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Background Recent advances in desensitization techniques and immunosuppressive therapy have led to improved outcomes after ABO-incompatible (ABO-i) kidney transplantation (KT). However, questions remain unanswered, particularly regarding which type of ABO isoagglutinin-immunoglobulin M (IgM) or immunoglobulin M (IgG)-is significantly involved in antibody-mediated rejection (AMR). Study design and methods We retrospectively analyzed data from 120 patients who underwent ABO-i KT between 2012 and 2014. Preoperative plasma exchange was performed until the IgM isoagglutinin titer was 4 or less, regardless of the IgG titer. Clinical data were compared between patient groups with pre-KT IgG isoagglutinin titer 16 or greater (high IgG; titer range, 16-256; n = 39) and 8 or less (low IgG; titer range, -8; n = 81). Results The median follow-up periods were 59 (high IgG) and 55 (low IgG) months. Patient survival at 5 years (p = 0.314) was 100% (high IgG) and 97.4% (low IgG). Graft survival at 5 years (p = 0.480) was 100% (high IgG) and 98.7% (low IgG). AMR by anti-ABO antibody occurred in only one patient in the low-IgG group. Conclusion Patients with high pre-KT IgG isoagglutinin titers had equally successful outcomes as those with low IgG titers. ABO-i KT can be successfully performed by reducing the pre-KT IgM isoagglutinin titer to 4 or less, as determined by the immediate spin tube method.

Background: Early allograft dysfunction (EAD) is a serious complication of liver transplantation (LT) and is associated with graft failure, which can result in patient mortality. Due to the shortage of organs for retransplantation, only a small proportion of EAD patients undergo retransplantation. Thus, liver support is needed for most patients with EAD. Methods: We evaluated the effects of therapeutic plasma exchange (TPE) in EAD patients. EAD was defined as a sustained hyperbilirubinemia (≥10 mg/dL) within 30 days of LT without concurrent biliary complications. In a 13-year period, 107 EAD patients underwent TPE while 36 EAD patients did not. We investigated the laboratory and clinical outcomes of TPE and non-TPE groups. Results: The TPE group showed 1-month and 1-year survival rates of 82.2% and 53.8%, respectively, whereas the non-TPE group showed 58.3% and 22.2%, respectively. In TPE group, statistically significant decreases (P

Activation of NK cells is triggered by combined signals from multiple activating receptors that belong to different families. Several NK cell activating receptors have been identified, but their role in the regulation of effector functions is primarily understood in the context of their individual engagement. Therefore, little is known about the signaling pathways broadly implicated by the multiple NK cell activation cues. Here we provide evidence pointing to glycogen synthase kinase (GSK)-3β as a negative regulator of multiple NK cell activating signals. Using an activation model that combines NKG2D and 2B4 and tests different signaling molecules, we found that GSK-3 undergoes inhibitory phosphorylation at regulatory serine residues by the engagement of NKG2D and 2B4, either individually or in combination. The extent of such phosphorylation was closely correlated with the degree of NK cell activation. NK cell functions, such as cytokine production and cytotoxicity, were consistently enhanced by the knockdown of GSK-3β or its inhibition with different pharmacological inhibitors, whereas inhibition of the GSK-3α isoform had no effect. In addition, NK cell function was augmented by the overexpression of a catalytically inactive form of GSK-3β. Importantly, the regulation of NK cell function by GSK-3β was common to diverse activating receptors that signal through both ITAM and non-ITAM pathways. Thus, our results suggest that GSK-3β negatively regulates NK cell activation and that modulation of GSK-3β function could be used to enhance NK cell activation.

Background The therapeutic efficacy of red blood cell (RBC) transfusions in patients with autoimmune hemolytic anemia (AIHA) is highly debated because of speculations on the increased risk of transfusion reactions; yet it is a suggested adjuvant therapy in anemic patients with life-threatening hypoxemia. In this study, we evaluated the safety and efficacy of RBC transfusions in AIHA patients. Methods Daily changes in hemoglobin, total bilirubin, and lactate dehydrogenase (LDH) were assessed in 161 AIHA patients without bleeding history who were transfused once with 1-5 units of the least-incompatible RBCs and monitored over a seven-day period. Post-transfusion patients positive for alloantibodies only or those without RBC-specific antibodies were considered as control groups (N=100 for both groups). Results The three groups revealed similar increases in hemoglobin of 1.40-1.70 g/dL (autoantibodies), 1.20-1.60 g/dL (alloantibodies only), and 1.40-1.55 g/dL (no antibodies) for seven days following transfusion of 10 mL RBCs/kg. During follow-up, no significant changes in total bilirubin or LDH levels were detected in the AIHA group compared with controls. Influences due to autoantibody type, direct antiglobulin test (DAT) specificity and strength, and steroid therapy status on transfusion reactions were not evident in AIHA patients. In addition, changes in hemoglobin levels were significantly higher (P

While ovarian cancer (OvCa) responds well to surgery and conventional chemotherapy, a high recurrence rate of advanced OvCa is observed. In this phase I/II study, 10 OvCa patients with minimal residual disease were treated with autologous dendritic cells (DCs) and IL-2 to evaluate the safety and feasibility of this therapeutic strategy and to characterize the antigen-specific immune alterations induced through this treatment. Approximately 4 months after initial debulking and chemotherapy, patients received two subcutaneous doses of autologous monocyte-derived DCs pulsed with autologous tumor lysate and keyhole limpet hemocyanin (KLH) at 4-week intervals. After each DC inoculation, low-dose (200 mIU) IL-2 was introduced for 14 consecutive days as an immune adjuvant. The vaccination was well tolerated. In three out of 10 patients, the inclusion status after the initial therapy showed the maintenance of complete remission (CR) after DC vaccination for 83, 80.9 and 38.2 months without disease relapse. One patient with stable disease (SD) experienced the complete disappearance of tumor after DC vaccination, and this status was maintained for 50.8 months until tumor recurrence. In two patients with partial response (PR) was not responding to DC vaccination and their disease recurred. In the three patients with disease free long-term survival, significant immune alterations were observed, including increased natural killer (NK) activity, IFN-γ-secreting T cells, immune-stimulatory cytokine secretion and reduced immune-suppressive factor secretion after DC vaccination. Thus, in patients with NED status and increased overall survival, DC vaccination induced tumor-related immunity, potentially associated with long-term clinical responses against OvCa.

