Science.gov

Sample records for receiving dual immunosuppressive

  1. South American Heart Transplantation Registry of patients receiving everolimus in their immunosuppressive regimens.

    PubMed

    Bortman, G V; Ceruti, B; Ahualli, L; Colque, R; Amuchástegui, M; Sgrosso, J L; Muñoz, J; Vulcano, N; Burgos, C; Diez, F; Rodriguez, M C; Perrone, S V

    2010-01-01

    The increasing number of heart transplant recipients receiving immunosuppression with mammalian target of rapamycin inhibitors prompted the implementation of a South American Transplant Physicians Group to register these patients in a database. Everolimus (EVL) is a signal proliferation inhibition that reduces graft vascular disease when used de novo. Recently, its administration has expanded to subjects with resistant rejection or with side effects due to other immunosuppressive drugs (calcineurin inhibitors and/or steroids), allowing for better regulation of the immunosuppressive regimen. Herein we have shown the data collected from patients receiving EVL in ten South American Heart Transplant Centers. We have concluded that the administration of EVL is a useful adjunctive therapy that allows the reduction or suspension of other immunosuppressive drugs that caused unwanted side effects, without a loss of immunosuppressive efficacy, with manageable side effects, and constituting a valuable therapeutic option. PMID:20172342

  2. A proposal for management of rheumatic disease patients with hepatitis B virus infection receiving immunosuppressive therapy.

    PubMed

    Harigai, Masayoshi; Mochida, Satoshi; Mimura, Toshihide; Koike, Takao; Miyasaka, Nobuyuki

    2014-01-01

    Reactivation of hepatitis B virus (HBV) and de novo HBV hepatitis in patients with rheumatic diseases given intensive and long-term immunosuppressive therapy with or without biological disease-modifying antirheumatic drugs is of great concern, especially in regions where the virus is endemic, including Japan. To ascertain a better benefit-risk balance for immunosuppressive therapy for patients with rheumatic diseases, the Japan College of Rheumatology developed this proposal. All patients with rheumatic diseases commencing immunosuppressive therapy should be screened for hepatitis B surface antigen (HBsAg); those who are negative for HBsAg should be screened for hepatitis B core antibody (HBcAb) and hepatitis B surface antibody (HBsAb) as well. HBV carriers and serum HBV DNA positive patients with resolved infection should receive nucleoside analog as soon as possible, prior to commencing immunosuppressive therapy. For serum HBV DNA negative patients with resolved infection, careful monthly monitoring using serum levels of aspartate and alanine aminotransferases and HBV DNA is recommended during and at least 12 months after withdrawal of immunosuppressive therapy. If serum HBV DNA becomes positive, patients should receive nucleoside analog treatment as soon as possible, while ongoing immunosuppressive therapy should be continued to avoid severe or fulminant hepatitis development. To facilitate proper management of patients with HBV infection, collaboration between rheumatologists and hepatologists is strongly encouraged.

  3. A dual Navstar GPS/Glonass satellite receiver

    NASA Astrophysics Data System (ADS)

    Raby, P.; Harris, K.; Gibson, P.; Mans, P.; Morrison, G.

    This paper describes the design and construction of a dual Navstar GPS/Glonass navigation satellite receiver. The receiver extracts data from a digitally tracked -130dBm satellite signal at L band (1.6 GHz). The incoming signal is tracked using a digital Costas loop in conjunction with a full time early-late code tracking loop, to decode the spread spectrum signal. The satellite data is decoded and logged recording a variety of parameters necessary for global positioning and time transfer.

  4. Dental extraction in patients receiving dual antiplatelet therapy

    PubMed Central

    Sánchez-Palomino, Paulino; Sánchez-Cobo, Paulino; Rodriguez-Archilla, Alberto; González-Jaranay, Maximino; Moreu, Gerardo; Calvo-Guirado, José-Luis; Peñarrocha-Diago, Miguel

    2015-01-01

    Background Dual anti platelet therapy consists of administering antiplatelet (antiaggregant) drugs (clopidogrel and aspirin) to prevent thrombotic processes, as a preventative measure in patients with acute coronary disease, or in patients subjected to percutaneous coronary intervention. Objectives The purpose of this study was to evaluate the efficacy of a protocol for performing dental extraction in patients receiving dual anti platelet therapy. Material and Methods Thirty-two patients undergoing dental extractions were included in the study. The variables evaluated were: collagen-epinephrine fraction, collagen- adenosine diphosphate fraction, surgical surface, post-surgical measures, and adverse effects. Alveolar sutures and gauzes impregnated with an antifibrinolytic agent (tranexamic acid), which the patient pressed in place for 30 minutes, were applied to all patients as post-surgical measures. Descriptive statistics were calculated and analyzed with Student’s t-test to compare pairs of quantitative variables; simple regression analysis was performed using Pearson’s correlation coefficient. Statistical significance was set at p<0.05. Results Collagen/epinephrine fraction was 264.53±55.624 seconds with a range of 135 to 300 seconds, and collagen/ADP fraction was 119.41±44.216 seconds, both values being higher than normal. As a result of the post-surgical measures taken, no patients presented postoperative bleeding, hematoma or infection. Conclusions Dental extraction was safe for patients receiving dual anti-platelet therapy when using sutures and gauze impregnated with tranexamic acid, which the patient pressed in place for 30 minutes. Key words: Aspirin, clopidogrel, tranexamic acid, dental extraction, platelet function. PMID:26241454

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

    NASA Astrophysics Data System (ADS)

    Chen, Guanyu; Yu, Yu; Zhang, Xinliang

    2016-05-01

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

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

    PubMed

    Chen, Guanyu; Yu, Yu; Zhang, Xinliang

    2016-05-20

    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.

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

    PubMed Central

    Chen, Guanyu; Yu, Yu; Zhang, Xinliang

    2016-01-01

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

  8. Serologic response after vaccination against influenza (A/H1N1)pdm09 in children with renal disease receiving oral immunosuppressive drugs.

    PubMed

    Tanaka, Seiji; Saikusa, Tomoko; Katafuchi, Yuno; Ushijima, Kosuke; Ohtsu, Yasushi; Tsumura, Naoki; Ito, Yuhei

    2015-09-11

    A limited number of reports are available regarding the effect of the influenza vaccine in pediatric patients receiving steroid and immunosuppressant therapy. The influenza A(H1N1)pdm09 vaccine was administered to 15 children with renal disease who were receiving steroid and immunosuppressant therapy (treatment group) and 23 children with who were not receiving these drugs (non-treatment group). Titer transition of the hemagglutination inhibition antibody was compared between the 2 groups immediately before vaccination and 4 weeks and 6 months after vaccination. Multivariate analysis showed a significant correlation between geometric mean titer, SCR, and SPR with age, while no correlation was observed between treatment with immunosuppressant therapy and efficacy. No serious adverse reactions occurred after vaccination. This strain is not present in existing influenza vaccines, and A(H1N1)pdm09HA vaccination was administered alone in 2009. The children in this study had not previously been exposed to this strain. Therefore, we evaluated the effect of the A(H1N1)pdm09HA vaccine without the effects of vaccination or past infection with A(H1N1)pdm09HA or A(H3N2) vaccination in the previous year.

  9. [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

  10. Dual-Polarization, Sideband-Separating, Balanced Receiver for 1.5 THz

    NASA Technical Reports Server (NTRS)

    Chattopadhyay, Goutman; Ward, John; Manohara, Harish; Siegel, Peter

    2009-01-01

    A proposed heterodyne receiver would be capable of detecting electromagnetic radiation in both of two orthogonal linear polarizations, separating sidebands, and providing balanced outputs in a frequency band centered at 1.5 THz with a fractional bandwidth greater than 40 percent. Dual polarization, sideband-separating, and balanced-output receivers are well-known and have been used extensively at frequencies up to about 100 GHz; and there was an earlier proposal for such a receiver for frequencies up to 900 GHz. However, the present proposal represents the first realistic design concept for such a receiver capable of operating above 1 THz. The proposed receiver is intended to be a prototype of mass-producible receiver units, operating at frequencies up to 6 THz, that would be incorporated into highly sensitive heterodyne array instruments to be used in astronomical spectroscopic and imaging studies.

  11. Bit Error Rate Performance of Partially Coherent Dual-Branch SSC Receiver over Composite Fading Channels

    NASA Astrophysics Data System (ADS)

    Milić, Dejan N.; Đorđević, Goran T.

    2013-01-01

    In this paper, we study the effects of imperfect reference signal recovery on the bit error rate (BER) performance of dual-branch switch and stay combining receiver over Nakagami-m fading/gamma shadowing channels with arbitrary parameters. The average BER of quaternary phase shift keying is evaluated under the assumption that the reference carrier signal is extracted from the received modulated signal. We compute numerical results illustrating simultaneous influence of average signal-to-noise ratio per bit, fading severity, shadowing, phase-locked loop bandwidth-bit duration (BLTb) product, and switching threshold on BER performance. The effects of BLTb on receiver performance under different channel conditions are emphasized. Optimal switching threshold is determined which minimizes BER performance under given channel and receiver parameters.

  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. 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

  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. 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.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. Miniaturized silicon photonic integrated swept source OCT receiver with dual polarization, dual balanced, in-phase and quadrature detection (Conference Presentation)

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

    Miniaturization and cost reduction of OCT systems are important for enabling many new clinical applications as well as accelerating the development of existing applications. Silicon photonics is an important low-cost, high-volume, multi-functional platform for integrated optics because it can benefit from existing semiconductor fabrication techniques to integrate many advanced optical functions onto a single microchip. We present a miniaturized silicon photonic integrated swept source OCT receiver, measuring 3×4mm2, with advanced functionalities including dual polarization, dual balanced, in-phase and quadrature detection, essentially enabling the detection of the full vector field (amplitude, phase, and polarization) of the optical signal. With this integrated receiver, we demonstrate full-range OCT for complex conjugate artifact suppression, polarization diversity detection for removing polarization fading artifact, and polarization sensitive OCT for tissue birefringence imaging. The silicon photonic integrated receiver is a key advance towards developing a miniaturized, multi-functional swept source OCT system.

  2. The performance of coherent receiver controlled by the phase lock loop in dual rate free-space laser communication

    NASA Astrophysics Data System (ADS)

    Ma, Xiaoping; Sun, Jianfeng; Hou, Peipei; Lu, Wei; Xu, Qian; Liu, Liren

    2015-09-01

    The technique of differential phase shift keying(DPSK) modulation is applied into demodulating phase information in the coherent optical receiver. The dual rate free-space receiving structure on the base of Mach-Zehnder delay interferometer with the lens is used suitably for differential delay which is equal to the one bit corresponding to a certain data rate. Delay distance at the interference receiver is varied with transmission rata from satellite to ground. Differential information is obtained by the subtraction of the two successive wave-front phases when made to interfere. The phase demodulation is extremely sensitive to phase fluctuation. Because of the incident light through atmospheric turbulence, the wave-front of optical signal became jittered in the temporal and spatial domain rapidly. In the paper, the dual rate free-space laser communication receiver for phase lock to stable signal light phase is proposed, increasing the homodyne efficiency and decreasing the bit error rate.

  3. 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.

  4. 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.

    2016-11-01

    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.

  5. 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.

  6. 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.

  7. 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

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

    PubMed

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

    2015-07-01

    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.

  9. A 16-Channel Receive, Forced Current Excitation Dual-Transmit Coil for Breast Imaging at 7T

    PubMed Central

    By, Samantha; Rispoli, Joseph V.; Cheshkov, Sergey; Dimitrov, Ivan; Cui, Jiaming; Seiler, Stephen; Goudreau, Sally; Malloy, Craig; Wright, Steven M.; McDougall, Mary Preston

    2014-01-01

    Purpose To enable high spatial and temporal breast imaging resolution via combined use of high field MRI, array coils, and forced current excitation (FCE) multi channel transmit. Materials and Methods A unilateral 16-channel receive array insert was designed for use in a transmit volume coil optimized for quadrature operation with dual-transmit RF shimming at 7T. Signal-to-noise ratio (SNR) maps, g-factor maps, and high spatial and temporal resolution in vivo images were acquired to demonstrate the utility of the coil architecture. Results The dual-transmit FCE coil provided homogeneous excitation and the array provided an increase in average SNR of 3.3 times (max 10.8, min 1.5) compared to the volume coil in transmit/receive mode. High resolution accelerated in vivo breast imaging demonstrated the ability to achieve isotropic spatial resolution of 0.5 mm within clinically relevant 90 s scan times, as well as the ability to perform 1.0 mm isotropic resolution imaging, 7 s per dynamics, with the use of bidirectional SENSE acceleration of up to R = 9. Conclusion The FCE design of the transmit coil easily accommodates the addition of a sixteen channel array coil. The improved spatial and temporal resolution provided by the high-field array coil with FCE dual-channel transmit will ultimately be beneficial in lesion detection and characterization. PMID:25420018

  10. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2011-07-01

    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 14,5dB with a sensitivity of -18.5dBm at 10 Gb/s.

  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. Update on immunosuppressive therapy.

    PubMed

    Singer, N G; McCune, W J

    1998-05-01

    In this review we summarize selected articles that have been published about immunosuppressive agents in the past year. These studies fall into three major categories: 1) use of pulse cyclophosphamide in autoimmune diseases other than systemic lupus erythematosus; 2) use of newer immunosuppressive agents such as cyclosporine and FK506 in a variety of rheumatic diseases; and 3) toxicity. PMID:9608317

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

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

    NASA Astrophysics Data System (ADS)

    Agrawal, D.; Moore, R. C.

    2012-12-01

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

  16. The critically ill immunosuppressed patient

    SciTech Connect

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

    1987-01-01

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

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

    PubMed

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

    2013-07-01

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

  18. Immunosuppressive Therapy in Transplantation.

    PubMed

    Allison, Terri L

    2016-03-01

    This article discusses immunosuppressive medications used in organ and hematopoietic stem cell transplantation. Induction, maintenance, and rescue therapy are administered throughout different periods during and after transplantation to modulate the immune system response in the recipient to prevent or treat rejection or graft-versus-host disease. Indications, dosing strategies, required monitoring, complications, adverse events, and concomitant drug interactions associated with immunosuppressive medications are presented. Classes of medications discussed include polyclonal and monoclonal antibodies, calcineurin inhibitors, antiproliferative agents, mammalian target of rapamycin inhibitors, and corticosteroids. Medications having significant interactions with immunosuppression are also examined.

  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. Therapeutic advances in immunosuppression.

    PubMed Central

    Thomson, A W; Forrester, J V

    1994-01-01

    Immunosuppressive therapy is appropriate for the prevention or reversal of allograft rejection, and for the treatment of autoimmune disorders and allergic disease. Recent advances in our understanding of the cellular and molecular mechanisms that regulate immune responses have paralleled elucidation of the modes of action of a variety of therapeutic immunosuppressive agents, both 'old' and new. These developments have identified potential targets for more refined and specific intervention strategies that are now being tested in the clinic. PMID:7994898

  1. 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.

  2. 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.

  3. Immunosuppressive measles encephalopathy.

    PubMed

    Pedersen, F K; Schiøtz, P O; Valerius, N H; Hertz, H

    1978-01-01

    A case of measles infection without a rash, which was followed by a severe encephalopathy after two months, is described in a 2 1/2 year old boy. At the age of 8 months he had been irradiated for an inoperable intrathoracic neuroblastoma, and at the time of exposure to measles he was being treated with cyclophosphamide and vincristine. This case closely resembles other cases recently described and termed immunosuppressive measles encephalopathy. The syndrome is believed to represent the effect of measles virus in patients with deficient cellular immunity induced by antineoplastic treatment. The importance of protecting children on immunosuppressive treatment for contracting measles is stressed.

  4. 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

  5. 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

  6. Immunosuppression by discodermolide.

    PubMed

    Longley, R E; Gunasekera, S P; Faherty, D; Mclane, J; Dumont, F

    1993-11-30

    In summary, discodermolide, a novel, marine-derived compound, is a potent in vitro and in vivo immunosuppressive agent. Discodermolide blocks cellular proliferation in lymphoid and nonlymphoid cells. This blocking action is not due to cytotoxicity. Blockage of cell proliferation by discodermolide appears to occur at the G2/M interface of the cell cycle, similar to that observed with other types of antiproliferative drugs (i.e., doxorubicin). The cell cycle block appears to be reversible, as cells recover normal cycling patterns within 48 h after removal of the compound. Additional work with this compound is targeted towards determining the exact nature of discodermolide's mitotic block and is currently under way.

  7. 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.

  8. 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.

  9. Temperature insensitive and ultra wideband silica-based dual polarization optical hybrid for coherent receiver with highly symmetrical interferometer design.

    PubMed

    Nasu, Yusuke; Mizuno, Takayuki; Kasahara, Ryoichi; Saida, Takashi

    2011-12-12

    To extend the operation wavelength range of dual-polarization optical hybrids (DPOH), we propose a highly symmetrical interferometer design for a polarization beam splitter and an optical hybrid to reduce temperature and wavelength dependence. The design successfully decreases this dependence, and a fabricated DPOH with silica-based planar lightwave circuits provides temperature-insensitive performance with a polarization extinction ratio of over 25 dB and phase errors of less than 3 degrees over the entire C- and L-bands.

  10. 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.

  11. The immunosuppressive side of PDT†

    PubMed Central

    Hamblin, Michael R.

    2012-01-01

    Photodynamic therapy (PDT) is a promising novel therapeutic procedure for the management of a variety of solid tumors and many non-malignant diseases. PDT has been described as having a significant effect on the immune system, which may be either immunostimulatory or, in some circumstances, immunosuppressive. The immunosuppressive effects of PDT have nearly all been concerned with the suppression of the contact hypersensitivity reaction in mice. Here, we review the immunosuppressive aspects of PDT treatment and discuss some additional mechanisms that may be involved. PMID:21437314

  12. A passive dual-circulator based transmit/receive switch for use with reflection resonators in pulse EPR.

    PubMed

    Subramanian, V S; Epel, Boris; Mailer, Colin; Halpern, Howard J

    2009-08-01

    In order to protect the low noise amplifier (LNA) in the receive arm of a pulsed 250 MHz EPR bridge, it is necessary to install as much isolation as possible between the power exciting the spin system and the LNA when high power is present in the receive arm of the bridge, while allowing the voltage induced by the magnetization in the spin sample to be passed undistorted and undiminished to the LNA once power is reduced below the level that can cause a LNA damage. We discuss a combination of techniques to accomplish this involving the power-routing circulator in the bridge, a second circulator acting as an isolator with passive shunt PIN diodes immediately following the second circulator. The low resistance of the forward biased PIN diode passively generates an impedance mismatch at the second circulator output port during the high power excitation pulse and resonator ring down. The mismatch reflects the high power to the remaining port of the second circulator, dumping it into a system impedance matched load. Only when the power diminishes below the diode conduction threshold will the resistance of the PIN diode rise to a value much higher than the system impedance. This brings the device into conduction mode. We find that the present design passively limits the output power to 14 dBm independent of the input power. For high input power levels the isolation may exceed 60 dB. This level of isolation is sufficient to fully protect the LNA of pulse EPR bridge. PMID:20052312

  13. 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

  14. [Tumor-induced immunosuppression].

    PubMed

    Paul, S; Calmels, B; Régulier, E

    2002-01-01

    Tumor immunology is based on two essential concepts: immune surveillance, which implicate the host immune reactions against tumor cells, and tumor immune escape, which refers to the tumor-cell evasion process against the host immune system. The notion that a deficit in immune cell functions permits tumor growth has received experimental support with the discovery of several different biochemical defects in T lymphocytes that infiltrate cancers. Furthermore, expression of self-antigens on the tumor surface impose potential barriers to the development of effective immune response. Tumors are able to overcome immune surveillance by changing the polarity of effectors cells, thus down-regulating the proliferation of tumor-specific cytotoxic T cells, or altering the effector compositions of immune cells within the tumor milieu, or both. Understanding the interaction between cancer cells and host immune cells is of importance for clinical applications or immunotherapy in cancer treatment. PMID:11937439

  15. New immunosuppressive agents in pediatric transplantation

    PubMed Central

    Nguyen, Christina; Shapiro, Ron

    2014-01-01

    Immunosuppressive therapy in pediatrics continues to evolve. Over the past decade, newer immunosuppressive agents have been introduced into adult and pediatric transplant patients with the goal of improving patient and allograft survival. Unfortunately, large-scale randomized clinical trials are not commonly performed in children. The purpose of this review is to discuss the newer immunosuppressive agents available for induction therapy, maintenance immunosuppression, and the treatment of rejection. PMID:24860853

  16. New immunosuppressive agents in pediatric transplantation.

    PubMed

    Nguyen, Christina; Shapiro, Ron

    2014-01-01

    Immunosuppressive therapy in pediatrics continues to evolve. Over the past decade, newer immunosuppressive agents have been introduced into adult and pediatric transplant patients with the goal of improving patient and allograft survival. Unfortunately, large-scale randomized clinical trials are not commonly performed in children. The purpose of this review is to discuss the newer immunosuppressive agents available for induction therapy, maintenance immunosuppression, and the treatment of rejection.

  17. Extending Medicare immunosuppressive medication coverage.

    PubMed

    Beaubrun, Anne Christine

    2012-02-01

    African Americans and the poor are at a high risk of suffering from kidney disease and are at an extreme disadvantage when it comes to obtaining the resources needed to maintain a functioning kidney post-transplant. Medicare currently covers 80% of the cost of immunosuppressive therapy for up to three years following a Medicare-covered transplant for patients whose Medicare entitlement was based solely on their end-stage renal disease diagnosis. Adequate insurance coverage has the potential to prevent graft failure and retransplantation resulting from cost-related immunosuppressive medication nonadherence. Given the multifactorial nature of medication nonadherence, extending insurance coverage in an attempt to reduce graft failures should be coupled with intensive interventions to prevent the socioeconomic and various other factors associated with medication nonadherence. Lifetime Medicare coverage for all kidney-transplant recipients, coupled with medication adherence promotion, has the potential to minimize poor outcomes associated with graft failure, especially among minorities and the impoverished.

  18. (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.

  19. 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

  20. Testis of prepubertal rhesus monkeys receives a dual catecholaminergic input provided by the extrinsic innervation and an intragonadal source of catecholamines.

    PubMed

    Mayerhofer, A; Danilchik, M; Pau, K Y; Lara, H E; Russell, L D; Ojeda, S R

    1996-09-01

    regulatory domain of the enzyme. The cDNA that was obtained predicts an amino acid sequence similar, but not identical, to that encoded by the alternatively spliced type 1 TH mRNA form present in the adrenal gland. These results indicate 1) that the primate testis receives a dual catecholaminergic input, one provided by the extrinsic innervation and the other by neuron-like cells located within the gonad itself, and 2) that the influence exerted by both sources on testicular function may be more prominent during the prepubertal period than in adulthood. The presence in the testis of a TH mRNA variant encoding amino acid substitutions in its 5' end suggests that regulation of testicular TH enzyme activity may include a gonad-specific component.

  1. Picornavirus infection leading to immunosuppression

    PubMed Central

    Cusick, Matthew F; Libbey, Jane E; Fujinami, Robert S

    2014-01-01

    Viruses, such as HIV, hepatitis A, poliovirus, coxsackievirus B3 and foot-and-mouth disease virus, use a variety of mechanisms to suppress the human immune system in order to evade clearance by the host. Therefore, investigating how a few changes in the viral genome of a nonlethal virus can lead to an alteration in disease, from survivable to immunosuppression and death, would provide valuable information into viral pathogenesis. In addition, we propose that gaining a better insight into how these viruses suppress an antiviral immune response could lead to viral-based therapeutics to combat specifc autoimmune diseases such as multiple sclerosis and Type 1 diabetes. PMID:25214881

  2. 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

  3. 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.

  4. 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.

  5. Cat scratch disease in an immunosuppressed patient with systemic lupus erythematosus.

    PubMed

    Vargas-Hitos, J A; Sabio, J M; Navarrete-Navarrete, N; Arenas-Miras, M del M; Zamora-Pasadas, M; Jiménez-Alonso, J

    2016-03-01

    Cat scratch disease is an infectious disorder transmitted by cats that typically affects children and young adults. Immunosuppression is a well-known risk factor for the development of severe and atypical forms of the disease; hence it is under-diagnosed in patients with compromised immunity. We are reporting the first case of cat scratch disease, which presented as fever and fatigue, in a patient with systemic lupus erythematosus while receiving immunosuppressant therapy after a kidney transplant.

  6. [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

  7. HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression

    PubMed Central

    Kawai, Tatsuo; Cosimi, A. Benedict; Spitzer, Thomas R.; Tolkoff-Rubin, Nina; Suthanthiran, Manikkam; Saidman, Susan L.; Shaffer, Juanita; Preffer, Frederic I.; Ding, Ruchuang; Sharma, Vijay; Fishman, Jay A.; Dey, Bimalangshu; Ko, Dicken S.C.; Hertl, Martin; Goes, Nelson B.; Wong, Waichi; Williams, Winfred W.; Colvin, Robert B.; Sykes, Megan; Sachs, David H.

    2010-01-01

    Summary Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a nonmyeloablative preparative regimen. Transient chimerism and reversible capillary leak syndrome developed in all recipients. Irreversible humoral rejection occurred in one patient. In the other four recipients, it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation, and renal function has remained stable for 2.0 to 5.3 years since transplantation. The T cells from these four recipients, tested in vitro, showed donor-specific unresponsiveness and in specimens from allograft biopsies, obtained after withdrawal of immunosuppressive therapy, there were high levels of P3 (FOXP3) messenger RNA (mRNA) but not granzyme B mRNA. PMID:18216355

  8. Effects of immunosuppressive treatment on protein expression in rat kidney

    PubMed Central

    Kędzierska, Karolina; Sporniak-Tutak, Katarzyna; Sindrewicz, Krzysztof; Bober, Joanna; Domański, Leszek; Parafiniuk, Mirosław; Urasińska, Elżbieta; Ciechanowicz, Andrzej; Domański, Maciej; Smektała, Tomasz; Masiuk, Marek; Skrzypczak, Wiesław; Ożgo, Małgorzata; Kabat-Koperska, Joanna; Ciechanowski, Kazimierz

    2014-01-01

    The structural proteins of renal tubular epithelial cells may become a target for the toxic metabolites of immunosuppressants. These metabolites can modify the properties of the proteins, thereby affecting cell function, which is a possible explanation for the mechanism of immunosuppressive agents’ toxicity. In our study, we evaluated the effect of two immunosuppressive strategies on protein expression in the kidneys of Wistar rats. Fragments of the rat kidneys were homogenized after cooling in liquid nitrogen and then dissolved in lysis buffer. The protein concentration in the samples was determined using a protein assay kit, and the proteins were separated by two-dimensional electrophoresis. The obtained gels were then stained with Coomassie Brilliant Blue, and their images were analyzed to evaluate differences in protein expression. Identification of selected proteins was then performed using mass spectrometry. We found that the immunosuppressive drugs used in popular regimens induce a series of changes in protein expression in target organs. The expression of proteins involved in drug, glucose, amino acid, and lipid metabolism was pronounced. However, to a lesser extent, we also observed changes in nuclear, structural, and transport proteins’ synthesis. Very slight differences were observed between the group receiving cyclosporine, mycophenolate mofetil, and glucocorticoids (CMG) and the control group. In contrast, compared to the control group, animals receiving tacrolimus, mycophenolate mofetil, and glucocorticoids (TMG) exhibited higher expression of proteins responsible for renal drug metabolism and lower expression levels of cytoplasmic actin and the major urinary protein. In the TMG group, we observed higher expression of proteins responsible for drug metabolism and a decrease in the expression of respiratory chain enzymes (thioredoxin-2) and markers of distal renal tubular damage (heart fatty acid-binding protein) compared to expression in the CMG

  9. Isogarcinol Is a New Immunosuppressant

    PubMed Central

    Cen, Juren; Shi, Mingshu; Yang, Yanfang; Fu, Yanxia; Zhou, Hailing; Wang, Mengqi; Su, Zhenyi; Wei, Qun

    2013-01-01

    Calcineurin (CN), a unique protein phosphatase, plays an important role in immune regulation. In this study we used CN as a target enzyme to investigate the immunosuppressive properties of a series of natural compounds from Garcinia mangostana L., and discovered an active compound, isogarcinol. Enzymatic assays showed that isogarcinol inhibited CN in a dose-dependent manner. At concentrations resulting in relatively low cytotoxicity isogarcinol significantly inhibited proliferation of murine spleen T-lymphocytes induced by concanavalin A (ConA) and the mixed lymphocyte reaction (MLR). In addition, it performed much better in acute toxicity tests and via oral administration in mice than cyclosporin A (CsA), with few adverse reactions and low toxicity in experimental animals. Oral administration of isogarcinol in mice resulted in a dose-dependent decrease in delayed type hypersensitivity (DTH) and prolonged graft survival in allogeneic skin transplantation. These findings suggest that isogarcinol could serve as a new oral immunomodulatory drug for preventing transplant rejection, and for long-term medication in autoimmune diseases. PMID:23785505

  10. 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

  11. 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.

  12. Immunosuppressive therapies after heart transplantation--The balance between under- and over-immunosuppression.

    PubMed

    Söderlund, Carl; Rådegran, Göran

    2015-07-01

    Since the first heart transplantation (HT) in 1967, survival has steadily improved. Issues related to over- and under-immunosuppression are, however, still common following HT. Whereas under-immunosuppression may result in rejection, over-immunosuppression may render other medical problems, including infections, malignancies and chronic kidney disease (CKD). As such complications constitute major limiting factors for long-term survival following HT, identifying improved diagnostic and preventive methods has been the focus of many studies. Notably, research on antibody-mediated rejection (AMR) and cardiac allograft vasculopathy (CAV) has recently led to the development of nomenclatures that may aid in their diagnosis and treatment. Moreover, novel immunosuppressants (such as mammalian target of rapamycin [m-TOR] inhibitors) and strategies aimed at minimizing the use of calcineurin inhibitors (CNIs) and corticosteroids (CSs), have provided alternatives to the traditional combination maintenance immunosuppressive therapy of CSs, cyclosporine (CSA) or tacrolimus (TAC), and azathioprine (AZA) or mycophenolate mofetil (MMF). Research within this field of medicine is not only extensive, but also in constant progress. The purpose of the present review was therefore to summarize some major points regarding immunosuppressive therapies after HT and the balance between under- and over-immunosuppression. Transplant immunology, rejection, common medical problems related to over-immunosuppression, as well as induction and maintenance immunosuppressive drugs and therapies, are addressed.

  13. 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

  14. Changes in circulating immunosuppressive cytokine levels of cancer patients after high intensity focused ultrasound treatment.

    PubMed

    Zhou, Qiang; Zhu, Xue-Qiang; Zhang, Jun; Xu, Zhong-Lin; Lu, Pei; Wu, Feng

    2008-01-01

    Immunosuppression in a patient with malignant tumor is a major obstacle in cancer treatment. In this study, we investigated changes in the circulating level of all measured immunosuppressive cytokines in patients with malignancy before and after high intensity focused ultrasound (HIFU) treatment. Fifteen patients with solid malignancy were enrolled in this study and an enzyme-linked immunoabsorbent assay (ELISA) method was used to measure serum level of vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), transforming growth factor-beta2 (TGF-beta2), interleukin 6 (IL-6) and interleukin 10 (IL-10), respectively before and 1 wk after HIFU treatment. Among them, seven patients had distant metastasis and the remaining eight had no metastasis. All patients received one-session HIFU treatment for primary cancer, including complete ablation in eight patients without metastasis, and partial ablation in seven patients with metastases. The results showed that serum immunosuppressive cytokine levels decreased after HIFU treatment, and there were significant decreases of VEGF, TGF-beta1, and TGF-beta2 before and after HIFU treatment. Compared with the values in the metastatic patients, serum levels of immunosuppressive cytokines were significantly lower in the nonmetastatic patients after HIFU treatment. It is concluded that HIFU can decrease tumor-secreted immunosuppressive cytokine production in addition to its direct tumor destruction. This change may lessen tumor-induced immunosuppression and renew antitumor immunity after HIFU in cancer patients.

  15. 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

  16. Taste-immunosuppression engram: reinforcement and extinction.

    PubMed

    Niemi, Maj-Britt; Härting, Margarete; Kou, Wei; Del Rey, Adriana; Besedovsky, Hugo O; Schedlowski, Manfred; Pacheco-López, Gustavo

    2007-08-01

    Several Pavlovian conditioning paradigms have documented the brain's abilities to sense immune-derived signals or immune status, associate them with concurrently relevant extereoceptive stimuli, and reinstate such immune responses on demand. Specifically, the naturalistic relation of food ingestion with its possible immune consequences facilitates taste-immune associations. Here we demonstrate that the saccharin taste can be associated with the immunosuppressive agent cyclosporine A, and that such taste-immune associative learning is subject to reinforcement. Furthermore, once consolidated, this saccharin-immunosuppression engram is resistant to extinction when avoidance behavior is assessed. More importantly, the more this engram is activated, either at association or extinction phases, the more pronounced is the conditioned immunosuppression.

  17. Tuberculous pyomyositis in an immunosuppressed patient.

    PubMed

    Osorio, Johanna; Barreto, Jackeline; Benavides, Jhonattan; López, Óscar; Cuenca, Ángela; García, Esperanza

    2016-01-01

    Tuberculous pyomyositis is a rare manifestation of extrapulmonary tuberculosis, most common in immunosuppressed patients, with clinical manifestations similar to pyomyositis of other etiologies, although with a lower age of presentation; notable risk factors include prior tuberculosis infection and pharmacological immunosuppression. Diagnosis depends on a high clinical suspicion of the infection in a susceptible population, given that microbiological isolation is often impossible. The response to treatment and prognosis are good. The case presented here is noteworthy given the rarity of this manifestation of tuberculosis and the slow response to first-line TB management in an HIV patient, despite susceptible microbiological isolation. PMID:27622621

  18. Cutaneous malignancies in immunosuppressed organ transplant recipients.

    PubMed

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

    2014-01-01

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

  19. Halo naevi and café au lait macule regression in a renal transplant patient on immunosuppression.

    PubMed

    Lolatgis, Helena; Varigos, George; Braue, Anna; Scardamaglia, Laura; Boyapati, Ann; Winship, Ingrid

    2015-11-01

    A case of halo naevi and café au lait macule regression in a renal transplant patient receiving long-term immunosuppressive therapy is described. We propose the direct transfer of an auto-reactive antibody, CD8 T-cells or tumour necrosis factor α from the transplant donor to the recipient as a possible cause. We have also considered insufficient immunosuppressive therapy as a possible mechanism.

  20. A Case of Persistent Helicobacter pylori Infection Occurring with Anti-IgE Immunosuppression

    PubMed Central

    Zandman, Daniel; Hahn, William

    2013-01-01

    The increasingly widespread use of novel immunosuppressive drugs may lead to unexpected infectious complications. We report a case of persistent Helicobacter pylori (H. pylori) infection that failed to respond to antimicrobial therapy in a patient receiving omalizumab (Xolair™, Genentech USA Inc., San Francisco, CA and Novartis Pharmaceuticals, Basel, Switzerland), an anti-IgE monoclonal antibody approved by the FDA for treatment of severe persistent asthma. To our knowledge, this is the first case report linking an immunosuppressive regimen containing anti-IgE biologic therapy to persistent H. pylori infection. PMID:26157810

  1. Putative bronchopulmonary flagellated protozoa in immunosuppressed patients.

    PubMed

    Kilimcioglu, Ali Ahmet; Havlucu, Yavuz; Girginkardesler, Nogay; Celik, Pınar; Yereli, Kor; Özbilgin, Ahmet

    2014-01-01

    Flagellated protozoa that cause bronchopulmonary symptoms in humans are commonly neglected. These protozoal forms which were presumed to be "flagellated protozoa" have been previously identified in immunosuppressed patients in a number of studies, but have not been certainly classified so far. Since no human cases of bronchopulmonary flagellated protozoa were reported from Turkey, we aimed to investigate these putative protozoa in immunosuppressed patients who are particularly at risk of infectious diseases. Bronchoalveolar lavage fluid samples of 110 immunosuppressed adult patients who were admitted to the Department of Chest Diseases, Hafsa Sultan Hospital of Celal Bayar University, Manisa, Turkey, were examined in terms of parasites by light microscopy. Flagellated protozoal forms were detected in nine (8.2%) of 110 cases. Metronidazole (500 mg b.i.d. for 30 days) was given to all positive cases and a second bronchoscopy was performed at the end of the treatment, which revealed no parasites. In conclusion, immunosuppressed patients with bronchopulmonary symptoms should attentively be examined with regard to flagellated protozoa which can easily be misidentified as epithelial cells.

