos; Makra, Ildikó; Kudlik, Gyöngyi; Uher, Ferenc; Katona, Róbert László; Monostori, Éva; Czibula, Ágnes

    2015-09-15

    When mesenchymal stem cells (MSCs) are used for therapy of immunological pathologies, they get into an inflammatory environment, altering the effectiveness of the treatment. To establish the impact of environmental inflammatory factors on MSCs' immunofunction in the mirror of intrinsic heterogeneity of mouse MSC population, individual MSC clones were generated and characterized. Adipogenic but not osteogenic differentiation and pro-angiogenic activity of five independent MSC cell lines were similar. Regarding osteogenic differentiation, clones MSC3 and MSC6 exhibited poorer capacity than MSC2, MSC4, and MSC5. To study the immunosuppressive heterogeneity, in vitro and in vivo experiments have been carried out using T-cell proliferation assay and delayed-type hypersensitivity (DTH) response, respectively. A remarkable difference was found between the clones in their ability to inhibit T-cell proliferation in the following order: MSC2≥MSC5>MSC4>MSC3 > MSC6. Nevertheless, the differences between the immunosuppressive activities of the individual clones disappeared on pretreatment of the cells with pro-inflammatory cytokines, a procedure called licensing. Stimulation of all clones with IFN-γ and TNF-α resulted in elevation of their inhibitory capability to a similar level. Nitric oxide (NO) and prostaglandin E2 (PGE2) were identified as major mediators of immunofunction of the MSC clones. The earlier findings were also supported by in vivo results. Without licensing, MSC2 inhibited DTH response, while MSC6 did not affect DTH response. In contrast, prestimulation of MSC6 with inflammatory cytokines resulted in strong suppression by this clone as well. Here, we have showed that MSC population is functionally heterogeneous in terms of immunosuppressive function; however, this variability is largely reduced under pro-inflammatory conditions. PMID:26153898

  20. Immunosuppressive activity of pogostone on T cells: Blocking proliferation via S phase arrest.

    PubMed

    Su, Ji-Yan; Luo, Xia; Zhang, Xiao-Jun; Deng, Xiang-Liang; Su, Zi-Ren; Zhou, Lian; Li, Shan-Shan; Dai, Zhenhua; Xu, Yang; Lai, Xiao-Ping

    2015-06-01

    Pogostone (PO) is one of the major chemical constituents of the essential oil of Pogostemon cablin (Blanco) Benth. In the present study, the effect of PO on T cell responsiveness was investigated to explore its potential in immunosuppression by a Concanavalin A (ConA)-stimulation model using splenocytes isolated from C57BL/6 mice. Cytotoxicity by PO on normal splenocytes was evaluated by MTS assays. Characteristics of apoptosis, proliferation, and cell cycle were analyzed by flow cytometry. Related expressions of cyclins and cyclin-dependent kinases (CDKs) were also determined by flow cytometry. Inflammatory cytokine profiling was performed emplying cytometric beads assays (CBA). Moreover, the T cell-mediated delayed Type hepersensity (DTH) model was applied to evaluate the immunosuppressive activity of PO. Neither viability reduction in normal splenocytes nor apoptosis in ConA-stimulated splenocytes was observed under PO treatments. Meanwhile, PO remarkably reduced the total population of ConA-stimulated T cell, blocked T cell proliferation induced by Con A, and inhibited the production of IFN-γ and IL-10. This blockade of stimulated T cell proliferation by PO was likely attributed to down-regulation of cyclin E, cyclin B and CDK1 and the subsequent S-phase arrest. Additionally, PO could inhibit the DTH reaction by alleviating ear swelling and inflammatory infiltrations in the DNCB-challenged ear. Taken together, PO exhibited an immunosuppressive property by directly blocking T cell proliferation as well as altering inflammatory cytokine profile, suggesting that PO may have clinical implications for treating autoimmune diseases and other immune-based disorders. PMID:25912345