We report here the results of surveys for External Quality Assessment (EQA) of blood bank tests carried out in 2013. The proficiency testing specimens were prepared at Ajou University Hospital and sent to 548 and 545 institutes participating in the 1st and 2nd trial, respectively. Test items for the surveys were ABO grouping, RhD typing, crossmatching, direct antiglobulin test (DAT), antibody screening test, and antibody identification test. The response rates for the 1st and 2nd trials were 94.3% and 96.0%, respectively. No answers were considered incorrect answers, and the average accuracy rates of different test items of the survey were as follows: ABO grouping, 98.9% to 100%; RhD typing, 98.4% to 99.2%; crossmatching, 94.4% to 100.0%; DAT using polyspecific reagent, 94.5% to 99.7%; DAT using IgG monospecific reagent, 94.7% to 98.8%; DAT using C3d monospecific reagent, 91.3% to 98.6%; unexpected antibody screening test, 90.9% to 100%; and antibody identification test, 87.3% to 100.0%. Overall, we obtained excellent survey results for the EQA of blood bank tests carried out in 2013, and the number of participating institutes was higher in 2013 than in 2012. (J Lab Med Qual Assur 2014;36:55-63)

ABO-incompatible (ABO-i) kidney transplantation (KT) has emerged for overcoming the shortage of organ donors. Although this technique initially achieved only low graft survival due to isoagglutinin, recently developed desensitization protocols have improved survival to levels that are comparable to ABO-compatible KT. However, isoagglutinin is still regarded as a major obstacle to ABO-i KT. In this study, we evaluate the impact of isoagglutinin titer on clinical outcomes as well as factors that may influence isoagglutinin titers. In total, data from 95 patients who underwent ABO-i KT were analyzed. Preoperatively, rituximab administration and plasmapheresis were performed until the titer was reduced to ≤1:4. Retrospective analysis included blood group; timing and dosage of rituximab; isoagglutinin titer; number of plasmapheresis; and clinical outcomes including graft survival and serum creatinine. Graft survival was 95.8% (n = 91) and average serum creatinine at 1- and 1.5-year post-ABOi-KT was 1.3. Three patients died of sepsis. The identified predictors of titer-rebound after transplant were short interval (

We evaluated the outcome of children and adolescents with acquired severe aplastic anemia (SAA) who received haploidentical hematopoietic stem cell transplantation (HHCT) with in vitro T cell–depleted peripheral blood stem cells. Twelve patients with acquired SAA received a total of 15 HHCTs with in vitro CD3-depleted grafts between July 2009 and July 2012. Among the 12 patients, 11 achieved neutrophil engraftment at a median of 10 days (range, 9 to 13 days) after HHCT. One patient failed to achieve primary engraftment, and two experienced graft rejection soon after engraftment. All three patients who experienced early graft failure received a second HHCT and achieved sustained engraftment. Thus, the final engraftment rate was 100%. Acute graft-versus-host disease was assessed in 9 patients, excluding the 3 patients with early graft failure. Three of these patients developed acute graft-versus-host disease (two ≥ grade II and one with grade III). All 12 patients survived and were transfusion-independent at a median follow-up of 14.3 months (range, 4.1 to 40.7 months). Hematopoietic stem cell transplantation from haploidentical family donors with in vitro CD3 T cell depletion is a reasonable therapeutic option for children and adolescents with acquired SAA. Our future trial with a uniform protocol will help to solve the problems associated with HHCT and provide a valuable platform for the further development of HHCT as a therapy for SAA.

We investigated the combination of human adipose tissue derived stem cells (ADSC) and in vivo gel-forming methoxy poly (ethyleneglycol)-poly (ɛ-caprolactone) (MPEG–PCL) as a muscle regeneration matrix, with and without inclusion of vascular endothelial cell growth factor (VEGF). VEGF165-treated stem cell grafts showed significant proliferation and differentiation into muscle tissue in vivo. Importantly, the inclusion of VEGF enhanced vascularization. This scaffold supported preconditioned ADSC, and allowed them to differentiate into mature muscle tissues in vivo, indicating that ADSC of human origin and MPEG–PCL scaffolds provided an appropriate environment for cellular growth and expansion. Our results thus provide a potential solution to the major obstacle encountered in the engineering of thick complex tissues, which require an adequate blood supply to maintain cell viability during tissue growth and to induce appropriate structural organization. Therefore, the combination of ADSC and in vivo gel-forming MPEG–PCL with VEGF165 might serve as a suitable non-invasive biomaterial for clinical muscle regeneration applications.

1 , Seog-Woon Kwon, M.D. 2 , Gil-Chun Park, M.D. Conclusions: The results of this study implicate that PP has a beneficial effect on the recovery of liver graft function, especially during the early posttransplant period. We suggest to perform active application of PP therapy for liver recipients showing severe graft dysfunction of total bilirubin greater than 15∼20 mg/dL.

Changes in isoagglutinin titers may have implications in the occurrence of hematological complications such as pure red cell aplasia or immune‐mediated hemolysis. Furthermore, isoagglutinin titers could reflect immunohematological reconstitution after transplantation. The objective of this study was to examine the relationship between donor‐derived isoagglutinins (DDIs) and graft‐versus‐host disease (GVHD). In total, 114 patients who underwent ABO‐incompatible allogeneic hematopoietic stem cell transplantation (HSCT) were analyzed. Among these patients, 27.7% demonstrated increased donor‐derived isoagglutinins (IDDIs) against red blood cells (RBCs) of the recipient, and 32.8% of the patients showed DDIs that were not against RBCs of the recipient. Patients with acute GVHD and DDIs against RBCs of the recipient tended to have higher incidences of IDDIs that occurred before posttransplant day 60 compared with patients without acute GVHD (17.3 vs. 3.9%, P=0.058). In patients with acute GVHD, IDDIs occurred significantly earlier (mean, day 32 vs. 181, P=0.046), the period of elevation was shorter (mean, day 36 vs. 134, P=0.033), and the donors were younger (mean, 28 vs. 36 years, P=0.01) than those without GVHD. Moreover, significant correlations were found between IDDIs and acute GVHD. Taken together, these data underscore a possible role for humoral immunity in GVHD after HSCT. J. Clin. Lab. Anal. 22:383–390, 2008. © 2008 Wiley‐Liss, Inc.