  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. Immunosuppressive auronol glycosides from Artocarpus tonkinensis.

    PubMed

    Thuy, T T; Kamperdick, C; Ninh, P T; Lien, T P; Thao, T T P; Sung, T V

    2004-04-01

    Activity-guided fractionation of the n-butanol extract from the leaves of Artocarpus tonkinensis led to the isolation of the auronol glycosides maesopsin 4-O-glucoside (1), as well as the new alphitonin-4-O-glucoside (2). These structures were identified on the basis of MS and NMR spectroscopic data. The lymphocyte stimulation test showed both compounds having immunosuppressive activity.

  4. 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

  5. Persistent Hypotony Associated with Immunosuppressive Therapy in Glaucoma Drainage Implant Surgery

    PubMed Central

    Duch, Susana; Milla, Elena; Stirbu, Oana; Andreu, David

    2016-01-01

    Purpose To describe the histopathology of non-valved implant capsules in three cases of persistent postoperative hypotony after the restrictive tube ligature was released in patients receiving immunosuppressive therapy. Observations The macroscopic appearance of the capsules 3 and 4 months postoperatively was immature and loose. Microscopic examination disclosed extremely irregular thin tissue, with thicknesses ranging from 0.02 to 0.6 mm, depending on the capsular location studied. Withdrawal of immunosuppressive therapy did not facilitate rebuilding of new capsules. Replacement with a valved implant device was necessary in two cases; the third case recovered with tapering of prednisone. Conclusions and Importance The use of chronic systemic immunosuppressive therapy might interfere with capsular formation around the plates of drainage devices inducing persistent hypotony. In these cases, the use of valved implants might be safer. PMID:27790128

  6. New Immunosuppressive Therapies in Uveitis Treatment.

    PubMed

    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.

  7. 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

  8. 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.

  9. Dexamethasone-induced immunosuppression: a rabbit model.

    PubMed

    Jeklova, Edita; Leva, Lenka; Jaglic, Zoran; Faldyna, Martin

    2008-04-15

    Rabbits are often used as animal models for experimental purposes; in many cases steroid-induced immunosuppression is necessary. The aim of this study was to characterise a model of immunosuppression in rabbits, based on changes in the lymphocyte subset distribution, changes in proliferative capacity of lymphocytes and activity of neutrophils 1, 3 and 7 days after the administration of 2mg/kg dexamethasone phosphate (DXP) three times at 6-h intervals. In peripheral blood, neutrophilia and lymphopenia together with eosinopenia, monocytopenia and basopenia in the absence of leukocytosis was detected. One day after DXP administration the absolute numbers of all lymphocyte subsets decreased in the blood, whereas in bone marrow, absolute numbers of all lymphocyte subsets increased significantly, except CD79alpha(+) cells that increased only in relative numbers. The effect of DXP on lymphocytes from the spleen, mesenteric and popliteal lymph nodes was less pronounced. In the thymus, DXP led to a marked reduction of the relative and absolute numbers of CD4(+)CD8(+) thymocytes. The proliferative capacity of lymphocytes after concanavalin A stimulation was lower in the peripheral blood and spleen only on day 1, no changes were detected in lymph nodes or in bone marrow. A marked increase in proliferative capacity was detected in the thymus. Spontaneous production of reactive oxygen metabolites by neutrophils was reduced on days 1 and 3 after DXP administration. The present results demonstrate clearly that this DXP application protocol is useful for the experimental induction of relatively short-lasting immunosuppression in rabbits.

  10. Role of exclusive enteral nutrition in the preoperative optimization of patients with Crohn's disease following immunosuppressive therapy.

    PubMed

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

    2015-02-01

    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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. Immunosuppressive activity of human neuroblastoma tumor gangliosides.

    PubMed

    Floutsis, G; Ulsh, L; Ladisch, S

    1989-01-15

    Gangliosides are shed in substantial amounts by some tumors, including human neuroblastoma, and these molecules modulate experimental tumor formation in vivo. We now demonstrate that neuroblastoma tumor gangliosides have potent immunoregulatory activity. Gangliosides of every one of 17 tumors studied were highly inhibitory for the normal in vitro human lymphoproliferative responses to the soluble antigen, tetanus toxoid; 30 nmol ganglioside/ml caused 43% to greater than 99% inhibition and the mean concentration causing 50% inhibition was only 17.3 nmol/ml. Furthermore, gangliosides isolated from clinically more aggressive tumors (Stage III or IV) were up to twice as immunosuppressive as those of the generally less aggressive tumors (Stage I or II) (p less than 0.05). Taken together with the lack of immunosuppressive activity of normal plasma gangliosides, the potent activity of neuroblastoma gangliosides supports the hypothesis that one mechanism by which these shed molecules may act to enhance tumor formation in vivo is through abrogation of the host cellular immune response at the site of tumor formation.

  16. 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.

  17. 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.

  18. Erythromycin prophylaxis for Legionnaire's disease in immunosuppressed patients in a contaminated hospital environment.

    PubMed

    Vereerstraeten, P; Stolear, J C; Schoutens-Serruys, E; Maes, N; Thys, J P; Liesnard, C; Rost, F; Kinnaert, P; Toussaint, C

    1986-01-01

    Between January 1 and June 30, 1983, immunosuppressive drugs were administered in 20 renal transplant recipients undergoing 23 rejection episodes and in 3 patients with renal failure secondary to systemic disease. Legionella pneumophila, serogroup 1, pneumonia was diagnosed on 12/26 (47%) occasions. In an attempt to decrease this high rate, a program of erythromycin prophylaxis was instituted for every new patient who received immunosuppressive chemotherapy until eradication of the organism from the water supply could be realized. From July 1, 1983 to April 30, 1984, erythromycin prophylaxis (1.5-3 g/day by mouth) was administered during 39 episodes of high-dose immunosuppression (20 kidney graft recipients and 4 patients with systemic diseases); no cases of Legionnaire's disease were recorded. During the same period, erythromycin prophylaxis was withheld from 9 other high-dose immunosuppression episodes (7 kidney graft recipients and one patient with sarcoidosis); 5 cases of Legionnaire's disease occurred (56%) in this group. We conclude that erythromycin effectively protects immunocompromised patients in an environment contaminated with L pneumophila.

  19. 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

  20. Immunosuppressant-driven de novo malignant neoplasms after solid-organ transplant.

    PubMed

    Billups, Kelsey; Neal, Jennifer; Salyer, Jeanne

    2015-06-01

    Solid-organ transplant recipients are at a 3- to 5-fold increased risk of a de novo malignant neoplasm developing compared with the general population. The most frequently developed virus-associated malignant neoplasms are Kaposi sarcoma (standardized incidence ratio [SIR], 208.0), nonmelanoma skin cancer (SIR, 28.6), and posttransplant lymphoproliferative disorder, primarily non-Hodgkin lymphoma (SIR, 8.1). Immunosuppressive agents such as corticosteroids, antimetabolites, calcineurin inhibitors, and mammalian target of rapamycin (mTOR) inhibitors play a key role in either causing or preventing this complication. It is hypothesized that some of these regimens can impair cancer surveillance, facilitate the action of oncogenic viruses, and promote direct oncogenic activity. Evolving research has shown promising dual antitumor and immunosuppressive properties of the mTOR inhibitor class. The effective management of posttransplant neoplasms most likely involves the use of these medications among other preventative options. These measures include monitoring certain viral loads as well as immunosuppressant drug levels. Reducing these levels to as low as possible for healthy engraftment and altering regimens when appropriate are management strategies that could lessen this complication of solid-organ transplant. More studies examining the effects of therapeutic drug monitoring are needed to determine specific plasma drug concentrations that will ensure organ engraftment without the development of de novo malignant neoplasms.

  1. 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.

  2. Longitudinal dose and type of immunosuppression in a national cohort of Australian liver, heart, and lung transplant recipients, 1984-2006.

    PubMed

    Na, Renhua; Laaksonen, Maarit A; Grulich, Andrew E; Webster, Angela C; Meagher, Nicola S; McCaughan, Geoffrey W; Keogh, Anne M; Vajdic, Claire M

    2015-11-01

    Unconfounded comparative data on the type and dose of immunosuppressive agents among solid organ transplant recipients are sparse, as are data on longitudinal immunosuppressive therapy since transplantation. We addressed this issue in a population-based cohort of Australian liver (n = 1895), heart (n = 1220), and lung (n = 1059) transplant recipients, 1984-2006. Data on immunosuppressive therapy were retrospectively collected at discharge, three months, and one, five, 10, and 15 yr after first transplant. We computed unadjusted and adjusted estimates for the association between the type and dose of immunosuppressive therapy and organ type. After adjustment for confounders, use of induction antibody and maintenance corticosteroids was more common in heart and lung compared to liver recipients (p < 0.001), and antibody therapy for rejection more common in liver recipients (p < 0.001). Liver recipients were more likely to receive calcineurin inhibitor monotherapy, with or without corticosteroids, compared to heart and lung recipients (p < 0.001). Liver recipients consistently received lower doses of azathioprine than heart and lung recipients (p < 0.001). These differences in immunosuppression may partly explain variations in immunosuppression-related morbidity by transplanted organ, for example, malignancy risk. Longitudinal changes in the type and the dose of immunosuppressive therapy over time since transplantation also demonstrate the need for time-dependent data in observational research.

  3. 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.

  4. An immunosuppressive antibody-drug conjugate.

    PubMed

    Wang, Rongsheng E; Liu, Tao; Wang, Ying; Cao, Yu; Du, Jintang; Luo, Xiaozhou; Deshmukh, Vishal; Kim, Chan Hyuk; Lawson, Brian R; Tremblay, Matthew S; Young, Travis S; Kazane, Stephanie A; Wang, Feng; Schultz, Peter G

    2015-03-11

    We have developed a novel antibody-drug conjugate (ADC) that can selectively deliver the Lck inhibitor dasatinib to human T lymphocytes. This ADC is based on a humanized antibody that selectively binds with high affinity to CXCR4, an antigen that is selectively expressed on hematopoietic cells. The resulting dasatinib-antibody conjugate suppresses T-cell-receptor (TCR)-mediated T-cell activation and cytokine expression with low nM EC50 and has minimal effects on cell viability. This ADC may lead to a new class of selective immunosuppressive drugs with improved safety and extend the ADC strategy to the targeted delivery of kinase inhibitors for indications beyond oncology.

  5. 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

  6. 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

  7. 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.

  8. Nonimmunologic targets of immunosuppressive agents in podocytes

    PubMed Central

    Yoo, Tae-Hyun; Fornoni, Alessia

    2015-01-01

    Proteinuria is a characteristic finding in glomerular diseases and is closely associated with renal outcomes. In addition, therapeutic interventions that reduce proteinuria improve renal prognosis. Accumulating evidence has demonstrated that podocytes act as key modulators of glomerular injury and proteinuria. The podocyte, or glomerular visceral epithelial cell, is a highly specialized and differentiated cell that forms interdigitated foot processes with neighboring podocytes, which are bridged together by an extracellular structure known as the “slit diaphragm” (SD). The SD acts as a size- and charge-selective barrier to plasma protein. Derangement of SD structure or loss of SD-associated protein results in podocyte injury and proteinuria. During the past decades, several immune-modulating agents have been used for the treatment of glomerular diseases and for the reduction of proteinuria. Interestingly, recent studies have demonstrated that immunosuppressive agents can have a direct effect on the SD-associated proteins and stabilize actin cytoskeleton in podocyte and have therefore introduced the concept of nonimmunologic mechanism of renoprotection by immunomodulators. This review focuses on the evidence that immuno-modulating agents directly target podocytes. PMID:26484025

  9. 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.

  10. Dangers of immunosuppressive therapy in hepatitis B virus carriers.

    PubMed Central

    Lueg, E; Heathcote, J

    1992-01-01

    OBJECTIVE: To identify the risk of hepatic failure in hepatitis B virus (HBV) carriers given intermittent immunosuppressive therapy. DATA SOURCES: The key words "immunosuppression" and "hepatitis B" were used to search MEDLINE for relevant articles in English published from 1970 to 1990; the bibliographies of these articles were reviewed for additional publications. Also included were articles published in 1991. STUDY SELECTION: Articles were included if they documented the use of immunosuppressive drugs to treat chronic hepatitis B or another condition in patients at high risk for the HBV carrier state. RESULTS: Long-term immunosuppressive therapy has not improved the survival of patients with chronic hepatitis B. The withdrawal of such therapy from HBV carriers has resulted in a flare-up of potentially fatal hepatitis in 20% to 50%, regardless of whether underlying liver disease was present. The presence of replicating viral DNA in the serum of HBV carriers may identify those who are at high risk of the deleterious effects of immunosuppressive therapy. CONCLUSIONS: Long-term immunosuppressive therapy is not advised for liver disease in HBV carriers. For other conditions in such people continuous rather than intermittent therapy is safer. Patients at high risk for hepatitis B should be screened for this virus when immunosuppressive therapy is contemplated. PMID:1393929

  11. Analysis of malignancies in patients after heart transplantation with subsequent immunosuppressive therapy

    PubMed Central

    Rivinius, Rasmus; Helmschrott, Matthias; Ruhparwar, Arjang; Schmack, Bastian; Klein, Berthold; Erbel, Christian; Gleissner, Christian A; Akhavanpoor, Mohammadreza; Frankenstein, Lutz; Darche, Fabrice F; Thomas, Dierk; Ehlermann, Philipp; Bruckner, Tom; Katus, Hugo A; Doesch, Andreas O

    2015-01-01

    Objective The aim of this study was to analyze the distribution of malignancies in patients after heart transplantation (HTX) and to evaluate the risk factors including immunosuppressive therapy with regard to the development of malignancies and survival. Special emphasis was placed on the effects of a mammalian target of rapamycin (mTOR) containing immunosuppressive regimen. Methods A total of 381 patients (age ≥18 years) receiving HTX were included in the present analysis. All patients were followed-up at the University of Heidelberg Heart Center, Heidelberg, Germany. Data were retrieved from the Heidelberg Registry for Heart Transplantation being collected between 1989 and 2014. According to center standard, all patients received induction therapy with anti-thymocyte globulin guided by T-cell monitoring since 1994. The initial immunosuppressive regimen consisting of cyclosporine A (CsA) and azathioprine (AZA) was replaced by CsA and mycophenolate mofetil (MMF) in 2001 and by tacrolimus (TAC) and MMF in 2006. Additionally, mTOR inhibitors (everolimus/sirolimus) were applied since 2003. Results Mean recipient age at HTX was 51.2±10.5 years and the mean follow-up period after HTX was 9.7±5.9 years. During follow-up, 130 patients developed a neoplasm (34.1% of total). Subgroup analysis revealed 58 patients with cutaneous malignancy only (15.2%), 56 patients with noncutaneous malignancy only (14.7%), and 16 patients with both cutaneous and noncutaneous malignancy (4.2%). Statistically significant risk factors associated with an increased risk of malignancy after HTX were older age (P<0.0001), male recipients (P=0.0008), dyslipidemia (P=0.0263), diabetes mellitus (P=0.0003), renal insufficiency (P=0.0247), and >1 treated rejection episode (TRE) in the first year after HTX (P=0.0091). Administration of CsA (P=0.0195), AZA (P=0.0008), or steroids (P=0.0018) for >1 year after HTX was associated with increased development of malignancy, whereas administration of MMF

  12. [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.

  13. Immunosuppressive protocols and immunological challenges related to hand transplantation.

    PubMed

    Ravindra, Kadiyala V; Ildstad, Suzanne T

    2011-11-01

    There are many immunological challenges related to hand transplantation. Curbing the immune system's ability to effectively mount an immune response against the graft is the goal. As the various components of the immune response are defined and their mechanisms of action delineated, more specific immunosuppressive agents and protocols have been developed. Complications related to immunosuppression in hand transplant recipients are similar to incidences among solid organ recipients. With longer follow-up, the increased cardiovascular risk factors or the development of a neoplasm will likely cause mortality. Standardizing immunosuppression in hand transplantation with the long-term goal of minimization is critically needed.

  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. 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.

  16. 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.

  17. 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

  18. 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

  19. [Immunosuppressive protocols in kidney transplantation: with or without induction?].

    PubMed

    Nehme Chelala, Dania; Mourani, Chebl; Moukarzel, Maroun; Azar, Hiba

    2015-01-01

    Kidney transplantation is the treatment of choice of end stage kidney disease. Over the years, kidney transplantation progressed tremendously, mainly by the improvement of immunosuppressive drugs used in the prevention of acute rejection. Since the introduction of cyclosporine in the 80s, many immunosuppressive protocols have been established. These protocols are characterized by two strategies: with or without induction. The agents used in induction therapies can be polyclonal or monoclonal antibodies. The decision of using induction therapy relies mainly on the evaluation of the immunological risk in the recipient. Even if protocols with induction have improved early results concerning acute rejection, the protocoles without induction seem justified in some candidates. The optimal immunosuppressive protocol is not yet established, and individualization of immunosuppressive treatment is necessary. PMID:26591195

  20. Subacute sclerosing panencephalitis after drug-induced immunosuppression.

    PubMed

    Coulter, J B; Balch, N; Best, P V

    1979-08-01

    A girl developed subacute sclerosing panencephalitis (SSPE). Eight years earlier she had had measles infection contracted shortly after cytotoxic treatment and radiotherapy for a spinal neuroblastoma. The case illustrates that typical SSPE, like immunosuppressive measles encephalopathy, can arise after drug-induced immunosuppression, and supports the view that these diseases probably represent opposite ends of a spectrum induced by measles virus infection in an individual with some form of immunological deficiency.

  1. Early and late effects of the immunosuppressants rapamycin and mycophenolate mofetil on UV carcinogenesis.

    PubMed

    de Gruijl, F R; Koehl, G E; Voskamp, P; Strik, A; Rebel, H G; Gaumann, A; de Fijter, J W; Tensen, C P; Bavinck, J N Bouwes; Geissler, E K

    2010-08-15

    Increased skin cancer risk in organ transplant recipients has been experimentally emulated with enhanced UV carcinogenesis from administering conventional immunosuppressants. However, newer generation immunosuppressive drugs, rapamycin (Rapa) and mycophenolate mofetil (MMF), have been shown to impair angiogenesis and outgrowth of tumor implants. To ascertain the overall effect on UV carcinogenesis, Rapa and MMF were admixed into the food pellets of hairless SKH1 mice receiving daily sub-sunburn UV dosages. With immunosuppressive blood levels neither of the drugs affected onset of tumors (<2 mm), but in contrast to MMF, Rapa significantly increased latency of large tumors (>or=4 mm, medians of 190 vs 125 days) and reduced their multiplicity (1.6 vs 4.5 tumors per mouse at 200 days). Interestingly, tumors (>2 mm) from the Rapa-fed group showed a reduction in UV-signature p53 mutations (39% vs 90%) in favor of mutations from putative base oxidation. This shift in mutation spectrum was not essentially linked to the reduction in large tumors because it was absent in large tumors similarly reduced in number when feeding Rapa in combination with MMF, possibly owing to an antioxidant effect of MMF. Significantly fewer tumor cells were Vegf-positive in the Rapa-fed groups, but a correspondingly reduced expression of Hif1alpha target genes (Vegf, Ldha, Glut1, Pdk1) that would indicate altered glucose metabolism with increased oxidative stress was not found. Remarkably, we observed no effect of the immunosuppressants on UV-induced tumor onset, and with impaired tumor outgrowth Rapa could therefore strongly reduce skin carcinoma morbidity and mortality rates in organ transplant recipients. PMID:19998342

  2. Effects of dexamethasone immunosuppression on turkey clostridial dermatitis.

    PubMed

    Thachil, Anil J; Shaw, Daniel P; Nagaraja, Kakambi V

    2014-09-01

    Clostridia represents a group of anaerobic spore-forming bacteria ubiquitous in the poultry environment. They are widely distributed in soil and survive for many years as highly resistant, inactive spores. They enter the body through wounds and contaminated feed as active bacteria or spores. Multiplication of clostridial bacteria occurs only in the absence of oxygen or in environments with very low concentrations of oxygen. During active multiplication, the clostridial organisms produce several toxins that are responsible for most of the clinical signs seen in clostridial diseases. Immunosuppression is a problem for the poultry industry. In modern, intensive poultry-rearing conditions, stress due to high population densities pose a considerable challenge for the immune system, and infectious agents can exploit this situation to cause disease. Immunosuppression may predispose turkeys to clostridial infection, resulting in clostridial dermatitis and mortality. The purpose of this study was to determine whether immunosuppression predisposes turkeys to clostridial infection and causes clostridial dermatitis. We immunosuppressed 10-wk-old turkey poults with dexamethasone. The birds immunosuppressed and not immunosuppressed were then challenged with Clostridium perfringens, Clostridium septicum, or both and examined for the development of clostridial dermatitis. The dexamethasone-treated birds were found to be more susceptible to C. peifingens/C. septicum challenge and developed clostridial dermatitis than the no-dexamethasone-treated birds through the subcutaneous route. However, oral inoculation of the same agents did not cause any dermatitis lesions in either of the groups.

  3. 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

  4. 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.

  5. 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.

  6. Prospects for personalized immunosuppression: pharmacologic tools--a review.

    PubMed

    Del Tacca, M

    2004-04-01

    In the last few years, novel immunosuppressive agents and new formulations, including sirolimus, mycophenolic acid (the active metabolite of mycophenolate mofetil), tacrolimus, and microemulsion cyclosporine, have significantly improved the clinical outcome of transplant recipients. However, the majority of immunosuppressive agents need a constant monitoring of drug levels to reduce the risk of graft rejection as well as drug-induced toxicities. Many factors may affect the pharmacokinetic characteristics of immunosuppressive agents, potentially reducing treatment effectiveness. Absorption and metabolism of immunosuppressive drugs are influenced by patient genotype and comedications, while comorbidities (ie, diabetes and cystic fibrosis) are responsible for altered pharmacokinetics. Dose individualization in transplant recipients is performed according to their health status, graft function, and drug therapeutic range. With respect to the last issue, therapeutic drug monitoring (TDM) plays a crucial role in achieving optimal immunosuppression, improving the efficacy of drugs, and lowering toxic effects. Pharmacokinetic analysis allowed the identification of specific parameters, such as plasma or blood levels, immediately before dosing (C(min) or trough levels) or 2 hours after administration (C(2)), which are significantly related to tissue exposure to the drug. More recently, studies have investigated treatment individualization by evaluating drug pharmacogenetics based on the expression level or mutations of their molecular targets, including calcineurin for cyclosporine and tacrolimus, and inosine monophosphate dehydrogenase for mycophenolic acid. Although no conclusive data may be drawn from these preliminary trials, further studies are underway to address the role of pharmacogenetics in clinical decision making.

  7. The utility of animal models in developing immunosuppressive agents.

    PubMed

    McDaid, James; Scott, Christopher J; Kissenpfennig, Adrien; Chen, Huifang; Martins, Paulo N

    2015-07-15

    The immune system comprises an integrated network of cellular interactions. Some responses are predictable, while others are more stochastic. While in vitro the outcome of stimulating a single type of cell may be stereotyped and reproducible, in vivo this is often not the case. This phenomenon often merits the use of animal models in predicting the impact of immunosuppressant drugs. A heavy burden of responsibility lies on the shoulders of the investigator when using animal models to study immunosuppressive agents. The principles of the three R׳s: refine (less suffering,), reduce (lower animal numbers) and replace (alternative in vitro assays) must be applied, as described elsewhere in this issue. Well designed animal model experiments have allowed us to develop all the immunosuppressive agents currently available for treating autoimmune disease and transplant recipients. In this review, we examine the common animal models used in developing immunosuppressive agents, focusing on drugs used in transplant surgery. Autoimmune diseases, such as multiple sclerosis, are covered elsewhere in this issue. We look at the utility and limitations of small and large animal models in measuring potency and toxicity of immunosuppressive therapies.

  8. Contrasting effects of immunosuppression on Theiler's virus infection in mice.

    PubMed

    Lipton, H L; Canto, C D

    1977-03-01

    In the present study, cyclophosphamide and rabbit anti-mouse thymocyte serum were used to immunosuppress SJL/J mice infected with Theiler's mouse encephalomyelitis virus (TMEV) in order to delineate the potential mechanism(s) of virus-induced cellular injury in this infection. Whereas both immunosuppressive agents produced a significant increase in mortality, this treatment had differing effects on the pathological involvement of gray and white-matter structures in the central nervous system. The central nervous system of immunosuppressed TMEV-infected mice had increased microglial cell proliferation and neuronal necrosis, longer maintenance of high virus levels and spread of virus antigen to involve the neocortex and hippocampal complex. These observations indicate that TMEV causes a cytolotic infection of neurons and possibly other cells in gray matter. In contrast, immunosuppression produced a dramatic reduction in mononuclear inflammatory cells in the leptomeninges and spinal cord white matter of infected mice and prevented demyelination. Further, virus antigen was not detected in the leptomeninges and white matter of immunosuppressed and infected mice. These findings suggest that demyelination of TMEV infection is immune mediated.

  9. Pyridoxine deficiency: new approaches in immunosuppression and chemotherapy.

    PubMed

    Trakatellis, A; Dimitriadou, A; Trakatelli, M

    1997-10-01

    Pyridoxine deficiency leads to impairment of immune responses. It appears that the basic derangement is the decreased rate of production of one-carbon units necessary for the synthesis of nucleic acids. The key factor is a pyridoxine enzyme, serine hydroxymethyltransferase. This enzyme is very low in resting lymphocytes but increases significantly under the influence of antigenic or mitogenic stimuli, thus supplying the increased demand for nucleic acid synthesis during an immune response. Serine hydroxymethyltransferase activity is depressed by deoxypyridoxine, a potent antagonist of pyridoxal phosphate, and also by known immunosuppressive or antiproliferative agents. The combination of these agents is additive. Our results lead us to suggest the following medical applications: (a) combination of deoxypyridoxine with immunosuppressive or chemotherapeutic drugs may be effective in cases of immunosuppressive therapy or organ transplantation, (b) the development of special agents directed against the serine hydroxymethyltransferase apoprotein may prove to be a valuable medical tool, since this enzyme presents an excellent target for chemotherapy, (c) lymphocytes of individual patients could be used to design tailor-made specific immunosuppressive or chemotherapeutic treatment, and (d) the serine hydroxymethyltransferase activity of lymphocyte culture presents an excellent indicator for the evaluation of potency of immunosuppressive, chemotherapeutic or genotoxic compounds in a simple and rapid test.

  10. 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

  11. The influence of immunosuppressive agents on BK virus risk following kidney transplantation, and implications for choice of regimen.

    PubMed

    Suwelack, Barbara; Malyar, Viola; Koch, Martina; Sester, Martina; Sommerer, Claudia

    2012-07-01

    The increasing incidence of BK-associated nephropathy following kidney transplantation has prompted an examination of strategies for risk reduction and management through immunosuppression manipulation. Evidence from retrospective and prospective studies suggests that BK viruria and viremia, and the need for BK virus treatment, are higher with tacrolimus than cyclosporine. Combined therapy with tacrolimus and mycophenolic acid may be associated with a particularly higher risk of BK infection, but data are conflicting as to whether mycophenolic acid per se is an independent risk factor. The incidence of BK-related events may be reduced in patients receiving mTOR inhibitors (everolimus or sirolimus) with cyclosporine vs a calcineurin inhibitor with mycophenolic acid. De novo immunosuppression regimens that avoid rabbit antithymocyte globulin and tacrolimus, particularly tacrolimus with mycophenolic acid, may be advantageous, whereas low-exposure cyclosporine with an mTOR inhibitor appears a favorable option. Routine screening for BK infection during the first 2 years posttransplant is recommended to allow preemptive modification of the immunosuppressive regimen. In patients at high risk of BK virus infection, appropriate de novo immunosuppression or very early conversion to an mTOR inhibitor to facilitate reduction or discontinuation of calcineurin inhibitors or antimetabolites should be considered. Extensive further research into optimal avoidance, screening, and treatment strategies is required.

  12. Idiopathic granulomatous vasculitis: response to immunosuppressive therapy.

    PubMed Central

    Alguacil-Garcia, G F; Moreno-Requena, J; Martinez-Albadalejo, M; Hallal-Hachem, H; Gonzalez-Pina, B; de Paco-Moya, M

    1995-01-01

    A case of idiopathic granulomatous vasculitis (disseminated visceral giant cell arteritis) is described in an old woman, the seventh case of this rare disorder reported to date. The main organ affected was the liver and, to our knowledge, this is the first patient to be diagnosed while still alive and the only case to have received medical treatment. It is also the first time that muscular involvement has been documented in this condition. Cyclophosphamide treatment resulted in disappearance of symptoms and increase in weight. The patient died of an unrelated condition. Images PMID:7665707

  13. Albendazole inhibits Pneumocystis carinii proliferation in inoculated immunosuppressed mice.

    PubMed Central

    Bartlett, M S; Edlind, T D; Lee, C H; Dean, R; Queener, S F; Shaw, M M; Smith, J W

    1994-01-01

    Albendazole, a benzimidazole derivative widely used for treating helminth infections, was successfully used to treat and prevent development of Pneumocystis carinii pneumonia in transtracheally inoculated immunosuppressed mice. For treatment, 3 weeks postinoculation, albendazole at 300 and 600 mg/kg of body weight per day was administered in food for 3 weeks. For prophylaxis, albendazole was begun on the same day as inoculation at 300 mg/kg/day for 7 days, and then the dose was reduced to 150 mg/kg/day for 35 additional days. With these regimens, albendazole was effective both for treatment and prophylaxis. Both dexamethasone-immunosuppressed and L3T4+ monoclonal antibody-immunosuppressed mouse models were used, and albendazole inhibited P. carinii infection in both. PMID:7986016

  14. 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.

  15. Immunosuppressive drugs in ulcerative colitis: twisting facts to suit theories?

    PubMed Central

    Sands, B E

    2006-01-01

    Immunosuppressive drugs have become a mainstay of therapy for the inflammatory bowel diseases. Although robust evidence exists in support of the use of these drugs in Crohn's disease, a close evaluation of the available data in ulcerative colitis reveals a much weaker evidence base. In particular, randomised controlled trials of azathioprine, the most commonly used immunosuppressive agent, do not provide rich evidence of efficacy whereas observational cohorts suggest this agent is effective, particularly in patients with relapsing disease who require corticosteroids. Ciclosporin is also effective in the most refractory cases but its efficacy needs to be carefully weighed against the possibility of rare but life threatening complications. Although the evidence base in support of immunosuppressive drugs in ulcerative colitis is not as strong as in Crohn's disease, these agents clearly have a role in the treatment of this disease. PMID:16531519

  16. 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

  17. Effect of immunosuppression on the course of cryptosporidiosis experimentally.

    PubMed

    Toulah, Fawzia H; El Shafei, Amal A; Al-Rashidi, Hyat S

    2012-12-01

    This study evaluated the effect of immunosuppression on experimental cryptosporidiosis, by parasitological and histopathological studies at different days post infection (p.i). A total of one hundred five clean laboratory bred male Wister rats were divided into four groups: normal control group (GI), infected group (GII), immunosuppressed control group (GIII) and immunosuppressed infected group (GIV). The infection was done by inoculation orally with 10(5) Cryptosporidium oocysts in 0.1 ml PBS. The immunosuppression was done by administration of cytotoxic drug (Endoxan) intraperitoneal in a dose of 5 mg/kg/d for 4 weeks. The results showed that in GII, most of animals attained its activities without apparent clinical symptoms except some of them had diarrhea while in GIV, all had diarrhea, loss of appetite, weakness, lethargy and hair loss. The death rate was (10%) in GII while in GIV was 51.4%. The infection rate among GII was 95% and GIV was 100%. The infection intensity was higher in GIV than in GIII and the greatest number of excreted oocysts was observed on day 15th post-infection (PI) in GIV and on day 11th PI in GII. The histopathological changes in the ileum were more advanced in GIV.

  18. Immunosuppressive agents and interstitial lung disease: what are the risks?

    PubMed

    Meyer, Keith C

    2014-06-01

    Idiopathic pulmonary fibrosis is unlikely to respond to immunosuppressive therapies, and patients with idiopathic pulmonary fibrosis may be harmed by such therapy. In contrast, some forms of interstitial lung disease can respond well to treatment with immunosuppressive drug therapies. Such agents can, however, be associated with significant risk of adverse effects such as infection, diabetes, osteoporosis, myopathy, bone marrow suppression, hepatitis, urinary tract injury, and drug-induced pneumonitis. Treating clinicians must be aware of potential adverse reactions to any immunosuppressive drug that they prescribe for their patients, and they should implement appropriate pre-therapy screening (e.g., tuberculosis, hepatitis, renal insufficiency) and monitoring that is recommended to avoid/minimize risk during the treatment period. Some disorders (e.g., cellular non-specific interstitial pneumonia, organizing pneumonia, or sarcoidosis) may respond very well to immunosuppressive therapies including corticosteroids as monotherapy, and the use of steroid-sparing agents can minimize corticosteroid side effects and may enhance treatment efficacy for disorders such as sarcoidosis or connective tissue disease-associated forms of interstitial lung disease.

  19. 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

  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. Marked alterations of neutrophil functions during sepsis-induced immunosuppression.

