Several studies provide evidence that cross-linking of CD137 on T cells either

with its naturally occurring ligand (CD137L) or by agonistic anti-CD137 monoclonal antibody (mAb) exerts various forms of immune activation both in vitro and in vivo[7–10]. In-vivo stimulation of CD137 resulted in rejection of INCB024360 tumours [11,12], cardiac allograft and skin transplants [13,14], inhibition of graft-versus-host disease (GVHD) [15] or autoimmune responses [16,17] and promotion of viral defence [18]. After the generation of CD137-deficient (CD137−/−) mice, the role of the CD137/CD137L pathway in T cell immunity was studied further [19]. T cells derived from CD137−/− mice showed

enhanced proliferation, whereas their capacity for secretion of cytokines interleukin (IL)-2, IL-4 and interferon (IFN)-γ was diminished [19]. The frequency and function of NK and NK T cells was reduced in CD137−/− mice. However, the influence of CD137 deficiency on maturation or steady-state CD4+ and CD8+ T cell populations has not yet been reported [20]. So far, CD137−/− mice have not been analysed in allergic airway disease models. In this regard, we and others have shown a critical role of CD137 in the immune response of allergic asthma [21–23]. Stimulation with agonistic anti-CD137 mAb not only prevented, but even reversed the complete asthma phenotype mediated partly by IFN-γ-producing CD8+ T cells [21]. In the present study, we followed a contrasting

approach and investigated Florfenicol the effect of CD137 deficiency https://www.selleckchem.com/products/E7080.html in the same OVA-based asthma model published previously [21] by comparative analysis of CD137−/− and wild-type (WT) mice. We were further interested in whether the absence of CD137 influences the establishment of respiratory tolerance, because several co-stimulatory molecules, including CD134 (OX-40), cytotoxic T lymphocyte antigen (CTLA)-4 and inducible co-stimulator (ICOS), have been shown to play a role in regulatory T cell (Treg) function and are thus implicated to be involved in the development and maintenance of tolerance [24,25]. CD137 is expressed constitutively on murine Tregs, whereas in humans CD137 is up-regulated rapidly on natural and inducible Tregs. The exact importance of CD137 in Tregs remains controversial, but an increasing body of evidence points towards a critical role for Treg expansion, survival and function [24,26,27]. However, so far the role of CD137/CD137L pathway in the context of development and maintenance of respiratory tolerance is uncertain. Therefore, aside from the classical OVA-based sensitization and challenge protocol, we compared WT and CD137−/− mice which were additionally tolerized with OVA prior to sensitization.

The Trappin-2/Elafin and β-actin primer/MGB probe sets were obtained from Applied Biosystems assays-on-demand (ID nos Hs00160066_m1 and Selumetinib molecular weight 4333762T, respectively). This primer-probe set recognizes both Trappin-2 and Elafin. PCR was conducted using the following cycle parameters: 12 min at 95° for one cycle, followed by 40 cycles of 20 seconds at 95° and

1 min at 60°. Analysis was conducted using the sequence detection software supplied with the ABI 7300. The software calculates the threshold cycle (Ct) for each reaction, which was used to quantify the amount of starting template in the reaction. The Ct values for each set of duplicate reactions were averaged for all subsequent calculations. A difference in Ct values (ΔCt) was calculated for each gene by taking the mean Ct of each gene of interest and subtracting the mean Ct for the housekeeping gene β-actin for

each cDNA sample. Assuming that each reaction functions at 100% PCR efficiency, a difference of one Ct represents a twofold difference. Relative expression levels were expressed as a fold-increase in mRNA expression and were calculated using the formula 2–ΔΔCt. The TZM indicator cell line (kindly provided by Dr Phalguni Gupta, University of Pittsburgh) is a HeLa NVP-BGJ398 chemical structure cell derivative that expresses high levels of CD4, CCR5 and CXCR4.51 The cells contain HIV long terminal repeat (LTR)-driven β-galactosidase and luciferase reporter cassettes that are activated by HIV tat expression. TZM cells were routinely subcultured every 3–4 days by trypsinization and were maintained in TZM media consisting of DMEM (Invitrogen Life Technologies) supplemented with 10% defined FBS (HyClone), 2 mm l-glutamine (Invitrogen Life Technologies) and 50 μg/ml

