Similar effects of cyclosporine and verapamil on lymphokine, interleukin 2 receptor, and proto-oncogene expression.

Abstract:

:Since calcium channel blocking agents and CsA exert an antiproliferative effect upon T cell mitogenesis, we have compared and characterized their immunosuppressive properties at the level of gene activation. Verapamil (greater than or equal to 30 microM), which blocks T cell mitogenesis and a rise in cytosolic calcium, was added to cultures of peripheral blood mononuclear cells stimulated with phytohemagglutinin (5 micrograms/ml) and phorbol myristate acetate (5 ng/ml). Northern blot analysis was performed using cDNA probes for the p55 interleukin 2 receptor (Tac; IL-2R), interleukin 2 and c-myc at 20 hr of culture. Accumulation of IL-2 encoding mRNA within the cytoplasm was completely abrogated by verapamil. However, IL-2R and c-myc encoding mRNA were clearly detectable in verapamil-treated cell cultures. Surface expression of the Tac protein in mitogen-activated T cells was also not blocked by verapamil as shown by FACS analysis. In companion experiments with CsA, verapamil only partially inhibits the intracellular processes leading to T cell activation. A calcium-independent pathway may exist for the expression of IL-2R and c-myc, while an increase of intracellular Ca2+ may provide the additional signal for IL-2 gene expression. Although the in vitro concentrations of verapamil used in these experiments are in excess of common clinically therapeutic levels, the results help clarify the mode of CsA action and may provide a new tool to dissect the early events of T cell activation.

journal_name

Transplantation

journal_title

Transplantation

authors

Walz G,Zanker B,Wieder K,Hadro E,Moscovitch-Lopatin M,Smith BR,Strom TB

doi

10.1097/00007890-198902000-00029

subject

Has Abstract

pub_date

1989-02-01 00:00:00

pages

331-4

issue

2

eissn

0041-1337

issn

1534-6080

journal_volume

47

pub_type

杂志文章
  • Improvement of donor myocardial function after treatment of autonomic storm during brain death.

    abstract:BACKGROUND:In experimental brain death models, autonomic storm (AS) triggers severe myocardial dysfunction, which can be attenuated by pharmacologic treatment. The aim of this study was to determine the incidence of AS in a cohort of human organ donors and to evaluate the potential interest of AS treatment on myocardia...

    journal_title:Transplantation

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    doi:10.1097/01.tp.0000235825.97538.d5

    authors: Audibert G,Charpentier C,Seguin-Devaux C,Charretier PA,Grégoire H,Devaux Y,Perrier JF,Longrois D,Mertes PM

    更新日期:2006-10-27 00:00:00

  • Comparison of arterialized and nonarterialized orthotopic liver transplantation in mice: prowess or relevant model?

    abstract:BACKGROUND:New insights into mechanisms of injury in orthotopic liver transplantation (OLT) often come from experiments in small animal models. Mice are particularly suitable because of the growing availability of gene-altered animals and specific antibodies. A validated model of OLT in mice is not available and, in pa...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200211150-00008

    authors: Tian Y,Rüdiger HA,Jochum W,Clavien PA

    更新日期:2002-11-15 00:00:00

  • A reevaluation of the role of IgM Non-HLA antibodies in cardiac transplantation.

    abstract:BACKGROUND:Preexisting IgG antibodies to donor human leukocyte antigens (HLA) are a risk factor for rapid allograft rejection. However, non-HLA antibodies, of the IgM class, also called autoreactive antibodies, are not believed to affect graft survival. The aim of this study was to determine the incidence and clinical ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e31819a65fa

    authors: Smith JD,Hamour IM,Burke MM,Mahesh B,Stanford RE,Haj-Yahia S,Robinson DR,Kaul P,Yacoub MH,Banner NR,Rose ML

    更新日期:2009-03-27 00:00:00

  • Transcriptional inhibition of insulin by FK506 and possible involvement of FK506 binding protein-12 in pancreatic beta-cell.