    PubMed

    Demaret, Julie; Venet, Fabienne; Friggeri, Arnaud; Cazalis, Marie-Angélique; Plassais, Jonathan; Jallades, Laurent; Malcus, Christophe; Poitevin-Later, Françoise; Textoris, Julien; Lepape, Alain; Monneret, Guillaume

    2015-12-01

    Severe septic syndromes deeply impair innate and adaptive immunity and are responsible for sepsis-induced immunosuppression. Although neutrophils represent the first line of defense against infection, little is known about their phenotype and functions a few days after sepsis, when the immunosuppressive phase is maximal (i.e., between d 3 and 8). The objective of the present study was to perform, for the first time, a global evaluation of neutrophil alterations in immunosuppressed septic patients (at d 3-4 and d 6-8) using phenotypic and functional studies. In addition, the potential association of these parameters and deleterious outcomes was assessed. Peripheral blood was collected from 43 septic shock patients and compared with that of 23 healthy controls. In the septic patients, our results highlight a markedly altered neutrophil chemotaxis (functional and chemokine receptor expressions), oxidative burst, and lactoferrin content and an increased number of circulating immature granulocytes (i.e., CD10(dim)CD16(dim)). These aspects were associated with an increased risk of death after septic shock. In contrast, phagocytosis and activation capacities were conserved. To conclude, circulating neutrophils present with phenotypic, functional, and morphologic alterations a few days after sepsis onset. These dysfunctions might participate in the deleterious role of sepsis-induced immunosuppression. The present results open new perspectives in the mechanisms favoring nosocomial infections after septic shock. They deserve to be further investigated in a larger clinical study and in animal models recapitulating these alterations. PMID:26224052

  2. Methotrexate for immunosuppression in life-supporting pig-to-cynomolgus monkey renal xenotransplantation.

    PubMed

    Cozzi, Emanuele; Cadrobbi, Roberto; Baldan, Nicola; Dedja, Arben; Calabrese, Fiorella; Castagnaro, Massimo; Fante, Fabio; Boldrin, Massimo; Iacopetti, Ilaria; Ravarotto, Licia; Carraro, Paolo; Bronte, Vincenzo; De Santo, Carmela; Busetto, Roberto; Plebani, Mario; Cancellotti, Francesco Maria; Rigotti, Paolo; Thiene, Gaetano; Ancona, Ermanno

    2003-11-01

    Methotrexate (MTX) has been used successfully as an immunosuppressant in rodent xenotransplantation models, but the data generated so far with MTX in pig-to-baboon cardiac transplantation studies have been disappointing. The potential of this agent was consequently explored in a life-supporting pig-to-primate renal model using the cynomolgus monkey as the recipient species. Introductory in vitro and in vivo pharmacokinetic and pharmacodynamic studies with MTX were conducted in three cynomolgus monkeys. Subsequently, 10 cynomolgus monkey recipients of a life-supporting kidney from human decay-accelerating factor transgenic pigs were administered MTX intravenously according to three different regimens. All the animals also received cyclosporine A and steroids. In addition, mycophenolate sodium (MPS) was administered post-operatively in two of the three groups of transplanted animals. At clinically relevant concentrations, MTX is able in vitro to inhibit the mixed lymphocyte reactions (MLR) in cynomolgus monkeys. After intravenous administration, moreover, exposure of cynomolgus monkeys to MTX appeared to be higher than had been previously reported in baboons. Graft function was observed in the transplanted animals, which survived from 0 to 41 days. All but two animals revealed acute humoral rejection in the explanted graft and developed diarrhea. Diarrhea was the cause of euthanasia in five cases. It was unrelated to the administration of MPS and associated with severe histopathological signs of enteritis. This study demonstrates that the pharmacokinetic and pharmacodynamic profiles if MTX vary substantially between non-human primate species. In vitro, MTX has immunosuppressive properties in the cynomolgus monkey at clinically relevant concentrations. In vivo, MTX has a very narrow therapeutic window in cynomolgus monkeys, however, as it does in baboons. We conclude that MTX is scarcely effective as an immunosuppressant, be it for induction or maintenance, in pig

  3. 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

  4. Theories of dual diagnosis in mental retardation.

    PubMed

    Matson, J L; Sevin, J A

    1994-02-01

    Dual diagnosis, defined in this instance as the co-occurrence of mental health disorders with mental retardation, has become a major area of clinical practice and research in the past 10 years. Whereas areas such as differential diagnosis, assessment, and prevalence have been major focuses of research, etiologies of dual diagnosis have received less attention. Current etiological theories have practical implications for the treatment and prevention of dual diagnoses and suggest important directions for future research. This article provides a historical review of theory development in the field of dual diagnosis. Current status of etiological theories and future directions are discussed with an aim toward encouraging further study.

  5. Testicular ischemia due to intravascular large B-cell lymphoma: a novel presentation in an immunosuppressed individual.

    PubMed

    Tranchida, Paul; Bayerl, Michael; Voelpel, Mary Jo; Palutke, Margarita

    2003-10-01

    A 56-year-old man presented with fever, disorientation, and testicular pain. He was receiving azathioprine immunosuppression for autoimmune hepatitis. Orchiectomy identified occlusion of spermatic cord vessels by intravascular large B-cell lymphoma (IVLBL) and ischemic changes in the testis. Tumor cells were positive for CD 10, CD 20, CD 30, and Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1) and early region RNA (EBER). He was treated with the cessation of azathioprine, chemotherapy, anti-CD 20 immunotherapy, and radiotherapy. Twenty months after diagnosis, he is alive with no evidence of lymphoma or hepatitis. This is the first report of IVLBL presenting with testicular ischemia. It highlights the importance of prompt diagnosis and intervention to achieve durable response. That this lymphoma arose in the setting of immunosuppressive therapy introduces additional complexity relating to pathogenesis, clinical behavior, and treatment.

  6. Outcome of a novel immunosuppressive strategy of cyclosporine, levamisole and danazol for severe aplastic anemia.

    PubMed

    Wang, Min; Li, Xingxin; Shi, Jun; Shao, Yingqi; Ge, Meili; Huang, Jinbo; Huang, Zhendong; Zhang, Jing; Nie, Neng; Zheng, Yizhou

    2015-08-01

    Treatment options for patients with severe aplastic anemia (SAA) in developing countries are limited. A cohort of 261 patients with SAA received a novel immunosuppressive strategy of cyclosporine alternately combined with levamisole plus danazol (CSA&LMS-based regimen), which included 70 VSAA and 191 moderate SAA [initial absolute neutrophil count (ANC) >200/μL] cases. The CSA&LMS-based regimen was administrated orally with an initial dose of CSA 3 mg/kg in adults and 5 mg/kg in children every other day, LMS 150 mg in adults and 2.5 mg/kg in children every other day, and danazol (5.0-10.0) mg/kg daily, continued for 12 more months, followed by slow tapering. The 6-month response rates were 24.3 and 52.9 % for VSAA and moderate SAA (P < 0.001), respectively. Univariate and multivariate analyses demonstrated that younger age, higher pretreatment absolute reticulocyte count and ANC were favorable factors for achieving response at 6 months. The estimated 5-year overall survival rates were 33.8 % (95 % CI 20.6-47 %) and 80.5 % (95 % CI 69.7-91.3 %) for VSAA and moderate SAA, respectively (P < 0.001). To date, nine patients relapsed, and six patients evolved to clonal disorders. Thus, CSA&LMS-based regimen may represent a promising immunosuppressive strategy for moderate SAA.

  7. Bioavailability of a generic of the immunosuppressive agent mycophenolate mofetil in pediatric patients.

    PubMed

    González-Ramírez, Rodrigo; González-Bañuelos, Jessica; Villa, María de la Salud; Jiménez, Braulio; García-Roca, Pilar; Cruz-Antonio, Leticia; Castañeda-Hernández, Gilberto; Medeiros, Mara

    2014-09-01

    The use of generic immunosuppressive agents is controversial, especially for the treatment of pediatric patients, as information on the bioavailability of generic immunosuppressants in children is particularly scarce. The aim of the study was to compare the bioavailabilities of two products containing mycophenolate mofetil, the innovator and a generic, in children. Pediatric patients with end-stage renal disease on the waiting list for renal transplantation received a single oral dose of mycophenolate mofetil as either the innovator product (CellCept(®) , Roche) or the generic (Tevacept(®) , Teva Pharmaceuticals). A nine point pharmacokinetic profile was obtained. Mycophenolic acid concentration was quantitated in plasma by HPLC, plasma concentration-against-time curves were constructed, and bioavailability parameters were determined. Pharmaceutical quality analysis of both formulations, including drug content and dissolution profile, was also performed. There were no statistically significant differences between formulations in bioavailability parameters. Interindividual variability was very important, but individual values of AUC, an indicator of the extent of drug absorption, were within the same range for both formulations. The two formulations exhibited similar drug content and dissolution profiles, as well as comparable mycophenolic acid plasma levels in an end-stage renal failure population.

  8. Protection from inflammation, immunosuppression and carcinogenesis induced by UV radiation in mice by topical Pycnogenol.

    PubMed

    Sime, Suzann; Reeve, Vivienne E

    2004-02-01

    Pycnogenol is a standardized extract of the bark of the French maritime pine, Pinus pinaster Ait., that has multiple biological effects, including antioxidant, anti-inflammatory and anticarcinogenic properties. This study describes the effect of topical application of lotions containing Pycnogenol to Skh:hr hairless mice undergoing minimally inflammatory daily exposures to solar-simulated UV radiation (SSUV). We report that concentrations of Pycnogenol of 0.05-0.2% applied to the irradiated dorsal skin immediately after exposure resulted in dose-dependent reduction of the inflammatory sunburn reaction, measured as its edema component. When mice received three consecutive daily exposures of minimally edematous SSUV, their ability to raise a contact hypersensitivity (CHS) reaction was suppressed by 54%. Pycnogenol lotions applied postirradiation reduced this immunosuppression to 22% (0.05% Pycnogenol) and 13% (0.1% Pycnogenol). Furthermore, when CHS was suppressed by 71% with exogenous treatment with cis-urocanic acid, the putative epidermal mediator of photoimmunosuppression, 0.2% Pycnogenol lotion reduced the immunosuppression to 18%. Chronic exposure to SSUV on 5 days/week for 10 weeks induced skin tumors from 11 weeks in both control mice and in mice receiving daily applications of 0.05% Pycnogenol, but tumor appearance was significantly delayed until 20 weeks in mice receiving 0.2% Pycnogenol. Furthermore, whereas 100% of control mice had at least one tumor by 30 weeks, and mice treated with 0.05% Pycnogenol by 33 weeks, the maximum tumor prevalence in mice treated with 0.2% Pycnogenol was significantly reduced to 85%, with some mice remaining tumor free. Average tumor multiplicity was also significantly reduced by 0.2% Pycnogenol, from 5.2 in control mice to 3.5 at 35 weeks. Thus, topical Pycnogenol offered significant and dose-dependent protection from SSUV-induced acute inflammation, immunosuppression and carcinogenesis, when applied to the skin after daily

  9. 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...

  10. On the adaptive significance of stress-induced immunosuppression.

    PubMed Central

    Råberg, L; Grahn, M; Hasselquist, D; Svensson, E

    1998-01-01

    We approach the field of stress immunology from an ecological point of view and ask: why should a heavy physical workload, for example as a result of a high reproductive effort, compromise immune function? We argue that immunosuppression by neuroendocrine mechanisms, such as stress hormones, during heavy physical workload is adaptive, and consider two different ultimate explanations of such immunosuppression. First, several authors have suggested that the immune system is suppressed to reallocate resources to other metabolic demands. In our view, this hypothesis assumes that considerable amounts of energy or nutrients can be saved by suppressing the immune system; however, this assumption requires further investigation. Second, we suggest an alternative explanation based on the idea that the immune system is tightly regulated by neuroendocrine mechanisms to avoid hyperactivation and ensuing autoimmune responses. We hypothesize that the risk of autoimmune responses increases during heavy physical workload and that the immune system is suppressed to counteract this. PMID:9753786

  11. Antibody-based immunosuppressive agents for corneal transplantation.

    PubMed

    Thiel, M A; Kaufmann, C; Coster, D J; Williams, K A

    2009-10-01

    The progress in antibody engineering over the last 20 years has created the tools for the development of novel antibody-based drugs and constructs, such as small antibody fragments, suitable for topical administration. In rheumatology, oncology, transplantation medicine and ophthalmology, therapeutic antibody constructs, and antibody fragments have been responsible for the clinical progress seen over the last decade. Although antibody-based therapies have become a well-established immunosuppressive option in solid organ transplantation, there are only very few reports with regard to corneal transplantation. The following review explains some of the important aspects of engineered antibody-based therapeutic agents and summarises the current use of such immunosuppressive therapies in transplantation medicine and corneal transplantation.

  12. Immunosuppression in pancreas transplantation: the Euro SPK trials and beyond.

    PubMed

    Malaise, J; De Roover, A; Squifflet, J P; Land, W; Neuhaus, P; Pratschke, J; Kahl, A; Pascher, A; Boas-Knoop, S; Arbogast, H; Hoffmann, J; Illner, W D; Seissler; Schlamp; Viebahn; Wunsch; Hajt; Klar, E; Scharek, W; Hopt; Pisarski, P; Drognitz, O; Thurow, C; Dette, K; Bechstein, W O; Woeste, G; Klempnauer, J; Becker, T; Lück; Neipp; Königsrainer, A; Steurer, W; Margreiter, R; Mark; Bonatti; Saudek, F; Boucek, P; Adamec, M; Havrdova, T; Koznarova, R; Vanrenterghem, Y; Pirenne, J; Maes, B; Kuypers, D; Coosemans, W; Evenepoel, P; van Ophem, D; Marcelis, V; van Vlem; Peeters; de Hemptinne; de Roose; Fernandez-Cruz, L; Ricart, M J; Nakache, R; Morel, P; Berney, T; Demuylder, S

    2008-01-01

    The Immunosuppression in Pancreas Transplantation was historically based on the fact that the pancreas is an extremely immunogenic organ. Quadruple drug therapy with polyclonal or monoclonal antibodies induction was the mainstay therapy since the introduction of Cyclosporine A. In the modern era of Immunosuppression, Mycophenolate Mofetil replaced Azathioprine while Tacrolimus-another potent calcineurin inhibitor-had-and still has-a difficult challenge to replaced Cyclosporine A, due to its potential diabetogenic effect. Thanks to the first two EuroSPK studies which prospectively tried to answer several questions in that field. But, the future challenge will be in understanding the impact of innate immunity and ischemic reperfusion injuries on the long-term graft function. Hopefully, new drugs will be available and tested to block unspecific deleterious reactions to attenuate the proinflammatory response. It will be the aim of the third Euro SPK Study.

  13. Insights into pharmacogenomics and its impact upon immunosuppressive therapy.

    PubMed

    Yagil, Yoram; Yagil, Chana

    2002-05-01

    The advent of the genomic era has brought about several new fields of study, one of them being pharmacogenomics, which seeks to link drug treatment (pharmaco-) with the individual's genetic make-up (genomics). Pharmacogenomics holds many promises for improved treatment of a large variety of medical conditions, including immunosuppression for organ transplantation and autoimmune disease. Many of these promises have, however, not yet been fulfilled. In this brief overview of the subject, we attempt to provide insights into the evolving field of pharmacogenomics and discuss some of its potential benefits and promises, technological tools used by pharmacogenomics, the reasons for delays in breakthroughs in the field, and the relevance of pharmacogenornics to immunosuppression.

  14. Immunosuppression Facilitates the Reactivation of Latent Papillomavirus Infections

    PubMed Central

    Maglennon, G. A.; McIntosh, P. B.

    2014-01-01

    At mucosal sites, papillomavirus genomes can persist in the epithelial basal layer following immune-mediated regression. Subsequent T-cell depletion stimulates a 3- to 5-log increase in the viral copy number, to levels associated with productive infection. Reappearance of microlesions was rare within the short time frame of our experiments but was observed in one instance. Our studies provide direct evidence that immunosuppression can trigger the reactivation of latent papillomavirus genomes, as previously proposed in humans. PMID:24173230

  15. AChR-specific immunosuppressive therapy of myasthenia gravis.

    PubMed

    Luo, Jie; Lindstrom, Jon

    2015-10-15

    Myasthenia gravis (MG) is an organ-specific autoimmune disease characterized by muscle fatigability. In most cases, it is mediated by autoantibodies targeting muscle nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction. Experimental autoimmune myasthenia gravis (EAMG) is an animal model for MG, which is usually induced by immunization with AChR purified from fish electric organ. Pathological autoantibodies to AChRs are directed at the extracellular surface, especially the main immunogenic region (MIR). Current treatments for MG can help many but not all patients. Antigen-specific immunosuppressive therapy for MG that specifically suppresses the autoimmune response without affecting the entire immune system and avoids side effects of general immunosuppression is currently unavailable. Early attempts at antigen-specific immunosuppression for EAMG using AChR extracellular domain sequences that form epitopes for pathological autoantibodies risked provoking autoimmunity rather than suppressing it. We discovered a novel approach to specific immunosuppression of EAMG with a therapeutic vaccine consisting of bacterially-expressed human AChR cytoplasmic domains, which has the potential to specifically suppress MG without danger of causing exacerbation. This approach prevents development of chronic EAMG when initiated immediately after the acute phase of EAMG, and rapidly reverses established chronic EAMG when started during the chronic phase of EAMG. Successfully treated rats exhibited long-term resistance to re-induction of EAMG. In this review we also discuss the current understanding of the mechanisms by which the therapy works. Vaccination with AChR cytoplasmic domains in adjuvant is promising as a safe, antigen-specific, potent, effective, rapidly acting, and long lasting approach to therapy of MG.

  16. Overcoming immunosuppression in the melanoma microenvironment induced by chronic inflammation.

    PubMed

    Umansky, Viktor; Sevko, Alexandra

    2012-02-01

    Malignant melanoma is known by its rapid progression and poor response to currently applied treatments. Despite the well-documented melanoma immunogenicity, the results of immunotherapeutic clinical trials are not satisfactory. This poor antitumor reactivity is due to the development of chronic inflammation in the tumor microenvironment characterized by infiltrating leukocytes and soluble mediators, which lead to an immunosuppression associated with cancer progression. Using the ret transgenic mouse melanoma model that closely resembles human melanoma, we demonstrated increased levels of chronic inflammatory factors in skin tumors and metastatic lymph nodes, which correlated with tumor progression. Furthermore, Gr1(+)CD11b(+) myeloid-derived suppressor cells (MDSC), known to block tumor-reactive T cells, were enriched in melanoma lesions and showed an enhanced immunosuppressive capacity. This MDSC accumulation was associated with a strong TCR ζ-chain downregulation in T cells suggesting that the tumor inflammatory microenvironment supports MDSC recruitment and immunosuppressive activity. Indeed, upon administration of phosphodiesterase-5 inhibitor sildenafil or paclitaxel in non-cytotoxic doses, we observed reduced levels of chronic inflammatory mediators in association with decreased MDSC amounts and immunosuppressive function. This led to a partial restoration of ζ-chain expression in T cells and to a significantly increased survival of tumor-bearing mice. CD8 T-cell depletion resulted in an abrogation of beneficial outcome of both drugs, suggesting the involvement of MDSC and CD8 T cells in the observed therapeutic effects. Our data imply that inhibition of chronic inflammation in the tumor microenvironment should be applied in conjunction with melanoma immunotherapies to increase their efficacy. PMID:22120757

  17. 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

  18. The effect of immunosuppressants on experimental infection with Fasciola hepatica.

    PubMed

    Corba, J; Spaldonová, R

    1975-01-01

    Results are presented on the effect of immunosuppressive substances such as chlorambucil, cyclophosphamide, azathioprine, amethopterine and a cortizone derivate of betamethasone, on the development of Fasciola hepatica in the rat. The suppression of the immune response of the host to immunosuppressants was reflected in an earlier start of migration of the flukes to the common bile duct, and in an earlier onset of egg production as compared with that in the controls. Of the substances employed, cyclophosphamide and betamethasone were the most effective ones within the period from week 2--6 p.i., which is the time during which the migration of the flukes in the liver parenchyma is highest. Pathological changes in the liver of the animals were less marked than those of the infected controls. Evidence was obtained on an increased pathogenicity of infective larval flukes causing a higher mortality of the hosts in comparison with that of the control animals. On the other hand, the administration of immunosuppressants did neither influence the total number of developed flukes nor the appearance of eosinophilia in the peripheral blood of the treated animals.

  19. A Rationale for Age-Adapted Immunosuppression in Organ Transplantation.

    PubMed

    Krenzien, Felix; ElKhal, Abdallah; Quante, Markus; Rodriguez Cetina Biefer, Hector; Hirofumi, Uehara; Gabardi, Steven; Tullius, Stefan G

    2015-11-01

    Demographic changes are associated with a steady increase of older patients with end-stage organ failure in need for transplantation. As a result, the majority of transplant recipients are currently older than 50 years, and organs from elderly donors are more frequently used. Nevertheless, the benefit of transplantation in older patients is well recognized, whereas the most frequent causes of death among older recipients are potentially linked to side effects of their immunosuppressants.Immunosenescence is a physiological part of aging linked to higher rates of diabetes, bacterial infections, and malignancies representing the major causes of death in older patients. These age-related changes impact older transplant candidates and may have significant implications for an age-adapted immunosuppression. For instance, immunosenescence is linked to lower rates of acute rejections in older recipients, whereas the engraftment of older organs has been associated with higher rejection rates. Moreover, new-onset diabetes mellitus after transplantation is more frequent in the elderly, potentially related to corticosteroids, calcineurin inhibitors, and mechanistic target of rapamycin inhibitors.This review presents current knowledge for an age-adapted immunosuppression based on both, experimental and clinical studies in and beyond transplantation. Recommendations of maintenance and induction therapy may help to improve graft function and to design future clinical trials in the elderly.

  20. Upper-Extremity Transplantation Using a Cell-Based Protocol to Minimize Immunosuppression

    PubMed Central

    Schneeberger, Stefan; Gorantla, Vijay S.; Brandacher, Gerald; Zeevi, Adriana; Demetris, Anthony J.; Lunz, John G.; Metes, Diana M.; Donnenberg, Albert D.; Shores, Jaimie T.; Dimartini, Andrea F.; Kiss, Joseph E.; Imbriglia, Joseph E.; Azari, Kodi; Goitz, Robert J.; Manders, Ernest K.; Nguyen, Vu T.; Cooney, Damon S.; Wachtman, Galen S.; Keith, Jonathan D.; Fletcher, Derek R.; Macedo, Camila; Planinsic, Raymond; Losee, Joseph E.; Shapiro, Ron; Starzl, Thomas E.; Andrew Lee, W. P.

    2014-01-01

    Objective To minimize maintenance immunosuppression in upper-extremity transplantation to favor the risk-benefit balance of this procedure. Background Despite favorable outcomes, broad clinical application of reconstructive transplantation is limited by the risks and side effects of multidrug immunosuppression. We present our experience with upper-extremity transplantation under a novel, donor bone marrow (BM) cell-based treatment protocol (“Pittsburgh protocol”). Methods Between March 2009 and September 2010, 5 patients received a bilateral hand (n = 2), a bilateral hand/forearm (n = 1), or a unilateral (n = 2) hand transplant. Patients were treated with alemtuzumab and methylprednisolone for induction, followed by tacrolimus monotherapy. On day 14, patients received an infusion of donor BM cells isolated from 9 vertebral bodies. Comprehensive follow-up included functional evaluation, imaging, and immunomonitoring. Results All patients are maintained on tacrolimus monotherapy with trough levels ranging between 4 and 12 ng/mL. Skin rejections were infrequent and reversible. Patients demonstrated sustained improvements in motor function and sensory return correlating with time after transplantation and level of amputation. Side effects included transient increase in serum creatinine, hyperglycemia managed with oral hypoglycemics, minor wound infection, and hyperuricemia but no infections. Immunomonitoring revealed transient moderate levels of donor-specific antibodies, adequate immunocompetence, and no peripheral blood chimerism. Imaging demonstrated patent vessels with only mild luminal narrowing/occlusion in 1 case. Protocol skin biopsies showed absent or minimal perivascular cellular infiltrates. Conclusions Our data suggest that this BM cell-based treatment protocol is safe, is well tolerated, and allows upper-extremity transplantation using low-dose tacrolimus monotherapy. PMID:23001085

  1. 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

  2. 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

  3. 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

  4. HIV subtype is not associated with dementia among individuals with moderate and advanced immunosuppression in Kampala, Uganda

    PubMed Central

    Sacktor, Ned; Nakasujja, Noeline; Redd, Andrew D.; Manucci, Jordyn; Laeyendecker, Oliver; Wendel, Sarah K.; Porcella, Stephen F; Martens, Craig; Bruno, Daniel; Skolasky, Richard L.; Okonkwo, Ozioma C.; Robertson, Kevin; Musisi, Seggane; Katabira, Elly; Quinn, Thomas C.

    2014-01-01

    Background HIV-associated neurocognitive disorders (HAND) are a common neurological manifestation of HIV infection. A previous study suggested that HIV dementia may be more common among patients with subtype D virus than among those with subtype A virus among HIV+ individuals with advanced immunosuppression. We conducted a study to evaluate the frequency of HIV dementia, and the association of HIV dementia with HIV subtype and compartmentalization among HIV+ individuals with moderate and advanced immunosuppression (CD4 lymphocyte count >150 cells/μL and < 250 cells/μL). Methods The study enrolled 117 antiretroviral naïve HIV+ individuals in Kampala, Uganda. HIV+ individuals received neurological, neuropsychological testing, and functional assessments, and gag and gp41 regions were subtyped. Subjects were considered infected with a specific subtype if both regions analyzed were from the same subtype. Results 41% of the HIV+ individuals had HIV dementia (mean CD4 lymphocyte count= 233 cells/μL). 67 individuals had subtype A, 25 individuals had subtype D, 24 individuals were classified as A/D recombinants, and one individual had subtype C. There was no difference in the frequency of HIV dementia when stratified by HIV subtype A and D and no association with compartmentalization between the cerebrospinal fluid and peripheral blood. Conclusions These results suggest that HIV dementia is common in HIV+ individuals in Uganda. There was no association between HIV subtype and dementia among HIV+ individuals with moderate and advanced immunosuppression. Future studies should be performed to confirm these results. PMID:24515303

  5. 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.

  6. 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

  7. 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

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

    SciTech Connect

    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.

  9. 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.

  10. Advantageous effects of immunosuppression with tacrolimus in comparison with cyclosporine A regarding renal function in patients after heart transplantation

    PubMed Central

    Helmschrott, Matthias; Rivinius, Rasmus; Ruhparwar, Arjang; Schmack, Bastian; Erbel, Christian; Gleissner, Christian A; Akhavanpoor, Mohammadreza; Frankenstein, Lutz; Ehlermann, Philipp; Bruckner, Tom; Katus, Hugo A; Doesch, Andreas O

    2015-01-01

    Background Nephrotoxicity is a serious adverse effect of calcineurin inhibitor therapy in patients after heart transplantation (HTX). Aim In this retrospective registry study, renal function within the first 2 years after HTX in patients receiving de novo calcineurin inhibitor treatment, that is, cyclosporine A (CSA) or tacrolimus (TAC), was analyzed. In a consecutive subgroup analysis, renal function in patients receiving conventional tacrolimus (CTAC) was compared with that of patients receiving extended-release tacrolimus (ETAC). Methods Data from 150 HTX patients at Heidelberg Heart Transplantation Center were retrospectively analyzed. All patients were continuously receiving the primarily applied calcineurin inhibitor during the first 2 years after HTX and received follow-up care according to center practice. Results Within the first 2 years after HTX, serum creatinine increased significantly in patients receiving CSA (P<0.0001), whereas in patients receiving TAC, change of serum creatinine was not statistically significant (P=not statistically significant [ns]). McNemar’s test detected a significant accumulation of patients with deterioration of renal function in the first half year after HTX among patients receiving CSA (P=0.0004). In patients receiving TAC, no significant accumulation of patients with deterioration of renal function during the first 2 years after HTX was detectable (all P=ns). Direct comparison of patients receiving CTAC versus those receiving ETAC detected no significant differences regarding renal function between patients primarily receiving CTAC or ETAC treatment during study period (all P=ns). Conclusion CSA is associated with a more pronounced deterioration of renal function, especially in the first 6 months after HTX, in comparison with patients receiving TAC as baseline immunosuppressive therapy. PMID:25759566

  11. Treatment of Hepatitis C in Patients Undergoing Immunosuppressive Drug Therapy

    PubMed Central

    Ooka, Kohtaro; Lim, Joseph K.

    2016-01-01

    Abstract With 185 million people chronically infected globally, hepatitis C is a leading bloodborne infection. All-oral regimens of direct acting agents have superior efficacy compared to the historical interferon-based regimens and are significantly more tolerable. However, trials of both types of regimens have often excluded patients on immunosuppressive medications for reasons other than organ transplantation. Yet, these patients—most often suffering from malignancy or autoimmune diseases—could stand to benefit from these treatments. In this study, we systematically review the literature on the treatment of hepatitis C in these neglected populations. Research on patients with organ transplants is more robust and this literature is reviewed here non-systematically. Our systematic review produced 2273 unique works, of which 56 met our inclusion criteria and were used in our review. The quality of data was low; only 3 of the 56 studies were randomized controlled trials. Sustained virologic response was reported sporadically. Interferon-containing regimens achieved this end-point at rates comparable to that in immunocompetent individuals. Severe adverse effects and death were rare. Data on all-oral regimens were sparse, but in the most robust study, rates of sustained virologic response were again comparable to immunocompetent individuals (40/41). Efficacy and safety of interferon-containing regimens and all-oral regimens were similar to rates in immunocompetent individuals; however, there were few interventional trials. The large number of case reports and case series makes conclusions vulnerable to publication bias. While firm conclusions are challenging, given the dearth of high-quality studies, our results demonstrate that antiviral therapy can be safe and effective. The advent of all-oral regimens offers patients and clinicians greatly increased chances of cure and fewer side effects. Preliminary data reveal that these regimens may confer such benefits in

  12. Effects of an immunosuppressive treatment on the rat prostate

    PubMed Central

    Grabowska, Marta; Kędzierska, Karolina; Michałek, Katarzyna; Słuczanowska-Głąbowska, Sylwia; Grabowski, Maciej; Piasecka, Małgorzata; Kram, Andrzej; Rotter, Iwona; Rył, Aleksandra; Laszczyńska, Maria

    2016-01-01

    The aim of this study was to determine the influence of different combinations of immunosuppressive drugs on the morphology, ultrastructure, and expression of proliferating cell nuclear antigen and cytoskeleton proteins in the rat dorsolateral prostate. The studies were conducted on 48 male Wistar rats. The animals were divided into eight groups: a control group and seven experimental groups. For 6 months, the animals in the experimental groups were administered a combination of drugs including rapamycin (Rapa), cyclosporin A, tacrolimus (Tac), mycophenolate mofetil, and prednisone (Pred), according to the standard three-drug regimens for immunosuppressive therapy used in clinical practice. An evaluation of the morphology and ultrastructure was conducted, and a quantitative evaluation of the expression of proliferating cell nuclear antigen and desmin- and cytokeratin-positive cells with weak, moderate, and strong expression was performed. The combination of Rapa, Tac, and Pred caused the smallest morphological and ultrastructural changes in the rat prostate cells. In the case of rats whose treatment was switched to Rapa monotherapy, a decreased percentage of proliferating cells of both the glandular epithelium and the stroma was found. Decreases in body weight and changes in the expression of cytokeratin and desmin were observed in all the experimental rats. The combination of Rapa, Tac, and Pred would seem to be the most beneficial for patients who do not suffer from prostate diseases. Our results justify the use of inhibitors of the mammalian target of Rapa in the treatment of patients with prostate cancer. The changes in the expression of cytoskeleton proteins may be the result of direct adverse effects of the immunosuppressive drugs, which are studied in this article, on the structure and organization of intermediate filament proteins. PMID:27672312

  13. Effects of an immunosuppressive treatment on the rat prostate

    PubMed Central

    Grabowska, Marta; Kędzierska, Karolina; Michałek, Katarzyna; Słuczanowska-Głąbowska, Sylwia; Grabowski, Maciej; Piasecka, Małgorzata; Kram, Andrzej; Rotter, Iwona; Rył, Aleksandra; Laszczyńska, Maria

    2016-01-01

    The aim of this study was to determine the influence of different combinations of immunosuppressive drugs on the morphology, ultrastructure, and expression of proliferating cell nuclear antigen and cytoskeleton proteins in the rat dorsolateral prostate. The studies were conducted on 48 male Wistar rats. The animals were divided into eight groups: a control group and seven experimental groups. For 6 months, the animals in the experimental groups were administered a combination of drugs including rapamycin (Rapa), cyclosporin A, tacrolimus (Tac), mycophenolate mofetil, and prednisone (Pred), according to the standard three-drug regimens for immunosuppressive therapy used in clinical practice. An evaluation of the morphology and ultrastructure was conducted, and a quantitative evaluation of the expression of proliferating cell nuclear antigen and desmin- and cytokeratin-positive cells with weak, moderate, and strong expression was performed. The combination of Rapa, Tac, and Pred caused the smallest morphological and ultrastructural changes in the rat prostate cells. In the case of rats whose treatment was switched to Rapa monotherapy, a decreased percentage of proliferating cells of both the glandular epithelium and the stroma was found. Decreases in body weight and changes in the expression of cytokeratin and desmin were observed in all the experimental rats. The combination of Rapa, Tac, and Pred would seem to be the most beneficial for patients who do not suffer from prostate diseases. Our results justify the use of inhibitors of the mammalian target of Rapa in the treatment of patients with prostate cancer. The changes in the expression of cytoskeleton proteins may be the result of direct adverse effects of the immunosuppressive drugs, which are studied in this article, on the structure and organization of intermediate filament proteins.

  14. 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

  15. Immunotherapy: A promising approach to reverse sepsis-induced immunosuppression.

    PubMed

    Patil, Naeem K; Bohannon, Julia K; Sherwood, Edward R

    2016-09-01

    Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host responses to infection (Third International Consensus definition for Sepsis and septic shock). Despite decades of research, sepsis remains the leading cause of death in intensive care units. More than 40 clinical trials, most of which have targeted the sepsis-associated pro-inflammatory response, have failed. Thus, antibiotics and fluid resuscitation remain the mainstays of supportive care and there is intense need to discover and develop novel, targeted therapies to treat sepsis. Both pre-clinical and clinical studies over the past decade demonstrate unequivocally that sepsis not only causes hyper-inflammation, but also leads to simultaneous adaptive immune system dysfunction and impaired antimicrobial immunity. Evidences for immunosuppression include immune cell depletion (T cells most affected), compromised T cell effector functions, T cell exhaustion, impaired antigen presentation, increased susceptibility to opportunistic nosocomial infections, dysregulated cytokine secretion, and reactivation of latent viruses. Therefore, targeting immunosuppression provides a logical approach to treat protracted sepsis. Numerous pre-clinical studies using immunomodulatory agents such as interleukin-7, anti-programmed cell death 1 antibody (anti-PD-1), anti-programmed cell death 1 ligand antibody (anti-PD-L1), and others have demonstrated reversal of T cell dysfunction and improved survival. Therefore, identifying immunosuppressed patients with the help of specific biomarkers and administering specific immunomodulators holds significant potential for sepsis therapy in the future. This review focusses on T cell dysfunction during sepsis and discusses the potential immunotherapeutic agents to boost T cell function during sepsis and improve host resistance to infection. PMID:27468649

  16. 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

  17. 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

  18. 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

  19. 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

  20. Immunosuppression and probiotics: are they effective and safe?

    PubMed

    Stadlbauer, V

    2015-01-01

    This opinion statement discusses indications, efficacy and safety of probiotics in immunosuppressed patients. The best evidence available is for the prophylaxis of infections in patients after liver transplantation and for patients with liver cirrhosis. For other organ transplantations and for bone marrow transplantation the efficacy of probiotic interventions has not been proven yet, but in these patient groups safety is a concern. Also in critically ill patients, the data on efficacy are inconclusive and safety is a concern. In HIV patients and patients after major surgery, probiotic bacteria seem to be safe since there are no associations with increased risks of side effects.

  1. 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

  2. [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

  3. 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.