of primocin (Invivogen), and did not contain phenol red. TZM cells were seeded at 2 × 104 cells per well in a 96-well microtiter plate and allowed to adhere overnight at 37°. Varying doses of recombinant human Trappin-2/Elafin (Peprotech, Rocky Hill, NJ) were incubated with HIV-1 IIIB and BaL at a multiplicity of infection (MOI) of 1 for 1 hr at 37° in a final volume of 100 μl. Following incubation, the media was aspirated from TZM cells, and the virus plus Trappin-2/Elafin was added Dimethyl sulfoxide to the cells along with 100 μl of TZM medium. Luciferase activity was measured after 48 hr at 37° with 5% CO2 in a humidified incubator. Briefly, the supernatants were aspirated and the cells were lysed using a Beta Glo luciferase assay substrate (Promega, Madis, WI). The light intensity of each well was measured using a luminometer. Uninfected cells were used to determine background luminescence. All infectivity assays were performed in quadruplicate. Other experiments were conducted in order to determine whether the inhibitory effects of Trappin-2/Elafin were at the cell-surface level, such as the blocking of a co-receptor.

Patients with thyroid disease or thyroid hormone replacement were excluded from the analysis. All-cause, infection-related and cardiovascular-related mortalities were compared between the dichotomized two groups based on the median PLX-4720 supplier levels of free thyroxine. The association of basal levels and annual variation with mortality was investigated with Kaplan-Meier curves and Cox proportional hazard models. Results: Among a total of 235 PD patients, 31 (13.2%) deaths occurred during mean follow-up period of 24 months. Infection (38.7%) was the most common cause of death. Patients with lower basal free thyroxine levels had significantly increased

all-cause and infection-related mortalities than patients with higher levels. Kaplan-Meier analysis also showed worse cumulative survival rates in patients with lower free thyroxine levels (P = 0.015 and P = 0.017, respectively). In multivariate analyses, lower basal free thyroxine levels were an independent predictor of all-cause and infection-related death (hazard ratio

[HR] = 3.201, P = 0.0041 and HR = 14.592, P = 0.0074, respectively). Longitudinally, patients with persistently lower free thyroxine levels during the 12-month period had significantly higher all-cause mortality than those having persistently high levels (HR = 3.448, P = 0.0269). Conclusion: Free thyroxine levels are an independent predictor of mortality especially attributable to infection in PD patients. This was consistent when considering both baseline measurements and annual variation patterns. Close attentions to infection in Lumacaftor molecular weight PD patients with relatively lower free thyroxine levels may improve the survival of patients. MIZUNO Vitamin B12 MASASHI1, ITO YASUHIKO1, SUZUKI YASUHIRO1, SAKA YOSUKE2, HIRAMATSU TAKEYUKI2, TAMAI HIROFUMI2,

MIZUTANI MAKOTO2, NARUSE TOMOHIKO2, OHASHI NORIMI2, KASUGA HIROTAKE2, SHIMIZU HIDEAKI2, KURATA HISASHI2, KURATA KEI2, SUZUKI SATOSHI2, MARUYAMA SHOICHI1, MATSUO SEIICHI1 1Nagoya University Graduate School of Medicine; 2Tokai PD Registry Research Group Introduction: In our previous study from 2005 to 2007 (Mizuno M, et al. Clin Exp Nephrol 2011.), we realized that early withdrawal within 3 years prevented long-term peritoneal dialysis (PD) therapy for ESRD patients and that PD-related peritonitis was one of important reason for the early withdrawal. From 2005, we have started several PD education programs for physicians and co-medicals. Therefore, to compare results of the previous study (2005 to 2007), we performed the following PD registry in Tokai area from 2010 for three years. Especially, we focused incidence of PD-related peritonitis. Methods: In PD patients during 3 years from 2010, we mainly investigated background, laboratory data, reasons of withdrawals from PD therapy, and incidence of peritonitis in 14 hospitals and clinic.

For control purposes, cell swelling or cell shrinkage see more of untreated BMDCs (mean FSC 473.6 ± 18.4) was induced by addition of 20% aqua bidest (mean FSC 523.3 ± 12.9) and staurosporin (4 µM) (mean FSC 366.7 ± 13.2), respectively, for 30 min (data not shown). Results were depicted as differences of the means between LPS-treated and untreated cells. As shown in Figure 1a, addition of LPS caused a rapid increase in the cell size in WT DCs after 30 min. Thereafter, the cells size of WT DCs remained on a high level up to 240 min.