Eosinophils play a major pathologic role in the pathogenesis of diverse inflammatory diseases including chronic rhinosinusitis (CRS). Dysregulated production of prostaglandin (PG), particularly PGD2, is considered to be an important contributing factor to eosinophilic inflammation in CRS primarily through proinflammatory and chemotactic effects on eosinophils. Here, we provide evidence that PGD2 can promote eosinophilic inflammation through a suppression of Natural killer (NK) cell effector function and NK cell-mediated eosinophil regulation. Eosinophil apoptosis mediated by NK cells was significantly decreased in CRS patients compared with healthy controls. This decrease was associated with NK cell dysfunction and eosinophilic inflammation. Tissue eosinophils were positively correlated with blood eosinophils in CRS patients. In a murine model of CRS, NK cell depletion caused an exacerbation of blood eosinophilia and eosinophilic inflammation in the sinonasal tissue. PGD2 and its metabolite, but not PGE2 and a panel of cytokines including TGF-β, were increased in CRS patients compared with controls. Effector functions of NK cells were potently suppressed by PGD2-dependent, rather than PGE2-dependent, pathway in controls and CRS patients. Thus, our results suggest decreased NK cell-mediated eosinophil regulation, possibly through an increased level of PGD2, as a previously unrecognized link between PG dysregulation and eosinophilic inflammation in CRS.

Early allograft dysfunction (EAD) is a serious complication of liver transplantation (LT) and is associated with graft failure, which can result in patient mortality. Due to the shortage of organs for retransplantation, only a small proportion of EAD patients undergo retransplantation. Thus, liver support is needed for most patients with EAD.We evaluated the effects of therapeutic plasma exchange (TPE) in EAD patients. EAD was defined as a sustained hyperbilirubinemia (≥10 mg/dL) within 30 days of LT without concurrent biliary complications. In a 13-year period, 107 EAD patients underwent TPE while 36 EAD patients did not. We investigated the laboratory and clinical outcomes of TPE and non-TPE groups.The TPE group showed 1-month and 1-year survival rates of 82.2% and 53.8%, respectively, whereas the non-TPE group showed 58.3% and 22.2%, respectively. In TPE group, statistically significant decreases (P 0.05) in total bilirubin (15.2 ± 5.2 to 13.1 ± 5.4 mg/dL), and INR (1.72 ± 1.04 to 1.38 ± 1.14), were seen after the final TPE session. TPE responder groups with age51 years, total bilirubin11.1 mg/dL, or INR1.15 after final TPE showed better prognosis. TPE decreased the hazard risk of death in EAD patients whereas older age, male gender, and higher INR on the day of EAD onset increased the risk.TPE effectively removed plasma bilirubin and improved coagulation function in EAD patients, with higher survival in the TPE group than in the non-TPE group. TPE may be an effective liver support for EAD patients. J. Clin. Apheresis 32:147-153, 2017. © 2016 Wiley Periodicals, Inc.

A nationwide survey on the status of plasma exchange in Korea was performed during the 2 year period 2001–02. Data from 496 patients were collected from 15 major hospitals. The most common indication was myasthenia gravis (15.3%), followed by thrombotic thrombocytopenic purpura (14.5%) and hemolytic uremic syndrome (9.7%). Clinical improvement was noted in 70.1% of the 415 cases. Plasma exchange by centrifugation alone accounted for 92.4%. Postcentrifugal filtration was carried out in 5.6% and double filtration in 2.0% of treatments. The most common instruments for the centrifugation were Cobe Spectra (71.3%) and Fenwal CS3000 (15.8%). Filtration was performed by either Kuraray KM8300 or Kuraray KM8800. The overall frequency of complications was 11.1% (293/2647 cases), of which symptomatic hypocalcemia was the most common (2.3%).

We investigated the changes in isoagglutinin titres in 62 patients who underwent ABO-incompatible allogeneic stem cell transplantation. After major [and/or (+/-) minor] ABO-incompatible transplantation, recipient-derived isoagglutinins against donor-type red blood cells (RBCs) disappeared more rapidly in unrelated recipients (P = 0.006) and in patients with acute graft-versus-host disease (GVHD, P = 0.025) than in sibling recipients and in patients without acute GVHD respectively. Pure red cell aplasia (PRCA) developed in 10 out of 35 evaluable patients who underwent major (+/- minor) ABO-incompatible transplantation, and the post-transplant increase of isoagglutinin titres was a significant predictor for the occurrence of PRCA. In five out of 36 patients who underwent minor (and/or (+/-) major) ABO-incompatible transplantation, donor-derived isoagglutinins against recipient RBCs were detectable without clinically overt haemolysis. Isoagglutinin titres against ABO antigens absent both on recipient and donor RBCs decreased during the early post-transplant period then rose subsequently in 24 out of 29 patients at (median) d 59 post transplant. Our study showed that changes in isoagglutinin titres might have clinical implications in the occurrence of immunohaematological complications such as PRCA or immune-mediated haemolysis, and might reflect immunohaematological reconstitution after transplantation. Furthermore, our data regarding time to disappearance of recipient-derived isoagglutinins against donor-type RBCs after major ABO-incompatible transplantation suggest the presence of a graft-versus-plasma cell effect.

Severe early graft dysfunction has been occasionally encountered following adult living donor liver transplantation (LDLT). We have assessed the effectiveness of plasmapheresis (PP) as liver support for LDLT recipients with severe early graft dysfunction.Of the 789 adult LDLTs performed between January 2007 and December 2009, 50 patients (6.3%) underwent PP as a supportive measure during the first month.The mean time from LDLT to start of plasmapheresis was 11.2 ± 6.8 days (range 2-28). The 50 patients underwent 517 sessions of PP, or a mean of 10.3 ± 6.8 sessions per patient, over a mean 21.6 ± 9.4 days. Thirty-four patients (68%) required concurrent hemodiafiltration. Mean serum total bilirubin concentration before PP was 16.2 ± 6.7 mg/dL, peaking at 20.3 ± 7.9 mg/dL during PP, and decreasing to 13.4 ± 5.4 mg/dL 1 week after completion of PP (P.001 compared with before PP). Except for prothrombin time, no other biochemical parameter was significantly altered by PP. There were no serious complications related to PP. Of the 50 patients, 17 (34%) died soon or a few months after PP. The 6-month graft survival rate after completion of PP was 66%; the overall 1-year patient survival rate was 64.0%.PP appeared to have beneficial effects for LDLT recipients with severe early graft dysfunction, namely total bilirubin concentrations greater than 10 mg/dL.