  4. Dual-histidine kinases in basidiomycete fungi.

    PubMed

    Lavín, José L; Sarasola-Puente, Vanessa; Ramírez, Lucía; Pisabarro, Antonio G; Oguiza, José A

    2014-02-01

    Dual-histidine kinases (HKs) are complex hybrid HKs containing in a single polypeptide two HK transmitter modules (T) and two-response regulator received domains (R) that are combined in a TRTR geometry. In fungi, this protein family is limited to some particular species of the phylum Basidiomycota and absent in the other phyla. This study extends the investigation of dual-HKs to 80 fully sequenced genomes of basidiomycetes, analyzing their distribution, domain architecture and phylogenetic relationships. Moreover, similarly to dual-HKs of basidiomycetes, several species of bacteria were found that contain hybrid HKs with a TRTR domain architecture encoded in a single gene. PMID:24581805

  5. 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

  6. Involvement of Regulatory T Cells in the Immunosuppression Characteristic of Patients with Paracoccidioidomycosis▿

    PubMed Central

    Ferreira, Maria Carolina; de Oliveira, Rômulo Tadeu Dias; da Silva, Rosiane Maria; Blotta, Maria Heloisa Souza Lima; Mamoni, Ronei Luciano

    2010-01-01

    Patients with paracoccidioidomycosis (PCM) exhibit a suppression of the cellular immune response characterized by negative delayed-type hypersensitivity (DTH) to Paracoccidioides brasiliensis antigens, the apoptosis of lymphocytes, and high levels of expression of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4), interleukin-10 (IL-10), and transforming growth factor β (TGF-β). The aim of this study was to investigate whether and how regulatory T cells (Treg cells) are involved in this immunosuppression by analyzing the number, phenotype, and activity of these cells in patients with active disease (AD group) and patients who had received treatment (TD group). Our results showed that the AD patients had more Treg cells than the TD patients or controls (C group) and also had elevated levels of expression of regulatory markers (glucocorticoid-induced tumor necrosis factor [TNF] receptor-related protein [GITR], CTLA-4, CD95L, LAP-1, and CD38). An analysis of regulatory activity showed that Treg cells from the AD group had greater activity than did cells from the other groups and that cell-cell contact is mandatory for this activity in the C group but was only partially involved in the regulatory activity of cells from AD patients. The addition of anti-IL-10 and anti-TGF-β neutralizing antibodies to the cultures showed that the production of cytokines may be another mechanism used by Treg cells. In conclusion, the elevated numbers of these cells with an increased regulatory phenotype and strong suppressive activity suggest a potential role for them in the immunosuppression characteristic of paracoccidioidomycosis. In addition, our results indicate that while Treg cells act by cell-cell contact, cytokine production also plays an important role. PMID:20643858

  7. 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.

  8. Herpetic whitlow during immunosuppressive therapy for Wegener’s Granulomatosis

    PubMed Central

    Solmaz, Dilek; Atalay, Ezgi; Lebe, Banu; Çetin, Pınar

    2014-01-01

    Skin involvement may occur in patients with Wegener’s granulomatosis (polyangiitis with granulomatosis; WG) and is more frequent in the generalised form. However, when a patient with vasculitis develops digital ulceration, in addition to disease activation, other pathologies should be considered. One of them may be the herpetic whitlow mimicking paronychia. Here, we present a patient who developed herpetic whitlow during the course of immunosuppressive therapy due to WG. Just before the third course of cyclophosphamide therapy, she was re-admitted to the outpatient clinic with the above-mentioned ulcerated lesions. On physical examination, there was erythema and a painful, crusted ulceration in the distal phalanx of the right index finger involving the proximal nail fold. Similar lesions were also present in her lower lip. Due to the absence of clinical and laboratory findings suggesting the activation of WG and the Tzanck smear result, which is compatible with herpes virus infection, we do not believe that WG was responsible for our patient’s complaints. All of the patient’s lesions completely disappeared following the interruption of immunosuppressive therapy.

  9. Tolerance in organ transplantation: from conventional immunosuppression to extracellular vesicles.

    PubMed

    Monguió-Tortajada, Marta; Lauzurica-Valdemoros, Ricardo; Borràs, Francesc E

    2014-01-01

    Organ transplantation is often the unique solution for organ failure. However, rejection is still an unsolved problem. Although acute rejection is well controlled, the chronic use of immunosuppressive drugs for allograft acceptance causes numerous side effects in the recipient and do not prevent chronic allograft dysfunction. Different alternative therapies have been proposed to replace the classical treatment for allograft rejection. The alternative therapies are mainly based in pre-infusions of different types of regulatory cells, including DCs, MSCs, and Tregs. Nevertheless, these approaches lack full efficiency and have many problems related to availability and applicability. In this context, the use of extracellular vesicles, and in particular exosomes, may represent a cell-free alternative approach in inducing transplant tolerance and survival. Preliminary approaches in vitro and in vivo have demonstrated the efficient alloantigen presentation and immunomodulation abilities of exosomes, leading to alloantigen-specific tolerance and allograft acceptance in rodent models. Donor exosomes have been used alone, processed by recipient antigen-presenting cells, or administered together with suboptimal doses of immunosuppressive drugs, achieving specific allograft tolerance and infinite transplant survival. In this review, we gathered the latest exosome-based strategies for graft acceptance and discuss the tolerance mechanisms involved in organ tolerance mediated by the administration of exosomes. We will also deal with the feasibility and difficulties that arise from the application of this strategy into the clinic. PMID:25278936

  10. 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

  11. Adherence to immunosuppressive therapy following liver transplantation: an integrative review

    PubMed Central

    Oliveira, Ramon Antônio; Turrini, Ruth Natália Teresa; Poveda, Vanessa de Brito

    2016-01-01

    ABSTRACT Objective: to investigate the evidence available in the literature on non-adherence to immunosuppressive therapy among patients undergoing liver transplantation. Method: integrative literature review, including research whose sample consisted of patients aged over 18 years undergoing liver transplantation. It excluded those containing patients undergoing multiple organ transplants. For the selection of articles, Medline / Pubmed, CINAHL, LILACS, Scopus and Embase were searched. The search period corresponded to the initial date of indexation of different bases, up to the deadline of February 10, 2015, using controlled and uncontrolled descriptors: liver transplantation, hepatic transplantation, liver orthotopic transplantation, medication adherence, medication non-adherence, medication compliance and patient compliance. Results: were located 191 investigations, 10 of which met the objectives of the study and were grouped into four categories, namely: educational process and non-adherence; non-adherence related to the number of daily doses of immunosuppressive medications; detection methods for non-adherence and side effects of therapy. Conclusion: there were risk factors related to the health service, such as control and reduction of the number of doses; related to the individual, such as being male, divorced, alcohol or other substances user, exposed to low social support and being mentally ill. PMID:27579933

  12. Use of multiple immunosuppressive agents in recalcitrant ACANTHAMOEBA scleritis.

    PubMed

    Igras, Estera; Murphy, Conor

    2015-01-01

    A 48-year-old woman who is a contact lens wearer presented with unilateral ACANTHAMOEBA keratitis, confirmed by PCR, which responded initially to topical polyhexamethylene biguanide (PHMB) and brolene. Three months later, despite continued treatment, she developed diffuse anterior scleritis with severe pain and marked scleral injection but without evidence of recurrence keratitis. Oral non-steroidal anti-inflammatories and oral high-dose corticosteroids were added without success. Subsequent treatment with intravenous methylprednisolone and high-dose cyclosporine led to a temporary improvement. Re-presenting with signs of recurrent scleritis and severe pain, the antitumor necrosis factor monoclonal antibody adalimumab, and later oral cyclophosphamide, were added. This led to complete quiescence of the scleritis. Unfortunately, frequent recurrences of ACANTHAMOEBA keratitis and anterior uveitis occurred on immunosuppression requiring continued treatment with PHMB, brolene and topical corticosteroids. This is the first case of severe refractory ACANTHAMOEBA scleritis requiring the concomitant use of four immunosuppressive agents to achieve continued disease control. The challenges in managing this case are discussed.

  13. 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

  14. Individualizing liver transplant immunosuppression using a phenotypic personalized medicine platform.

    PubMed

    Zarrinpar, Ali; Lee, Dong-Keun; Silva, Aleidy; Datta, Nakul; Kee, Theodore; Eriksen, Calvin; Weigle, Keri; Agopian, Vatche; Kaldas, Fady; Farmer, Douglas; Wang, Sean E; Busuttil, Ronald; Ho, Chih-Ming; Ho, Dean

    2016-04-01

    Posttransplant immunosuppressive drugs such as tacrolimus have narrow therapeutic ranges. Inter- and intraindividual variability in dosing requirements conventionally use physician-guided titrated drug administration, which results in frequent deviations from the target trough ranges, particularly during the critical postoperative phase. There is a clear need for personalized management of posttransplant regimens to prevent adverse events and allow the patient to be discharged sooner. We have developed the parabolic personalized dosing (PPD) platform, which is a surface represented by a second-order algebraic equation with experimentally determined coefficients of the equation being unique to each patient. PPD uses clinical data, including blood concentrations of tacrolimus--the primary phenotypic readout for immunosuppression efficacy--to calibrate these coefficients and pinpoint the optimal doses that result in the desired patient-specific response. In this pilot randomized controlled trial, we compared four transplant patients prospectively treated with tacrolimus using PPD with four control patients treated according to the standard of care (physician guidance). Using phenotype to personalize tacrolimus dosing, PPD effectively managed patients by keeping tacrolimus blood trough levels within the target ranges. In a retrospective analysis of the control patients, PPD-optimized prednisone and tacrolimus dosing improved tacrolimus trough-level management and minimized the need to recalibrate dosing after regimen changes. PPD is independent of disease mechanism and is agnostic of indication and could therefore apply beyond transplant medicine to dosing for cancer, infectious diseases, and cardiovascular medicine, where patient response is variable and requires careful adjustments through optimized inputs.

  15. 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

  16. Opioid-induced immunosuppression: is it centrally mediated or peripherally mediated?

    PubMed

    Wei, Gang; Moss, Jonathan; Yuan, Chun Su

    2003-06-01

    Opioid compounds are commonly used pain medications. However, their administration is associated with a number of side-effects. Among them, opioid-induced immunosuppression is a significant medical problem, which is evidenced by a strong association between the use of opioids and exacerbated infections, including AIDS. Research data have demonstrated the effects of opioids to be suppressive on phagocytic, natural killer (NK), B and T cells. However, these immunosuppressive effects may be mediated by mechanisms different from those for antinociceptive actions. This article reviews possible central and peripheral mechanisms of opioid-induced immunosuppression. To the extent that peripherally mediated immunosuppressive effects play a significant role in opioid-induced immunosuppression, novel peripheral opioid antagonists may have a therapeutic role in attenuating opioid-induced immunosuppression without affecting analgesia.

  17. Hepatitis B and immunosuppressive therapies for chronic inflammatory diseases: When and how to apply prophylaxis, with a special focus on corticosteroid therapy

    PubMed Central

    López-Serrano, Pilar; de la Fuente Briongos, Elsa; Alonso, Elisa Carrera; Pérez-Calle, Jose Lázaro; Rodríguez, Conrado Fernández

    2015-01-01

    Currently immunosuppressive and biological agents are used in a more extensive and earlier way in patients with inflammatory bowel disease, rheumatic or dermatologic diseases. Although these drugs have shown a significant clinical benefit, the safety of these treatments is a challenge. Hepatitis B virus (HBV) reactivations have been reported widely, even including liver failure and death, and it represents a deep concern in these patients. Current guidelines recommend to pre-emptive therapy in patients with immunosuppressants in general, but preventive measures focused in patients with corticosteroids and inflammatory diseases are scarce. Screening for HBV infection should be done at diagnosis. The patients who test positive for hepatitis B surface antigen, but do not meet criteria for antiviral treatment must receive prophylaxis before undergoing immunosuppression, including corticosteroids at higher doses than prednisone 20 mg/d during more than two weeks. Tenofovir and entecavir are preferred than lamivudine because of their better resistance profile in long-term immunosuppressant treatments. There is not a strong evidence, to make a general recommendation on the necessity of prophylaxis therapy in patients with inflammatory diseases that are taking low doses of corticosteroids in short term basis or low systemic bioavailability corticosteroids such as budesonide or beclomethasone dipropionate. In these cases regularly HBV DNA monitoring is recommended, starting early antiviral therapy if DNA levels begin to rise. In patients with occult or resolved hepatitis the risk of reactivation is much lower, and excepting for Rituximab treatment, the prophylaxis is not necessary. PMID:25848477

  18. 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.

  19. 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

  20. Synthesis and biological evaluation of pseudolaric acid B derivatives as potential immunosuppressive agents.

    PubMed

    Chen, Shou-Qiang; Wang, Jie; Zhao, Chuan; Sun, Qiang-Wen; Wang, Yi-Teng; Ai, Ting; Li, Tan; Gao, Ying; Wang, Huo; Chen, Hong

    2015-01-01

    Pseudolaric acid B (PB) derivatives with immunosuppressive activity were found by our group. In order to find potential immunosuppressive agents with high efficacy and low toxicity, a series of novel PB derivatives were synthesized and evaluated on their immunosuppressive activities. Most of the synthesized compounds were tested in vitro on murine T and B proliferation. In particular, compound 11 exhibited excellent inhibitory activity toward murine T cells (up to 19-fold enhancement compared to that of mycophenolatemofetil) and little cytotoxicity toward normal murine spleen cells. These experimental data demonstrated that some of these PB derivatives have great potential for future immunosuppressive studies.

  1. [Immunosuppressive components of extracellular lipopolysaccharide highly virulent strain Salmonella typhimurium 1468].

    PubMed

    Molozhavaia, O S; Borisova, E V

    2002-01-01

    Immunosuppressive activity of culture liquid substrate (CFS) of highly virulent strain Salmonella typhimurium has been studied. A model of delayed hypersensitivity (DHS) to nonbacterial antigen in mice, a method of gel-filtration through the sephadex column G-200, immunosorbents were used. Three components with immunosuppressive activity: thermolabile component and thermostable one with direct immunosuppressive action and the third thermolabile component which manifested inductive immunosuppressive activity only after redox treatment have been revealed in the strain CFS. O-specific and lipid parts were found in the composition of all the components. This allowed them to be related to lipopolysaccharide.

  2. Listeriosis in patients receiving biologic therapies.

    PubMed

    Bodro, M; Paterson, D L

    2013-09-01

    The evolution of inflammatory diseases has radically changed since the introduction of biologic therapies, such as tumour necrosis factor alpha inhibitors (anti-TNFα). They, therefore, represent a widely used therapeutic modality. Nevertheless, post-marketing studies reveal an increased risk of infection in patients taking these drugs, especially granulomatous infections such as listeriosis. We aimed to evaluate the reported cases of listeriosis in patients treated with biologic treatments. We used the United States Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) from 2004 to 2011. We also perform a literature review of previously reported cases of listeriosis in patients taking biologic therapies. We identified 266 cases of Listeria monocytogenes infection associated with biologic therapies. The majority of patients were receiving infliximab (77.1 %), followed by etanercept (11.7 %), adalimumab (9.8 %), rituximab (4.1 %), abatacept (0.4 %) and golimumab (0.4 %). Indications for the use of biologics were as follows: 47.7 % for rheumatologic diseases, 38 % for inflammatory bowel diseases, 3.4 % for haematological diseases and 10.5 % for other indications. Seventy-three percent of the patients were receiving concomitant immunosuppressant drugs, especially steroids (56 %) and methotrexate (31.6 %). The median time to the onset of infection was 184 days. Mortality rates range from 11.1 % in adalimumab-treated patients to 27.3 % in rituximab-treated patients (p = 0.7). Listeriosis is common in biologics-treated patients, especially related to infliximab use given concomitantly with other immunosuppressive therapies. Infections after treatment with biologics mostly occurred in the first year after initiating treatment. PMID:23568606

  3. Secretory pathways generating immunosuppressive NKG2D ligands

    PubMed Central

    Baragaño Raneros, Aroa; Suarez-Álvarez, Beatriz; López-Larrea, Carlos

    2014-01-01

    Natural Killer Group 2 member D (NKG2D) activating receptor, present on the surface of various immune cells, plays an important role in activating the anticancer immune response by their interaction with stress-inducible NKG2D ligands (NKG2DL) on transformed cells. However, cancer cells have developed numerous mechanisms to evade the immune system via the downregulation of NKG2DL from the cell surface, including the release of NKG2DL from the cell surface in a soluble form. Here, we review the mechanisms involved in the production of soluble NKG2DL (sNKG2DL) and the potential therapeutic strategies aiming to block the release of these immunosuppressive ligands. Therapeutically enabling the NKG2D-NKG2DL interaction would promote immunorecognition of malignant cells, thus abrogating disease progression. PMID:25050215

  4. [Regulatory T cell based transplant tolerance--freedom from immunosuppression].

    PubMed

    Koshiba, Takaaki; Ito, Atsushi; Li, Ying; Wu, Yanling; Takemura, Mami; Sakaguchi, Shimon

    2007-03-01

    Tolerance after clinical transplantation (Tx) is still extremely rare. However, Kyoto elective protocol enabled a substantial number of patients to weaned off immunosuppression after liver Tx. This is referred to as an immunoprivilege. Nevertheless, the operating mechanisms for liver Tx tolerance remain elusive. The authors demonstrated that regulatory T cells (Tregs) are likely to play an important role in liver Tx tolerance. In addition, we found that precursor like Tregs exist in the human peripheral blood. This can propagate upon stimulation with allo-antigen, in contrast to anergic property of Tregs. Thus, the exploitation of precursor like Tregs as a cellular source of ex vivo and in vivo expansion may lead to the widespread clinical use of Tregs for Tx.

  5. 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.

  6. 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

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

    PubMed

    Bamgbola, Oluwatoyin

    2016-06-01

    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.

  8. The epidemiology of classic, African, and immunosuppressed Kaposi's sarcoma.

    PubMed

    Wahman, A; Melnick, S L; Rhame, F S; Potter, J D

    1991-01-01

    The etiology of Kaposi's sarcoma remains somewhat obscure. While lesions of classic Kaposi's sarcoma, African Kaposi's sarcoma, and immunosuppressed Kaposi's sarcoma have been found to be indistinguishable from one another, the reasons for the variations in type and severity have not been established. The origin of the spindle cell is yet to be agreed on. Geographic variation does not seem as important as ethnic variation. The very young and the very old, perhaps two ages of weakened immunity, tend to have a higher incidence of Kaposi's sarcoma. Children and AIDS patients tend to develop more virulent disease. Males tend to get Kaposi's sarcoma at higher rates than do females. Jewish and Mediterranean males have the highest incidence of classic Kaposi's sarcoma, and African Bantu have the highest incidence of African Kaposi's sarcoma, classifications which do not apply to the Kaposi's sarcoma population in the United States. Male homosexuals have much higher incidence of Kaposi's sarcoma than do male heterosexuals, but since the early 1980s, its incidence as the presenting manifestation of AIDS has decreased dramatically. There is no unequivocal association with HLA haplotype (though DR5 carriers may be at especially high risk) or evidence of family clustering. There is an impressive but not always consistent association between Kaposi's sarcoma development and immunodeficiency. Environmental factors, such as nitrite use, immunosuppression, and repeated cytomegalovirus infection, are associated with Kaposi's sarcoma, but the exact mechanism is unclear and the associations remain inconsistent. Finally, it is still unclear if there is a causative infectious agent for Kaposi's sarcoma. While cytomegalovirus has been linked to Kaposi's sarcoma, there are weaknesses in its hypothetical role as an etiologic agent as is the case for HIV itself.(ABSTRACT TRUNCATED AT 400 WORDS)

  9. 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

  10. A Review on Therapeutic Drug Monitoring of Immunosuppressant Drugs

    PubMed Central

    Mohammadpour, Niloufar; Elyasi, Sepideh; Vahdati, Naser; Mohammadpour, Amir Hooshang; Shamsara, Jamal

    2011-01-01

    Immunosuppressants require therapeutic drug monitoring because of their narrow therapeutic index and significant inter-individual variability in blood concentrations. This variability can be because of factors like drug-nutrient interactions, drug-disease interactions, renal-insufficiency, inflammation and infection, gender, age, polymorphism and liver mass. Drug monitoring is widely practiced especially for cyclosporine, tacrolimus, sirolimus and mycophenolic acid. Cyclosporine Therapeutic monitoring of immunosuppressive therapy with cyclosporine is a critical requirement because of intra- and inter-patient variability of drug absorption, narrow therapeutic window and drug induced nephrotoxicity. Mycophenolic acid (MPA) Some reasons for therapeutic drug monitoring of MPA during post-transplant period include: relationship between MPA pharmacokinetic parameters and clinical outcomes, Inter-patient pharmacokinetic variability for MPA despite fixed MMF doses, alternations of MPA pharmacokinetics during the first months after transplantation, drug- drug interaction and influence of kidney function on MPA pharmacokinetic. Sirolimus A recent review of the pharmacokinetics of sirolimus suggested a therapeutic range of 5 to 10 μg l−1 in whole blood. However, the only consensus guidelines published on the therapeutic monitoring of sirolimus concluded that there was not enough information available about the clinical use of the drug to make recommendations. Tacrolimus Sudies have shown, in kidney and liver transplant patients, significant associations of low tacrolimus concentrations with rejection and of high concentrations with nephrotoxicity. Although the feasibility of a limited sampling scheme to predict AUC has been demonstrated, as yet, trough, or pre-dose, whole blood concentration monitoring is still the method of choice. PMID:23493821

  11. Zoledronic acid overcomes chemoresistance and immunosuppression of malignant mesothelioma.

    PubMed

    Salaroglio, Iris Chiara; Campia, Ivana; Kopecka, Joanna; Gazzano, Elena; Orecchia, Sara; Ghigo, Dario; Riganti, Chiara

    2015-01-20

    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

  12. 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

  13. Solar heat receiver

    DOEpatents

    Hunt, Arlon J.; Hansen, Leif J.; Evans, David B.

    1985-01-01

    A receiver for converting solar energy to heat a gas to temperatures from 700.degree.-900.degree. 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.

  14. 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.

  15. Pueblo Community College, Dual Credit Handbook, 1998-99.

    ERIC Educational Resources Information Center

    Griffith, Mary

    This Dual Credit Handbook from Pueblo Community College (CO) provides information and guidelines to assist instructors in meeting their assignment. These guidelines apply to dual credit courses offered to high school students during their regular school hours, for which students receive high school- and college-level credit simultaneously. This…

  16. 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.

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

    PubMed Central

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

    2016-01-01

    Anal fistula is common in patients with Crohn's disease (CD) and leads to significant morbidity. The efficacy of seton drainage combined with anti-tumor necrosis factor-α monoclonal antibody (anti-TNF-α) or immunosuppressant in the treatment of CD-related anal fistula remains unclear. The aim of the present study was to compare the efficacy between seton drainage combined with anti-TNF-α and seton drainage combined with immunosuppressant postoperatively on the treatment of CD-related anal fistula. A total of 65 patients with CD-related anal fistula who had received seton drainage combined with postoperative medication were divided into an antibiotics only group, anti-TNF-α group and immunosuppressant group; all patients were treated with antibiotics. Fistula closure, external orifice exudation rate and recurrence rate were assessed among these patients. The duration of follow-up ranged from 3 to 84 months with an average of 25.3 months. There were 11 (16.9%) cases of recurrence after seton drainage, 9 of which underwent a second seton drainage. In the total study group, 34 (52.3%) cases achieved complete fistula closure, and 10 (15.4%) cases showed external orifice exudation. No significant difference was found among these three groups, regarding fistula closure rate, closure time of fistula and recurrence rate. The external orifice exudation rate was significantly higher in the anti-TNF-α group compared with the antibiotics only group and immunosuppressant group (P=0.004 and P=0.026, respectively). Seton drainage is an effective treatment for CD-related anal fistula. The efficacy is similar whether combined with anti-TNF-α or immunosuppressant. PMID:27588113

  18. 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.

  19. 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.

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

    PubMed Central

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

    2013-01-01

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

  1. Nodular malignant melanoma and multiple cutaneous neoplasms under immunosuppression with azathioprine.

    PubMed

    Guenova, Emmanuella; Lichte, Verena; Hoetzenecker, Wolfram; Woelbing, Florian; Moehrle, Matthias; Roecken, Martin; Schaller, Martin

    2009-08-01

    Immunosuppressed patients are at increased risk of skin cancer. A 67-year-old renal transplant recipient developed a nodular malignant melanoma after 30 years of immunosuppression with azathioprine and prednisolone. The patient died of metastatic disease 3 months after the diagnosis was made. The function of the renal graft was not affected at all. Renal transplant recipients are at high risk of developing nonmelanocytic skin tumors when on immunosuppressive therapy with cyclosporine A. Less common is the development of skin cancer during immunosuppression with azathioprine. Latest reports show the increased incidence of malignant melanoma in immunosuppressed patients. Our case illustrates the necessity of close dermatological surveillance of allograft recipients, to assure an early recognition of any malignant skin tumor and to reduce the risk of systemic metastatic disease. PMID:19550360

  2. 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).

  3. 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.

  4. 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

  5. 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.

  6. Dual relationships in psychotherapy.

    PubMed

    Pope, Kenneth S

    1991-01-01

    A dual relationship in psychotherapy occurs when the therapist engages in another, significantly different relationship with the patient. The two relationships may be concurrent or sequential. For both sexual and nonsexual dual relationships, men are typically the perpetrators and women are typically the victims. This article presents examples of dual relationships, notes the attention that licensing boards and other agencies devote to this topic, reviews the meager research concerning nonsexual dual relationships, and discusses common strategies that promote both sexual and nonsexual dual relationships. PMID:11649348

  7. 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

  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.

  9. Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients

    PubMed Central

    Tedesco-Silva, Helio; Peddi, V. Ram; Sánchez-Fructuoso, Ana; Marder, Brad A.; Russ, Graeme R.; Diekmann, Fritz; Flynn, Alison; Hahn, Carolyn M.; Li, Huihua; Tortorici, Michael A.; Schulman, Seth L.

    2016-01-01

    Background Calcineurin inhibitor–associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. Methods This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus. The primary end point was percentage of patients with 5 mL/min per 1.73 m2 or greater improvement in estimated glomerular filtration rate from randomization to month 24. Results The on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No between-group difference was noted in percentage of patients with 5 mL/min per 1.73 m2 or greater estimated glomerular filtration rate improvement (sirolimus, 34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment discontinuation attributed to adverse events (21% vs 3%; P < 0.001), and lower rates of squamous cell carcinoma of the skin (0% vs 5%; P = 0.012). Conclusions Our findings suggest that renal function improvement at 24 months is similar for patients with early conversion to sirolimus after kidney transplantation versus those remaining on tacrolimus. PMID:27500260

  10. 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.

  11. Data-fusion receiver

    SciTech Connect

    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".

  12. What is the impact of immunosuppressive treatment on the post-transplant renal osteopathy?

    PubMed

    Blaslov, Kristina; Katalinic, Lea; Kes, Petar; Spasovski, Goce; Smalcelj, Ruzica; Basic-Jukic, Nikolina

    2014-05-01

    Although glucocorticoid therapy is considered to be the main pathogenic factor, a consistent body of evidence suggests that other immunosuppressants might also play an important role in the development of the post-transplant renal osteopathy (PRO) through their pleiotropic pharmacological effects. Glucocorticoids seem to induce osteoclasts' activity suppressing the osteoblasts while data regarding other immunosuppressive drugs are still controversial. Mycophenolate mofetil and azathioprine appear to be neutral regarding the bone metabolism. However, the study analyzing any independent effect of antimetabolites on bone turnover has not been conducted yet. Calcineurin inhibitors (CNIs) induce trabecular bone loss in rodent, with contradictory results in renal transplant recipients. Suppression of vitamin D receptor is probably the underlying mechanism of renal calcium wasting in renal transplant recipients receiving CNI. In spite of an increased 1,25(OH)2 vitamin D level, the kidney is not able to reserve calcium, suggesting a role of vitamin D resistance that may be related to bone loss. More efforts should be invested to determine the role of CNI in PRO. In particular, data regarding the role of mammalian target of rapamycin inhibitors (mTORi), such as sirolimus and everolimus, in the PRO development are still controversial. Rapamycin markedly decreases bone longitudinal growth as well as callus formation in experimental models, but also lowers the rate of bone resorption markers and glomerular filtration in clinical studies. Everolimus potently inhibits primary mouse and human osteoclast activity as well as the osteoclast differentiation. It also prevents the ovariectomy-induced loss of cancellous bone by 60 %, an effect predominantly associated with a decreased osteoclast-mediated bone resorption, resulting in a partial preservation of the cancellous bone. At present, there is no clinical study analyzing the effect of everolimus on bone turnover in renal

  13. 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

  14. 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

  15. Cancer-generated lactic acid: a regulatory, immunosuppressive metabolite?

    PubMed Central

    Choi, Stephen Yiu Chuen; Collins, Colin C; Gout, Peter W; Wang, Yuzhuo

    2013-01-01

    The common preference of cancers for lactic acid-generating metabolic energy pathways has led to proposals that their reprogrammed metabolism confers growth advantages such as decreased susceptibility to hypoxic stress. Recent observations, however, suggest that it generates a novel way for cancer survival. There is increasing evidence that cancers can escape immune destruction by suppressing the anti-cancer immune response through maintaining a relatively low pH in their micro-environment. Tumours achieve this by regulating lactic acid secretion via modification of glucose/glutamine metabolisms. We propose that the maintenance by cancers of a relatively low pH in their micro-environment, via regulation of their lactic acid secretion through selective modification of their energy metabolism, is another major mechanism by which cancers can suppress the anti-cancer immune response. Cancer-generated lactic acid could thus be viewed as a critical, immunosuppressive metabolite in the tumour micro-environment rather than a ‘waste product’. This paradigm shift can have major impact on therapeutic strategy development. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:23729358

  16. Experimental rabies in skunks: effects of immunosuppression induced by cyclophosphamide.

    PubMed

    Charlton, K M; Casey, G A; Campbell, J B

    1984-01-01

    Striped skunks (Mephitis mephitis) were inoculated with street rabies virus and immunosuppressed with several doses of cyclophosphamide. Control skunks were inoculated with street virus only. The skunks were killed in terminal stages of the disease and several tissues were collected for examination by immunofluorescence, light microscopy and viral titration. Sera collected at euthanasia from most of the principals did not contain detectable rabies neutralizing antibodies, whereas high titers occurred terminally in controls. Immunofluorescence was much more entensive in submandibular salivary glands of cyclophosphamide-treated than control skunks. Similarly, virus was isolated from this tissue more consistently and at higher titer from principals than from controls. Immunofluorescence was extensive in brains of all skunks (both groups), but virus was isolated consistently only from brains of cyclophosphamide-treated skunks. Most of the cyclophosphamide-treated skunks had very few inflammatory cells in brain and cerebrospinal ganglia. Neuronal degeneration occurred in dorsal root ganglia of both principals and controls. The results suggest that the immune response has no effect on the development of rabies-induced aggressive behavior, that the immune response may inhibit salivary gland infection and that it is not essential for the development of neuronal degeneration in dorsal root ganglia.

  17. 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

  18. The role of apoptosis in immunosuppression of dogs with demodicosis.

    PubMed

    Singh, Shanker K; Dimri, Umesh; Sharma, Mahesh C; Swarup, Devendra; Sharma, Bhaskar; Pandey, Hari Om; Kumari, Priyambada

    2011-12-15

    The aim of the present study was to evaluate the status of apoptosis in peripheral blood leukocytes of dogs with demodicosis. A total of 26 dogs suffering from demodicosis, and positive for Demodex canis mites by skin scraping, participated in the study, 13 with localized demodicosis (LD) and 13 with generalized demodicosis (GD). A further 13 clinically healthy dogs, all of whom were negative for mites upon skin scraping, were used as controls. The dogs with GD revealed significantly higher (P ≤ 0.0001) percentage of leukocytes with externalization of phosphatidylserine (PS) and depolarized mitochondrial membrane potentials (ΔΨm) as compared with the dogs with LD and healthy controls. These dogs also revealed significantly lower values (P ≤ 0.0001) of hematological parameters viz. hemoglobin, total erythrocytes count total leukocytes count, lymphocytes, monocytes and neutrophils. Significantly higher (P ≤ 0.0001) percentages of leukocytes with externalization of PS and depolarized ΔΨm were also found in dogs with LD as compared with the healthy controls. These dogs also revealed significantly lower values of Hb (P ≤ 0.0001), TEC (P=0.025), TLC (P ≤ 0.0001), lymphocytes (P=0.008), monocytes (P ≤ 0.0001) and neutrophils (P=0.03). It is concluded that premature apoptosis of PBL may be implicated in the immunosuppression of the dogs with demodicosis.

  19. 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.

  20. Immunosuppressive activity of tilmicosin on the immune responses in mice.

    PubMed

    Guan, Shuang; Song, Yu; Guo, Weixiao; Chu, Xiao; Zhang, Xiaozhe; Wang, Dacheng; Lu, Jing; Deng, Xuming

    2011-06-01

    Tilmicosin, a semi-synthetic macrolide antibiotic that is only used in the veterinary clinic, was evaluated for its immunosuppressive activity on the immune responses to ovalbumin (OVA) in mice. Tilmicosin suppressed concanavalin A (Con A)- and lipopolysaccharide (LPS)-stimulated splenocyte proliferation in vitro. BALB/c mice were immunized subcutaneously with OVA on day 1 and 4. Beginning on the day of boosting immunization, the mice were administered intraperitoneally with tilmicosin at a single dose of 10, 30, and 90 mg/kg for 10 consecutive days. On day 14, blood samples were collected for measuring specific total-immunoglobulin G (total-IgG), IgG1, IgG2b, and splenocytes were harvested for determining lymphocyte proliferation and interleukin-2 (IL-2), interferon-γ (IFN-γ), IL-4 production. The results demonstrated that tilmicosin could significantly suppress Con A-induced splenocyte proliferation in a dose-dependent manner, decrease LPS-and OVA-induced splenocyte proliferation only at high concentration, produced less IL-2, IL-4, and IFN-γ as compared to the control in the OVA-immunized mice. Moreover, the OVA-specific IgG, IgG1, and IgG2b levels in the OVA-immunized mice were reduced by tilmicosin. These results suggest that tilmicosin could suppress the cellular and humoral immune response in mice.

  1. Cancer-generated lactic acid: a regulatory, immunosuppressive metabolite?

    PubMed

    Choi, Stephen Yiu Chuen; Collins, Colin C; Gout, Peter W; Wang, Yuzhuo

    2013-08-01

    The common preference of cancers for lactic acid-generating metabolic energy pathways has led to proposals that their reprogrammed metabolism confers growth advantages such as decreased susceptibility to hypoxic stress. Recent observations, however, suggest that it generates a novel way for cancer survival. There is increasing evidence that cancers can escape immune destruction by suppressing the anti-cancer immune response through maintaining a relatively low pH in their micro-environment. Tumours achieve this by regulating lactic acid secretion via modification of glucose/glutamine metabolisms. We propose that the maintenance by cancers of a relatively low pH in their micro-environment, via regulation of their lactic acid secretion through selective modification of their energy metabolism, is another major mechanism by which cancers can suppress the anti-cancer immune response. Cancer-generated lactic acid could thus be viewed as a critical, immunosuppressive metabolite in the tumour micro-environment rather than a 'waste product'. This paradigm shift can have major impact on therapeutic strategy development.

  2. Immunosuppressive minimization with mTOR inhibitors and belatacept.

    PubMed

    Diekmann, Fritz

    2015-08-01

    Immunosuppressive therapy after kidney transplantation consists of a calcineurin inhibitor (CNI)-based therapy in combination with mycophenolic acid and steroids in most cases. In spite of low acute rejection rates and excellent graft survival, it is associated with major long-term complications, such as cardiovascular events, malignancy, and nephrotoxicity, and does not favor tolerogenic processes. Mammalian target of rapamycin (mTOR) inhibitors in combination with low-dose CNI offer good rejection rates and acceptable allograft function; however, de novo mTOR inhitibor-based treatment in combination with mycophenolate is not widely used due to higher acute rejection rates. Early conversion from a CNI to an mTOR inhibitor is a feasible option in selected patients with a slightly higher acute rejection rate, but equal or better GFR. Costimulation blockade has been proven to facilitate antirejection prophylaxis without CNI-associated side effects. So far, belatacept has been approved in combination with mycophenolate and steroids with better graft function, however, a slightly higher acute rejection rate. Recently, the combination of an mTOR inhibitor and belatacept with lymphocyte-depleting antibody induction and without maintenance steroids has been explored in two pilot studies with very low acute rejection rates, very good graft function, and an acceptable side effect profile. PMID:25959589

  3. 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

  4. Bordetella bronchiseptica in the immunosuppressed population - a case series and review.

    PubMed

    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

  5. Bordetella bronchiseptica in the immunosuppressed population - a case series and review.

    PubMed

    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.

  6. 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.