In contrast, volume changes in TLR4-deficient DCs were significantly abolished indicating that the increase in the cell volume upon LPS treatment was dependent on TLR4 signaling. Due to the rapid kinetics, these data suggest that cell swelling is an early step in LPS-induced DC migration. Accordingly, it has been reported that LPS induces the dissolution of podosomes, adhesion structures selleckchem of immature DCs, in a TLR4-dependent manner [6]. To analyze the role of LPS/TLR4 signaling in migration of DCs, transwell migration assays were performed. DCs were seeded in the upper wells of a transwell system and migration to the lower wells was analyzed after

4 hr by flow cytometry. To analyze the spontaneous migration rates, the bottom wells were filled with medium alone. By addition of CCL21 to the medium in the bottom wells, the CCL21-directed migration rates were determined. The activity of DCs to migrate towards a CCL21 Urease gradient was depicted as the migration rate to CCL21 divided by the migration rate to medium alone (chemotactic index). As shown in Figure 1b, neither DCs derived from WT nor TLR4−/− mice substantially migrated in a CCL21-directed manner to the bottom wells (chemotactic index: 1.0 and 1.1, respectively). However, stimulation of WT DC by addition of LPS to the upper wells caused an increase in CCL21-directed migration (chemotactic index: 1.9). This effect was nearly abolished in TLR4-deficient DC (chemotactic index: 1.2)

demonstrating that the directed movement of immature BMDC towards CCL21 is dependent on LPS/TLR4-signaling. It is widely accepted that KCa3.1 channels are required for migration of different cell types including cells of the immune system [11, 16-18]. In non-excitable migrating cells, these calcium-activated potassium channels are usually present at the rear end of the cell and are activated by increase in free cytosolic Ca2+ [19]. Activation of KCa3.1 channels may cause an efflux of intracellular K+ and subsequently an osmotic water efflux thereby promoting localized shrinkage and retraction of the rear cell pole which may facilitate migration [19]. In order to analyze the role of KCa3.1 channels in LPS-induced migration, DCs were generated from KCa3.1−/− and WT controls. To analyze LPS-dependent cell volume changes in KCa3.

The mean clinicalEAEscore was only mildly reduced inDC-depleted mice when DCs were ablated beforeEAEinduction. The frequency of activatedTh cells was not altered, andMOG-inducedTh17 orTh1-cell responses were not altered, in the spleens ofDC-depleted mice. Similar results were obtained ifDCswere ablated the first 10 days afterMOGimmunization with repeatedDCdepletions.

Unexpectedly, transient depletion of DCs did not affect priming or differentiation of MOG-inducedTh17 andTh1-cell Pexidartinib price responses or the incidence ofEAE. Thus, the mechansim of priming ofTh cells inEAEremains to be elucidated. Dendritic cells (DCs) are key actors of adaptive immune responses against infections [1-3]. There are several DC subsets in mice which are characterized by differential expression of cell surface markers and their location;

e.g. myeloid DCs (mDCs), plasmacytoid DCs (pDCs), dermal DCs, CD11b+ DCs, and CD11b− DCs [4, 5]. Ly6Chi monocytes are considered to be precursors of inflammatory DCs (inflDCs) which are recruited to site of inflammation [4]. InflDCs express intermediate to high levels of CD11c and MHC class II (MHC II). mDCs are highly specialized in priming naïve T cells in vitro GSK-3 inhibition [3]. In vivo depletion of murine CD11c+ mDCs by diphtheria toxin (DTx)-based transgenic systems has demonstrated an indispensible role for DCs during priming of CD8+ T-cell responses to viruses, intracellular bacteria and malaria parasites [1, 6]. Priming of Th1 responses and Th2 responses to parasites also depends on DCs [2, 7]. Furthermore, ablation of DCs leads to dissemination CYTH4 of Streptococcus pyogenes [8]. In contrast, constitutive ablation of CD11c+ DCs leads to spontaneous fatal autoimmunity, high numbers of Th17 and Th1 cells and production of autoantibodies such as antinuclear Ab [9]. This suggests that DC-mediated deletion of autoreactive single-positive thymocytes is important and failure leads to the observed pathology [9]. Constitutive

deletion of DCs in vivo in lupus-prone mice results in amelioration of disease, but DCs are not required for initial priming of autoimmune Th cells. Instead, DCs are important for functional differentiation and expansion of T cells [10]. Little is known about the role of mDCs in priming and de novo differentiation of autoimmune Th cells in the organ-specific autoimmune disease EAE, an animal model for human multiple sclerosis [11]. We have previously demonstrated that myelin oligodendrocyte glycoprotein (MOG)-induced EAE is mediated by MyD88-dependent mechanisms [12]. IL-6 expression by mDCs depended on MyD88 and was upregulated between 4 and 10 days after MOG immunization [12]. Furthermore, depletion of pDC prior to MOG immunization ameliorated the clinical and histopathological signs of MOG-induced EAE compared with control mice [13].