    abstract::FK506 (tacrolimus) is a strong immunosuppressant: it has been approved as a drug for liver transplantation in Japan, the United States, and the United Kingdom. One of its main adverse effects is hyperglycemia. Thus, in this study, we investigated the mechanism and the reversibility of the hyperglycemia caused by FK506...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:

    authors: Tamura K,Fujimura T,Tsutsumi T,Nakamura K,Ogawa T,Atumaru C,Hirano Y,Ohara K,Ohtsuka K,Shimomura K

    更新日期:1995-06-15 00:00:00

  • Human herpesvirus-6 infection after lung and heart-lung transplantation: a prospective longitudinal study.

    abstract:BACKGROUND:Although human herpesvirus (HHV)-6 is now recognized as a frequent pathogen after transplantation, the real impact of this infection in patients undergoing transplantation remains unclear. METHODS:During 27 months, 30 consecutive heart-lung- and lung-transplant recipients were included on the day of transpl...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.TP.0000058809.42027.66

    authors: Jacobs F,Knoop C,Brancart F,Gilot P,Mélot C,Byl B,Delforge ML,Estenne M,Liesnard C,Brussels Heart and Lung Transplantation Group.

    更新日期:2003-06-27 00:00:00

  • Evaluation and clinical significance of circulating immune complexes after renal transplantation.

    abstract::Using C1q binding, Kg binding, and Raji cell radioimmunoassays, the relationship between renal allograft rejection and the circulating immune complexes was examined in 90 patients with renal transplants. The data showed that there was a significant quantitative correlation between C1q-binding and Raji-cell-binding act...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198308000-00009

    authors: Fukuda M

    更新日期:1983-08-01 00:00:00

  • Living-related donor renal transplantation in HIV+ recipients using alemtuzumab preconditioning and steroid-free tacrolimus monotherapy: a single center preliminary experience.

    abstract:BACKGROUND:End-stage renal disease (ESRD) is an increasing problem in patients infected with the human immunodeficiency virus (HIV). The use of highly active antiretroviral therapy (HAART) has decreased the morbidity associated with HIV and has prompted renewed interest in renal transplantation. METHODS:We performed f...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.tp.0000145880.38548.0d

    authors: Tan HP,Kaczorowski DJ,Basu A,Khan A,McCauley J,Marcos A,Fung JJ,Starzl TE,Shapiro R

    更新日期:2004-12-15 00:00:00

  • Thymoglobulin, sirolimus, and reduced-dose cyclosporine provides excellent rejection prophylaxis for pancreas transplantation.

    abstract:BACKGROUND:We investigated a novel immunosuppressive protocol including thymoglobulin induction in combination with sirolimus and corticosteroids, followed by introduction of markedly reduced exposures to cyclosporine to prevent pancreas-transplant rejection. METHODS:A 7-day course of thymoglobulin (1.5 mg/kg per day)...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.TP.0000061768.98058.EC

    authors: Knight RJ,Kerman RH,Zela S,Podder H,Van Buren CT,Katz S,Kahan BD

    更新日期:2003-04-27 00:00:00

  • Transfusion rate for 500 consecutive liver transplantations: experience of one liver transplantation center.

    abstract:BACKGROUND:Orthotopic liver transplantation (OLT) has been associated with major blood loss and the need for blood product transfusions. During the last decade, improved surgical and anesthetic management has reduced intraoperative blood loss and blood product transfusions. A first report from our group published in 20...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e318250fc25

    authors: Massicotte L,Denault AY,Beaulieu D,Thibeault L,Hevesi Z,Nozza A,Lapointe R,Roy A

    更新日期:2012-06-27 00:00:00

  • Long-term outcome of controlled, non-heart-beating donor liver transplantation.

    abstract:BACKGROUND:Previous reports have established the feasibility of using livers from controlled, non-heart-beating donors (CNHBD) with good immediate graft function. This has been largely borne out of necessity because of the donor shortage. METHODS:Retrospective database review for the last 7 years (1995-2002), encompas...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.tp.0000128327.95311.e3

    authors: Manzarbeitia CY,Ortiz JA,Jeon H,Rothstein KD,Martinez O,Araya VR,Munoz SJ,Reich DJ

    更新日期:2004-07-27 00:00:00

  • Composite tissue (limb) allografts in rats. I. Dose-dependent increase in survival with cyclosporine.