  7. 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

  8. Code and codeless ionospheric measurements with NASA's Rogue GPS Receiver

    NASA Technical Reports Server (NTRS)

    Srinivasan, Jeff M.; Meehan, Tom K.; Young, Lawrence E.

    1989-01-01

    The NASA/JPL Rogue Receiver is an 8-satellite, non-multiplexed, highly digital global positioning system (GPS) receiver that can obtain dual frequency data either with or without knowledge of the P-code. In addition to its applications for high accuracy geodesy and orbit determination, the Rogue uses GPS satellite signals to measure the total electron content (TEC) of the ionosphere along the lines of sight from the receiver to the satellites. These measurements are used by JPL's Deep Space Network (DSN) for calibrating radiometric data. This paper will discuss Rogue TEC measurements, emphasizing the advantages of a receiver that can use the P-code, when available, but can also obtain reliable dual frequency data when the code is encrypted.

  9. Ultrasonic pulser-receiver

    DOEpatents

    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.

  10. 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.

  11. Immunosuppressive Effects of Erythropoietin on Human Alloreactive T Cells

    PubMed Central

    Cravedi, Paolo; Manrique, Joaquin; Hanlon, Katherine E.; Reid-Adam, Jessica; Brody, Joshua; Prathuangsuk, Praeophayom; Mehrotra, Anita

    2014-01-01

    Correction of anemia with erythropoietin (EPO) is associated with improved kidney transplant outcomes. Emerging evidence, predominantly from animal models, indicates that these observations may be erythropoiesis-independent and that EPO exhibits immunosuppressive properties. We examined the effects of EPO on human T-cell alloimmunity by first documenting that CD4+ and CD8+ T cells express EPO receptor (EPO-R) on their surfaces. In mixed lymphocyte reactions, EPO induced a dose-dependent decrease in allogeneic CD4+ T-cell proliferation (EPO 1000 U/ml: 44.6%±22.9% of vehicle, P<0.05; 2000 U/ml: 11.1%±4% of vehicle, P<0.001) without inducing cell death. The effects required signals transmitted directly through the EPO-R expressed on T cells, resulting in diminished Th1 differentiation without effects on regulatory T-cell induction. Mechanistic studies revealed that EPO prevented IL-2–induced proliferation by uncoupling IL-2 receptor signaling, inhibiting phosphorylation of the intracellular intermediaries AKT and extracellular signal-regulated kinase that are known to mediate T-cell expansion. EPO treatment reduced expansion of human naïve CD4+ T cells after adoptive transfer into NOD scid γcnull mouse recipients, verifying the effects in vivo. Although activated T cells expressed CD131, an alternative EPO receptor, addition of a specific CD131 agonist peptide, ARA290, did not alter T-cell proliferation or cytokine production. Our findings link EPO-R signaling on T cells to inhibition of T-cell immunity, providing one mechanism that could explain the observed protective effects of EPO in kidney transplant recipients. PMID:24676641

  12. Immunosuppressive effects of erythropoietin on human alloreactive T cells.

    PubMed

    Cravedi, Paolo; Manrique, Joaquin; Hanlon, Katherine E; Reid-Adam, Jessica; Brody, Joshua; Prathuangsuk, Praeophayom; Mehrotra, Anita; Heeger, Peter S

    2014-09-01

    Correction of anemia with erythropoietin (EPO) is associated with improved kidney transplant outcomes. Emerging evidence, predominantly from animal models, indicates that these observations may be erythropoiesis-independent and that EPO exhibits immunosuppressive properties. We examined the effects of EPO on human T-cell alloimmunity by first documenting that CD4(+) and CD8(+) T cells express EPO receptor (EPO-R) on their surfaces. In mixed lymphocyte reactions, EPO induced a dose-dependent decrease in allogeneic CD4(+) T-cell proliferation (EPO 1000 U/ml: 44.6%±22.9% of vehicle, P<0.05; 2000 U/ml: 11.1%±4% of vehicle, P<0.001) without inducing cell death. The effects required signals transmitted directly through the EPO-R expressed on T cells, resulting in diminished Th1 differentiation without effects on regulatory T-cell induction. Mechanistic studies revealed that EPO prevented IL-2-induced proliferation by uncoupling IL-2 receptor signaling, inhibiting phosphorylation of the intracellular intermediaries AKT and extracellular signal-regulated kinase that are known to mediate T-cell expansion. EPO treatment reduced expansion of human naïve CD4(+) T cells after adoptive transfer into NOD scid γc(null) mouse recipients, verifying the effects in vivo. Although activated T cells expressed CD131, an alternative EPO receptor, addition of a specific CD131 agonist peptide, ARA290, did not alter T-cell proliferation or cytokine production. Our findings link EPO-R signaling on T cells to inhibition of T-cell immunity, providing one mechanism that could explain the observed protective effects of EPO in kidney transplant recipients.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 76 FR 39976 - Petition for Exemption; Summary of Petition Received

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-07

    ... continued safe flight and landing, following a dual hydraulic-system failure or any single failure in combination with a probable hydraulic failure. The relief sought would apply to the petitioner's Dassault... (65 FR 19477-78). Docket: To read background documents or comments received, go to...

  19. 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

  20. 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

  1. Failure of immunosuppression in a severe haemophilia B patient with specific antibody.

    PubMed

    Allain, J P; Frommel, D

    1976-08-31

    Prevention of a secondary response to factor IX by cyclophosphamide was attempted in an 11 year old patient with severe Christmas disease. An antibody to factor IX had been present for 4 years before immunosuppressive therapy was tried. Despite profound lymphopenia, synthesis of factor IX antibody was not depressed. The difficulties of modifying the anamnestic response to factor IX by chemical immunosuppression may be as real as has been reported for factor VIII in classical haemophilia.

  2. 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.

  3. 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

  4. 26 CFR 1.751-1 - Unrealized receivables and inventory items.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Presence of section 751 property. The partnership has no unrealized receivables, but the dual test provided... in value. (c) The properties exchanged. The analysis stated in paragraph (c) of example 3 of...

  5. 26 CFR 1.751-1 - Unrealized receivables and inventory items.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) Presence of section 751 property. The partnership has no unrealized receivables, but the dual test provided... in value. (c) The properties exchanged. The analysis stated in paragraph (c) of example 3 of...

  6. 26 CFR 1.751-1 - Unrealized receivables and inventory items.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) Presence of section 751 property. The partnership has no unrealized receivables, but the dual test provided... in value. (c) The properties exchanged. The analysis stated in paragraph (c) of example 3 of...

  7. 26 CFR 1.751-1 - Unrealized receivables and inventory items.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) Presence of section 751 property. The partnership has no unrealized receivables, but the dual test provided... in value. (c) The properties exchanged. The analysis stated in paragraph (c) of example 3 of...

  8. 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.

  9. 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

  10. 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.

  11. Silicon Photo-Receivers

    NASA Astrophysics Data System (ADS)

    Zimmermann, Horst

    The properties of photodiodes being exploitable in standard bipolar, CMOS, and BiCMOS technologies are summarized. In addition examples of advanced photodiodes will be introduced in order to show how the properties of integrated photodiodes can be improved significantly by minor process modifications. Furthermore, examples of optoelectronic integrated circuits (OEICs) for such important applications like optical storage systems and optical fiber receivers are described. New trends for the circuit topology of digital-video-disk (DVD) and digital-video-recording (DVR) read-OEICs are covered. Progress of OEIC receivers for optical data transmission and communication as well as optical interconnects is also summarized.

  12. 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…

  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. High-dose immunosuppressive therapy for severe systemic sclerosis: initial outcomes

    PubMed Central

    McSweeney, Peter A.; Nash, Richard A.; Sullivan, Keith M.; Storek, Jan; Crofford, Leslie J.; Dansey, Roger; Mayes, Maureen D.; McDonagh, Kevin T.; Nelson, J. Lee; Gooley, Theodore A.; Holmberg, Leona A.; Chen, C. S.; Wener, Mark H.; Ryan, Katherine; Sunderhaus, Julie; Russell, Ken; Rambharose, John; Storb, Rainer; Furst, Daniel E.

    2010-01-01

    Systemic sclerosis (SSc) is a multisystem disease of presumed autoimmune pathogenesis for which no proven effective treatment exists. High-dose immunosuppressive therapy (HDIT) has been proposed as an investigational treatment for severe autoimmune diseases. Nineteen patients with poor-prognosis SSc underwent HDIT. The median age was 40 years (range, 23–61 years), the median modified Rodnan skin score (a measure of dermal sclerosis) was 31, and the median DLCO was 57%. Conditioning therapy involved 800 cGy total body irradiation (TBI) (± lung shielding to approximately 200 cGy), 120 mg/kg cyclophosphamide, and 90 mg/kg equine antithymocyte globulin. CD34-selected granulocyte–colony-stimulating factor–mobilized autologous blood stem cells provided hematopoietic rescue. With median follow-up at 14.7 months, the Kaplan-Meier estimated 2-year survival rate was 79%. Three patients died of treatment complications and one of disease progression. Two of the first 8 patients had fatal regimen-related pulmonary injury, a complication not found among 11 subsequent patients who received lung shielding for TBI. Overall, internal organ functions were stable to slightly worse after HDIT, and 4 patients had progressive or nonresponsive disease. As measured by modified Rodnan skin scores and modified health assessment questionnaire disability index (mHAQ-DI) scores, significant disease responses occurred in 12 of 12 patients evaluated at 1 year after HDIT. In conclusion, though important treatment-related toxicities occurred after HDIT for SSc, modifications of initial approaches appear to reduce treatment risks. Responses in skin and mHAQ-DI scores exceed those reported with other therapies, suggesting that HDIT is a promising new therapy for SSc that should be evaluated in prospective randomized studies. PMID:12176878

  15. Zero-power receiver

    DOEpatents

    Brocato, Robert W.

    2016-10-04

    An unpowered signal receiver and a method for signal reception detects and responds to very weak signals using pyroelectric devices as impedance transformers and/or demodulators. In some embodiments, surface acoustic wave devices (SAW) are also used. Illustrative embodiments include satellite and long distance terrestrial communications applications.

  16. 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.

  17. 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.

  18. 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.

  19. Hanson receives Macelwane Medal

    NASA Astrophysics Data System (ADS)

    Ravishankara, A. R.; Hanson, David R.

    At the 1996 Spring Meeting in Baltimore, Maryland, David R. Hanson received the 1996 James B. Macelwane Medal, which recognizes significant contributions to the geophysical sciences by a young scientist of outstanding ability. The medal citation and Hanson's response are given here.

  20. The dual targeting of immunosuppressive cells and oxidants promotes effector and memory T-cell functions against lung cancer

    PubMed Central

    Sawant, Anandi; Schafer, Cara C; Ponnazhagan, Selvarangan; Deshane, Jessy S

    2014-01-01

    We have recently demonstrated that the combination of gemcitabine and a superoxide dismutase mimetic protects mice against lung cancer by suppressing the functions of myeloid-derived suppressor cells and by activating memory CD8+ T-cell responses. Persistent memory cells exhibited a glycolytic metabolism, which may have directly enhanced their effector functions. This combinatorial therapeutic regimen may reduce the propensity of some cancer patients to relapse. PMID:24711958

  1. BK virus replication following kidney transplant: does the choice of immunosuppressive regimen influence outcomes?

    PubMed

    Acott, Phillip; Babel, Nina

    2012-01-01

    The increasing prevalence of BK virus nephropathy (BKVN) observed in recent years, with its consequent impact on kidney allograft survival rates, has focused attention on the relationship between immunosuppression regimens and risk of BK virus reactivation. The adoption of more potent immunosuppressive regimens over the last two decades, notably tacrolimus with mycophenolic acid and corticosteroids, appears to be associated with higher rates of BK activation. There is also evidence of a specific increase in risk for tacrolimus-based immunosuppression vs. cyclosporine, which in vitro data suggest may be at least partly due to differences in antiviral activity. Early concerns that mammalian target of rapamycin (mTOR) inhibitor use was associated with development of BKVN do not appear to have been borne out. Protocol-driven BK virus screening is recommended to facilitate early diagnosis and intervention, which primarily comprises the controlled reduction or discontinuation of immunosuppressive drugs. Although a consensus on the optimal strategy for immunosuppression modification is still lacking, early diagnosis of BK reactivation and pre-emptive modification of immunosuppression has resulted in a marked improvement in graft outcomes. Typically, intervention consists of reducing calcineurin inhibitor exposure before or after antimetabolite dose reduction, withdrawal of one agent from a triple therapy regimen, or switching between agents within a therapeutic class. A benefit for antiviral therapy is not yet confirmed. While more data are required, the current evidence base is adequate to justify routine screening with early modification of the intensity and nature of the immunosuppression regimen to reduce the toll of BKVN in the kidney transplant population.

  2. 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…

  3. Immunosuppressive and autoimmune effects of thimerosal in mice

    SciTech Connect

    Havarinasab, S.; Haeggqvist, B.; Bjoern, E.; Pollard, K.M.; Hultman, P. . E-mail: perhu@imk.liu.se

    2005-04-15

    conclusion, the organic mercury compound thimerosal (EtHg) has initial immunosuppressive effects similar to those of MeHg. However, in contrast to MeHg, thimerosal treatment leads in genetically susceptible mice to a second phase with strong immunostimulation and autoimmunity, which is T-cell dependent, H-2 linked and may at least partly be due to the inorganic mercury derived from the metabolism of ethyl mercury.

  4. Immunosuppressive and autoimmune effects of thimerosal in mice.

    PubMed

    Havarinasab, S; Häggqvist, B; Björn, E; Pollard, K M; Hultman, P

    2005-04-15

    compound thimerosal (EtHg) has initial immunosuppressive effects similar to those of MeHg. However, in contrast to MeHg, thimerosal treatment leads in genetically susceptible mice to a second phase with strong immunostimulation and autoimmunity, which is T-cell dependent, H-2 linked and may at least partly be due to the inorganic mercury derived from the metabolism of ethyl mercury.

  5. 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.

  6. Host-derived neoangiogenesis with short-term immunosuppression allows incorporation and remodeling of vascularized diaphyseal allogeneic rabbit femur transplants.

    PubMed

    Giessler, Goetz A; Zobitz, Mark; Friedrich, Patricia F; Bishop, Allen T

    2009-06-01

    The purpose of this study was to demonstrate that living bone allotransplants can incorporate, remodel, and maintain mechanical properties without long-term immunosuppression in a fashion comparable to living autotransplants. For this, viability is maintained by repair of nutrient vessels and neovascularization from implanted host-derived vasculature. Microsurgically revascularized femoral diaphysis allotransplants were transferred from young male New-Zealand-White (NZW) into 4 groups of male Dutch-Belted (DB) rabbits. Short-term immunosuppression by tacrolimus (IS, groups 4 and 5) and host-derived neovascularization (NV) from implanted fascial flaps was used to maintain viability (groups 3 and 5) as independent variables. Group 2 received neither IS nor NV. Vascularized pedicled autotransplants were orthotopically transplanted in group 1. After 16 weeks, transplants were evaluated using radiologic, histologic, biomechanical, and histomorphometric parameters. Vascularized bone allotransplants treated with both short-term IS and host-derived NV (group 5) healed in a fashion similar to pedicled autotransplants (group 1). Their radiographic scores were higher than other groups. Groups with patent fascial flaps (3 and 5) showed significantly greater neoangiogenesis than ligated controls (2 and 4). Tacrolimus administration did not affect neoangiogenesis. Elastic modulus and ultimate stress were significantly greater in autogenous bone than in allotransplanted femora. Biomechanical properties were not significantly different among allotransplants. Bone turnover was decreased with IS, but increased with NV by the implanted fascial flaps. Living allogeneic femoral allotransplants treated with short-term IS and host-derived neoangiogenesis can lead to stable transplant incorporation in this rabbit model. The combination of both factors optimizes bone healing. Transplant mineralization is improved with neoangiogenesis but diminished with IS.

  7. 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.

  8. 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.

  9. 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.

  10. Design of radar receivers

    NASA Astrophysics Data System (ADS)

    Sokolov, M. A.

    This handbook treats the design and analysis of of pulsed radar receivers, with emphasis on elements (especially IC elements) that implement optimal and suboptimal algorithms. The design methodology is developed from the viewpoint of statistical communications theory. Particular consideration is given to the synthesis of single-channel and multichannel detectors, the design of analog and digital signal-processing devices, and the analysis of IF amplifiers.

  11. 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.

  12. 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

  13. Hair follicle dermal sheath derived cells improve islet allograft survival without systemic immunosuppression.

    PubMed

    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.

  14. Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans.

    PubMed

    Yiasemides, Eleni; Sivapirabu, Geetha; Halliday, Gary M; Park, Joohong; Damian, Diona L

    2009-01-01

    Cutaneous immunity, which is a key defence against the development of skin cancers, is suppressed by even small doses of ultraviolet (UV) radiation. Preventing this UV-induced immunosuppression may therefore reduce the incidence of skin cancer. Nicotinamide (vitamin B3) has immune-protective and cancer-preventive effects against UV radiation in mice, and we have shown previously that topical nicotinamide is immune protective in humans. Using the Mantoux model of skin immunity in healthy volunteers, we compared oral nicotinamide to placebo (both administered for 1 week) in a randomized, double-blinded, crossover design against the effects of solar-simulated ultraviolet (ssUV) radiation on delayed-type hypersensitivity to tuberculin purified protein derivative. Discrete areas of the back were irradiated with low doses of ssUV daily for three consecutive days. Immunosuppression, calculated as the difference in Mantoux-induced erythema of irradiated sites compared with unirradiated control sites, was determined in volunteers taking oral nicotinamide and placebo. Significant immunosuppression occurred in an UV dose-dependent manner in the presence of placebo. Oral nicotinamide, at doses of either 1500 or 500 mg daily, was well tolerated and significantly reduced UV immunosuppression with no immune effects in unirradiated skin. Oral nicotinamide is safe and inexpensive and looks promising as a chemopreventive supplement for reducing the immunosuppressive effects of sunlight.

  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.

  16. Human Amnion-Derived Stem Cells Have Immunosuppressive Properties on NK Cells and Monocytes.

    PubMed

    Li, Jiali; Koike-Soko, Chika; Sugimoto, Jun; Yoshida, Toshiko; Okabe, Motonori; Nikaido, Toshio

    2015-01-01

    Human amnion-derived cells are considered to be a promising alternative cell source for their potential clinical use in tissue engineering and regenerative medicine because of their proliferation and differentiation ability. The cells can easily be obtained from human amnion, offering a potential source without medical intervention. It has been proven that human amnion-derived cells express immunosuppressive factors CD59 and HLA-G, implying that they may have an immunosuppressive function. To assess the immunosuppressive activity, we investigated the effect of human amnion-derived cells on NK cell and monocyte function. Amnion-derived cells inhibited the cytotoxicity of NK cells to K562 cells. The inhibition depended on the NK/amnion-derived cell ratio. The inhibition of NK cytotoxicity was recovered by continuous culturing without amnion-derived cells. The inhibition of NK cytotoxicity was related to the downregulation of the expression of the activated NK receptors and the production of IFN-γ, as well as the upregulation of the expression of IL-10 and PGE2 in human amnion-derived cells. The addition of antibody to IL-10 or PGE2 inhibitor tended to increase NK cytotoxicity. IL-10 and PGE2 might be involved in the immunosuppressive activity of amniotic cells toward NK cells. Amniotic cells also suppressed the activity of cytokine production in monocytes analyzed with TNF-α and IL-6. These data suggested that amniotic cells have immunosuppressive activity.

  17. Systemic therapy with immunosuppressive agents and retinoids in hidradenitis suppurativa: a systematic review.

    PubMed

    Blok, J L; van Hattem, S; Jonkman, M F; Horváth, B

    2013-02-01

    Hidradenitis suppurativa (HS) is a difficult disease to treat. Although the pathogenesis of this inflammatory skin disease is largely unknown, the important role of the immune system has been demonstrated in both experimental and clinical studies. Clinicians are therefore increasingly prescribing systemic treatments with immunosuppressive agents, but the more traditionally used systemic retinoids, especially isotretinoin, also remain relatively common therapies. In order to provide an overview of all currently available systemic immunosuppressive agents and retinoids for the treatment of HS, a systematic search was performed using the Medline and Embase databases. All published papers concerning systemic retinoids or immunosuppressive treatments for HS in adults were included. The primary endpoints were the percentages of significant responders, moderate responders and nonresponders. Other endpoints were the relapse rate and adverse events. In total 87 papers were included, comprising 518 patients with HS who were treated with systemic retinoids, biological agents or another immunosuppressive agents, including colchicine, ciclosporin, dapsone or methotrexate. The highest response rates were observed with infliximab, adalimumab and acitretin. Overall, the quality of evidence was low and differed between the agents, making direct comparisons difficult. However, based on the amount of evidence, infliximab and adalimumab were the most effective agents. Acitretin was also effective in HS, although the quality of the evidence was low. The therapeutic effect of isotretinoin is questionable. Randomized controlled trials are needed to confirm the effectiveness of acitretin, and to identify the most effective immunosuppressive agents in HS.

  18. 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

  19. 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

  20. 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

  1. [Lung cavities caused by Nocardia cyriacigeorgica in an immunosuppressed boy].

    PubMed

    Berring, Dahlia Caroline; Nygaard, Ulrikka

    2014-09-29

    The identification of nodules and/or cavitations in the chest X-ray of a chronically or acute ill patient will rise the suspicion of tuberculosis. However, it is important to be aware of pulmonary nocardiosis as a rare but important differential diagnosis, especially in case of no hilar adenitis. In this case report, we describe a six-year-old boy receiving prednisolone due to nephrotic syndrome, who developed pneumothorax because of pulmonal nocardiosis. The prognosis is good in case of early diagnosis and antibiotic treatment. PMID:25294520

  2. 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.

  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, 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.

  5. 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.

  6. Central receiver technology

    SciTech Connect

    Holl, R.L. )

    1989-09-01

    The research and development described in this document was conducted within the US Department of Energy's (DOE) Solar Thermal Technology Program. The goal of this program is to advance the engineering and scientific understanding of solar thermal technology and to establish the technology base from which private industry can develop solar thermal power production options for introduction into the competitive energy market. This report describes central receiver technology: its accomplishments to date, its current technology status, and the efforts still necessary to fully exploit it.

  7. Potent immunosuppressive principles, dimeric sesquiterpene thioalkaloids, isolated from nupharis rhizoma, the rhizoma of Nuphar pumilum (nymphaeaceae): structure-requirement of nuphar-alkaloid for immunosuppressive activity.

    PubMed

    Yamahara, J; Shimoda, H; Matsuda, H; Yoshikawa, M

    1996-09-01

    Potent immunosuppressants, the dimeric sesquiterpene thioalkaloids, 6-hydroxythiobinupharidine (2), 6,6'-dihydroxythiobinupharidine (3), 6-hydroxythionuphlutine B (5) and 6'-hydroxythionuphlutine B (6), were isolated from a natural medicine, Nupharis Rhizoma, the rhizoma of Nuphar pumilum (TIMM.) DC., through bioassay-guided separation together with five quinolizidine alkaloids (8, 9, 10, 11, 12). Dimeric sesquiterpene thioalkaloids (2, 3, 5, 6) were found to significantly inhibit anti-sheep erythrocyte plaque forming cell formation in mice spleen cells at 10(-6) M concentration. At this concentration, 2, 5 and 6 were found to exhibit no cytotoxicity to mice spleen cells, and 3 also showed only a little cytotoxicity. In addition, the inhibitory activity of several Nuphar alkaloids, dimeric sesquiterpene thioalkaloids (1, 4, 7, 8), and monomeric sesquiterpene alkaloids (9, 10, 11, 12) on anti-sheep erythrocyte plaque forming cell formation was examined and some structural requirement of Nuphar alkaloid for immunosuppressive activity was determined.

  8. Are Dual Eligibles Admitted to Poorer Quality Skilled Nursing Facilities?

    PubMed Central

    Rahman, Momotazur; Grabowski, David C; Gozalo, Pedro L; Thomas, Kali S; Mor, Vincent

    2014-01-01

    Background Dual eligibles, persons who qualify for both Medicare and Medicaid coverage, often receive poorer quality care relative to other Medicare beneficiaries. Objectives To determine whether dual eligibles are discharged to lower quality post-acute skilled nursing facilities (SNFs) compared with Medicare-only beneficiaries. Research Design Following the random utility maximization model, we specified a discharge function using a conditional logit model and tested how this discharge rule varied by dual-eligibility status. Subjects A total of 692,875 Medicare fee-for-service patients (22% duals) who were discharged for Medicare paid SNF care between July 2004 and June 2005. Measures Medicare enrollment and the Medicaid Analytic Extract files were used to determine dual eligibility. The proportion of Medicaid patients and nursing staff characteristics provided measures of SNF quality. Results Duals are more likely to be discharged to SNFs with a higher share of Medicaid patients and fewer nurses. These results are robust to estimation with an alternative subsample of patients based on primary diagnoses, propensity of being dual eligible, and likelihood of remaining in the nursing home. Conclusions Disparities exist in access to quality SNF care for duals. Strategies to improve discharge planning processes are required to redirect patients to higher quality providers, regardless of Medicaid eligibility. PMID:24354695

  9. Comparison of immunosuppressive and cytotoxic cells in angiosarcoma: development of a possible supportive therapy for angiosarcoma.

    PubMed

    Kambayashi, Yumi; Fujimura, Taku; Furudate, Sadanori; Hashimoto, Akira; Haga, Takahiro; Aiba, Setsuya

    2013-01-01

    An imbalance of immunosuppressive and cytotoxic cells plays an important role in inhibiting the anti-tumor immune response of the tumor-bearing host. The purpose of this study was to elucidate the involvement of immunosuppressive cells, such as regulatory T cells and CD163+ M2 macrophages as well as cytotoxic cells, such as granulysin-bearing cells and TIA-1+ cells in cutaneous angiosarcoma (AS) by immunohistochemical staining. In addition we evaluated the potencies of bisphosphonate, which was previously reported to suppress the expression of matrix metalloproteinase 9 (MMP-9), as a supportive therapy for AS together with docetaxel in 6 cases of cutaneous AS. These findings suggest that a high number of immunosuppressive cells might be related to the prognosis of AS, and that a combination of docetaxel with bisphosphonate risedronate sodium might be effective for MMP-9-expressing AS.

  10. A new model of corneal transplantation in the miniature pig: efficacy of immunosuppressive treatment.

    PubMed

    Tavandzi, Urania; Procházka, Radek; Usvald, Dusan; Hlucílová, Jana; Vitásková, Martina; Motlík, Jan; Vítová, Andrea; Filipec, Martin; Forrester, John V; Holán, Vladimír

    2007-05-27

    Corneal allograft rejection is frequently studied in small rodent or rabbit models. To study mechanisms of rejection in a model that more closely mimics transplantation in humans, we performed orthotopic corneal transplantation in the miniature pig using a 7-mm diameter donor graft. Four groups of recipients were studied: 1) untreated naive, 2) untreated vascularized (high risk), 3) high-risk grafts treated by topical application of prednisolone, or 4) high-risk grafts treated with a combined systemic immunosuppression regime of oral prednisone, cyclosporine A, and mycophenolate mofetil. Both the clinical features and histological assessment of corneal graft rejection showed close similarities to graft rejection in humans. Interestingly, preliminary results indicated that topical steroid treatment was superior to systemic immunosuppression in significantly promoting graft survival. Thus, corneal transplantation in the pig represents an animal model most closely resembling corneal grafting in humans, and offers possibilities for testing various clinically applicable immunosuppressive treatments.

  11. 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

  12. 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

  13. Alternative matrices for therapeutic drug monitoring of immunosuppressive agents using LC-MS/MS.

    PubMed

    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.

  14. Less is more: the detrimental consequences of immunosuppressive therapy in the treatment of type-1 diabetes.

    PubMed

    Askenasy, Nadir

    2015-01-01

    The prevalent current approach to type 1 diabetes (T1D) is the abrogation of pathogenic potential by immunosuppressive therapy, an intuitive approach aiming to slow down disease progression by the reduction of pathogenic burden. In spite of promising initial results in rodent models, there has been little efficacy of most lymphoreductive strategies in human subjects. Our analysis suggests that lymphopenia is the common denominator of ineffective immunosuppressive therapies: Immune rebound from lymphopenia is associated per se with increased susceptibility to immune reactivity, including relapse of autoimmunity. In addition, immune homeostasis and self-tolerance are not restored. These considerations raise the following question: What is the allowed degree of immunosuppressive therapy that does not elicit recurrent autoimmunity. More effective therapeutic strategies include targeted deletion of pathogenic cells, preferably in the pancreatic islets and regional lymphatics using selective T cell activation markers, re-education and remodeling of effector responses.

  15. Synthesis of N-dialkylphosphoryl iminosugar derivatives and their immunosuppressive activities.

    PubMed

    Yang, Xuemei; Xiong, De-Cai; Song, Chengcheng; Tai, Guihua; Ye, Xin-Shan

    2015-09-28

    Twelve novel N-dialkylphosphoryliminosugar derivatives were synthesized and their immunosuppressive activities were evaluated on the proliferation of the mouse splenocytes and the secretion of IFN-γ and IL-4. The experimental data demonstrated that the iminosugars with the double long alkyl chains exhibited better inhibitory effects than those with the single long alkyl chain, and the iminosugars with the 10-carbon linear alkyl chain exhibited the strongest immunosuppressive activities. The assay of the cytokine secretion showed that the introduction of dialkyl chains on iminosugars could regulate the polarization of immune inhibition by varying the length of the alkyl chains. The disclosure of the structure-activity relationships may benefit the structural modifications of iminosugars to find new types of immunosuppressive agents.

  16. Immunosuppressive C₂₁ steroidal glycosides from the root of Cynanchum atratum.

    PubMed

    Zhang, Zhi-Jun; Ding, Mei-Ling; Tao, Li-Jun; Zhang, Mian; Xu, Xiang-Hong; Zhang, Chao-Feng

    2015-09-01

    Six new C21 steroidal glycosides (1-6) and one dideoxysaccharide (7), named atratcynosides A-F and atratcynose A, were isolated from the 80% ethanol extract of the root of Cynanchum atratum, together with three known compounds (8-10). The structures of the new compounds were determined on the basis of extensive spectral analyses and qualitative chemical methods. All compounds were subjected to detect the immunosuppressive activities by an in vitro model of concanavalin A-induced proliferation of T-lymphocytes from mice. Compounds 1-3 showed significant immunosuppressive activities in dose-dependent manners with the IC50 values from 3.3 to 7.0 μM. Moreover, the structure-activity relationship of the steroidal glycosides on the immunosuppression was analyzed.

  17. Modified Aloe Polysaccharide Restores Chronic Stress-Induced Immunosuppression in Mice

    PubMed Central

    Lee, Youngjoo; Im, Sun-A; Kim, Jiyeon; Lee, Sungwon; Kwon, Junghak; Lee, Heetae; Kong, Hyunseok; Song, Youngcheon; Shin, Eunju; Do, Seon-Gil; Lee, Chong-Kil; Kim, Kyungjae

    2016-01-01

    Chronic stress generally experienced in our daily lives; is known to augment disease vulnerability by suppressing the host immune system. In the present study; the effect of modified Aloe polysaccharide (MAP) on chronic stress-induced immunosuppression was studied; this Aloe compound was characterized in our earlier study. Mice were orally administered with MAP for 24 days and exposed to electric foot shock (EFS; duration; 3 min; interval; 10 s; intensity; 2 mA) for 17 days. The stress-related immunosuppression and restorative effect of MAP were then analyzed by measuring various immunological parameters. MAP treatment alleviated lymphoid atrophy and body weight loss. The numbers of lymphocyte subsets were significantly normalized in MAP-treated mice. Oral administration of MAP also restored the proliferative activities of lymphocytes; ovalbumin (OVA)-specific T cell proliferation; antibody production; and the cell killing activity of cytotoxic T lymphocytes. In summary; oral administration of MAP ameliorated chronic EFS stress-induced immunosuppression. PMID:27706024

  18. Novel surgical techniques, regenerative medicine, tissue engineering and innovative immunosuppression in kidney transplantation

    PubMed Central

    Nowacki, Maciej; Nazarewski, Łukasz; Tyloch, Dominik; Pokrywczyńska, Marta; Pietkun, Katarzyna; Jundziłł, Arkadiusz; Tyloch, Janusz; Habib, Samy L.; Drewa, Tomasz

    2016-01-01

    On the 60th anniversary of the first successfully performed renal transplantation, we summarize the historical, current and potential future status of kidney transplantation. We discuss three different aspects with a potential significant influence on kidney transplantation progress: the development of surgical techniques, the influence of regenerative medicine and tissue engineering, and changes in immunosuppression. We evaluate the standard open surgical procedures with modern techniques and compare them to less invasive videoscopic as well as robotic techniques. The role of tissue engineering and regenerative medicine as a potential method for future kidney regeneration or replacement and the interesting search for novel solutions in the field of immunosuppression will be discussed. After 60 years since the first successfully performed kidney transplantation, we can conclude that the greatest achievements are associated with the development of surgical techniques and with planned systemic immunosuppression. PMID:27695507

  19. Novel surgical techniques, regenerative medicine, tissue engineering and innovative immunosuppression in kidney transplantation

    PubMed Central

    Nowacki, Maciej; Nazarewski, Łukasz; Tyloch, Dominik; Pokrywczyńska, Marta; Pietkun, Katarzyna; Jundziłł, Arkadiusz; Tyloch, Janusz; Habib, Samy L.; Drewa, Tomasz

    2016-01-01

    On the 60th anniversary of the first successfully performed renal transplantation, we summarize the historical, current and potential future status of kidney transplantation. We discuss three different aspects with a potential significant influence on kidney transplantation progress: the development of surgical techniques, the influence of regenerative medicine and tissue engineering, and changes in immunosuppression. We evaluate the standard open surgical procedures with modern techniques and compare them to less invasive videoscopic as well as robotic techniques. The role of tissue engineering and regenerative medicine as a potential method for future kidney regeneration or replacement and the interesting search for novel solutions in the field of immunosuppression will be discussed. After 60 years since the first successfully performed kidney transplantation, we can conclude that the greatest achievements are associated with the development of surgical techniques and with planned systemic immunosuppression.

  20. 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.

  1. Adverse Fetal Outcomes Associated with Immunosuppressive Medications for Chronic Immune Mediated Diseases in Pregnancy

    PubMed Central

    Cooper, William O.; Cheetham, T. Craig; Li, De-Kun; Stein, C. Michael; Callahan, S. Todd; Morgan, Thomas M.; Shintani, Ayumi K.; Chen, Ning; Griffin, Marie R.; Ray, Wayne A.

    2014-01-01

    Objective We assessed the risk of adverse fetal outcomes following exposure to individual immunosuppressive drugs in pregnant women with chronic immune mediated diseases. Methods We used health plan data from Tennessee Medicaid and Kaiser Permanente Northern California and Southern California linked with vital records and medical records. Women with inflammatory arthropathies, systemic lupus erythematosus, and inflammatory bowel disease who filled prescriptions for immunosuppressive treatments during pregnancy were included. Major congenital malformations, fetal deaths, and life-threatening neonatal complications were identified from electronic data and validated with medical record review. Results The cohort included 608 infants, including 437 with exposure during pregnancy (402 first trimester, 35 second and third trimester only) and 171 whose mothers filled prescriptions for immunosuppressives before, but not during, pregnancy. There were 25 pregnancies (4.1% of the cohort) with confirmed major congenital malformations, 10 fetal deaths (1.6%), 23 life-threatening neonatal complications among preterm infants (20.4%), and 10 (2.1%) life-threatening complications among term infants. Compared to the reference group (medication treatment before, but not during, pregnancy), the risk ratios for adverse fetal outcomes associated with immunosuppressive use during pregnancy by exposure category included: methotrexate [risk ratio 1.39 (95% confidence interval 0.43,4.53)], tumor necrosis factor inhibitors [0.98 (0.38,2.55)], hydroxychloroquine [1.33 (0.69,2.55)], and other immunosuppressives [0.98, (0.48,1.98)]. Conclusions We found no evidence of a large increase in risk of adverse fetal outcomes from first trimester exposure to immunosuppressive medications, though confidence intervals for risk ratios were wide. Further studies will be needed as use of these medications increases over time. PMID:24504818

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

    PubMed

    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

    2015-12-01

    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.