To investigate reconstitution of T and NK cells after αβ T lymphocyte-depleted haploidentical hematopoietic cell transplantation (HHCT) and the clinical implications of γδ T cells, we analyzed 50 pediatric patients who received 55 HHCTs using αβ T cell-depleted grafts. The number of CD3+ T cells and CD8+ T cells recovered rapidly and reached donor levels at days 180 and 60, respectively. Recovery of NK cells was rapid, and the median of NK cells at day 14 was comparable to the donor level. At day 14, median percentage of γδ T lymphocytes was 70.5%. After day 14, the percentage of γδ T cells gradually decreased, while the percentage of αβ T cells gradually increased. Patients with a low percentage (≤21%) of γδ T cells at day 30 had significantly higher incidence of cytomegalovirus (CMV) reactivation compared to patients with a high percentage (>70%) of γδ T cells (P < .01). In patients with acute leukemia, patients with high percentage of γδ T cells at day 30 showed significantly higher relapse-free survival compared to those with low percentage of γδ T cells (P = .02). Data suggest that early recovery of γδ T cells decreases the risk of CMV reactivation and leukemia relapse.

The assessment of the biological activity of capsaicin, the compound responsible for the spicy flavor of chili pepper, produced controversial results, showing either carcinogenicity or cancer prevention. The innate immune system plays a pivotal role in cancer pathology and prevention; yet, the effect of capsaicin on natural killer (NK) cells, which function in cancer surveillance, is unclear. This study found that capsaicin inhibited NK cell-mediated cytotoxicity and cytokine production (interferon-γ and tumor necrosis factor-α). Capsaicin impaired the cytotoxicity of NK cells, thereby inhibiting lysis of standard target cells and gastric cancer cells by modulating calcium mobilization in NK cells. Capsaicin also induced apoptosis in gastric cancer cells, but that effect required higher concentrations and longer exposure times than those required to trigger NK cell dysfunction. Furthermore, capsaicin inhibited the cytotoxicity of isolated NK cells and of an NK cell line, suggesting a direct effect on NK cells. Antagonists of transient receptor potential vanilloid subfamily member 1 (TRPV1), a cognate capsaicin receptor, or deficiency in TRPV1 expression failed to prevent the defects induced by capsaicin in NK cells expressing functional TRPV1. Thus, the mechanism of action of capsaicin on NK cells is largely independent of TRPV1. Taken together, capsaicin may have chemotherapeutic potential but may impair NK cell function, which plays a central role in tumor surveillance.

In the Stone Age, livelihood required only a few tools, including stone axes, stone blades, stone mortars, and earthenware. These simple tools may have been adequate for survival in that period. However, human lifestyle has dramatically changed over a long history of "ups and downs." There have been many remarkable advances in the fields of knowledge, education, and science. These advances have brought us many benefits and led us to marvelous scientific breakthroughs, truly a great leap for mankind. The invention of computers is one of the greatest masterworks. According to the records, the world's first programmable automatic computing machine was invented in early 1940s. In 1981, International Business Machines Corporation (IBM) introduced its first personal computer (PC) equipped with 16 kilobytes of memory (expandable to 256 kilobytes) and using the Microsoft Disk Operating System (MS-DOS). Although Bill Gates once said (and later denied) that "640 kilobytes ought to be enough for anybody" with respect to the IBM PC at that time, we now use PCs with more than 4 gigabytes of memory. The invention of the Internet along with the search engines, including Google (which derives its name from a misspelling of "Googol," which means 10100), is another triumph for humanity. These powerful tools enable us to surf worldwide information networks, including GenBank (the NIH genetic sequence database), and provide us a mechanism for dissemination of information and a forum for collaboration and interaction between scientists. In 1665, an English scientist, Robert Hooke, discovered the cell. He saw the "small rooms" through his microscope and coined the word "cell" simply because they looked like small rooms where the monks lived in. Now we can see the "cosmos" in the cell, where an overwhelming number of functional molecules are living. In 1953, James Watson and Francis Crick saw the double helix structure of DNA [1]. We can now see the complete DNA sequence or genomes of numerous species, including human genome. By virtue of the Human Genome Project, which was started in 1990 and completed in 2004, approximately 3.3 billion base-pairs of human genome have been fully sequenced and identified, and we became to know that there are approximately 20,500 genes in human beings [2], roughly the same range as in mice. Having a great diversity, the genes are expressed by specific signals in the microenvironments, and sometimes, are actively involved in disease development and progress. Scientists are now confronted by a vast number of tasks required for understanding the expression of these genes and their association with various diseases. The Sanger sequencing method definitely contributed to the completion of the Human Genome Project, and ushered in the age of genomics. However, this generated a requirement for a new tool for performing high-throughput sequencing. The advent of next-generation sequencing (NGS) technology has enabled rapid sequencing of large stretches of DNA base-pairs [3]. Up to one terabase of data can be obtained in a single sequencing run by using NGS technology. It is really breathtaking to realize that researchers are now able to sequence more than five human genomes in a single run, producing data in a week by computer at a low cost of less than $5,000 per genome. This revolutionary advance in genomic science will surely help scientists extract genetic information from biological systems as much as they need and provide a powerful tool to explore cells and diseases. Scientists frequently encounter limitations because of large data sets in not only meteorology (the study of atmosphere) and connectomics (the study of the connectivity of synapses in the brain) but also genomics. In being committed to our work as hematologists, we have to look into the fine details of blood cells (including immune cells), both healthy and malignant, at the genetic and molecular levels. This generates data about genomic sequences, protein sequences, protein structure and function, molecular interactions, signaling and metabolic pathways, regulatory motifs, etc. [4]. We are inevitably facing these "big data" challenges as well as those from laboratory and clinical findings. Maybe we have to learn how to manage these "big data" for surviving.

ABO-incompatible (ABO-i) kidney transplantation (KT) has emerged for overcoming the shortage of organ donors. Although this technique initially achieved only low graft survival due to isoagglutinin, recently developed desensitization protocols have improved survival to levels that are comparable to ABO-compatible KT. However, isoagglutinin is still regarded as a major obstacle to ABO-i KT. In this study, we evaluate the impact of isoagglutinin titer on clinical outcomes as well as factors that may influence isoagglutinin titers. In total, data from 95 patients who underwent ABO-i KT were analyzed. Preoperatively, rituximab administration and plasmapheresis were performed until the titer was reduced to ≤1:4. Retrospective analysis included blood group; timing and dosage of rituximab; isoagglutinin titer; number of plasmapheresis; and clinical outcomes including graft survival and serum creatinine. Graft survival was 95.8% (n = 91) and average serum creatinine at 1- and 1.5-year post-ABOi-KT was 1.3. Three patients died of sepsis. The identified predictors of titer-rebound after transplant were short interval (7 days) between rituximab and first plasmapheresis (P = 0.004); high initial titer (≥256) (P = 0.023); low titer-reduction rate (P 0.001); and blood group O (P 0.001). One patient who experienced a rebound developed antibody-mediated rejection. With low-dose (200 mg) rituximab, the change in isoagglutinin titer-rebound was not significant and the infection rate was significantly decreased (P = 0.001). In conclusion, isoagglutinin titer-rebound within the first 2 weeks after KT may be a risk factor for rejection. The factors identified as affecting titer-rebound after KT were high initial isoagglutinin titer, low titer-reduction rate, short interval, and blood group O.