    abstract::The dose-response effect of cyclosporine on rat limb transplant prolongation was investigated across the LBN-to-LEW histocompatibility barrier. This composite tissue allograft model has been shown to represent a strong transplantation barrier. Median limb allograft survival times increased in a dose-dependent manner w...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198504000-00004

    authors: Hewitt CW,Black KS,Fraser LA,Howard EB,Martin DC,Achauer BM,Furnas DW

    更新日期:1985-04-01 00:00:00

  • FDA perspective: enrolment of elderly transplant recipients in clinical trials.

    abstract::Since 1989, the U.S. Food and Drug Administration (FDA) has encouraged the study of new drug and therapeutic products in elderly patients. However, despite the aging population in the United States, elderly patients continue to be underrepresented in clinical trials across a variety of therapeutic areas, including tra...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e31828279d9

    authors: Meyer JM,Archdeacon P,Albrecht R

    更新日期:2013-04-15 00:00:00

  • Lectin-dependent cell-mediated cytotoxicity and natural killer function in rejecting and infected lung allografts.

    abstract::Differentiation between rejection and infection of lung allografts remains difficult. The effects of these two pathologic entities on the cytolytic activity of bronchoalveolar lavage (BAL) and PBL were investigated. Left lung allotransplantation was performed on 16 mongrel dogs of which 12 were available for complete ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199306000-00008

    authors: Nguyen DM,Mulder DS,Shennib H

    更新日期:1993-06-01 00:00:00

  • Differential immune response of congenic mice to ultraviolet-treated major histocompatibility complex class II-incompatible skin grafts.

    abstract::The influence of ultraviolet (UVB) irradiation on the survival of H-2 class II-disparate skin grafts was studied in congenic mouse strains. Isolated skin was UVB irradiated in vitro at a dose of 40 mJ/cm2 from both sides to remove Ia immunogenicity. Immediately after irradiation the skin was transplanted onto the flan...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-198803000-00020

    authors: Vermeer BJ,Santerse B,Van De Kerckhove BA,Schothorst AA,Claas FH

    更新日期:1988-03-01 00:00:00

  • Induction of kidney allograft tolerance after transient lymphohematopoietic chimerism in patients with multiple myeloma and end-stage renal disease.

    abstract:BACKGROUND:Two patients with end-stage renal disease secondary to multiple myelomas were treated with combined kidney and bone marrow transplantation in an effort to achieve donor-specific allotolerance through the induction of mixed lymphohematopoietic chimerism. METHODS:Two female patients (55 and 50 years of age) w...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200211270-00011

    authors: Bühler LH,Spitzer TR,Sykes M,Sachs DH,Delmonico FL,Tolkoff-Rubin N,Saidman SL,Sackstein R,McAfee S,Dey B,Colby C,Cosimi AB

    更新日期:2002-11-27 00:00:00

  • Membranous glomerulopathy following kidney transplantation. Association with renal vein thrombosis in two of nine cases.

    abstract::The association of renal vein thrombosis and membranous glomerulopathy in native kidneys has been well documented. However, this association has only occasionally been described following renal transplantation. A review of 693 renal transplant recipients revealed 77 (11%) in whom persistent, heavy proteinuria (greater...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:

    authors: First MR,Mendoza N,Maryniak RK,Weiss MA

    更新日期:1984-12-01 00:00:00

  • Increased levels of GALbeta1-4GLCNACalpha2-6 sialyltransferase pretransplant predict delayed graft function in kidney transplant recipients.

    abstract:BACKGROUND:Galbeta1-4GlcNAcalpha2-6 sialyltransferase (ST6GalI) is an acute phase reactant whose release from cells can be induced by proinflammatory cytokines. Because patients with chronic renal failure have high circulating levels of proinflammatory cytokines, we hypothesized that patients on the renal transplant wa...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200003150-00022

    authors: Thorne-Tjomsland G,Hosfield T,Jamieson JC,Liu B,Nickerson P,Gough JC,Rush DN,Jeffery JR,McKenna RM

    更新日期:2000-03-15 00:00:00

  • Long-term metabolic control of autoimmune diabetes in spontaneously diabetic nonobese diabetic mice by nonvascularized microencapsulated adult porcine islets.