  3. A 27-Year-Old Severely Immunosuppressed Female with Misleading Clinical Features of Disseminated Cutaneous Sporotrichosis

    PubMed Central

    Patel, Atiyah; Mudenda, Victor; Lakhi, Shabir; Ngalamika, Owen

    2016-01-01

    Sporotrichosis is a subacute or chronic granulomatous mycosis caused by fungus of the Sporothrix schenckii complex. It is considered to be a rare condition in most parts of the world. It mostly causes cutaneous infection but can also cause multisystemic disease. Unlike most deep cutaneous mycoses which have a primary pulmonary focus, it is usually caused by direct inoculation of the fungus into the skin causing a classical linear, lymphocutaneous nodular eruption. However, atypical presentations of the condition can occur especially in immunosuppressed individuals. We report the case of a severely immunosuppressed female who presented with disseminated cutaneous sporotrichosis which was initially diagnosed and treated as disseminated cutaneous Kaposi's sarcoma. PMID:26881148

  4. Immunosuppression for ipilimumab-related toxicity can cause pneumocystis pneumonia but spare antitumor immune control

    PubMed Central

    Arriola, Edurne; Wheater, Matthew; Krishnan, Radhika; Smart, James; Foria, Vipul; Ottensmeier, Christian

    2015-01-01

    Ipilimumab is a standard therapy for advanced melanoma. Severe immune related adverse events occur in up to 30% of patients and require treatment with immunosuppressants such as steroids or the anti-TNFα antibody, infliximab. We describe two patients with advanced melanoma treated with ipilimumab. Both suffered from severe immune related side effects and required prolonged immunosuppression with steroids and/or infliximab. Both patients recovered and in spite of the immune suppression, demonstrate clinical evidence of tumor control. This argues that distinct immunological effector functions control nosocomial infection and tumor, respectively. To our knowledge, these are also the first two case reports of pneumocystis pneumonia in this setting. PMID:26451305

  5. Sun, sangria and sandflies: Leishmaniasis in an immunosuppressed patient returning from Spain.

    PubMed

    Moore, James; Brown, Kevin

    2013-01-01

    Despite the global financial downturn, millions of people continue to travel abroad each year. Many travel with co-morbidities such as immunosuppression, placing them at greater risk of bacterial, viral and parasitic infections.(1) Leishmaniasis is one of the principal neglected tropical diseases.(2) Although it threatens 350 million people each year(3) it is not an infection that most General Physicians would associate with travel to Southern Europe. A case of visceral leishmaniasis is described in a lady with mild immunosuppression caused by systemic lupus erythematosus, following a holiday in Southern Spain, a destination not normally associated with this leishmaniasis. PMID:23369438

  6. The inhibitory effects of polyphenols on skin UV immunosuppression .

    PubMed

    Mucha, Paulina; Budzisz, Elżbieta; Rotsztejn, Helena

    2013-05-06

    Long-term exposure to UV radiation leads to skin ageing and may initiate carcinogenesis. In both cases immunosuppressive activity of UV radiation plays an important role. The aim of the study is to present polyphenols commonly seen in flora and their properties protecting the skin from the damaging influence of UV rays. Polyphenols are a group of compounds which are present in plants. Their common features are: the ring structure of a molecule, hydroxyl groups in the rings and a conjugated double bond system. Such structure makes polyphenols active antioxidants. They also demonstrate anti-immunosuppressive properties.

  7. Atopic dermatitis-like pre-Sézary syndrome: role of immunosuppression.

    PubMed

    Sokołowska-Wojdyło, Małgorzata; Barańska-Rybak, Wioletta; Cegielska, Agnieszka; Trzeciak, Magdalena; Lugowska-Umer, Hanna; Gniadecki, Robert

    2011-09-01

    We describe here 4 patients with Sézary syndrome masquerading as adult-onset atopic dermatitis. The patients presented with a clinical picture compatible with wide-spread atopic dermatitis and did not fulfil the criteria for Sézary syndrome (lack of lymphoadenopathy and blood involvement, skin histology without presence of atypical cells). In our patients, overt Sézary syndrome developed after immunosuppressive treatment (including cyclosporine). These cases support the validity of the concept of pre-Sézary syndrome, which is a long-lasting, pre-malignant condition, and which may develop to true malignancy in a state of immunosuppression. PMID:21681350

  8. Fatal recurrence of fulminant giant cell myocarditis and recovery after initialisation of an alternative immunosuppressive regime

    PubMed Central

    Fluschnik, Nina; Escher, Felicitas; Blankenberg, Stefan; Westermann, Dirk

    2014-01-01

    We report on a challenging case of a 34-year-old male patient with giant cell myocarditis (GCM) and fulminant relapse after discontinuing immunomodulatory therapy 2 years after the initial event. Specific combined immunosuppressive therapy with antithymocyte globulin (ATG), cyclosporine and high-dose glucocorticoids combined with guideline-based heart failure medication led to the recovery of GCM, improvement of systolic left ventricular function and clinical remission. This case report emphasises the importance of an immunosuppressive therapy for the prognosis and outcome and the risk of discontinuation. Most importantly, ATG seems to be one new possible potential treatment option for patients with acute GCM. PMID:25246472

  9. 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.

  10. 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.

  11. 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.

  12. Autoimmune Hepatitis-related Cirrhosis: Clinical Features and Effectiveness of Immunosuppressive Treatment in Chinese Patients

    PubMed Central

    Li, Yan-Ni; Ma, Huan; Zhou, Lu; Zhang, Jie; Guo, Li-Ping; Li, Shu-Qian; Qian, Yi-Qi; Wang, Bang-Mao

    2016-01-01

    Background: The long-term outcomes of patients with autoimmune hepatitis (AIH) given the immunosuppressive treatment are considered to be preferable. However, little is known about the response of AIH patients with cirrhosis to immunosuppressive treatment. We assessed the effects of immunosuppressive therapy in Chinese AIH patients with cirrhosis from a tertiary hospital. Methods: Patients with a clinical diagnosis of AIH January 2000 and December 2015 were retrospectively reviewed. Two-hundred and fourteen patients who were followed up and satisfied the simplified AIH criteria were included in the study. Among these patients, 87 presented with cirrhosis when initially diagnosed for AIH. Immunosuppressive treatments were employed in 57 AIH patients who did not present with cirrhosis and 39 patients who presented with cirrhosis. Initial responses to immunosuppressive treatment of patients with and without cirrhosis were analyzed. Independent risk factors were assessed for predicting the prognosis of patients. The t-test and Cox regression statistical analysis were used. Results: In total, 96 AIH patients including 39 with cirrhosis and 57 without cirrhosis underwent immunosuppressive therapy. The overall complete remission after initial immunosuppressive treatment was achieved in 81/96 patients (84.4%), whereas 9/96 (9.4%) achieved incomplete response, and 6/96 (6.3%) occurred treatment failure. Compared to noncirrhotic patients, patients who presented with cirrhosis responded to treatment to a comparable extent regarding complete response (noncirrhosis 50/57 [87.7%] vs. cirrhosis 31/39 [79.5%], P = 0.275), incomplete remission (noncirrhosis 4/57 [7.0%] vs. cirrhosis 5/39 [12.8%], P = 0.338), and treatment failure (noncirrhosis 3/57 [5.3%] vs. cirrhosis 3/39 [7.7%], P = 0.629). Importantly, the remission rate was comparable (54/57 [94.7%] and 36/39 [92.3%], P = 0.629) for noncirrhotic and cirrhotic patients after immunosuppressive therapy. Compared to patients who

  13. 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.

  14. Association of Anti-PLA2R Antibodies with Outcomes after Immunosuppressive Therapy in Idiopathic Membranous Nephropathy

    PubMed Central

    Hofstra, Julia M.; Brenchley, Paul E.; Wetzels, Jack F.M.

    2014-01-01

    Background The optimal timing and duration of immunosuppressive therapy for idiopathic membranous nephropathy (iMN) have been debated. This study aimed to evaluate whether measuring the antibody against the phospholipase A2 receptor (PLA2R-ab) at start and end of therapy predicts long-term outcome and therefore may inform this debate. Design, setting, participants, & measurements This observational study included all consecutive high-risk patients with progressive iMN observed from 1997 to 2005 and treated with oral cyclophosphamide (CP) or mycophenolate mofetil (MMF) in combination with corticosteroids for 12 months. Patients were prospectively followed, and outcome was ascertained up to 5 years after completion of immunosuppressive therapy. Serum samples were collected before and after completion of therapy. PLA2R antibodies were determined retrospectively in stored samples using ELISA. Results In total, 48 patients (37 men) were included. The median age was 55 years (range, 34–75), and the median serum creatinine level was 1.60 mg/dl (range, 0.98–3.37 mg/dl). Twenty-two patients received MMF and 26 received CP. At baseline, PLA2R-abs were present in 34 patients (71%). Baseline characteristics and outcome did not significantly differ between patients negative or positive for PLA2R-ab. In PLA2R-ab–positive patients, treatment resulted in a rapid decrease of antibodies: median anti–PLA2R-ab, 428 U/ml (range, 41–16,260 U/ml) at baseline and 24 U/ml (range, 0–505 U/ml) after 2 months. The PLA2R-ab levels at baseline did not predict initial response, but antibody status at end of therapy predicted long-term outcome: After 5 years, 14 of 24 (58%) antibody-negative patients were in persistent remission compared with 0 of 9 (0%) antibody-positive patients (P=0.003). Conclusions These data suggest that in PLA2R-ab–positive patients, measuring PLA2R-abs at the end of therapy predicts the subsequent course. PMID:25035272

  15. 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.

  16. Antibody responses in normal infants and in infants receiving chemotherapy for congenital neuroblastoma.

    PubMed

    Orgel, H A; Hamburger, R N; Mendelson, L M; Miller, J R; Kung, F H

    1977-09-01

    Three infants with congenital neuroblastoma received a primary series of diptheria-pertassis-tetanus (DPT) immunizations during and after courses of chemotherapy with immunosuppressive medications. Serum IgG, IgA and IgM levels and antidiphthria and antitetanus antibody responses were measured and compared with those of normal infants of similar age. Protective levels of antibody were achieved by the study patients as well as by the control group. These results support the view that children with malignancies who are receiving chemotherapy should not be denied immunization with inactivated vaccines.

  17. Ultra-compact coherent receiver with serial interface for pluggable transceiver.

    PubMed

    Itoh, Toshihiro; Nakajima, Fumito; Ohno, Tetsuichiro; Yamanaka, Shogo; Soma, Shunichi; Saida, Takashi; Nosaka, Hideyuki; Murata, Koichi

    2014-09-22

    An ultra-compact integrated coherent receiver with a volume of 1.3 cc using a quad-channel transimpedance amplifier (TIA)-IC chip with a serial peripheral interface (SPI) is demonstrated for the first time. The TIA with the SPI and photodiode (PD) bias circuits, a miniature dual polarization optical hybrid, an octal-PD and small optical coupling system enabled the realization of the compact receiver. Measured transmission performance with 32 Gbaud dual-polarization quadrature phase shift keying signal is equivalent to that of the conventional multi-source agreement-based integrated coherent receiver with dual channel TIA-ICs. By comparing the bit-error rate (BER) performance with that under continuous SPI access, we also confirmed that there is no BER degradation caused by SPI interface access. Such an ultra-compact receiver is promising for realizing a new generation of pluggable transceivers.

  18. 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

  19. 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.

  20. 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

  1. Influence of the murine MHC (H-2) on Friend leukemia virus-induced immunosuppression

    PubMed Central

    1986-01-01

    Friend murine leukemia virus complex (FV)-induced immunosuppression was studied by assaying splenic anti-SRBC PFC responses and plasma antibody titers in mice at various times after FV inoculation. Genes located within the H-2 complex were found to influence resistance to FV-induced immunosuppression. Near normal responses were observed in mice having the H-2a/b or H-2b/b genotype, whereas mice having the H-2a/a genotype were suppressed. This H-2 effect was observed not only in mice having heterozygous C57BL/10 X A background genes, including Rfv-3r/s, but also was apparent in mice having homozygous A-strain background genes, including Rfv-3s/s. Therefore, the Rfv-3 gene did not appear to convey resistance to FV-induced immunosuppression. The suppression in susceptible H-2a/a mice was characterized by a partial suppression of the IgM response and a profound suppression of both the primary and secondary IgG responses. Neither splenomegaly nor viremia alone appeared to be sufficient for the induction or maintenance of the immunosuppression. The mechanism of suppression was unclear, but both B lymphocyte and T lymphocyte functions appeared to be altered. PMID:3456010

  2. 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...

  3. Acute measles encephalitis of the delayed type in an immunosuppressed child.

    PubMed

    Colamaria, V; Marradi, P; Merlin, D; Moser, C; Dulac, O; Dompieri, P; Dalla Bernardina, B

    1989-01-01

    The authors described a case of an immunosuppressed child with acute measles encephalitis of the delayed type (AMED). The authors also discussed the relationship between the AMED, epilepsia partialis continua and the neuroradiological picture, in which bilateral putaminal lucency was evident.

  4. 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

  5. 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

  6. 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

  7. Association of human immunodeficiency virus-induced immunosuppression with human papillomavirus infection and cervical intraepithelial neoplasia.

    PubMed

    Henry, M J; Stanley, M W; Cruikshank, S; Carson, L

    1989-02-01

    Human papillomavirus infection plays an important causal role in cervical intraepithelial neoplasia and carcinoma. The rate of infection with human papillomavirus as well as the incidence of cervical intraepithelial neoplasia and carcinoma are increased in immunosuppressed patients. We report a possible association between infection with human immunodeficiency virus and cervical intraepithelial neoplasia with human papillomavirus infection.

  8. 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...

  9. 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.

  10. [Dependence of immunosuppressive action of lipopolysaccharide on degree of Salmonella pathogenicity].

    PubMed

    Borisova, E V; Bondarenko, V M; Molozhavaia, O S; Borisov, V A

    2001-01-01

    Immunosuppressive activity of Salmonella typhimurium extracellular lipopolysaccharide (LPS) was studied. In this study isogenic S. typhimurium strains with different degree of virulence were used. The attenuation of these strains was linked with mutations on their chromosome (altered synthesis of RNA polymerase or gyrase DNA) or their own virulence plasmid (the insertion of transposon Tn-5). To obtain LPS fraction with different molecular weights, the filtrate of bacterial culture was subjected to gel filtration through a column packed with Sephadex G-200. The immunosuppressive action of LPS fractions was determined on the model of delayed-type hypersensitivity to nonbacterial antigen in experiments on BALB/c mice. The study revealed that transposon-mediated mutation on plasmid, accompanied by the attenuation of salmonellae, led to the loss of immunosuppressive activity of the high-molecular heat-sensitive component of LPS; only the second heat-resistant component with medium molecular weight retained its activity. The presence of two chromosomal attenuating mutations (rifr nalr) was accompanied by the loss of immunosuppressive activity in both components of LPS.

  11. 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...

  12. 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

  13. 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

  14. 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.

  15. 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…

  16. 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.

  17. 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

  18. Relationship between Ah receptor-mediated polychlorinated biphenyl (PCB)-induced humoral immunosuppression and thymic atrophy.

    PubMed

    Silkworth, J B; Antrim, L

    1985-12-01

    Thymic atrophy and humoral immunosuppression by certain polychlorinated biphenyls is associated with the aromatic hydrocarbon (Ah) receptor in mice. We examined the relationship between these two toxic effects. 3,3',4,4'-Tetrachlorobiphenyl (TCB), which causes immunosuppression and thymic atrophy, and 2,3,3',4,4',5-hexachlorobiphenyl, which causes immunosuppression without thymic atrophy, were administered i.p. to C57BL/6 mice at 0, 35 and 350 mumol/kg b.wt. 2 days before i.v. immunization with 10 micrograms of Escherichia coli lipopolysaccharide. Both congeners caused significant suppression of the day 4 anti-lipopolysaccharide plaque-forming cell response/spleen (less than or equal to 46% of control). TCB (350 mumol/kg) was also administered 2 days before either a primary or secondary i.p. immunization with sheep erythrocytes. TCB treatment before primary immunization had no effects on the day 5 secondary response, whereas treatment before the secondary immunization significantly inhibited both day 5 immunoglobulin M and immunoglobulin G plaque-forming cells (less than 10 and less than 2% of control, respectively) and decreased serum antibody. TCB administered either 8 or 2 days before or 2 or 4 days after immunization with sheep erythrocytes demonstrated that significant suppression of both plaque-forming cells and serum antibody could occur without thymic atrophy. Immunity was most impaired when TCB was given 2 days before immunization. These results demonstrate that thymic atrophy does not always accompany the severe immunosuppression caused by Ah receptor ligands and suggests that it may not be a sensitive measure of Ah receptor-mediated immunosuppression. The data also suggests that differentiation of B lymphocytes into antibody producing cells is impaired during Ah receptor-mediated gene activation.

  19. Impact of immunosuppressive drugs on the therapeutic efficacy of ex vivo expanded human regulatory T cells.

    PubMed

    Scottà, Cristiano; Fanelli, Giorgia; Hoong, Sec Julie; Romano, Marco; Lamperti, Estefania Nova; Sukthankar, Mitalee; Guggino, Giuliana; Fazekasova, Henrieta; Ratnasothy, Kulachelvy; Becker, Pablo D; Afzali, Behdad; Lechler, Robert I; Lombardi, Giovanna

    2016-01-01

    Immunosuppressive drugs in clinical transplantation are necessary to inhibit the immune response to donor antigens. Although they are effective in controlling acute rejection, they do not prevent long-term transplant loss from chronic rejection. In addition, immunosuppressive drugs have adverse side effects, including increased rate of infections and malignancies. Adoptive cell therapy with human Tregs represents a promising strategy for the induction of transplantation tolerance. Phase I/II clinical trials in transplanted patients are already underway, involving the infusion of Tregs alongside concurrent immunosuppressive drugs. However, it remains to be determined whether the presence of immunosuppressive drugs negatively impacts Treg function and stability. We tested in vitro and in vivo the effects of tacrolimus, mycophenolate and methylprednisolone (major ISDs used in transplantation) on ex vivo expanded, rapamycin-treated human Tregs. The in vitro results showed that these drugs had no effect on phenotype, function and stability of Tregs, although tacrolimus affected the expression of chemokine receptors and IL-10 production. However, viability and proliferative capacity were reduced in a dose-dependent manner by all the three drugs. The in vivo experiments using a humanized mouse model confirmed the in vitro results. However, treatment of mice with only rapamycin maintained the viability, function and proliferative ability of adoptively transferred Tregs. Taken together, our results suggest that the key functions of ex vivo expanded Tregs are not affected by a concurrent immunosuppressive therapy. However, the choice of the drug combination and their timing and dosing should be considered as an essential component to induce and maintain tolerance by Treg.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. Influenza vaccination in children with cancer receiving chemotherapy.

    PubMed

    Esposito, Susanna; Cecinati, Valerio; Russo, Fabio Giovanni; Principi, Nicola

    2009-06-01

    Influenza has a significant clinical impact on pediatric cancer patients because it causes frequent febrile episodes and respiratory tract infections, possibly severe complications, delays in chemotherapy administration and even death, all of which supports the importance of prevention and the widespread use of influenza vaccination. Results from clinical studies show that influenza vaccination can be considered safe in children undergoing chemotherapy and, although weaker than in healthy children, the immune response seems to be sufficient in patients with leukemia or solid tumors even if it is less in children receiving chemotherapy than in those who are not. However, there is an urgent need for universally accepted guidelines concerning the type of vaccine that leads to the best immunological results, the number of administrations, and their timing in relation to the severity of immunosuppression and chemotherapy schedules. Such recommendations, together with a clear demonstration of vaccine efficacy, are also needed to increase influenza vaccination coverage in this high-risk category of patients.

  5. 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

  6. 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

  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. Dual beam optical interferometer

    NASA Technical Reports Server (NTRS)

    Gutierrez, Roman C. (Inventor)

    2003-01-01

    A dual beam interferometer device is disclosed that enables moving an optics module in a direction, which changes the path lengths of two beams of light. The two beams reflect off a surface of an object and generate different speckle patterns detected by an element, such as a camera. The camera detects a characteristic of the surface.

  9. 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…

  10. 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…

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  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. 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

  18. 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.

  19. 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

  20. Parasitological and histopathological effects of immunosuppression in guinea-pigs (Cavia porcellus) experimentally infected with Schistosoma haematobium.

    PubMed

    Okeke, O C; Ubachukwu, P O; Okafor, F C; Shoyinka, S V O

    2012-12-01

    The parasitological and histopathological effects of immunosuppression in guinea-pigs (Cavia porcellus) experimentally infected with Schistosoma haematobium were studied. A total of 16 guinea-pigs were divided into four groups (four per group): non-immunosuppressed, non-infected group (NN); immunosuppressed, non-infected group (IN); immunosuppressed, infected group (II); non-immunosuppressed, infected group (NI). The IN and II groups were immunosuppressed with 5 mg/kg prednisolone while the II and NI animals were infected with 200-300 S. haematobium cercariae. Excretion of eggs in urine/faeces, worm burden and histopathology of some vital organs of the guinea-pigs were studied. Eggs of S. haematobium were observed in the urine of the NI and II groups from 9 weeks post-infection and in faeces from 10 and 13 weeks post-infection for the NI and II groups, respectively. However, II animals excreted more viable eggs in urine and faeces than those of the NI group. Worm recovery at 14 weeks post-infection showed that NI and II guinea-pigs had more female worms than male worms and a greater proportion of worm recovery for NI animals was of immature worms. Significant differences (P < 0.05) existed between female, male and immature worm burden of the two groups but not in their total worm burden (P>0.05). Histological changes, which were notably reactions to adult S. haematobium worms, were observed in the organs of the NI and II groups but these changes were seen more in the organs of the immunosuppressed, infected (II) than in the non-immunosuppressed, infected (NI) guinea-pigs. The results suggest that immunosuppression before infection increased worm survival and had a moderate effect on liver and bladder histology of S. haematobium infected guinea-pigs.

  1. 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.

  2. Simultaneous dual-band radar development

    NASA Technical Reports Server (NTRS)

    Liskow, C. L.

    1974-01-01

    Efforts to design and construct an airborne imaging radar operating simultaneously at L band and X band with an all-inertial navigation system in order to form a dual-band radar system are described. The areas of development include duplex transmitters, receivers, and recorders, a control module, motion compensation for both bands, and adaptation of a commercial inertial navigation system. Installation of the system in the aircraft and flight tests are described. Circuit diagrams, performance figures, and some radar images are presented.

  3. 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.

  4. 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.

  5. 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

  6. Catalytic activity of bovine seminal ribonuclease is essential for its immunosuppressive and other biological activities.

    PubMed Central

    Kim, J S; Soucek, J; Matousek, J; Raines, R T

    1995-01-01

    Bovine seminal ribonuclease (BS-RNase) is a homologue of RNase A with special biological properties, including potent immunosuppressive activity. A mutant BS-RNase was created in which His-119, the active-site residue that acts as a general acid during catalysis, was changed to an aspartic acid. H119D BS-RNase formed a dimer with quaternary structure similar to that of the wild-type enzyme but with values of kcat. and kcat./Km for the cleavage of UpA [uridylyl(3'-->5')adenosine] that were 4 x 10(3)-fold lower. The mutant protein also demonstrated dramatically decreased immunosuppressive, anti-tumour, aspermatogenic, and embryotoxic activities. The catalytic activity of BS-RNase is therefore necessary for its special biological properties. PMID:7772040

  7. Hepatitis B Virus Reactivation in the Setting of Cancer Chemotherapy and Other Immunosuppressive Drug Therapy.

    PubMed

    Gonzalez, Stevan A; Perrillo, Robert P

    2016-06-01

    Hepatitis B virus reactivation (HBVr) is an important complication of immunosuppressive drug therapy (ISDT). It can occur with active or resolved hepatitis B virus (HBV) infection with a clinical spectrum that ranges from mild elevations in liver tests to fulminant hepatic failure. The risk of it occurring is determined by the interplay between HBV serological status, level of viremia, and the immunosuppressive potency of the drug(s) used. Reactivation is most common during treatment of hematologic malignancies but also occurs with chemotherapy for breast cancer and numerous other solid organ malignancies, organ transplant, and immune suppression for nonmalignant conditions. The expansion of new biologic treatments for malignant and nonmalignant disorders has enlarged the population at risk. Increased awareness of HBVr among healthcare providers who prescribe ISDT, adoption of routine HBV screening, and linking the results of screening to antiviral prophylaxis are needed to reduce the incidence of this potentially fatal but preventable disorder.

  8. 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

  9. A risk classification for immunosuppressive treatment-associated progressive multifocal leukoencephalopathy.

    PubMed

    Chahin, Salim; Berger, Joseph R

    2015-12-01

    Progressive multifocal leukoencephalopathy (PML) is a rare, complex opportunistic infection of the central nervous system caused by the JC virus. This past decade, PML was increasingly recognized to be associated with the use of immunosuppressive and biologic agents. The risk for PML differs among these agents and remains difficult to quantify because of the complex pathogenesis of PML and the presence of confounding factors. This paper explores and updates the association of PML with different biologic and immunosuppressive agents and proposes an expanded classification system for the risk of PML. We identify three classes of drug that vary by PML risk, latency to infection, and underlying illness. We also review some of the most common agents with known associations to PML and explore risk mitigation strategies that aim to inform the decision-making process for clinicians and patients in the face of the changing incidence of PML and the growing landscape of immunologic agents.

  10. Differential modulation of apoptosis and necrosis by antioxidants in immunosuppressed human lymphocytes.

    PubMed

    Rojas, Mauricio; Rugeles, María Teresa; Gil, Diana Patricia; Patiño, Pablo

    2002-04-15

    In the present study, we explored whether mitogenic stimulation of dexamethasone (DXM)- and cyclosporine A (CsA)-immunosuppressed peripheral blood lymphocytes (PBML) induced apoptosis or necrosis and their relation with the production of reactive oxygen intermediates. Our results indicate that both phenomena can occur in these cells and that antioxidants such as N-acetyl cysteine (NAC) and ascorbic acid (AA) can modulate them. However, DXM-induced apoptosis was only partially inhibited by NAC and AA, suggesting that DXM-treated PBMC had an additional apoptotic pathway independent of ROIs. Furthermore, we observed that the inhibition of apoptosis by antioxidants correlated with an increased cell proliferation, suggesting that the immunomodulation of both DXM and CsA may be related to induction of apoptosis. The ability to differentially modulate apoptosis and necrosis by antioxidants opens new possibilities in the management of immunosuppressive therapy, since the inhibition of necrosis may avoid inflammation and the tissue damage associated with immunosuppressors.

  11. In Vitro and In Vivo Immunosuppressive Activity of a Novel Anthracycline, 13-deoxy, 5-iminodoxorubicin 1

    PubMed Central

    Olson, Richard D.; Headley, Mark B.; Hodzic, Alma; Walsh, Gerald M.; Wingett, Denise G.

    2007-01-01

    We report that the novel anthracycline analog, 13-deoxy, 5-iminodoxorubicin (DIDOX), represents a potentially new class of immunosuppressive agents. DIDOX has been structurally modified from the parent compound, doxorubicin, to remove the carbonyl group at carbon-13 and the quinone moiety at carbon-5 since these structures likely mediate the cardiotoxic side effects of this family of chemotherapeutic drugs. Our studies demonstrate that DIDOX inhibits T cell proliferation and the expression of the T cell activation molecules, CD25 and CD40L. DIDOX also inhibits the production of the proinflammatory cytokine, TNF-α and IL-2. Studies using animal models demonstrate that DIDOX inhibits the inflammation accompanying contact hypersensitivity reactions and possesses reduced cardiotoxicity compared to doxorubicin. These findings indicate that DIDOX has important immunosuppressive activities that may warrant the development of this new and improved anthracycline for the treatment of T cell-mediated inflammatory diseases. PMID:17466907

  12. [Immunosuppressive therapy in patients with HBeAg-positive chronic active hepatitis B?].

    PubMed

    Maier, K P; Lepiorz, H; Berthold, H; Gerok, W

    1982-08-01

    The course of HBsAg-positive chronic active hepatitis was followed in 36 patients who were treated by immunosuppression and in 45 controls by means of serial determinations of HBeAg titers and by repeated biopsies of the liver. In the treated group remission occurred in 52% (HBeAg negative) resp. 48% (HBeAg positive); in the control group these percentages were almost identical, that is to say 61% resp. 41%. During therapy 5 out of 9 HBeAg positive patients and 7 out of 12 HBeAg negative patients developed cirrhosis of the liver as compared to 5 resp. 10, and 2 resp. 12 patients in the control group. Judging from these results it seems unlikely, that the course of HBsAg positive, chronic-active hepatitis in patients, whose serum shows a positive HBeAg titer by immunodiffusion, might be influenced in a positive way by immunosuppressive therapy.

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

    PubMed

    Marques, Raquel M; Teixeira, Luzia; Aguas, Artur P; Ribeiro, Joana C; Costa-e-Silva, António; Ferreira, Paula G

    2014-02-04

    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.

  14. Tuberculous pericarditis leading to cardiac tamponade: importance of screening prior to immunosuppression.

    PubMed

    Wee, Edmund; Denton, Eve; Daffy, John

    2015-12-01

    Mycobacterium tuberculosis (TB) presenting with pericardial disease complicated by cardiac tamponade is rare in the developed world, although it occurs more frequently in the context of immunosuppression. In this report, a 74-year-old man on methotrexate for rheumatoid arthritis presented with fever, productive cough and cough-induced syncope. During his admission, he developed clinical signs of cardiac tamponade confirmed on an echocardiogram, which showed a massive pericardial effusion. He was treated with an urgent pericardiocentesis and a pericardial window. Subsequently, TB polymerase chain reaction of pericardial fluid unexpectedly returned positive, and he was commenced on standard quadruple therapy for TB, as well as high-dose prednisolone. Notably, the patient did not have a history suggestive of previous TB exposure, and no screening investigations had been performed prior to initiation of methotrexate. This case highlights the importance of TB screening prior to immunosuppressive therapy, even in populations considered low risk for latent disease. PMID:26740879

  15. T-cell specific immunosuppression by prodigiosin isolated from Serratia marcescens.

    PubMed

    Han, S B; Kim, H M; Kim, Y H; Lee, C W; Jang, E S; Son, K H; Kim, S U; Kim, Y K

    1998-01-01

    Prodigiosin was isolated from the culture broth of Serratia marcescens B-1231. This compound inhibited the T-cell mediated immune responses such as concanavalin-A induced proliferation, mixed lymphocyte response, local graft vs host reaction and T-dependent antibody response at non-toxic concentrations. However, prodigiosin did not affect B-cell mediated immune functions such as lipopolysaccharide-induced proliferation and-activated polyclonal antibody production at the same concentrations. Prodigiosin did not cause death in vitro to lymphocytes at effective concentrations (< 100 nM) and also did not show toxicity in vivo to lymphoid organs at effective dosages (10 and 30 mg/kg). The pharmacological potencies were comparable to the activities of other T-cell specific immunosuppressants such as cyclosporin A and FK-506. In conclusion, it might be suggested that prodigiosin could be used as an immunosuppressant in clinical and immunological studies.

  16. Follicular dendritic cell disruption as a novel mechanism of virus-induced immunosuppression

    PubMed Central

    Melzi, Eleonora; Caporale, Marco; Rocchi, Mara; Martín, Verónica; Gamino, Virginia; di Provvido, Andrea; Marruchella, Giuseppe; Entrican, Gary; Sevilla, Noemí; Palmarini, Massimo

    2016-01-01

    Arboviruses cause acute diseases that increasingly affect global health. We used bluetongue virus (BTV) and its natural sheep host to reveal a previously uncharacterized mechanism used by an arbovirus to manipulate host immunity. Our study shows that BTV, similarly to other antigens delivered through the skin, is transported rapidly via the lymph to the peripheral lymph nodes. Here, BTV infects and disrupts follicular dendritic cells, hindering B-cell division in germinal centers, which results in a delayed production of high affinity and virus neutralizing antibodies. Moreover, the humoral immune response to a second antigen is also hampered in BTV-infected animals. Thus, an arbovirus can evade the host antiviral response by inducing an acute immunosuppression. Although transient, this immunosuppression occurs at the critical early stages of infection when a delayed host humoral immune response likely affects virus systemic dissemination and the clinical outcome of disease. PMID:27671646

  17. Future of Medicare Immunosuppressive Drug Coverage for Kidney Transplant Recipients in the United States

    PubMed Central

    Stone, Patricia W.; Mohan, Sumit; Cohen, David J.; Gaston, Robert S.

    2013-01-01

    Summary Kidney transplantation is the preferred treatment for patients with ESRD. It improves the quality of life in recipients, increases patient survival, and is also substantially less costly than maintenance dialysis. Long-term transplant success requires immunosuppressant drug therapy for the life of the allograft. Under current law, Medicare coverage for most recipients (except for those recipients over 65 years of age or with nonkidney-related disabilities) lasts only 3 years, leaving many recipients unable to afford these medications. Lack of drug therapy often leads to allograft rejection, resulting in premature graft failure, return to dialysis, or death. This article reviews the current policy for Medicare immunosuppressive drug coverage and analyzes the potential impact of pending legislative proposals H.R. 2969 and S. 1454 and the Patient Protection and Affordable Care Act. PMID:23559679

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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.

  5. Genome Mining of a Prenylated and Immunosuppressive Polyketide from Pathogenic Fungi

    PubMed Central

    Chooi, Yit-Heng; Fang, Jinxu; Liu, Hong; Filler, Scott G.; Wang, Pin; Tang, Yi

    2013-01-01

    Activation of the polycyclic polyketide prenyltransferases (pcPTase)-containing silent clusters in Aspergillus fumigatus and Neosartorya fischeri led to isolation of a new metabolite neosartoricin (3). The structure of 3 was solved by X-ray crystallography and NMR to be a prenylated anthracenone. 3 Exhibits T-cell antiproliferative activity with an IC50 of 3 μM, suggestive of a physiological role as an immunosuppressive agent. PMID:23368997

  6. The fatal alliance of cancer and T cells: How pancreatic tumor cells gather immunosuppressive T cells.

    PubMed

    Grage-Griebenow, Evelin; Schäfer, Heiner; Sebens, Susanne

    2014-01-01

    Immune evasion is a hallmark of cancer. We recently identified the adhesion molecule L1CAM as biomarker of pancreatic ductal adenocarcinoma (PDAC) associated with poor prognosis. During inflammation-associated carcinogenesis, L1CAM drives the enrichment of highly immunosuppressive CD4(+)CD25(-)CD69(+) T cells. Thus, L1CAM may serve as a target in immunomodulatory therapy for PDAC. PMID:25114835

  7. 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

  8. 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

  9. 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.

  10. Dual-comb MIXSEL

    NASA Astrophysics Data System (ADS)

    Link, S. M.; Zaugg, C. A.; Klenner, A.; Mangold, M.; Golling, M.; Tilma, B. W.; Keller, U.