Background: Hematopoietic stem cell transplantation (HSCT) remains the preferred frontline curative modality for patients with aplastic anemia in the presence of a matched familial donor (MFD). In the absence of MFD, the general consensus is frontline immunosuppressive therapy followed by HSCT from a matched unrelated donor (MUD) in case of failure or relapse, and recently haploidentical family donor (HFD) is emerging as an alternative donor in aplastic anemia. We evaluated the outcome of HSCT in children and adolescents with acquired severe aplastic anemia (SAA), and compared outcomes of transplantation according to the donor types. Methods : We performed a retrospectively analysis of 61 patients with acquired SAA at a single center between July 1998 and May 2016. Conditioning regimen was a reduced-intensity combination of fludarabine, cyclophosphamide, and rabbit anti-thymocyte globulin in most cases, and low dose total body irradiation was added for haploidentical hematopoietic stem cell transplantation (HHCT). Grafts for HHCT were manipulated by ex vivo T-cell depletion. Results: Of the 61 patients reviewed, total 66 HSCTs were done. The median age at HSCT was 12.5 years (range, 0.7-21.7 years). By donor types, 15 patients received grafts from MFD, 20 from MUD, and 26 from HFD. Grafts for HHCTs were CD3-depleted in 12 patients, CD3/CD19-depleted in 4, and ¥á¥â+ T-cell depleted in 10 patients. Among 61 patients, 59 patients achieved neutrophil engraftment at a median of 11 days (range, 9-18 days). The medians of neutrophil engraftment were 10 days in HFD recipients, 13 days in MFD and 12 days in MUD HSCTs, respectively, and HHCT group had significantly faster neutrophil engraftment than others (Figure 1). There were 9 patients who experienced graft failure (GF) among 61 patients. Of the 35 patients with matched donors, 1 patient failed to achieve primary engraftment, and 3 experienced graft rejection after engraftment. Of the 26 HFD recipients included, neutrophil engraftment was achieved in 25 patients, except 1 patient. Additional 4 HHCT recipients experienced graft rejection within 1 month post-HHCT. Five (1 MUD, 4 HFD) out of 9 patients who experienced GF received a second HSCT and achieved sustained engraftment, another 1 patient was alive without transfusion or further treatment, and the other 3 patients died after GF. A total of 18 patients developed grade II-IV acute GvHD (13 with grade II and 5 with grade III); 9 had received MUD transplant, 7 HFD, and 2 MFD. Seven patients developed chronic GvHD; 4 patients were MUD recipients, and 3 HFD. The cumulative incidence (CI) of grade II-III acute GvHD was 34% (MUD : 45%, HFD : 33.3%, MFD : 16.7%), and 1-year CI of chronic GvHD was 14.4%. There was no statistically significant difference in GvHD occurrence according to the donor types. As for survival results, total four patients died; one HFD recipient died of CMV pneumonia on day +157 of HHCT, and other 3 patients (1 MFD, 1 MUD, 1 HFD) died after GF. Two out of these 3 patients received a second HSCT; one MUD recipient died of acute respiratory distress syndrome and acute renal failure, and another HFD recipient died of pure red cell aplasia. The other MFD recipient died of poor graft function after GF. The overall transplant-related mortality was 7.6%. At a median follow up 45.7 months (range, 1.5-195.2 months), the estimated 5-year overall survival (OS) was 92.7% in 61 patients. There was no statistical difference in OS among HSCTs from three different donor types (MFD : 92.9% vs MUD : 94.4% vs HFD : 91.3% at 5 years, respectively, p value = 0.915) (Figure 2). Conclusions: Our study demonstrated that survival outcomes of HHCT were comparable to HSCT from matched familial or matched unrelated donors in pediatric patients with acquired SAA. HHCT was associated with rapid neutrophil recovery, and tolerable treatment related toxicities in SAA patients. These data suggest that hematopoietic stem cell transplantation from haploidentical family donors is a reasonable therapeutic option for children and adolescents with acquired SAA. Disclosures No relevant conflicts of interest to declare.

Background: Phlebotomy has been used as a primary method for the treatment of erythrocytosis. As a new phlebotomy method, we used an automated component collection system (Alyx, Fenwal), which has been used to obtain two units of leukoreduced red blood cells (RBCs) from donors. We evaluated the effectiveness of “double red-cell” phlebotomy (DRP) and compared it with conventional “whole-blood” phlebotomy (WBP). Materials and Methods: We have performed a total of 596 phlebotomies in 158 patients with erythrocytosis between June 2008 and November 2011. Forty patients underwent 84 DRPs and 118 patients underwent 512 WBPs. We removed 360–420 mL of RBCs in DRP and 360–600 mL of whole blood in WBP according to patient's total blood volume (TBV). Changes in hematologic parameters after phlebotomy were compared. Results: DRP removed more RBC volume (399.4 ± 20.2 mL vs. 235.9 ± 29.8 mL, P < 0.05) and lowered more hematocrit than WBP (6.9% ± 2.3% vs. 3.0% ± 1.7%, P < 0.05). Hematocrit reduction per kilogram of body weight was higher by DRP than WBP (0.106% ± 0.043% vs. 0.039% ± 0.025%, P < 0.05). Mild adverse events occurred in 32.5% (13/40) during DRP and 4.2% (5/118) during WBP. Conclusion: DRP lowered more RBC mass than WBP by selectively removing more RBC volume with less TBV. DRP can be an effective and safe technique for the treatment of erythrocytosis. J. Clin. Apheresis 27:255–259, 2012. © 2012 Wiley Periodicals, Inc.