    abstract:BACKGROUND:The long-term metabolic function of microencapsulated xenogeneic adult porcine islets (API) was assessed in a murine model of type 1 diabetes mellitus. METHODS:API were encapsulated in barium-gelled alginate and transplanted intraperitoneally in diabetic nonobese diabetic (NOD) mice given no immunosuppressi...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e3181abbfc1

    authors: Cui H,Tucker-Burden C,Cauffiel SM,Barry AK,Iwakoshi NN,Weber CJ,Safley SA

    更新日期:2009-07-27 00:00:00

  • The effects of FK506 and cyclosporine on the exocrine function of the rat pancreas.

    abstract::The effects of FK506 on exocrine function of the pancreas in Sprague-Dawley rats were examined and compared with those of cyclosporine. FK506 did not affect the levels of amylase and lipase in the pancreas of rats given the drug orally in a daily dose of 1 or 5 mg/kg for 2 weeks. Furthermore, the pancreas of the rats ...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199211000-00023

    authors: Hirano Y,Hisatomi A,Ohara K,Noguchi H

    更新日期:1992-11-01 00:00:00

  • The extent and predictors of waiting time geographic disparity in kidney transplantation in the United States.

    abstract:BACKGROUND:Waiting time to deceased donor kidney transplant varies greatly across the United States. This variation violates the final rule, a federal mandate, which demands geographic equity in organ allocation for transplantation. METHODS:Retrospective analysis of the United States Renal Data System and United Netwo...

    journal_title:Transplantation

    pub_type: 杂志文章,多中心研究

    doi:10.1097/01.tp.0000438623.89310.dc

    authors: Davis AE,Mehrotra S,McElroy LM,Friedewald JJ,Skaro AI,Lapin B,Kang R,Holl JL,Abecassis MM,Ladner DP

    更新日期:2014-05-27 00:00:00

  • Antibody testing strategies for deceased donor kidney transplantation after immunomodulatory therapy.

    abstract:BACKGROUND:Immunomodulatory protocols including intravenous immunoglobulin/rituximab (IVIG/R) are employed to decrease anti-human leukocyte antigen (HLA) antibody levels for patients broadly sensitized to HLA and increase chances for transplantation with a compatible deceased donor (DD). The aim of our study was to ide...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/TP.0b013e31821eab8a

    authors: Lai CH,Cao K,Ong G,Naim M,Wang Q,Mirocha J,Vo A,Jordan SC,Reinsmoen NL

    更新日期:2011-07-15 00:00:00

  • mTOR Inhibition Role in Cellular Mechanisms.

    abstract::The mammalian target of rapamycin inhibitors (mTOR-I), drugs widely used in transplant medicine and oncology, exert their function by inhibiting a serine/threonine kinase with a pivotal role in cellular metabolism and in a wide range of eukaryotic biological/cellular functions and signaling networks. Additionally, as ...

    journal_title:Transplantation

    pub_type: 杂志文章,评审

    doi:10.1097/TP.0000000000001806

    authors: Zaza G,Granata S,Caletti C,Signorini L,Stallone G,Lupo A

    更新日期:2018-02-01 00:00:00

  • The effects of pretransplant cyclosporine therapy on rats grafted with twelve-hour cold-stored livers--with special reference to reperfusion injury.

    abstract::The effect of pretreatment with cyclosporine on liver preservation was studied using a rat liver transplant model. In a preliminary 1-week survival study, 59 liver transplants were performed. In group A, neither donors nor recipients were treated. In group B, the recipients were pretreated by a 3-day course of CsA (10...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199110000-00007

    authors: Goto S,Kim YI,Shimada T,Kawano K,Kobayashi M

    更新日期:1991-10-01 00:00:00

  • Activation of autoimmune B cells and chronic rejection.

    abstract::Allotransplantation into immunosuppressed individuals results in long-term survival of grafts. However, the grafts are damaged, probably at many stages before, during and after implantation. The hypothesis to be presented is that release of antigens and autoantigens from the chronically damaged graft results in breaki...