    2015-03-01

    We present a single semiconductor disk laser simultaneously emitting two different gigahertz modelocked pulse trains. A birefringent crystal inside a modelocked integrated external-cavity surface-emitting laser (MIXSEL) separates the cavity beam into two spatially separated beams with perpendicular polarizations on the MIXSEL chip. This MIXSEL then generates two orthogonally polarized collinear modelocked pulse trains from one simple straight cavity. Superimposing the beams on a photo detector creates a microwave beat signal, representing a strikingly simple setup to down-convert the terahertz optical frequencies into the electronically accessible microwave regime. This makes the dual-comb MIXSEL scheme an ultra-compact and cost-efficient candidate for dual-comb spectroscopy applications.

  11. Type I Interferons Exert Anti-tumor Effect via Reversing Immunosuppression Mediated by Mesenchymal Stromal Cells

    PubMed Central

    Shou, Peishun; Chen, Qing; Jiang, Jingting; Xu, Chunliang; Zhang, Jimin; Zheng, Chunxing; Jiang, Menghui; Velletri, Tania; Cao, Wei; Huang, Yin; Yang, Qian; Han, Xiaoyan; Zhang, Liying; Wei, Lixin; Rabson, Arnold B.; Chin, Y. Eugene; Wang, Ying; Shi, Yufang

    2016-01-01

    Mesenchymal stromal cells (MSCs) are strongly immunosuppressive via producing nitric oxide (NO) and known to migrate into tumor sites to promote tumor growth, but the underlying mechanisms remain largely elusive. Here, we found that IFNα-secreting MSCs showed more dramatic inhibition effect on tumor progression than that of IFNα alone. Interestingly, IFNα-primed MSCs could also effectively suppress tumor growth. Mechanistically, we demonstrated that both IFNα and IFNβ (type I IFNs) reversed the immunosuppressive effect of MSCs on splenocyte proliferation. This effect of type I IFNs was exerted through inhibiting iNOS (inducible nitric oxide synthase) expression in IFNγ and TNFα-stimulated MSCs. Notably, only NO production was inhibited by IFNα; production of other cytokines or chemokines tested was not suppressed. Furthermore, IFNα promoted the switch from Stat1 homodimers to Stat1-Stat2 heterodimers. Studies using the luciferase reporter system and chromatin immunoprecipitation assay revealed that IFNα suppressed iNOS transcription through inhibiting the binding of Stat1 to iNOS promoter. Therefore, the synergistic anti-tumor effects of type I IFNs and MSCs were achieved by inhibiting NO production. This study provides essential information for understanding the mechanisms of MSC-mediated immunosuppression and for the development of better clinical strategies using IFNs and MSCs for cancer immunotherapy. PMID:27109100

  12. Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2).

    PubMed

    Collins, Peter; Baudo, Francesco; Knoebl, Paul; Lévesque, Hervé; Nemes, László; Pellegrini, Fabio; Marco, Pascual; Tengborn, Lilian; Huth-Kühne, Angela

    2012-07-01

    Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive regimen is unclear; therefore, data from 331 patients entered into the prospective EACH2 registry were analyzed. Steroids combined with cyclophosphamide resulted in more stable complete remission (70%), defined as inhibitor undetectable, factor VIII more than 70 IU/dL and immunosuppression stopped, than steroids alone (48%) or rituximab-based regimens (59%). Propensity score-matched analysis controlling for age, sex, factor VIII level, inhibitor titer, and underlying etiology confirmed that stable remission was more likely with steroids and cyclophosphamide than steroids alone (odds ratio = 3.25; 95% CI, 1.51-6.96; P < .003). The median time to complete remission was approximately 5 weeks for steroids with or without cyclophosphamide; rituximab-based regimens required approximately twice as long. Immunoglobulin administration did not improve outcome. Second-line therapy was successful in approximately 60% of cases that failed first-line therapy. Outcome was not affected by the choice of first-line therapy. The likelihood of achieving stable remission was not affected by underlying etiology but was influenced by the presenting inhibitor titer and FVIII level.

  13. 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

  14. Isolation and molecular cloning of a secreted immunosuppressant protein from Dermacentor andersoni salivary gland.

    PubMed

    Bergman, D K; Palmer, M J; Caimano, M J; Radolf, J D; Wikel, S K

    2000-06-01

    A 36-kDa immunosuppressant protein (Da-p36) was isolated from salivary glands of feeding female ixodid ticks Dermacentor andersoni, using its affinity for UltraLink Biosupport Medium (Pierce, Rockford, Illinois)/protein complexes. Using a nested set of forward degenerate oligonucleotide primers corresponding to Da-p36 N-terminal amino acids, a cDNA encoding the immunosuppressant protein was isolated by 3' rapid amplification of cDNA ends. The resulting 772-base pair cDNA encodes a novel protein with predicted molecular weight of 24.9 kDa. Sequence analysis revealed the presence of 5 potential glycosylation sites and 1 myristylation site. Immunoblot analyses showed native Da-p36 is present in salivary glands and saliva from both male and female D. andersoni but not in salivary glands or saliva from Amblyomma americanum or Ixodes scapularis. Reverse transcription polymerase chain reaction and immunoblot analyses showed that Da-p36 expression is temporally regulated in salivary glands with maximum mRNA levels preceding maximum Da-p36 accumulation that occurred at day 6 of feeding. The levels of Da-p36 mRNA and protein were greatly reduced in salivary glands from near-replete females removed from sheep after 8 days of feeding. These data are consistent with a role of Da-p36 in immunosuppression during feeding. PMID:10864249

  15. 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

  16. Evaluation of adherence to immunosuppressive drugs in kidney transplantation by control of medication dispensing.

    PubMed

    Brahm, M M T; Manfro, R C; Mello, D; Cioato, S; Gonçalves, L F S

    2012-10-01

    Nonadherence to immunosuppressive medications represents a burden to organ transplantation being associated with rejection episodes and graft loss. In this cross-sectional study we evaluated the prevalence and risk factors for nonadherence in kidney transplant patients by measuring the retrieval of the immunosuppressive drugs in the registry kept by the state Rio Grande do Sul public health system. We considered nonadherence the failure to retrieval of medication at least one time over a 1-year period of evaluation. In 288 patients evaluated, the frequency of failure to retrieve was 58.7%. Being fully employed (66.4% × 33.6%, P = .008) and younger age at transplantation (39 ± 13 × 46 ± 11, P = .011) were associated with nonadherence. Multivariate analysis showed a greater prevalence ratio (PR) of non- adherence in patients using tacrolimus. Estimated glomerular filtration rate was significantly lower in the nonadherence groups as compared with adherent groups (45.3 ± 21.6 × 51.3 ± 19.4, P = .016). In conclusion, we found a high prevalence of nonadherence to immunosuppressive drugs with association to active working situation and use of tacrolimus. Importantly, glomerular filtration rate was found to be lower in nonadherent patients.

  17. Retroviral induction of acute lymphoproliferative disease and profound immunosuppression in adult C57BL/6 mice

    PubMed Central

    1985-01-01

    We have shown that a mixture of murine leukemia viruses (MuLV) causes the acute onset of lymphoproliferation and immunosuppression when injected into adult C57BL/6 mice. The ecotropic/MCF (mink cell focus- inducing) mixture of MuLV stimulates polyclonal B lymphocyte proliferation and differentiation to antibody-secreting cells. Serum Ig levels are elevated for all isotypes except IgA. The viral infection leads to a rapid decline in T lymphocyte responses to mitogens and alloantigens, as well as a decrease in helper cell activity. Specific antibody responses to both T-dependent and T-independent antigens are impaired, and the response of B lymphocytes to mitogens is abolished. The profound immunosuppression seems to be due to the MuLV-induced polyclonal activation of lymphocytes. No active suppression of normal lymphocyte responses by cells from virus-infected mice was observed. The disease induced by the LP-BM5 MuLV isolate thus seems a promising model for the study of lymphocyte activation and the mechanisms of retrovirus-induced immunosuppression. PMID:2984305

  18. Pre-exposure to the unconditioned or conditioned stimulus does not affect learned immunosuppression in rats.

    PubMed

    Lueckemann, Laura; Bösche, Katharina; Engler, Harald; Schwitalla, Jan-Claudius; Hadamitzky, Martin; Schedlowski, Manfred

    2016-01-01

    In order to analyze the effects of pre-exposure to either the unconditioned (US) or conditioned stimulus (CS) on learned immunosuppression, we employed an established conditioned taste aversion (CTA) paradigm in rats. In our model, a sweet-tasting drinking solution (saccharin) serves as CS and injection of the immunosuppressive drug cyclosporine A (CsA) is used as US. The conditioned response is reflected by a pronounced CTA and diminished cytokine production by anti-CD3 stimulated splenic T cells. In the present study, experimental animals were exposed either to the US or the CS three times prior to the acquisition phase. On the behavioral level, we found a significantly diminished CTA when animals were pre-exposed to the US or the CS before acquisition. In contrast, US or CS pre-exposure did not affect the behaviorally conditioned suppression of interleukin (IL)-2 production. From the clinical perspective, our data may suggest that conditioning paradigms could be systemically integrated as supportive therapeutic interventions in patients that are already on immunosuppressive therapy or have had previous contact to the gustatory stimulus. Such supportive therapies to pharmacological regimens could not only help to reduce the amount of medication needed and, thus, unwanted toxic side effects, but may also maximize the therapeutic outcome.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. [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.

  5. Prevention of UV radiation-induced immunosuppression by IL-12 is dependent on DNA repair.

    PubMed

    Schwarz, Agatha; Maeda, Akira; Kernebeck, Kerstin; van Steeg, Harry; Beissert, Stefan; Schwarz, Thomas

    2005-01-17

    The immunostimulatory cytokine IL-12 is able to antagonize immunosuppression induced by solar/ultraviolet (UV) radiation via yet unknown mechanisms. IL-12 was recently found to induce deoxyribonucleic acid (DNA) repair. UV-induced DNA damage is an important molecular trigger for UV-mediated immunosuppression. Thus, we initiated studies into immune restoration by IL-12 to discern whether its effects are linked to DNA repair. IL-12 prevented both UV-induced suppression of the induction of contact hypersensitivity and the depletion of Langerhans cells, the primary APC of the skin, in wild-type but not in DNA repair-deficient mice. IL-12 did not prevent the development of UV-induced regulatory T cells in DNA repair-deficient mice. In contrast, IL-12 was able to break established UV-induced tolerance and inhibited the activity of regulatory T cells independent of DNA repair. These data identify a new mechanism by which IL-12 can restore immune responses and also demonstrate a link between DNA repair and the prevention of UV-induced immunosuppression by IL-12.

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

    PubMed Central

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

    2015-01-01

    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

  7. De novo mTOR inhibitor-based immunosuppression in ABO-incompatible kidney transplantation.

    PubMed

    Koch, Martina; Wiech, Thorsten; Marget, Matthias; Peine, Sven; Thude, Hansjörg; Achilles, Eike G; Fischer, Lutz; Lehnhardt, Anja; Thaiss, Friedrich; Nashan, Bjoern

    2015-11-01

    ABO-incompatible (ABOi) kidney transplantation (KTx) has become an accepted therapeutic option in renal replacement therapy for patients without a blood group-compatible living donor. Using different desensitization strategies, most centers apply B-cell depletion with rituximab and maintenance immunosuppression (IS) with tacrolimus and mycophenolic acid. This high load of total IS leads to an increased rate of surgical complications and virus infections in ABOi patients. Our aim was to establish ABOi KTx using an immunosuppressive regimen, which is effective in preventing acute rejection without increasing the risk for viral infections. Therefore, we selected a de novo immunosuppressive protocol with low-dose calcineurin inhibitor and the mTOR inhibitor everolimus for our ABOi program. Here, we report the first 25 patients with a complete three-yr follow-up treated with this regimen. Three-yr patient survival and graft survival were 96% and 83%. The rate of acute T-cell-mediated rejections was low (12%). Cytomegalovirus (CMV) infection was evident in one patient only (4%). Surgical complications were common (40%), but mild in 80% of cases. We demonstrate that ABOi KTx with a de novo mTOR inhibitor-based regimen is feasible without severe surgical or immunological complications and a low rate of viral infections.

  8. Immunosuppressive activity of human amniotic fluid of normal and abnormal pregnancies.

    PubMed

    Shohat, B; Faktor, J M

    1988-01-01

    Twenty specimens of amniotic fluid (AF) obtained between week 16 and 18 of gestation from normal pregnant women and six specimens from pregnant women in which trisomia of chromosome 21 was found were tested for immunosuppressive activity. Incubation of normal human donor lymphocytes with 0.2-1 mL of AF from normal pregnant women for one hour at 37 degrees C was sufficient for induction of significant inhibition of the ability of these cells to induce a local xenogeneic graft-versus-host reaction (GVHR) as well as inhibition of E and E-active rosette formation, the GVHR being the most sensitive test. On the other hand, amniotic fluid obtained from the six pregnant women in which trisomia of chromosome 21 was found showed no inhibitory activity in either the E or E-active rosette formation, nor in the local xenogeneic graft-versus-host reaction. AF from all the women tested was found to have no effect on phenotype expression of the lymphocytes, as tested by the monoclonal antibodies OKT4+ and OKT8+, nor on B-lymphocytes, as tested by surface immunoglobulins. No correlation was found between the alpha-fetoprotein levels in the sera of those women and the immunosuppressive activity. These findings indicate that genetic defects of the conceptus are not limited to the embryo but may affect the composition of immunosuppressive components present in normal amniotic fluid.

  9. Immunosuppressive Interactions among Calcium Channel Antagonists and Selected Corticosteroids and Macrolides Using Human whole Blood Lymphocytes

    PubMed Central

    Chow, Fung-Sing; Jusko, William J.

    2014-01-01

    Summary The immunosuppressive interactions of calcium channel antagonists [diltiazem (Dil), verapamil (Ver) and nifedipine (Nif)], with corticosteroids [methylprednisolone (Mpl), prednisolone (Prd)], and macrolides [tacrolimus (Tac) and sirolnnus (Sir)] were examined in human whole blood lymphocyte cultures. Gender-related differences in responses in the interactions between these drug classes were studied using blood from 6 males and 6 females. The nature and intensity of interactions were determined using an extended Loewe additivity model. All immunosuppressants exhibited higher potency than the calcium channel antagonists with mean IC50 values of: Dil (mM)Ver (mM)Nif (mM)Mpl (nM)Prd (nM)Tac (nM)Sir (nM)Male13541.921312.118.6150327Female11431.847.44.68.8111106 Gender-related differences in responses to Mpl and Prd were observed while the others were not significant. Additive interactions were found among calcium channel antagonists and corticosteroids. Significant synergistic interactions were observed between calcium channel antagonists and tacrolimus and sirolimus, although these are unlikely to be of clinical importance. These studies demonstrate diverse drug interactions in the examination of an important array of immunosuppressant drug combinations. PMID:15681895

  10. Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)

    PubMed Central

    Baudo, Francesco; Knoebl, Paul; Lévesque, Hervé; Nemes, László; Pellegrini, Fabio; Marco, Pascual; Tengborn, Lilian; Huth-Kühne, Angela

    2012-01-01

    Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive regimen is unclear; therefore, data from 331 patients entered into the prospective EACH2 registry were analyzed. Steroids combined with cyclophosphamide resulted in more stable complete remission (70%), defined as inhibitor undetectable, factor VIII more than 70 IU/dL and immunosuppression stopped, than steroids alone (48%) or rituximab-based regimens (59%). Propensity score-matched analysis controlling for age, sex, factor VIII level, inhibitor titer, and underlying etiology confirmed that stable remission was more likely with steroids and cyclophosphamide than steroids alone (odds ratio = 3.25; 95% CI, 1.51-6.96; P < .003). The median time to complete remission was approximately 5 weeks for steroids with or without cyclophosphamide; rituximab-based regimens required approximately twice as long. Immunoglobulin administration did not improve outcome. Second-line therapy was successful in approximately 60% of cases that failed first-line therapy. Outcome was not affected by the choice of first-line therapy. The likelihood of achieving stable remission was not affected by underlying etiology but was influenced by the presenting inhibitor titer and FVIII level. PMID:22517903

  11. 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

  12. 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

  13. Oral Mucosal Progenitor Cells Are Potently Immunosuppressive in a Dose-Independent Manner

    PubMed Central

    Davies, Lindsay C.; Lönnies, Helena; Locke, Matthew; Sundberg, Berit; Rosendahl, Kerstin; Götherström, Cecilia; Le Blanc, Katarina

    2012-01-01

    Oral mucosal lamina propria progenitor cells (OMLP-PCs) are a novel, clonally derived PC population of neural crest origin with the potential to differentiate down both mesenchymal and neuronal cell lineages. In this study we aimed to determine the immunological properties of OMLP-PCs and to establish whether they would be suitable candidates for allogeneic tissue engineering and in the treatment of immune-related diseases. OMLP-PCs demonstrated no inherent immunogenicity with insignificant expression of costimulatory molecules (CD40, CD80, CD86, CD154, and CD178) or human leukocyte antigen (HLA) class II. OMLP-PCs required 7 days of stimulation with interferon-γ (IFN-γ) to induce cell surface expression of HLA II. Mixed lymphocyte cultures and mitogen stimulation demonstrated the potent immunosuppressive capability of OMLP-PCs in a contact-independent manner. Complete inhibition of lymphocyte proliferation was seen at doses as low as 0.001% OMLP-PCs to responder lymphocytes, while annexin V staining confirmed that this immunosuppressive effect was not due to the induction of lymphocyte apoptosis. These data demonstrate, for the first time, that OMLP-PC immunomodulation, unlike that for mesenchymal stem cells, occurs via a dose- and HLA II–independent mechanism by the release of immunosuppressive soluble factors and suggests these cells may have wide ranging potential in future immune-related therapies. PMID:21988324

  14. 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

  15. 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.

  16. 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

  17. 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

  18. Effects of SCR-3 on the immunosuppression accompanied with the systemic inflammatory response syndrome.

    PubMed

    Li, Jun; Niu, Jie; Ou, Shan; Ye, Zhan-Yong; Liu, Deng-Qun; Wang, Feng-Chao; Su, Yong-Ping; Wang, Jun-Ping

    2012-05-01

    Steroid receptor coactivator-3 (SRC-3) is a multifunctional protein that plays an important role in mammary gland growth, development, and tumorigenesis. In this study, SCR-3 gene knockout mice were used to study the effects of SCR-3 on the immunosuppression accompanied with systemic inflammatory response syndrome (SIRS). Bacterial clearance assay was performed by blood culture and frozen sections, and the results showed that the absence of SCR-3 protein serious damaged the innate immune system and the body's ability to inactivate or phagocytosis of bacteria was significantly decreased, and the absence of SCR-3 protein also weakened phagocytes' ability to degrade bacteria and their metabolites. Furthermore, animal model of inflammatory reaction was established and the immune function was determined, and the results revealed that SRC-3 protein may play an important role in maintenance of T-cells' immune function, and severe T-cell immune function disorder would be resulted once SRC-3 protein is missing. In addition, the results of our study showed the steady-state of lymphocyte subsets was destroyed after SIRS, leading the suppression of cellular immune function, and the absence of SCR-3 protein may aggravate the suppression of T-lymphocyte function. Therefore, the present study demonstrated that the absence of SCR-3 protein would aggravate immunosuppression. In addition, SRC-3 protein is a significant regulator of infection and inflammation, and SRC-3 protein play an essential role in the development of immunosuppression accompanied with SIRS.

  19. [Persistent inflammation immunosuppression catabolism syndrome: a special type of chronic critical illness].

    PubMed

    Ding, Renyu; Ma, Xiaochun

    2016-07-01

    After the concept of "chronic critical illness (CCI)" was proposed, the new concept persistent inflammation immunosuppression catabolism syndrome (PICS) is present recently. Patients with PICS are manifested by fast decreasing body weight, poor nutritional status, long-term immunosuppression and repeated nosocomial infections. These patients are faced with great challenges of persistent inflammation, acquired immunosuppression and high catabolism, which finally results in repeated nosocomial infections, prolonged hospital stay and increased mortality. At present, main problems of PICS diagnosis standard include varying length of ICU stay, difference in normal C reactive protein value, poor value of nutrition indexes, absence of clinical verification. Though associated pathophysiology mechanism is not clear, PICS is preventable and magageable with certain therapy, including early comprehensive prevention and treatment focused on infection control for CCI patients to stop the progression of PICS, application of immune modulator to improve immune function and prognosis of patients, and reasonable nutritional support and treatment. Besides, through the analysis of the association between PICS and CCI, authors draw a conclusion that PICS is a new phenotype of CCI, and immune paralysis is its main feature. PMID:27452746

  20. 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

  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. Personalization of the immunosuppressive treatment in renal transplant recipients: the great challenge in "omics" medicine.

    PubMed

    Zaza, Gianluigi; Granata, Simona; Tomei, Paola; Dalla Gassa, Alessandra; Lupo, Antonio

    2015-01-01

    Renal transplantation represents the most favorable treatment for patients with advanced renal failure and it is followed, in most cases, by a significant enhancement in patients' quality of life. Significant improvements in one-year renal allograft and patients' survival rates have been achieved over the last 10 years primarily as a result of newer immunosuppressive regimens. Despite these notable achievements in the short-term outcome, long-term graft function and survival rates remain less than optimal. Death with a functioning graft and chronic allograft dysfunction result in an annual rate of 3%-5%. In this context, drug toxicity and long-term chronic adverse effects of immunosuppressive medications have a pivotal role. Unfortunately, at the moment, except for the evaluation of trough drug levels, no clinically useful tools are available to correctly manage immunosuppressive therapy. The proper use of these drugs could potentiate therapeutic effects minimizing adverse drug reactions. For this purpose, in the future, "omics" techniques could represent powerful tools that may be employed in clinical practice to routinely aid the personalization of drug treatment according to each patient's genetic makeup. However, it is unquestionable that additional studies and technological advances are needed to standardize and simplify these methodologies.

  3. 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.

  4. Comparison between spousal donor transplantation treated with anti-thymocyte globulin induction therapy and, living related donor transplantation treated with standard immunosuppression.

    PubMed

    Demir, Erkan; Paydas, Saime; Erken, Ugur

    2014-05-01

    The worldwide shortage of organs available for transplantation has led to the use of living-unrelated kidney donors. In this context, spouses represent an important source of organ donors. We compared the allograft outcomes of spousal donor transplantation (SDT) with anti-thymocyte globulin (ATG) induction therapy and living related donor transplantation (LRDT) with triple immonosuppression and basiliximab, in addition. Among the 335 living and deceased donor kidney transplantations performed between April 2001 and June 2010, there were 274 living donor kidney transplantations including 34 SDT and 240 LRDT. The minimum follow-up period was 36 months. All recipients of SDT received ATG (1.5 mg/kg) induction therapy, which was stopped five to seven days after surgery. Maintenance immunosuppression included tacrolimus (TAC), mycophenolate mofetil (MMF) and prednisolone. LRDT recipients received triple immunosuppressive protocol consisting of cyclosporine or TAC, MMF and prednisolone, in addition to basiliximab. There was a significant difference between the two groups in recipient age, while pre-operative duration on dialysis, recipient sex and donor age and sex were not significantly different. There was also a significant difference between the two groups in the number of human leukocyte antigen (HLA) mismatches. The 1-, 3- and 5-year graft survival rates of SDT were 94.1%, 88.2% and 79.4%, respectively, and the frequency of acute rejection episodes was 5.8% (two cases). The 1-, 3- and 5-year graft survival rates of LRDT were 95.8%, 91.6% and 83.3%, respectively, with the frequency of acute rejection being 16.2%. The graft survival rates of SDT were as good as LRDT, while the acute rejection rates in SDT were lower than in LRDT, although the difference was not statistically different (P = 0.13).

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

    PubMed

    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 10(2.55)TCID50/ml, group B 10(5.25)TCID50/ml and group C 10(6.7)TCID 50/ml. A fourth group (D) was inoculated with a medium dose (10(5.25)TCID50/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

  6. Low cost omega navigation receiver

    NASA Technical Reports Server (NTRS)

    Lilley, R. W.

    1974-01-01

    The development of a low cost Omega navigation receiver is discussed. Emphasis is placed on the completion and testing of a modular, multipurpose Omega receiver which utilizes a digital memory-aided, phase-locked loop to provide phase measurement data to a variety of applications interfaces. The functional units contained in the prototype device are described. The receiver is capable of receiving and storing phase measurements for up to eight Omega signals and computes two switch-selectable lines of position, displaying this navigation data in chart-recorded form.

  7. The effect of interferon treatment in rabies prophylaxis in immunocompetent, immunosuppressed, and immunodeficient mice.

    PubMed

    Marcovistz, R; Germano, P M; Rivière, Y; Tsiang, H; Hovanessian, A G

    1987-02-01

    The development of rabies is modulated by many interacting factors, most of which are dependent on the host immune response. For this reason, we studied the action of interferon (IFN) treatment on street rabies virus infection in mice, immunocompetent or immunosuppressed with cyclophosphamide. In immunocompetent mice, paralysis of hind limbs is the first symptom characteristic of rabies disease before weight loss and general prostration leading to death. Paralysis does not occur in immunosuppressed mice, which develop a shaggy hair and eventually lose weight and die. Administration of interferon (10(5) units, intraperitoneally) 1 h after virus inoculation and every 24 h led to a delay in the onset of first disease signs, but in general did not rescue immunocompetent or immunosuppressed mice from death. In both types of mice, rabies virus production in the brain was reduced by 1 log in response to IFN treatment. In immunocompetent mice treated with IFN, there was a significant increase of antibody synthesis against rabies virus. As expected, antibody synthesis in immunosuppressed mice was almost negligible. However, in mice treated with IFN and cyclophosphamide there was still significant antibody synthesis specific for rabies virus. IFN administered intravenously, subcutaneously, or intraperitoneally crosses the blood-brain barrier to cause enhanced levels of the two double-stranded RNA-dependent enzymes, the protein kinase and 2',5'-oligoadenylate (2-5A) synthetase in the brain. However in spite of this effect, IFN treatment seems to be unable to prevent the evolution of rabies disease in immunocompetent and immunosuppressed mice. Since the suppressing effect of cyclophosphamide is nonselective on both the cellular and humoral immune responses of mice, we investigated the action of IFN in rabies virus-infected athymic nude mice, which lack T cells. Athymic nude mice infected with street rabies virus become cachectic and die without any apparent symptom of

  8. 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...

  9. Safety and Efficacy of Granulocyte/Monocyte Apheresis in Steroid-Dependent Active Ulcerative Colitis with Insufficient Response or Intolerance to Immunosuppressants and/or Biologics [the ART Trial]: 12-week Interim Results

    PubMed Central

    Akbar, Ayesha; Hart, Ailsa; Subramanian, Sreedhar; Bommelaer, Gilles; Baumgart, Daniel C.; Grimaud, Jean-Charles; Cadiot, Guillaume; Makins, Richard; Hoque, Syed; Bouguen, Guillaume; Bonaz, Bruno

    2016-01-01

    Background and Aims: Patients with active, steroid-dependent ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologic therapies have limited treatment options. Adacolumn, a granulocyte/monocyte adsorptive apheresis device, has shown clinical benefit in these patients. This study aimed to provide additional clinical data regarding the safety and efficacy of Adacolumn in this patient subgroup. Methods: This single-arm, open-label, multicentre trial [ART] was conducted at 18 centres across the UK, France, and Germany. Eligible patients were 18–75 years old with moderate-to-severe, steroid-dependent active ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologics. Patients received ≥ 5 weekly apheresis sessions with Adacolumn. The primary endpoint was clinical remission rate [clinical activity index ≤ 4] at Week 12. Results: In all, 86 patients were enrolled. At Week 12, 33/84 [39.3%] of patients in the intention-to-treat population achieved clinical remission, with 47/84 [56.0%] achieving a clinical response [clinical activity index reduction of ≥ 3]. Clinical remission was achieved in 30.0% of patients with previous immunosuppressant and biologic failure; steroid-free clinical remission and response were observed in 22.6% and 35.7% of these patients, respectively. Quality of life [Short Health Scale] significantly improved at Week 12 [p < 0.0001]. The majority of adverse events were of mild/moderate intensity. Conclusions: At Week 12, Adacolumn provided significant clinical benefit in a large cohort of steroid-dependent ulcerative colitis patients with previous failure to immunosuppressant and/or biologic treatment, with a favourable safety profile. These results are consistent with previous studies and support Adacolumn use in this difficult-to-treat patient subgroup. PMID:26818659

  10. 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

  11. Receiver design and performance characteristics

    NASA Technical Reports Server (NTRS)

    Simon, M. K.; Yuen, J. H.

    1982-01-01

    The basic design, principles of operation, and characteristics of deep space communications receivers are examined. In particular, the basic fundamentals of phase-locked loop and Costas loop receivers used for synchronization, tracking, and demodulation of phase-coherent signals in residual carrier and suppressed carrier systems are addressed.

  12. Receiver design and performance characteristics

    NASA Astrophysics Data System (ADS)

    Simon, M. K.; Yuen, J. H.

    1982-07-01

    The basic design, principles of operation, and characteristics of deep space communications receivers are examined. In particular, the basic fundamentals of phase-locked loop and Costas loop receivers used for synchronization, tracking, and demodulation of phase-coherent signals in residual carrier and suppressed carrier systems are addressed.

  13. Prostaglandin E2-prostaglandin E receptor subtype 4 (EP4) signaling mediates UV irradiation-induced systemic immunosuppression.

    PubMed

    Soontrapa, Kitipong; Honda, Tetsuya; Sakata, Daiji; Yao, Chengcan; Hirata, Takako; Hori, Shohei; Matsuoka, Toshiyuki; Kita, Yoshihiro; Shimizu, Takao; Kabashima, Kenji; Narumiya, Shuh

    2011-04-19

    UV radiation induces systemic immunosuppression. Because nonsteroidal anti-inflammatory drugs suppress UV-induced immunosuppression, prostanoids have been suspected as a crucial mediator of this UV effect. However, the identity of the prostanoid involved and its mechanism of action remain unclear. Here, we addressed this issue by subjecting mice deficient in each prostanoid receptor individually or mice treated with a subtype-specific antagonist to UV irradiation. Mice treated with an antagonist for prostaglandin E receptor subtype 4 (EP4), but not those deficient in other prostanoid receptors, show impaired UV-induced immunosuppression, whereas administration of an EP4 agonist rescues the impairment of the UV-induced immunosuppression in indomethacin-treated mice. The EP4 antagonist treatment suppresses an increase in the number of CD4(+)/forkhead box P3-positive (Foxp3(+)) regulatory T cells (Treg cells) in the peripheral lymph nodes (LNs) and dendritic cells expressing DEC205 in the LNs and the skin after UV irradiation. Furthermore, the EP4 antagonist treatment down-regulates UV-induced expression of receptor activator of NF-κB ligand (RANKL) in skin keratinocytes. Finally, administration of anti-RANKL antibody abolishes the restoration of UV-induced immunosuppression by EP4 agonism in indomethacin-treated mice. Thus, prostaglandin E(2) (PGE(2))-EP4 signaling mediates UV-induced immunosuppression by elevating the number of Treg cells through regulation of RANKL expression in the epidermis.

  14. 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.

  15. 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.

  16. Noise Stability of SIS Receivers

    NASA Astrophysics Data System (ADS)

    Kooi, J. W.; Chattopadhyay, G.; Thielman, M.; Phillips, T. G.; Schieder, R.

    2000-05-01

    There is a strong interest in the submillimeter astronomy community to increase the IF bandwidth of SIS receivers in order to better facilitate broad spectral linewidth and continuum observations of extragalactic sources. However, with an increase in receiver IF bandwidth there is a decrease in the mixer stability. This in turn effects the integration efficiency and quality of the measurement. In order to better understand the noise mechanisms responsible for reducing the receiver stability, we employed a technique first described by D.W. Allan and later elaborated upon by Schieder et al. In this paper we address a variety of factors that degrade the noise stability of SIS receivers. The goal of this exercise is to make recommendations aimed at maximizing SIS receiver stability.

  17. Dual relationships and professional boundaries.

    PubMed

    Kagle, J D; Giebelhausen, P N

    1994-03-01

    Social workers enter into dual relationships when they engage in more than one relationship with a client, becoming social worker and friend, employer, teacher, business associate, or sex partner. This article reviews the research on dual relationships in the therapeutic professions and outlines the legal, ethical, and practice issues involved. The article defines dual relationships as boundary violations and provides a case example to show how even a posttermination friendship can be harmful to a client. Recommendations for preventing and responding to dual relationships are included.

  18. 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

  19. 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

    2015-09-28

    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.

  20. 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.

  1. 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.

  2. Dual cure photocatalyst systems

    SciTech Connect

    DeVoe, R.J.; Brown-Wensley, K.A.; Holmes, G.L.; Mathis, M.D.; McCormick, F.B.; Palazzotto, M.C.; Spurgeon, K.M. . Corporate Research Labs.)

    1990-01-01

    A family of dual cure photocatalyst systems is being developed to be used in the solventless processing of organic coatings. The photocatalyst systems consist of organometallic compounds often in combination with other agents. Upon photolysis, the photocatalyst system generates a Lewis acid and a free radical. The Lewis acid can initiate the polymerization of epoxies or the addition of isocyanates and polyols to form polyurethanes while the free radical can initiate the polymerization of acrylates. The performance of the various photocatalyst systems will be compared on the basis of the physical properties of the cured compositions they produce. 17 figs.

  3. Immunosuppressive therapy of cyclosporin A for severe benzene-induced haematopoietic disorders and a 6-month follow-up.

    PubMed

    Song, Yuguo; Du, Xuqin; Hao, Fentong; Gu, Xiaoxin; Zhang, Zhenghua; Zhang, Songquan; Li, Chunsheng; Li, Huiling; Ma, Jing

    2010-06-01

    Long-term exposure to benzene can potentially result in severe haematotoxicities, including pancytopaenia, aplastic anaemia and myelodysplastic syndrome, which are often accompanied by life-threatening symptoms and high mortality. Previous studies demonstrate that benzene-induced haematotoxicities are immune-mediated and that cyclosporin A is a prominent treatment in acquired aplastic anaemia. This study aims to evaluate the potential role of cyclosporin A immunosuppressive therapy for severe benzene-induced haematotoxicity. Between January 2002 and December 2008, 41 patients with severe benzene-induced haematopoietic disorders from five hospitals were enrolled in the study, 22 patients received cyclosporin A, supportive treatments and/or oral testosterone undecanoate, 19 patients were treated with supportive treatments and/or oral testosterone undecanoate as the control group, and a 6-month follow-up was conducted. The results showed that in the cyclosporin A group, 19 of 22 patients (86.36%) had responded to the treatments completely or partially with increased platelets, white blood cells and hemoglobulin counts by the fourth week (P=0.005), the sixth week (P=0.001) and the third month post-treatment (P=0.034), respectively. However, in the control group treated by supportive methods, only 5 of 19 patients (26.32%) responded to the treatments partially (P<0.001). Cyclosporin A in conjunction with supportive treatments may be an effective treatment modality for patients with severe benzene-induced haematopoietic disorders, which in turn implies that these haematotoxicities are immune-mediated. PMID:20381478

  4. Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning: a nationwide study.

    PubMed

    Wu, Wen-Pyng; Lai, Ming-Nan; Lin, Ching-Heng; Li, Yu-Fen; Lin, Ching-Yuang; Wu, Ming-Ju

    2014-01-01

    Paraquat poisoning associates very high mortality rate. Early treatment with hemoperfusion is strongly suggested by animal and human studies. Although the survival benefit of additional immunosuppressive treatment (IST) in combination with hemoperfusion is also reported since 1971, the large-scale randomized control trials to confirm the effects of IST is difficult to be executed. Therefore, we designed this nationwide large-scale population-based retrospective cohort study to investigate the outcome of paraquat poisoning with hemoperfusion and the additional effects of IST combined with hemoperfusion. This nationwide retrospective cohort study utilized data retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 1811 hospitalized patients with a diagnosis of paraquat poisoning who received hemoperfusion between 1997 and 2009 were enrolled. The mean age of all 1811 study subjects was 47.3 years. 70% was male. The overall survival rate was only 26.4%. Respiratory failure and renal failure were diagnosed in 56.2% and 36% patients. The average frequency of hemoperfusion was twice. IST was added in 42.2% patients. IST significantly increases survival rate (from 24.3% to 29.3%, P<0.001). The combined IST with methylprednisolone, cyclophosphamide and dexamethasone associates with the highest survival rate (48%, P<0.001). Moreover, patients younger than 45 years of age in the IST group had the best survival (41.0% vs. 33.7%, p<0.001). Our results support the use of IST with hemoperfusion for paraquat-poisoned patients. The best survival effect of IST is the combination of methylprednisolone, cyclophosphamide and daily dexamethasone, especially in patients with younger age.