Background Ten cancer patients (Six renal cell carcinoma and four breast cancer patients) were treated in a phase I/II study with a vaccine composed of autologous dendritic cells (DCs) and IL-2 to evaluate the DC vaccine-related toxicity and antigen-specific immune alteration. Methods Cancer patients were treated twice with autologous CD34+ hematopoietic stem cell-derived, GM-CSF/IFN-γ-differentiated DCs pulsed with autologous tumor lysate and KLH, by 4-week interval. Following each subcutaneous injection of therapeutic DCs, low-dose (200 MIU) IL-2 was introduced for 14 consecutive days as an immune adjuvant. To determine the DC vaccine-induced immunological alterations, the KLH-specific lymphocyte proliferation, number of IFN-γ secreting T cells (ELISPOT assay), NK activity and the cytokine modulation were measured. Results Cultured-DCs expressing HLA-DR, CD11c, CD83, and B7.1/B7.2 produced IL-12p70. After vaccination, the patients tolerated it. Clinical response was observed in one RCC patient as stable disease. However DC-vaccine related antigen-specific immune responses including peripheral blood lymphocyte proliferation and the number of IFN-r secreting cells were induced in six patients without clear correlation with clinical responses. Also NK activity was induced significantly in six patients after vaccination. DC vaccine-related decrease of TGF-β level or increase of IL-12p70 level and decline of CD4+CD25+ T cells were observed in three patients. However only in the RCC patient whose disease stabilized, combination of stimulatory as well as inhibitory immune alterations including induction of IFN-γ secreting T cell with reduction of CD4+ CD25+ T cell were correlated with clinical responses. Conclusion Data indicated that DC vaccine combined with IL-2 is well tolerated without major side effects. DC vaccine induced the specific immunity against introduced antigen. Combinatorial alterations of immunological parameters indicating antigen-specific immune induction along with reduction of inhibitory immunity were correlated with clinical responses in DC vaccine treated patients.

ABO antigens are composed of sugar chains and exist not only on red cells but also on many other cells including endothelial cells and epithelial cells of various organs such as kidney, heart, bowel, lung, and pancreas (Marionneau et al., 2001). ABO antibodies, which have been called as isoagglutinins, are preformed antibodies directed against missing A or B antigens. The source of anti-A/B antibodies is thought to be gastrointestinal and environmental bacteria, such as the enterobacteriaceae, which possess ABO-like structures on their lipopolysaccharide coats (Yamamoto, 2004). These preformed ABO antibodies are clinically important in transfusion and organ transplantation medicine because they can cause acute hemolytic transfusion reaction in ABO-incompatible (ABO-I) blood transfusion and hyperacute rejection in ABO-I organ transplantation.

On March 31, 2010, the first English issue of the Korean Journal of Hematology (KJH) was published and dispatched to overseas libraries and domestic readers. It was the emotional zenith of my editorial career. At last, the KJH has been reborn as an international journal to fulfill our mission of delivering new and important scientific knowledge and information regarding all aspects of hematology to readers worldwide. In fact, with this important event, KJH has witnessed the dawn of a new epoch. The Korean Society of Hematology (KSH) was founded on June 16, 1958, at a time when our whole country still bore the scars from the Korean War (1950-1953). Incidentally, the American Society of Hematology was born in the same year. And meaningfully, the title of the very first conference was "Anemia in Korea," a title that reflects the poverty-stricken conditions at the time. Overcome by a "hungry spirit", Koreans worked very hard recovering from war-inflicted wounds. Students studied night and day, and workers toiled by the sweat of their brow even under poor circumstances. In the medical field, doctors cared for their patients with a passion even with the dearth of medical facilities and instruments. Some ambitious doctors studied abroad in developed countries like the USA and imbibed advanced medical knowledge in preparation for the future. The field of Hematology evolved and grew in Korea through the enthusiasm and frontier spirit of the founding members and senior hematologists who followed in their footsteps. Although still in the "anemic" stage, the first issue of the KJH was successfully published on July 1, 1966 by the KSH. It was indeed the first splendid step of baby KJH. Dr. Byung Hee Lee, a chairman of the KSH at the time, described the overwhelming moment vividly in the Editorial of the first issue: "In publishing this first issue of the Korean Journal of Hematology, I am truly moved to tears by the researcher's dedication and professionalism. I celebrate and wish that this Journal would not end in the first issue but improve continuously in the future to become a brilliant floodlight in the field of hematology, and I desperately hope that our members and officials give unstinting support and promotion in the years to come." - KJH Vol. 1, No. 1, July 1966. During the early period, the Journal, written in Korean interspersed with Chinese characters, was an annual publication. Thereafter, the growing number of submitted articles led to more frequent publication of the journal-biannually since 1971, three times a year since 1994, and quarterly since 2001. With the grown and evolution of Korean hematology, other subdivided hematology-related academic societies were subsequently established the Korean Society of Blood Transfusion in 1982, the Korean Society on Thrombosis and Hemostasis (KSTH) in 1991, the Korean Society of Pediatric Hematology-Oncology (KSPHO) in 1993, and the Korean Society of Blood and Marrow Transplantation (KSBMT) in 1996. Since then, these societies have published their own journals. As part of its international academic activities, the KSH successfully hosted numerous international meetings, including the Asian-Pacific Regional Congress of the International Society of Hematology (ISH) in 1979, the Korean-Japanese Hematology Symposium in 1995, and the World Congress of the ISH in 2002. The year 2005 was of great significance to the KJH, having attained the status of the unified official journal of four hematology-related societies-the KSH, KSBMT, KSPHO, and KSTH-which marked the basis for further advancement of the KJH. In the same year, the Online Submission and Review System was successfully launched, allowing authors, peer reviewers, and editors to send and receive all correspondence conveniently through this system. Starting 2007, all full-text articles from the first issue could be searched and downloaded in PDF format. Furthermore, this system is linked to KoreaMed, a service of the Korean Association of Medical Journal Editors (KAMJE), which provides access to articles published in Korean medical journals. It is also linked to KoreaMed Synapse, a digital archive and the reference linking platform of Korean medical journals, which adopted the PubMed Central (PMC) XML to display full-text articles. At present, one of the most important missions of the KJH is the "globalization" of domestic hematology. We should not be lagging behind the advances in hematology, with scientific research in the field and medical practice progressing at breakneck pace. We should rise through continuous evolution. We are now equipped with a good online system, good peer reviewers, good journal contributors, and distinguished international Editorial Board members. All these preparations should drive the KJH toward setting sail as an international journal. The time has come to make a commitment and take a passage at full sail to place the KJH on the list of SCI journals. To this end, authors should submit well-written manuscripts, while reviewers should carefully review them and offer constructive feedback for corrections and enhancements. It is also important that the accepted manuscripts be published in good style and format. To ensure this, the authors, reviewers, and editors must all work together aboard this ship-the KJH. In spite of sharing Odysseus' fate in being cornered by sea monsters like Scylla and Charybdis, we are off to sail over the horizon!