Animal biodistribution studies with Tyrosine Kinase Inhibitor Library manufacturer radioiodinated rhTRAIL (125I-rhTRAIL) have demonstrated that intravenous injection of TRAIL does not yield detectable levels of TRAIL in the brain. Therefore, local

delivery strategies, such as convection-enhanced delivery (CED), seem more appropriate. CED uses positive pressure infusion to achieve locoregional delivery of therapeutic agents through an intracerebral catheter [90,91]. In animal models, CED can achieve locally high and effective concentrations. By now CED has progressed into phase III clinical studies for immunotoxin delivery [92,93], results of which are likely to yield insight into the feasibility of using CED on a routine basis in GBM patients and its potential applicability for TRAIL-based therapy. The ample preclinical data on GBM cell lines and primary GBM tissue, as well as the notable absence of TRAIL-related toxicity in phase I clinical trials,

clearly highlight that TRAIL receptor-targeted strategies hold great appeal for future cancer and more specifically GBM therapy. However, it is also evident from the available literature that GBM is unlikely to be sufficiently responsive to single-agent therapy with TRAIL receptor-targeted strategies. Indeed, when taking into account the inherent heterogeneity of GBM it seems most prudent to examine the feasibility of combinatorial strategies that on the one hand sensitize GBM cells to apoptosis, and Smoothened Agonist in vivo on the other hand induce apoptosis using TRAIL or agonistic TRAIL receptor antibodies. As highlighted in this

review, TRAIL can be combined with a variety of different conventional and novel therapeutic strategies to yield synergistic Methane monooxygenase pro-apoptotic activity. Of particular appeal in our opinion is the use of dual purpose TRAIL-based molecules, such as the EGFR-targeted TRAIL fusion protein scFv425:sTRAIL. This fusion protein simultaneously blocks EGFR mitogenic signalling; thereby sensitizing tumour cells to apoptosis, and induces apoptosis via TRAIL receptor signalling. This fusion protein efficiently activates apoptosis and shows promising in vivo activity. Obviously, further rational combination with other therapeutic strategies may help to optimize anti-GBM activity. An important aspect in considering GBM therapy is the observation that, as in many other types of tumour, a so-called ‘stem cell’ population can be identified in GBM. These glioblastoma stem cells (GSCs) can regrow into original glioblastoma in xenograft nude mouse models and express neural stem cell markers, such as CD133. Importantly, GSCs are particularly refractory to radiotherapy and chemotherapy due to, e.g. overexpression of multidrug resistance pumps and overexpression of aldehyde dehydrogenase. A recent report identified, in two primary patient-derived GSC cultures, that these cells were also refractory to sTRAIL treatment, partly due to selective down-regulation of caspase-8.

Limitations: This study was only a single-centre analysis of retrospective data and could be subject to selection bias. BGB324 Clinical

outcomes and quality of life in elderly patients on PD versus HD.  Harris et al.9 ran a prospective, cohort study of 174 new dialysis patients from four hospital-based renal units in London, specifically looking at an elderly cohort of 70 years and above and comparing modality outcomes. This ‘new’ patient cohort was compared with a prevalent patient cohort during the study period of 12 months. There were no significant differences in comorbidity between the PD and HD groups in new and prevalent patients. The results demonstrated no effect of modality on 12-month survival after controlling for potential confounding factors

such as patient comorbidity and included analysis of dialysis adequacy. Limitations: This was an observational cohort study of a single centre with small numbers that cannot be interpreted without considering LY294002 clinical trial selection bias and generalizability. Thirty per cent of the dialysis population elected not to take part in the study, which could represent a participation bias and there was only a 12-month follow up. Although this study made adjustments for patient comorbid factors, the analysis did not examine specific diseases or their severity. Survival on haemodialysis and peritoneal dialysis over 12 years with emphasis on nutritional parameters.  Avram et al.2 performed a study enrolling 959 patients on HD and PD, commencing dialysis at a single centre in the United States from 1987 to 1999, to compare modality survival. This was DNA ligase a retrospective analysis of medical records. The cumulative survival over 12 years was