  5. 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

  6. Sensitivity of terahertz photonic receivers

    NASA Astrophysics Data System (ADS)

    Matsko, A. B.; Strekalov, D. V.; Yu, N.

    2008-04-01

    We theoretically discuss sensitivity limitations of a THz receiver which is based on up-conversion of the THz radiation into optical domain using high quality factor crystalline whispering gallery mode resonators. We show that the sensitivity of the receiver operating in the nonlinear regime approaches the sensitivity of an ideal THz photon counter. Thermal noise of the counter can be substantially reduced because of transparency of the nonlinear material in the THz frequency range. We also show that the density of power fluctuations of the receiver operating in the linear regime is given by the THz shot noise.

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

    SciTech Connect

    Wang, Ding; Chen, Ke; Du, Wei Ting; Han, Zhi-Bo; Ren, He; Chi, Ying; 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.

  8. Pretreatment of donor islets with papain improves allograft survival without systemic immunosuppression in mice.

    PubMed

    Kumano, Kenjiro; Nishinakamura, Hitomi; Mera, Toshiyuki; Itoh, Takeshi; Takahashi, Hiroyuki; Fujiwara, Toshiyoshi; Kodama, Shohta

    2016-09-01

    Although current immunosuppression protocols improve the efficacy of clinical allogenic islet transplantation, T cell-mediated allorejection remains unresolved, and major histocompatibility complexes (MHCs) play a crucial role in this process. Papain, a cysteine protease, has the unique ability to cleave the extracellular domain of the MHC class I structure. We hypothesized that pretreatment of donor islets with papain would diminish the expression of MHC class I on islets, reducing allograft immunogenicity and contributing to prolongation of islet allograft survival. BALB/c islets pretreated with papain were transplanted into C57BL/6J mice as an acute allorejection model. Treatment with 1 mg/mL papain significantly prolonged islet allograft survival. In vitro, to determine the inhibitory effect on T cell-mediated alloreactions, we performed lymphocyte proliferation assays and mixed lymphocyte reactions. Host T cell activation against allogenic islet cells was remarkably suppressed by pretreatment of donor islet cells with 10 mg/mL papain. Flow cytometric analysis was also performed to investigate the effect of papain treatment on the expression of MHC class I on islets. One or 10 mg/mL papain treatment reduced MHC class I expression on the islet cell surface. Pretreatment of donor islets with papain suppresses MHC class I-mediated allograft rejection in mice and contributes to prolongation of islet allograft survival without administration of systemic immunosuppressants. These results suggest that pretreatment of human donor islets with papain may reduce the immunogenicity of the donor islets and minimize the dosage of systemic immunosuppressants required in a clinical setting. PMID:27618231

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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

    2013-12-06

    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

  14. Effects of Lactobacillus plantarum NCU116 on Intestine Mucosal Immunity in Immunosuppressed Mice.

    PubMed

    Xie, Junhua; Yu, Qiang; Nie, Shaoping; Fan, Songtao; Xiong, Tao; Xie, Mingyong

    2015-12-30

    The effects of Lactobacillus plantarum (L. plantarum) NCU116 isolated from pickled vegetables on intestine mucosal immunity in cyclophosphamide treated mice were investigated. Animals were divided into six groups: normal group (NIM), immunosuppression group (IM), immunosuppression plus L. plantarum NCU116 groups with three different doses (NCU-H, NCU-M, and NCU-L), and plus Bifidobacterium BB12 as positive control group (BB12). Results showed that the thymus indexes of the four treatment groups were significantly higher than that of the IM group (2.02 ± 0.16) (p < 0.05) and close to the index of the NIM group (2.61 ± 0.37) at 10 days. The level of immune factor IL-2 notably increased (IM, 121 ± 9.0) (p < 0.05) and was close to 65% of NIM group's level (230 ± 10.7). The levels of other immune factors (IFN-γ, IL-10, IL-12p70, and sIgA), the gene expression levels of IL-2 and IFN-γ, and the number of IgA-secreting cells showed similar patterns (p < 0.05). However, the level of immune factor IL-4 remarkably decreased (IM, 128 ± 10.2) (p < 0.05) and was only approximately 50% of the NIM group (154 ± 18.2). The levels of other immune factors (IL-6 and IgE) and the gene expression level of IL-6 at 10 days exhibited similar changes (p < 0.05) but showed a slight recovery at 20 days, accompanied by the altered protein expression levels of T-bet and GATA-3 in the small intestine. These findings suggest that L. plantarum NCU116 enhanced the immunity of the small intestine in the immunosuppressed mice.

  15. 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

  16. Preventive and therapeutic effects of sugar cane extract on cyclophosphamide-induced immunosuppression in chickens.

    PubMed

    El-Abasy, Moshira; Motobu, Maki; Nakamura, Kikuyasu; Koge, Kenji; Onodera, Takashi; Vainio, Olli; Toivanen, Paavo; Hirota, Yoshikazu

    2004-08-01

    Effects of oral administration of sugar cane extract (SCE) on immunosuppression in chickens treated with cyclophosphamide (CPA) were evaluated. Three-week-old inbred chickens were inoculated into the crop with SCE (500 mg/kg/day) for three consecutive days before or after injection of CPA 12 or 20 mg/chicken. At the last day of SCE or CPA treatment, all chickens were immunized intravenously with sheep red blood cells (SRBC) and Brucella abortus (BA). Chickens administered SCE showed a significant increase in body weight, gain in body weight/day, relative weight of the bursa of Fabricius and antibody responses to SRBC and BA than untreated control chickens. Chickens injected with CPA alone showed significantly decreased body weight, gain in body weight/day, relative weight of the bursa and antibody responses to SRBC and BA, showing immunosuppression in the bursa-dependent immune system. All chickens administered SCE before or after the treatment with CPA showed significantly higher values in body weight, gain in body weight/day, relative bursal weight and antibody responses to both antigens, when compared to chickens treated with CPA alone. In histological examination, chickens administered SCE showed a typical bursa with well constituted follicles, although chickens treated with CPA alone showed a severely atrophied bursa with rudimentary follicles and enormous proliferation of interfollicular connective tissue. Chickens treated with SCE and CPA showed a well-reconstituted bursa with almost normal structure. These results suggest that SCE has functionally and morphologically reconstituting effects on the bursa-dependent immune system in immunosuppressed chickens induced by injection of CPA.

  17. Effects of Lactobacillus plantarum NCU116 on Intestine Mucosal Immunity in Immunosuppressed Mice.

    PubMed

    Xie, Junhua; Yu, Qiang; Nie, Shaoping; Fan, Songtao; Xiong, Tao; Xie, Mingyong

    2015-12-30

    The effects of Lactobacillus plantarum (L. plantarum) NCU116 isolated from pickled vegetables on intestine mucosal immunity in cyclophosphamide treated mice were investigated. Animals were divided into six groups: normal group (NIM), immunosuppression group (IM), immunosuppression plus L. plantarum NCU116 groups with three different doses (NCU-H, NCU-M, and NCU-L), and plus Bifidobacterium BB12 as positive control group (BB12). Results showed that the thymus indexes of the four treatment groups were significantly higher than that of the IM group (2.02 ± 0.16) (p < 0.05) and close to the index of the NIM group (2.61 ± 0.37) at 10 days. The level of immune factor IL-2 notably increased (IM, 121 ± 9.0) (p < 0.05) and was close to 65% of NIM group's level (230 ± 10.7). The levels of other immune factors (IFN-γ, IL-10, IL-12p70, and sIgA), the gene expression levels of IL-2 and IFN-γ, and the number of IgA-secreting cells showed similar patterns (p < 0.05). However, the level of immune factor IL-4 remarkably decreased (IM, 128 ± 10.2) (p < 0.05) and was only approximately 50% of the NIM group (154 ± 18.2). The levels of other immune factors (IL-6 and IgE) and the gene expression level of IL-6 at 10 days exhibited similar changes (p < 0.05) but showed a slight recovery at 20 days, accompanied by the altered protein expression levels of T-bet and GATA-3 in the small intestine. These findings suggest that L. plantarum NCU116 enhanced the immunity of the small intestine in the immunosuppressed mice. PMID:26651209

  18. Mifepristone (RU486) restores humoral and T cell-mediated immune response in endotoxin immunosuppressed mice.

    PubMed

    Rearte, B; Maglioco, A; Balboa, L; Bruzzo, J; Landoni, V I; Laborde, E A; Chiarella, P; Ruggiero, R A; Fernández, G C; Isturiz, M A

    2010-12-01

    Sepsis and septic shock can be caused by Gram-positive and -negative bacteria and other microorganisms. In the case of Gram-negative bacteria, endotoxin, a normal constituent of the bacterial wall, also known as lipopolysaccharide (LPS), has been considered as one of the principal agents causing the undesirable effects in this critical illness. The response to LPS involves a rapid secretion of proinflammatory cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, interferon (IFN)-γ and the concomitant induction of anti-inflammatory mediators such as IL-10, transforming growth factor (TGF)-β or glucocorticoids, which render the host temporarily refractory to subsequent lethal doses of LPS challenge in a process known as LPS or endotoxin tolerance. Although protective from the development of sepsis or systemic inflammation, endotoxin tolerance has also been pointed out as the main cause of the non-specific humoral and cellular immunosuppression described in these patients. In this report we demonstrate, using a mouse model, that mifepristone (RU486), a known glucocorticoid receptor antagonist, could play an important role in the restoration of both adaptive humoral and cellular immune response in LPS immunosuppressed mice, suggesting the involvement of endogenous glucocorticoids in this phenomenon. On the other hand, using cyclophosphamide and gemcitabine, we demonstrated that regulatory/suppressor CD4(+) CD25(+) forkhead boxP3(+) and GR-1(+) CD11b(+) cells do not play a major role in the establishment or the maintenance of endotoxin tolerance, a central mechanism for inducing an immunosuppression state. PMID:20964639

  19. Dual fluorescence of syringaldazine

    NASA Astrophysics Data System (ADS)

    Rajendiran, N.; Balasubramanian, T.

    2007-11-01

    The absorption and fluorescence spectra of syringaldazine (SYAZ) has been recorded in solvents of different polarity, pH and β-cyclodextrin (β-CD) and compared with syringaldehyde (SYAL). The inclusion complex of SYAZ with β-CD is investigated by UV-vis, fluorimetry, AM 1, FT-IR, 1H NMR and scanning electron microscope (SEM). Δ G value suggests the inclusion process is an exothermic and spontaneous. In all solvents a dual fluorescence is observed for SYAZ, whereas, SYAL shows a dual luminescence only in polar solvents. The excitation spectra for the 410 nm is different from 340 nm indicate two different species present in this molecule. In pH solutions: (i) a large red shifted maxima is observed in the dianion and is due to large interactions between the aromatic ring and (ii) the large blue shift at pH ˜4.5, is due to dissociation of azine group and formation of aldehyde. β-CD studies reveal that, SYAZ forms a 1:2 complex from 1:1 complex with β-CD.

  20. 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.

  1. Stevenson received the Whipple award

    NASA Astrophysics Data System (ADS)

    Shoemaker, Eugene M.; Stevenson, David J.

    1996-02-01

    David J. Stevenson received the Whipple Award at the 1994 Spring Meeting in Baltimore. The award is given for outstanding scientific contributions to the field of planetology. The citation and Stevenson's response are given here.

  2. [Tropical sprue as a differential diagnosis to coeliac disease in a patient on immunosuppressive medication].

    PubMed

    Hvattum, Stine Astrup; Schaffalitzky de Muckadell, Ove B

    2014-01-01

    A Danish woman who was on immunosuppressive medication due to a previous liver transplantation travelled to Indonesia for three weeks. After returning she developed nonfebrile severe, watery diarrhoea, dehydration and malnutrition. A thorough examination revealed small intestine changes, which were compatible with coeliac disease. However, the HLA-type and the serology did not support this diagnosis. Treatment for tropical sprue was initiated, resulting in complete remission. Tropical sprue is suggested to be an infectious disease. It is usually seen in people with prolonged stay in tropical areas, but this patient's medication may have predisposed her.

  3. Effects of methyl substitutions on benz[a]anthracene derivatives-induced immunosuppression

    SciTech Connect

    Saas, P.; Bohuon, C.; Pallardy, M.

    1996-11-01

    Polycyclic aromatic-hydrocarbons are ubiquitous environmental contaminants known to be carcinogenic as well as immunosuppressive. Structure-activity studies have demonstrated that modifications in the number of methyl groups of benzanthracenic compounds lead to major changes in their biological activities such as induction of tumors. In the present study, we investigated the immunosuppressive effects of three benzanthracene derivatives differing by number or position of methyl radicals. 7,12-Dimethylbenz[a]anthracene, 12-methylbenz[a]anthracene, and 7-methylbenz[a]anthracene were tested for their ability to inhibit T-cell proliferation. For this purpose, we employed an in vitro activation model utilizing concanavalin A (ConA) or anti-CD3 monoclonal antibody (anti-CD3 mAb) to induce proliferation of murine T-lymphocytes form B6C3F1 mice. The three compounds inhibited splenocyte proliferation stimulated with anti-CD3 mAb, whereas DMBA and 12-MBA, but not 7-MBA, inhibited ConA-induced lymphoproliferation. Results concerning parameters involving interleukin-2 (IL-2) were correlated with those obtained for lymphoproliferation. IL-2 production and number of IL-2 receptors (IL-2R) per cell were inhibited by the three molecules tested, except for IL-2 production following ConA activation cells treated with 7-MBA. Only DMBA profoundly affected IL-2 responsiveness, suggesting that this compound may inhibit both G0 to G1 and G1 to S transitions of the cell cycle. Addition of exogenous cytokines such as IL-1 and IL-6 with IL-2, or L-2 alone, suggested that, for the three compounds tested, IL-1 and IL-6 production are not involved in benz[a]anthracene-induced immunosuppression. These results demonstrate that methylation at both 7 and 12 positions of the benzanthracene ring significantly enhances immunosuppression. DMBA may act on signal transduction mediated by the T-cell receptor (TCR) and the IL-2R, while this is not the case for 7-MBA and 12-MBA. 32 refs., 5 figs., 1 tab.

  4. [Long-term course of immunosuppressive therapy of Vogt-Koyanagi-Harada syndrome].

    PubMed

    Wand, K; Abraham, S; Loos, D; Stumpfe, S; Lohmann, C; Maier, M; Feucht, N

    2015-10-01

    This article describes the case of a 22-year old female patient, who first presented with holocephalic headaches and bilateral loss in vision. After diagnosis of a complete Vogt-Koyanagi-Harada syndrome, high-dose corticosteroid therapy was initiated. Due to recurrent headaches 6 weeks later, immunosuppressive therapy was initiated with cyclosporine A. Because of an adverse effect (hirsutism) treatment was changed to azathioprine. In a long-term follow-up over 2 years the patient showed stable clinical findings with good visual acuity.

  5. Discodermolide--a new, marine-derived immunosuppressive compound. II. In vivo studies.

    PubMed

    Longley, R E; Caddigan, D; Harmody, D; Gunasekera, M; Gunasekera, S P

    1991-10-01

    The in vivo immunosuppressive properties of a novel, marine-derived compound, discodermolide, are reported here. Discodermolide was effective in suppressing the graft-versus-host splenomegaly response of BALB/c----CB6F1 (BALB/c X C57BL/6J)F1 grafted mice at 5.0, 2.5, and 1.25 mg/kg, when administered as daily, i.p. injections, for 7 days. Mice treated with 5.0 and 2.5 mg/kg demonstrated a high degree of suppression (219 and 150%, respectively); however, these dosages were associated with some degree of morbidity (2/5 and 4/5 survivors for 5.0 and 2.5 mg/kg, respectively). Mice that were treated with 1.25, 0.625, and 0.313 mg/kg remained healthy after a 7-day regimen, and continued to demonstrate suppression of splenomegaly (106%, 72%, and 76% suppression, respectively). Splenocytes obtained from discodermolide-treated, allogeneic grafted mice were suppressed in their ability to respond in vitro to optimal mitogenic concentrations of concanavalin A, and natural-killer-cell activity directed against YAC-1 tumor cells, compared with vehicle-treated, allogeneic grafted control mice. Lower dosages (2.5 and 1.25 mg/kg) of discodermolide, however, did not affect the subsequent ability of splenocytes obtained from these mice to produce IL-2 following in vitro stimulation with Con A. This was observed to be in contrast to the immunosuppressive activity observed with cyclosporine treatment of mice (150 mg/kg) for the ex vivo suppression of splenocyte production of IL-2. Treatment of normal, nongrafted mice with similar high dosages of discodermolide (5.0 mg/kg) for 4 days did not affect the primary antibody response of mice immunized with sheep red blood cells as measured by hemagglutination activity of their serum. These results suggest that discodermolide's in vivo immunosuppressive action appears not to be that of a generalized immunosuppressive agent and that its specific in vivo mechanism of action warrants further preclinical evaluation.

  6. Spontaneous septic arthritis in a patient without trauma, coinfection, or immunosuppression.

    PubMed

    Griffin, Peter L; Griffin, Gregory D; Simon, Erin L

    2013-11-01

    Septic arthritis is a rare infection, most often affecting the knee and hip [1]. Infections are often secondary to joint repair or replacement surgery, systemic infection, or intravenous recreational drug use [1,2].Diabetes, rheumatoid arthritis, hepatic dysfunction, and immunosuppression are common risk factors [1,2]. Although septic arthritis can occur spontaneously, such occurrences are rare. We report a case of a previously healthy 54-year-old woman with no known risk factors presenting to a freestanding emergency department with 5 days of shoulder pain.

  7. Early pregnancy factor is an immunosuppressive contaminant of commercial preparations of human chorionic gonadotrophin.

    PubMed Central

    Rolfe, B E; Morton, H; Clarke, F M

    1983-01-01

    Early pregnancy factor (EPF) is a pregnancy associated substance detected in human serum and urine throughout the first and second trimesters of pregnancy. It has also been detected in several commercial preparations of human chorionic gonadotrophin (hCG). The various molecular weight forms of EPF which occur in human pregnancy serum, urine and commercial hCG preparations have been partially characterized and found to be similar to each other but distinct from hCG. Further evidence is presented which suggests that it is EPF rather than hCG which is responsible for the immunosuppressive activity of some crude hCG preparations. PMID:6831771

  8. Relationship between the immunosuppressive potential and the pathotype of Marek's disease virus isolates.

    PubMed

    Calnek, B W; Harris, R W; Buscaglia, C; Schat, K A; Lucio, B

    1998-01-01

    Isolates of Marek's disease virus (MDV) representing three pathotypes of differing virulence were compared for relative immunosuppressive properties in genetically susceptible P2a-strain and genetically resistant N2a-strain chickens. Criteria of immunosuppression were 1) persistence of early cytolytic infection (i.e., a delay or failure to enter latency) in lymphoid organs, 2) atrophy of the bursa of Fabricius and thymus as measured by organ weight proportional to body weight at 8 and 14 days postinfection (DPI), and 3) histopathologic evidence of necrosis and atrophy in lymphoid organs. No significant differences in infection level were observed among the pathotypes during the early (4-5 DPI) period of infection. However, the extent of persistent cytolytic infection at 7-8 DPI, based on numbers of tissues positive and mean scores in immunofluorescence tests, was greater (P < 0.05) for three isolates (RK1, 584A, 648A) in the highest virulence pathotype (very virulent-plus MDV [vv + MDV]) than for two isolates (JM16, GA5) in a lower virulence (virulent MDV [vMDV]) pathotype. Results from two isolates (RB1B, Md5) classified in the intermediate very virulent pathotype (very virulent MDV [vvMDV]) fell between those from the other two pathotypes. Similarly, there was a stepwise effect of viral pathotype in which the vv + MDV isolates caused the most severe damage to lymphoid organs in terms of atrophy (relative organ weights) and histopathologic changes. Organs from chickens infected with vv + MDVs showed little recovery between 8 and 14 DPI. The vMDV isolates caused the least severe damage, and lymphoid organs showed a significant return toward normal by 14 DPI; vvMDV isolates induced intermediate degrees of atrophy and recovery. The same pattern of relationship between virulence pathotype and degree of bursal and thymic atrophy was also observed in genetically resistant N2a chickens. These results suggest that the degree of immunosuppression is linked to virulence and

  9. [Anti-inflammatory and immunosuppressive effects of laser therapy in patients with rheumatoid arthritis].

    PubMed

    Tupikin, G V

    1985-01-01

    The clinical and laboratory findings were examined of 10 patients with seropositive rheumatoid arthritis (RA) treated with a first applied technique of intravenous irradiation of the circulating blood with helium-neon laser combined with external irradiation of the inflamed joints. A distinct antiinflammatory and immunosuppressant effect was attained in all the RA patients. In 80% of the test subjects, the rheumatoid blood factor reduced to 1:20 titres. The treatment method did not cause any side effects or complications and shortened the time of the patients' stay at hospital. PMID:4071434

  10. 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…

  11. Benefits of Dual Language Education

    ERIC Educational Resources Information Center

    Wallstrum, Kiara

    2009-01-01

    The focus of this paper examines how dual language education (DLE) programs are valuable. The literature shows that children do much more than just thrive in a dual language environment. According to research, children who are bilingual are cognitively, academically, intellectually, socially and verbally more advantaged than their monolingual…

  12. Overexpression of Glutamate Decarboxylase in Mesenchymal Stem Cells Enhances Their Immunosuppressive Properties and Increases GABA and Nitric Oxide Levels

    PubMed Central

    González, Marisol; Vilches, Rodrigo; Rojas, Pablo; Vásquez, Manuel; Kurte, Mónica; Vega-Letter, Ana María; Carrión, Flavio; Figueroa, Fernando; Rojas, Patricio; Irarrázabal, Carlos

    2016-01-01

    The neurotransmitter GABA has been recently identified as a potent immunosuppressive agent that targets both innate and adaptive immune systems and prevents disease progression of several autoimmunity models. Mesenchymal stem cells (MSCs) are self-renewing progenitor cells that differentiate into various cell types under specific conditions, including neurons. In addition, MSC possess strong immunosuppressive capabilities. Upon cytokine priming, undifferentiated MSC suppress T-cell proliferation via cell-to-cell contact mechanisms and the secretion of soluble factors like nitric oxide, prostaglandin E2 and IDO. Although MSC and MSC-derived neuron-like cells express some GABAergic markers in vitro, the role for GABAergic signaling in MSC-mediated immunosuppression remains completely unexplored. Here, we demonstrate that pro-inflammatory cytokines selectively regulate GAD-67 expression in murine bone marrow-MSC. However, expression of GAD-65 is required for maximal GABA release by MSC. Gain of function experiments using GAD-67 and GAD-65 co-expression demonstrates that GAD increases immunosuppressive function in the absence of pro-inflammatory licensing. Moreover, GAD expression in MSC evokes an increase in both GABA and NO levels in the supernatants of co-cultured MSC with activated splenocytes. Notably, the increase in NO levels by GAD expression was not observed in cultures of isolated MSC expressing GAD, suggesting crosstalk between these two pathways in the setting of immunosuppression. These results indicate that GAD expression increases MSC-mediated immunosuppression via secretion of immunosuppressive agents. Our findings may help reconsider GABAergic activation in MSC for immunological disorders. PMID:27662193

  13. Solar dynamic heat receiver technology

    NASA Technical Reports Server (NTRS)

    Sedgwick, Leigh M.

    1991-01-01

    A full-size, solar dynamic heat receiver was designed to meet the requirements specified for electrical power modules on the U.S. Space Station, Freedom. The heat receiver supplies thermal energy to power a heat engine in a closed Brayton cycle using a mixture of helium-xenon gas as the working fluid. The electrical power output of the engine, 25 kW, requires a 100 kW thermal input throughout a 90 minute orbit, including when the spacecraft is eclipsed for up to 36 minutes from the sun. The heat receiver employs an integral thermal energy storage system utilizing the latent heat available through the phase change of a high-temperature salt mixture. A near eutectic mixture of lithium fluoride and calcium difluoride is used as the phase change material. The salt is contained within a felt metal matrix which enhances heat transfer and controls the salt void distribution during solidification. Fabrication of the receiver is complete and it was delivered to NASA for verification testing in a simulated low-Earth-orbit environment. This document reviews the receiver design and describes its fabrication history. The major elements required to operate the receiver during testing are also described.

  14. Post-traumatic immunosuppression is reversed by anti-coagulated salvaged blood transfusion: deductions from studying immune status after knee arthroplasty

    PubMed Central

    Islam, N; Whitehouse, M; Mehendale, S; Hall, M; Tierney, J; O'Connell, E; Blom, A; Bannister,, G; Hinde, J; Ceredig, R; Bradley, B A

    2014-01-01

    Major trauma increases vulnerability to systemic infections due to poorly defined immunosuppressive mechanisms. It confers no evolutionary advantage. Our objective was to develop better biomarkers of post-traumatic immunosuppression (PTI) and to extend our observation that PTI was reversed by anti-coagulated salvaged blood transfusion, in the knowledge that others have shown that non-anti-coagulated (fibrinolysed) salvaged blood was immunosuppressive. A prospective non-randomized cohort study of patients undergoing primary total knee arthroplasty included 25 who received salvaged blood transfusions collected post-operatively into acid–citrate–dextrose anti-coagulant (ASBT cohort), and 18 non-transfused patients (NSBT cohort). Biomarkers of sterile trauma included haematological values, damage-associated molecular patterns (DAMPs), cytokines and chemokines. Salvaged blood was analysed within 1 and 6 h after commencing collection. Biomarkers were expressed as fold-changes over preoperative values. Certain biomarkers of sterile trauma were common to all 43 patients, including supranormal levels of: interleukin (IL)-6, IL-1-receptor-antagonist, IL-8, heat shock protein-70 and calgranulin-S100-A8/9. Other proinflammatory biomarkers which were subnormal in NSBT became supranormal in ASBT patients, including IL-1β, IL-2, IL-17A, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and annexin-A2. Furthermore, ASBT exhibited subnormal levels of anti-inflammatory biomarkers: IL-4, IL-5, IL-10 and IL-13. Salvaged blood analyses revealed sustained high levels of IL-9, IL-10 and certain DAMPs, including calgranulin-S100-A8/9, alpha-defensin and heat shock proteins 27, 60 and 70. Active synthesis during salvaged blood collection yielded increasingly elevated levels of annexin-A2, IL-1β, Il-1-receptor-antagonist, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-γ, TNF-α, transforming growth factor (TGF)-β1, monocyte chemotactic protein-1 and macrophage inflammatory

  15. Phlyctenular keratoconjunctivitis – an atypically severe case treated with systemic biologic immunosuppressive therapy

    PubMed Central

    Valério Sequeira Valadares, Joana; Bastos-Carvalho, Ana; Pedroso Franco, José Manuel; Mourão, Ana Filipa; Monteiro-Grillo, Manuel

    2014-01-01

    Purpose: To report an atypically severe and refractory phlyctenular keratoconjunctivitis case treated successfully with systemic biologic immunosuppressive therapy. Methods: A 10-year-old female was followed in the ophthalmology clinic for three years for a severe form of bilateral PKC. The patient was treated for blepharitis and intestinal parasitosis, and underwent topical corticosteroid therapy, followed by subconjunctival injections and systemic corticosteroids with no clinical improvement. An association of topical cyclosporine A and oral methotrexate had no clinical response either. Phlyctenae of the cornea remained evident with neovascularization, progressive peripheral corneal thinning and occasional anterior chamber reaction. Results: The patient was treated with a combination of infliximab and methotrexate and corticosteroid therapy was tapered, with a fast and sustained resolution of the symptoms and corneal signs. Eleven months past initiation of the treatment, the patient remains asymptomatic and without any recurrence of the disease. Conclusion: Phlyctenular keratoconjunctivitis may present with a broad spectrum of symptoms and signs, and its severity varies significantly. In cases of severe PKC, which are refractory to conventional therapy, systemic biologic immunosuppressive therapy may be a valuable alternative.

  16. Effective delivery of immunosuppressive drug molecules by silica coated iron oxide nanoparticles.

    PubMed

    Hwang, Jangsun; Lee, Eunwon; Kim, Jieun; Seo, Youngmin; Lee, Kwan Hong; Hong, Jong Wook; Gilad, Assaf A; Park, Hansoo; Choi, Jonghoon

    2016-06-01

    Iron oxide nanoparticles have been used in a wide range of biomedical applications, including drug delivery, molecular imaging, and cellular imaging. Various surface modifications have been applied to the particles to stabilize their surface and to give them a moiety for anchoring tags and/or drug molecules. Conventional methods of delivering immunosuppressant drugs often require a high dose of drugs to ensure therapeutic effects, but this can lead to toxic side effects. In this study, we used silica-coated iron oxide nanoparticles (IOSs) for a drug delivery application in which the nanoparticles carry the minimum amount of drug required to be effective to the target cells. IOSs could be loaded with water-insoluble immunosuppressive drug molecules (MPA: mycophenolic acid) and be used as a contrast agent for MRI. We characterized the IOSs for their physicochemical properties and found their average hydrodynamic diameter and core size to be 40.5nm and 5nm, respectively. Following the introduction of MPA-loaded IOSs (IOS/M), we evaluated the secretion dynamics of cytokines from peripheral blood mononuclear cells stimulated with phytohemagglutinin (PHA). The results showed that IOS/M effectively inhibited the secretion of the cytokines interleukin-2 and tumor necrosis factor α, with a minimal concentration of MPA. In conclusion, IOS/M may have potential applications in both efficient drug delivery and MRI. PMID:26966999

  17. Immunosuppression promotes CNS remyelination in chronic virus-induced demyelinating disease.

    PubMed

    Rodriguez, M; Lindsley, M D

    1992-02-01

    Immunosuppression using cyclophosphamide or anti-T cell monoclonal antibodies (mAbs) directed at CD4 or CD8 promoted remyelination of CNS axons in the spinal cords of mice infected chronically with Theiler's virus. Treatment with a mAb directed at class II major histocompatibility gene products did not increase the extent of CNS remyelination. Following immunosuppressive treatment, quantitative morphometry revealed a five- to sevenfold increase in new myelin synthesis. Proliferating nervous system cells were identified at the edges of remyelinated lesions by their incorporation of [3H]thymidine. CNS remyelination occurred in mice depleted of selected subsets of T lymphocytes despite the local persistence of viral antigen. These findings indicate that CNS remyelination occurs as a normal consequence of primary myelin injury, but factors associated with immune T cells somehow impair remyelination. Interference with the function of immune T cells enhances CNS remyelination by oligodendrocytes. Similar depletion of immune T cells may allow for enhanced remyelination in the CNS of patients with chronic multiple sclerosis.

  18. Canine Distemper Virus Epithelial Cell Infection Is Required for Clinical Disease but Not for Immunosuppression

    PubMed Central

    Sawatsky, Bevan; Wong, Xiao-Xiang; Hinkelmann, Sarah; Cattaneo, Roberto

    2012-01-01

    To characterize the importance of infection of epithelial cells for morbillivirus pathogenesis, we took advantage of the severe disease caused by canine distemper virus (CDV) in ferrets. To obtain a CDV that was unable to enter epithelial cells but retained the ability to enter immune cells, we transferred to its attachment (H) protein two mutations shown to interfere with the interaction of measles virus H with its epithelial receptor, human nectin-4. As expected for an epithelial receptor (EpR)-blind CDV, this virus infected dog and ferret epithelial cells inefficiently and did not cause cell fusion or syncytium formation. On the other hand, the EpR-blind CDV replicated in cells expressing canine signaling lymphocyte activation molecule (SLAM), the morbillivirus immune cell receptor, with similar kinetics to those of wild-type CDV. While ferrets infected with wild-type CDV died within 12 days after infection, after developing severe rash and fever, animals infected with the EpR-blind virus showed no clinical signs of disease. Nevertheless, both viruses spread rapidly and efficiently in immune cells, causing similar levels of leukopenia and inhibition of lymphocyte proliferation activity, two indicators of morbillivirus immunosuppression. Infection was documented for airway epithelia of ferrets infected with wild-type CDV but not for those of animals infected with the EpR-blind virus, and only animals infected with wild-type CDV shed virus. Thus, epithelial cell infection is necessary for clinical disease and efficient virus shedding but not for immunosuppression. PMID:22278252

  19. Corneal Immunosuppressive Mechanisms, Anterior Chamber-Associated Immune Deviation (ACAID) and Their Role in Allograft Rejection.

    PubMed

    Treacy, Oliver; Fahy, Gerry; Ritter, Thomas; O'Flynn, Lisa

    2016-01-01

    Corneal transplantation is the most frequently performed transplant procedure in humans. Human leukocyte antigen matching, while imperative for other types of organ transplants, is usually not performed before cornea transplantation. With the use of topical steroid immunosuppressants, which are subsequently tailed off to almost zero, most corneal transplants will not be rejected in recipients with low risk of graft rejection. This phenomenon has been described as immune privilege by Medawar many years ago. However, this immune privilege is relative and can be easily eroded, e.g. by postoperative nonspecific inflammation or other causes of corneal or ocular inflammation. Interestingly, corneas that are at high risk of rejection have a higher failure rate than other organs. Considerable progress has been made in recent years to provide a better understanding of corneal immune privilege. This chapter will review current knowledge on ocular immunosuppressive mechanisms including anterior chamber-associated immune deviation and discuss their role(s) in corneal allograft rejection. Ultimately, this evolving information will be of benefit in developing therapeutic strategies to prevent corneal transplant rejection.

  20. Immunosuppressive Effect of Litsea cubeba L. Essential Oil on Dendritic Cell and Contact Hypersensitivity Responses

    PubMed Central

    Chen, Hsin-Chun; Chang, Wen-Te; Hseu, You-Cheng; Chen, Hsing-Yu; Chuang, Cheng Hsuan; Lin, Chi-Chen; Lee, Meng-Shiou; Lin, Ming-Kuem

    2016-01-01

    Litsea cubeba L., also named as Makauy, is a traditional herb and has been used as cooking condiment or tea brewing to treat diseases for aborigines. The present study was undertaken to explore the chemical compositions of the fruit essential oil of L. cubeba (LCEO) and the immunomodulatory effect of LCEO on dendritic cells and mice. The LCEO was analyzed using gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) with direct injection (DI/GC) or headspace-solid phase microextraction (HS-SPME/GC). In total, 56 components were identified, of which 48 were detected by DI/GC and 49 were detected by HS-SPME/GC. The principal compounds were citral (neral and geranial). An immunosuppressive activity of LCEO was investigated with bone marrow-derived dendritic cells (DCs) which have a critical role to trigger the adaptive immunity. Additionally, the inhibitory effect of LCEO on immune response was elucidated by performing the contact hypersensitivity (CHS) responses in mice. Our results clearly showed that LCEO decreases the production of TNF-α and cytokine IL-12 in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated DCs. CHS response and the infiltrative T cells were inhibited in the tested ears of the mice co-treated with LCEO. We demonstrate, for the first time, that the LCEO mainly containing citral exhibits an immunosuppressive effect on DCs and mice, indicating that LCEO can potentially be applied in the treatment of CHS, inflammatory diseases, and autoimmune diseases. PMID:27529236