ABO blood group compatibility has been regarded as an essential prerequisite for successful adult living donor liver transplantation (LDLT). Novel strategies for overcoming the ABO blood group barrier, however, have markedly improved the results of ABO-incompatible (ABOi) LDLT. We describe our strategies for dual graft LDLT to cope with ABO-incompatibility and small-for-size graft syndrome in 3 patients who underwent dual graft LDLT with ABOi and ABO-compatible (ABOc) grafts. One patient received a modified right lobe graft from an ABOi living donor and a left lateral section graft from an ABOc deceased donor, whereas the other 2 patients received 2 left lobe or left lateral section grafts from ABOi and ABOc living donors. To overcome the ABO-blood barrier, each patient was treated with preoperative anti-CD20 antibody (rituximab 375 mg/m(2)), perioperative plasma exchange, and hepatic arterial infusion. All 3 patients were males, of mean age 47.7 years (range, 40 approximately 52 years) and mean Model for End-Stage Liver Disease score 12.3 (range, 9 approximately 15). The mean graft-to-recipient weight ratio was 0.99%. All patients remain alive after a mean follow-up period of 9.5 months (range, 8.0 approximately 10.7 months). All 6 grafts have functioned normally. There were no episodes of antibody-mediated rejection or biliary complication. Dual LDLT with ABOi and ABOc grafts can be a feasible solution for simultaneously overcoming both the ABO blood group barrier and small-for-size graft syndrome.

National apheresis registries can be used to evaluate changes in technology, clinical indications, and applications over the years. Since the establishment of the Korean Society of Apheresis (KSFA) in 1999, basic data on the status of apheresis have been collected using letters and e-mails on a biennial basis. In February 2006, a KSFA homepage and an on-line apheresis registry were constructed (http://www.apheresis.or.kr/). The registry consists of two sub-registries, one addressing overall aspects, e.g., the numbers and types of apheresis machines, total numbers of apheresis procedures, and the other addressing therapeutic plasmapheresis, e.g., diagnoses, modes of treatment, instrument used, replacement fluids, volumes processed, vascular access, anticoagulants, complications, and clinical responses. Data registered on-line is presumed to represent about 95% of total apheresis procedures performed in Korea. In this report, we introduce our on-line registry system and compared the data obtained by on-line registry with the previous ones.

The [corrected] use of adult stem cells for cell-based tissue engineering and regeneration strategies represents a promising approach for skeletal muscle repair. We have evaluated the combination of adipose tissue-derived adult stem cells (ADSCs) obtained from autologous liposuction and injectable poly(lactic-co-glycolic acid) (PLGA) spheres for muscle regeneration. ADSCs attached to PLGA spheres and PLGA spheres alone were cultured in myogenic medium for 21 days and injected subcutaneously into the necks of nude mice. After 30 and 60 days, the mice were sacrificed, and newly formed tissues were analyzed by immunostaining, H and E staining, and RT-PCR. We found that ADSCs attached to PLGA spheres, but not PLGA spheres alone, were able to generate muscle tissue. These findings suggest that ADSCs and PLGA spheres are useful materials for muscle tissue engineering and that their combination can be used in clinical settings for muscle regeneration.

In chronic inflammatory conditions such as ulcerative colitis (UC), the migration of granulocytes and monocytes/macrophages from the circulation into the colonic mucosa is especially important in maintaining inflammation. The aim of this trial was to assess safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with moderate-to-severe UC refractory to conventional drug therapies.Twenty-seven patients with moderate (55.6%) to severe (44.4%) active UC refractory to conventional drug therapies who had no changes in their conventional therapy regimen in the past two weeks before the recruitment were enrolled in an open-label trial. Concomitant medications were allowed, and steroids were tapered down according to the clinical activity during the course. We used an adsorptive type extracorporeal column (Adacolumn; JIMRO, Takasaki, Japan), which selectively adsorb granulocytes and monocytes. Patients took five apheresis sessions, each with 60 minutes duration for 5 consecutive weeks. The primary efficacy variables were clinical disease activity, short inflammatory bowel disease questionnaire (SIBDQ), C-reactive protein (CRP), and endoscopic scores. These variables were scored at regular intervals, and analyzed at week 7 on an intention-to-treat (ITT) principles.At 7 weeks, 70.4% of patients showed overall improvement. Clinical disease activity (p0.0001), endoscopic score (p0.001), and the quality of life as assessed by SIBDQ (p0.0001) were significantly improved after the therapy. In 56.3% of concomitant steroid users, tapering down or discontinuation of steroids was possible. Treatment was well tolerated, and no severe adverse events were observed.Adacolumn was very efficacious in patients with moderate-to-severe active UC refractory to conventional drug therapy, but further assessment is needed.

We investigated the changes in isoagglutinin titres in 62 patients who underwent ABO-incompatible allogeneic stem cell transplantation. After major [and/or (+/-) minor] ABO-incompatible transplantation, recipient-derived isoagglutinins against donor-type red blood cells (RBCs) disappeared more rapidly in unrelated recipients (P = 0.006) and in patients with acute graft-versus-host disease (GVHD, P = 0.025) than in sibling recipients and in patients without acute GVHD respectively. Pure red cell aplasia (PRCA) developed in 10 out of 35 evaluable patients who underwent major (+/- minor) ABO-incompatible transplantation, and the post-transplant increase of isoagglutinin titres was a significant predictor for the occurrence of PRCA. In five out of 36 patients who underwent minor (and/or (+/-) major) ABO-incompatible transplantation, donor-derived isoagglutinins against recipient RBCs were detectable without clinically overt haemolysis. Isoagglutinin titres against ABO antigens absent both on recipient and donor RBCs decreased during the early post-transplant period then rose subsequently in 24 out of 29 patients at (median) d 59 post transplant. Our study showed that changes in isoagglutinin titres might have clinical implications in the occurrence of immunohaematological complications such as PRCA or immune-mediated haemolysis, and might reflect immunohaematological reconstitution after transplantation. Furthermore, our data regarding time to disappearance of recipient-derived isoagglutinins against donor-type RBCs after major ABO-incompatible transplantation suggest the presence of a graft-versus-plasma cell effect.