significantly higher in HD patients. This study demonstrated a 44% lower mortality risk for patients on HD compared with PD. Limitations: There were limited data on dialysis adequacy as PD adequacy was not routinely measured in the United States before 1992. A selection bias, once again, may have influenced the outcomes. There was no data adjustment for comorbid conditions other than diabetes and AIDS. Comparative mortality of haemodialysis and peritoneal dialysis patients in Canada.  Murphy et al.10 performed a prospective cohort study analysing mortality data from 822 consecutive patients commencing dialysis in 11 Canadian centres between March 1993 and November 1994. Extensive comorbidity data were collected prior to patient commencement. Average follow up was 24 months. The PD and HD patient groups differed considerably at baseline with respect to age, haemoglobin (Hb), albumin and comorbidity score (significantly higher in the HD group). Data were also obtained regarding acuity of onset of renal failure (majority in HD cohort) and severity of disease. When the mortality data for both groups were adjusted for comorbidity, survival for both groups was similar.

Inflammasomes are molecular scaffolds that trigger the activation of caspase 1 and subsequent maturation of IL-1β and IL-18. Typically, inflammasomes are formed from at least one member of the cytosolic innate immune sensor family, the nucleotide oligomerization domain (NOD)-like

receptors (NLR), which include NLRP1, NLRP3 and NLRC4 (IPAF), Alisertib concentration coupled with the adaptor apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC or PYCARD) and caspase 1 [31]. Studies have implicated IL-1β in the immune response to mycobacteria. In humans, IL-1 receptor agonist/IL-1β polymorphisms influence cytokine responses to Mtb[32] and polymorphisms in the IL-1 receptor are associated with increased susceptibility to Mtb[33]. Mice deficient in IL-1R1 are more susceptible to pulmonary

tuberculosis after infection with Mtb, with increased mortality, defective granuloma formation and enhanced mycobacterial growth in the lungs, spleen and liver [34,35]. Mycobacterium tuberculosis may suppress secretion of IL-1β and thereby inhibit host bactericidal activity. A mycobacterial gene, zmp1, which encodes a putative Zn2+ metalloprotease, has been shown to suppress inflammasome activation in infected macrophages [36]. Macrophages infected with zmp1−/−M. bovis bacilli Calmette–Guérin (BCG) secreted more IL-1β than those infected with wild-type (WT) BCG. The study demonstrated that IL-1β increases maturation of mycobacteria-containing phagosomes and enhances killing selleck inhibitor of the bacilli by macrophages. Survival of zmp1−/− BCG was rescued after siRNA knock-down of caspase 1, IL-1β, ASC

and IPAF [36]. In another study, Koo et al. [37] found that macrophages infected with live, virulent strains of M. marinum or M. tuberculosis secreted more IL-1β than those infected with attenuated strains or heat-killed bacilli. Secretion, but not synthesis, of IL-1β and IL-18 was dependent on the mycobacterial ESX-1 secretion system and correlated with lysosome exocytosis [37]. In this study, processing and secretion of IL-1β and IL-18 was dependent on caspase 1, ASC and NLRP3, but not IPAF. A more recent study has demonstrated almost that IL-1β secretion is not only important for host resistance to Mtb in mice, but can be generated through a caspase 1-independent mechanism [38]. Thus, while it is clear that IL-1β has an important role to play in host immune responses to Mtb, multiple mechanisms for its activation may be induced by the bacilli. Given that IL-1β clearly has a role to play in immunity against Mtb, it is interesting that autophagy has been shown to modulate secretion of the cytokine through at least two separate mechanisms. Saitoh et al.

Less is known about the effects of RA on B cells, although studies suggest that it is important in the maturation of IgA-producing B cells [47]. Exposure of PBMC to RA in vitro yields an increase in the frequency of CD19+CD24+CD38+ B cells. Thus, we propose that RA is one direct mediator of iDC action to promote the expansion of Bregs, largely through proliferation, although the effect of RA addition to CD19+ B cells does

not result in an expansion of Bregs as large as when the B cells are cultured with iDC. We believe therefore that RA is one, but not the only, mediator of DC action on Bregs and/or their precursors. The findings of Maseda et al. [50] suggest further that B10 Bregs emerge from a transitional and/or memory population consequent to antigen exposure and B cell receptor (BCR) activation and that the Selumetinib concentration BCR repertoire is polyclonal. Furthermore, those data show that B10 Bregs come to rest as Ig-producing cells. This finding is intriguing, and raises the possibility that T1D-related autoantibodies may not be a consequence of only a series of proinflammatory islet-directed