    journal_title:Transplantation

    pub_type: 杂志文章,评审

    doi:10.1097/01.tp.0000153294.38939.5f

    authors: Rose ML

    更新日期:2005-02-15 00:00:00

  • The distribution of HLA antigens and phenotypes among donors and patients in the UNOS registry.

    abstract::We have analyzed HLA data from the UNOS registry on 20,230 patients on the renal waiting list in 1991 and 18,708 donors from 1988-1992. Significant differences were found in the distribution of HLA antigens for comparisons of the total donor pool and the various racial groups of patients as well as for inter- and intr...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:

    authors: Leffell MS,Steinberg AG,Bias WB,Machan CH,Zachary AA

    更新日期:1994-11-27 00:00:00

  • Donor factors influencing graft outcomes in live donor kidney transplantation.

    abstract::Living donor renal allograft survival is superior to that achieved from deceased donors, although graft outcome is suboptimal in some of these patients. In an effort to identify the subset of patients at high risk for poor outcomes we studied donor risk factors in 248 living kidney donor-recipient pairs. Unadjusted do...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/01.tp.0000256284.78721.ba

    authors: Issa N,Stephany B,Fatica R,Nurko S,Krishnamurthi V,Goldfarb DA,Braun WE,Dennis VW,Heeger PS,Poggio ED

    更新日期:2007-03-15 00:00:00

  • Hepatic artery pseudoaneurysm after liver transplantation: treatment with percutaneous thrombin injection.

    abstract::Pseudoaneurysms of the hepatic artery are a rare complication of liver transplantation. Early diagnosis and treatment are essential to avoid life-threatening hemorrhage. Conventional treatment consists of surgical resection and vascular reconstruction or transarterial coil embolization. More recently, percutaneous thr...

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    pub_type: 杂志文章

    doi:10.1097/01.TP.0000063936.94587.10

    authors: Patel JV,Weston MJ,Kessel DO,Prasad R,Toogood GJ,Robertson I

    更新日期:2003-05-27 00:00:00

  • Clinical Trials for Immunosuppression in Transplantation: The Case for Reform and Change in Direction.

    abstract::Currently trials of immunosuppression in transplantation are in decline because their objectives remain focused on improving acute rejection rates and graft survival in the first 12 months. With 1 year renal graft survival rates of greater than 90% the best that can be hoped for is noninferiority trial outcomes compar...

    journal_title:Transplantation

    pub_type:

    doi:10.1097/TP.0000000000001648

    authors: OʼConnell PJ,Kuypers DR,Mannon RB,Abecassis M,Chadban SJ,Gill JS,Murphy B,Nickerson PW,Schold JD,Stock PG,Seron D,Alloway RR,Bromberg JS,Budde K,Jordan SC,Legendre C,Lefaucheur C,Sarwall M,Segev DL,Stegall MD,Tull

    更新日期:2017-07-01 00:00:00

  • Guillain-Barre syndrome in organ and bone marrow transplant patients.

    abstract:BACKGROUND:Guillain-Barre Syndrome (GBS) is believed to be caused by autoimmune mechanisms that are predominantly T-cell mediated. We report GBS in organ transplant patients and bone marrow transplant patients, both of whom have iatrogenically suppressed T-cell function. METHODS:We reviewed the Duke University Medical...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-200104270-00026

    authors: Bulsara KR,Baron PW,Tuttle-Newhall JE,Clavien PA,Morgenlander J

    更新日期:2001-04-27 00:00:00

  • Long-term duct-occluded segmental pancreatic autografts: absence of microvascular diabetic complications.

    abstract:BACKGROUND:Current insulin therapies for control of glucose metabolism in patients with type I diabetes mellitus prevent major metabolic consequences of insulin deficiency, but none prevents or arrests long-term complications. In experimental models of canine diabetes, retinopathy, neuropathy, and nephropathy have been...

    journal_title:Transplantation

    pub_type: 杂志文章

    doi:10.1097/00007890-199710150-00003

    authors: Hawthorne WJ,Wilson TG,Williamson P,Stewart GJ,Allen RD,Little JM,Deane SA,Ekberg H

    更新日期:1997-10-15 00:00:00