The identification and characterization of viral epitopes across the Human Leukocyte Antigen (HLA) polymorphism is critical for the development of actives-specific or adoptive immunotherapy of virally-mediated diseases. This work investigates whether cytokine mRNA transcripts could be used to identify epitope-specific HLA-restricted memory T lymphocytes reactivity directly in fresh peripheral blood mononuclear cells (PBMCs) from viral-seropositive individuals in response to ex vivo antigen recall. PBMCs from HLA-A*0201 healthy donors, seropositive for Cytomegalovirus (CMV) and Influenza (Flu), were exposed for different periods and at different cell concentrations to the HLA-A*0201-restricted viral FluM158–66 and CMVpp65495–503 peptides. Quantitative real time PCR (qRT-PCR) was employed to evaluate memory T lymphocyte immune reactivation by measuring the production of mRNA encoding four cytokines: Interferon-γ (IFN-γ), Interleukin-2 (IL-2), Interleukin-4 (IL-4), and Interleukin-10 (IL-10). We could characterize cytokine expression kinetics that illustrated how cytokine mRNA levels could be used as ex vivo indicators of T cell reactivity. Particularly, IFN-γ mRNA transcripts could be consistently detected within 3 to 12 hours of short-term stimulation in levels sufficient to screen for HLA-restricted viral immune responses in seropositive subjects. This strategy will enhance the efficiency of the identification of viral epitopes independently of the individual HLA phenotype and could be used to follow the intensity of immune responses during disease progression or in response to in vivo antigen-specific immunization.

The identification and characterization of viral epitopes across the Human Leukocyte Antigen (HLA) polymorphism is critical for the development of actives-specific or adoptive immunotherapy of virally-mediated diseases. This work investigates whether cytokine mRNA transcripts could be used to identify epitope-specific HLA-restricted memory T lymphocytes reactivity directly in fresh peripheral blood mononuclear cells (PBMCs) from viral-seropositive individuals in response to ex vivo antigen recall. PBMCs from HLA-A*0201 healthy donors, seropositive for Cytomegalovirus (CMV) and Influenza (Flu), were exposed for different periods and at different cell concentrations to the HLA-A*0201-restricted viral FluM158–66 and CMVpp65495–503 peptides. Quantitative real time PCR (qRT-PCR) was employed to evaluate memory T lymphocyte immune reactivation by measuring the production of mRNA encoding four cytokines: Interferon-γ (IFN-γ), Interleukin-2 (IL-2), Interleukin-4 (IL-4), and Interleukin-10 (IL-10). We could characterize cytokine expression kinetics that illustrated how cytokine mRNA levels could be used as ex vivo indicators of T cell reactivity. Particularly, IFN-γ mRNA transcripts could be consistently detected within 3 to 12 hours of short-term stimulation in levels sufficient to screen for HLA-restricted viral immune responses in seropositive subjects. This strategy will enhance the efficiency of the identification of viral epitopes independently of the individual HLA phenotype and could be used to follow the intensity of immune responses during disease progression or in response to in vivo antigen-specific immunization.

연구배경 : Endothelin(이하 ET로 약함)은 폐혈관 내피세포에서 생산되며 강한 혈관 수축작용이 있는 peptide이다. 일차성 폐동맥고혈압과 급성 폐동맥색전증 환자의 혈장내 ET이 증가하고 이들 질환에서의 심폐기능장애에 ET이 중요한 역할을 하리라고 추측되나 ET증가의 기전에 대해서는 알려진 바 없다. 이들 두 질환은 모두 혈전증이 중요한 병태생리 소견이므로 저자들은 혈소판과 활성화된 혈소판에서 유리된 매개체들이 폐혈관 내피세포에서 ET 생산을 증가시킬 것이라고 가정하고 이를 확인하기 위하여 연구를 시행하였다. 방 법 : 소 폐동맥내피세포 배양배지에 혈소판, thrombin(0.1~10u/ml), transforming growth factor- ${\beta}1$ (TGF- ${\beta}1$ , 1-1000pM), serotonin(1-100uM), 및 내독소(1ug/ml)를 첨가한 후 18시간 배양하여 배지내로 유리된 immunoreactive ET(이하 ir-ET로 약함)을 방사선면역측정법으로 정량분석 하였다. 결과 : 소 폐동맥내피세포 배양 상청액내 ir-ET은 배양 시간에 비례하여 증가하였으며 혈소판 $10^8/ml$ 을 첨가한 군에서는 배양 8시간 및 18시간 후에 대조배지군에 비해 유의하게 높았다(p $10^8/ml$ 에서는 대조배지군에 비해 유의하게 높았다 (0 $10^7/ml$ )에 ir-ET을 유의하게 증가시키지 않는 농도의 thrombin (0.1u/ml) 또는 내독소(1ug/ml)를 각각 첨가한 군에서 배양 상청액내 ir-ET은 배지 대조군과 단독 첨가군 (thrombin 0.1u/ml, 내독소 1ug/ml)에 비해 각각 유의하게 높았다(p ${\beta}1$ (100-1000pM) 첨가군에서 각각 대조배지군에 비해 유의하게 높았으며 (p ${\beta}1$ 등의 매개물에 의한 내피세포의 자극으로 생각되며 이외에 혈소판에 의한 내피세포의 ET 생산 반응 조절(priming) 가능성도 추측할 수 있다. 【Background : Endothelin(ET) is a very potent vasoconstrictive peptide produced by endothelial cells of pulmonary artery. The endothelin level was increased in plasma of primary pulmonary hypertension and acute pulmonary thromboembolism and it was suggested that the endothelin might do a critical role in the cardiopulmonary dysfunction in these two conditions. But the exact mechanism of increase of ET has not been known. In these two conditions, platelet activation and thrombosis are the main pathophysiologic findings. So there is a possibility that the platelet might stimulate endothelin secretion from endothelial cells. Therefore, we performed this study to evaluate the role of platelet and its mediators on endothelin production in bovine pulmonary artery endothelial(BPAE) cells. Method : Bovine pulmonary artery endothelial cells, ATCC certified cell line 209, were cultured and treated with human platelets( $10^6{\sim}10^8/ml$ ), thrombin (0.1~10u/ml), TGF- ${\beta}1$ (1~100uM), serotonin(1~100uM), and endotoxin(1ug/ml) in a final volume of 500ul for 18 hours. Levels of ir(immunoreactive)-ET in each conditioned medium were measured by a radioimmunoassay specific for ET. Result : The increase of ir-ET levels was platelet number and time dependent over 18 hours. When washed human platelets were added( $10^8/ml$ ), the ir-ET levels were significantly higher than that of control(p $10^7/ml$ ) coincubated with endotoxin(1ug/ml) or subthreshold dose of thrombin(0.1u/ml) stimulated ir-ET secretion from BPAE cells significantly(p ${\beta}1$ (100pM, 1000pM) significantly increased ir-ET secretion from BP AE cells(p ${\beta}1$ , secreted from activated platelets. And, in this study, the priming effect of platelets on endothelin secretion from BPAE cells could be another possibility.】