B cell-mediated pathogenic events, but they could also be a consequence of an immunosuppressive counter-regulation involving Bregs which, as demonstrated by Maseda et al., produce Ig. Very recently, Volchenkov and colleagues discovered that immature DC, generated in the presence of dexamethasone and 1α,25-dihydroxyvitamin D3, gave concomitant rise to Treg and Breg frequency Selleckchem GDC0449 in vitro [56]. These findings strengthen our conclusion that immunosuppressive DC act through regulatory T cells and Bregs [57]. It is tempting to speculate that tripartite DC : Breg : Treg communication occurs in vivo in regulating tolerance. B cells can interact with FoxP3+ Tregs; B cells facilitate

early accumulation of FoxP3+ Tregs in the central nervous system Rebamipide of mice with experimental autoimmune encephalomyelitis (EAE). In two important studies, the authors demonstrated that IL-10 producing Bregs were necessary to restore Tregs and to promote recovery from EAE independently of IL-10, but through glucocorticoid-induced TNF receptor (GITR) ligand [58] and B7 signalling [59]. Adoptive transfer of LPS-activated B cells expressing a glutamic acid decarboxylase (GAD)–IgG fusion protein into NOD diabetic mice was shown to stimulate a rapid increase in CD4+CD25+ Treg numbers [60]. Furthermore, protection from diabetes by splenocytes from diabetes-free, B cell-administered NOD mice was contingent on the presence of CD4+CD25+ T cells [61]. Also, CD40L-activated B cells have been shown recently to generate CD4+ and CD8+ Tregs from naive precursors [62, 63] and a novel Breg population was shown to differentiate T cells into a regulatory IL-10+CD4+ population that account partially for an improvement in lupus [64].

ABO-incompatible donors were accepted for 63 patients; 14 recipients Daporinad in vitro (18%) of an ABO-incompatible donor kidney were distributed across 12 loops that resulted in 31 recipients being transplanted. Thus, without ABO-incompatible matching, only 49 recipients in 19 chains would have been transplanted. Conclusion: KPD using virtual

crossmatch is a valid and effective solution for patients with immunologically incompatible donors even in the context of highly sensitised recipients. HAN SEUNGYEUP1,3, KIM YAERIM1, PARK SUNGBAE1,3, KIM HYUNGTAE2,3 1Department of Internal medicine, Keimyung University School of Medicine; 2Department of Surgery, Keimyung University School of Medicine; 3Keimyung University Kidney Institute Introduction: Kidney transplantation is the most effective treatment in the patients with chronic kidney disease. Recently, survival rate of allograft kidney has been

markedly increased with developed Palbociclib chemical structure immunosuppressant. According to Symphony report published in 2007 and 2009, tacrolimus/MMF showed excellent results than cyclosporin/MMF in allograft function and rejection, but only limited data exist concerning which is better in long-term clinical outcomes. We investigated long term clinical outcomes of tacrolimus/MMF versus cyclosporine/MMF for kidney transplantation recipients. Methods: We compared patient survival rate, graft survival rate, incidence of rejection and metabolic complications between two groups of patients who received immunosuppressant with tacrolimus/MMF and cyclosporin/MMF in kidney transplantation. All patients were received kidney transplantation in Keimyung university Dongsan hospital between Jan. 1997 and Dec. 2003 and followed up over 10 years. Total of 177 patients were included. Results: Among 177 patients, 116 were treated with tacrolimus/MMF, 61 patients with cyclosporin/MMF. Mean follow up duration was 122 months. There LY294002 were no significant difference between two groups in 10 year patient survival rate (90.0% vs. 90.9%) and graft survival rate

(78.9% vs. 71.4%). The incidence rate of acute rejection were higher in cyclosporin/MMF group (23% vs. 29%), but there were no significant difference. New onset diabetes after transplantation was frequent in tacrolimus/MMF group and Cyclosporin/MMF group seemed higher rate of hypertension and hyperlipidemia. Conclusion: There were no differences between tacrolimus/MMF and cyclosporin/MMF as maintenance immunosuppressant in long-term clinical outcomes of kidney transplantation. HIRANO HAJIME1, NOMI HAYAHITO1, UEHARA HIROSHI1, KOMURA KAZUMASA1, MORI TATSUHIKO2, AZUMA HARUHITO1 1Department of Urology, Osaka medical collage; 2Departtment of Nephrology, Osaka medical collage Introduction: In some small islands, there have been no facilities for renal transplants, so that the patients need to leave the island to receive the transplantation.