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INTRODUCTION: This study examined associations between the graft-to-recipient weight ratio (GRWR) for adult-to-adult living donor liver transplantation (LDLT) and hepatocellular carcinoma (HCC) outcomes. MATERIALS AND METHODS: Data from patients in the Korean Organ Transplantation Registry who underwent LDLT for HCC from 2014 to 2021 were retrospectively reviewed. Patients were categorized using the cutoff GRWR for HCC recurrence determined by an adjusted cubic spline (GRWR <0.7% vs. GRWR ≥0.7%). Recurrence-free survival (RFS) and HCC recurrence were analyzed in the entire and a 1:5 propensity-matched cohort. RESULTS: The eligible cohort consisted of 2005 LDLT recipients [GRWR <0.7 ( n =59) vs. GRWR ≥0.7 ( n =1946)]. In the entire cohort, 5-year RFS was significantly lower in the GRWR <0.7 than in the GRWR ≥0.7 group (66.7% vs. 76.7%, P =0.019), although HCC recurrence was not different between groups (77.1% vs. 80.7%, P =0.234). This trend was similar in the matched cohort ( P =0.014 for RFS and P =0.096 for HCC recurrence). In multivariable analyses, GRWR <0.7 was an independent risk factor for RFS [adjusted hazard ratio (aHR) 1.89, P =0.012], but the result was marginal for HCC recurrence (aHR 1.61, P =0.066). In the pretransplant tumor burden subgroup analysis, GRWR <0.7 was a significant risk factor for both RFS and HCC recurrence only for tumors exceeding the Milan criteria (aHR 3.10, P <0.001 for RFS; aHR 2.92, P =0.003 for HCC recurrence) or with MoRAL scores in the fourth quartile (aHR 3.33, P <0.001 for RFS; aHR 2.61, P =0.019 for HCC recurrence). CONCLUSIONS: A GRWR <0.7 potentially leads to lower RFS and higher HCC recurrence after LDLT when the pretransplant tumor burden is high.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Living Donors , Humans , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/mortality , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Liver Neoplasms/mortality , Retrospective Studies , Male , Female , Middle Aged , Adult , Organ Size , Neoplasm Recurrence, Local/pathology , Republic of Korea/epidemiology , Liver/pathology , Liver/surgeryABSTRACT
Liver transplantation is a critical procedure for patients with end-stage liver disease, but it is often hindered by ABO-incompatibility between the donor and recipient, which can lead to immediate humoral rejection. We present a unique case involving a 10-month-old patient who, by accident, received an ABO-incompatible partial liver transplant from a type A mother without undergoing desensitization. Remarkably, during a 21-year follow-up period, the patient exhibited no signs of humoral or graft rejection, despite nonadherence to medication. This case highlights the possibility of dual tolerance in pediatric ABO-incompatible liver transplantation and provides insights into immune tolerance mechanisms, with implications for enhancing patient care and reducing healthcare costs. Further research is necessary to clarify these mechanisms and to evaluate the long-term durability of tolerance in pediatric transplant recipients.
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The purpose of this study was to evaluate the proper position of single large hepatocellular carcinoma (HCC) in the Barcelona Clinic Liver Cancer (BCLC) staging system. The data were collected from the nationwide multicentre database of the Korean Liver Cancer Association. Patients with single large (≥5 cm) HCC were separated from BCLC stage A patients and designated as Group X. The remaining BCLC stage A and stage B patients were classified as Group A and Group B, respectively. The survival outcomes of propensity score-matched groups were compared. Among the 3965 randomly selected patients, the number of patients in Group X, Group A, and Group B was 414, 2787, and 760, respectively. TriMatch analysis allowed us to obtain 116 well-balanced triplets. The 1-, 3-, and 5-year overall survival rates in Group X were worse than in Group A (91%, 71%, and 48% vs 90%, 78%, and 64%, respectively; P < .000). However, the rates were not different compared with those in Group B (91%, 71%, and 48% vs 90%, 69%, and 48%, respectively; P < .09). In multivariate analysis, Group X, Group B, age over 60 years, prothrombin time-international normalized ratio, and creatinine level were independent predictors of worse overall survival. Our findings suggest that Group X should be relocated to BCLC stage B rather than BCLC stage A.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Middle Aged , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Neoplasm Staging , Survival Rate , Prothrombin Time , Retrospective Studies , Hepatectomy , PrognosisABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with the overproduction of serum amyloid A protein, resulting in systemic AA amyloidosis. In this report, we describe a case of gastrointestinal (GI) AA amyloidosis following SARS-CoV-2 infection. A 75-year-old male presented to the emergency department with upper abdominal pain 6 weeks post kidney transplantation. He had a history of SARS-CoV-2 infection 4 weeks prior. On day 7 of hospitalization, while receiving conservative management, the patient developed symptoms of cough and fever, leading to a diagnosis of SARS-CoV-2 reinfection. The patient's abdominal pain persisted, and hematochezia developed on day 30 of hospitalization. Esophagogastroduodenoscopy and colonoscopy revealed multiple ulcers in the stomach and colon, with histologic findings revealing the presence of amyloid A. The patient was managed conservatively and was also given remdesivir for the SARS-CoV-2 infection. His clinical symptoms subsequently improved, and endoscopic findings demonstrated improvement in multiple gastric ulcers. GI amyloidosis may be a subacute complication following SARS-CoV-2 infection in immunocompromised patients.
Subject(s)
Amyloidosis , COVID-19 , Male , Humans , Aged , SARS-CoV-2 , Abdominal PainABSTRACT
BACKGROUND: Patient physical performance has been emphasized in liver transplant recipients; however, evidence for living donor liver transplantation (LDLT) patients is lacking. This study investigated the impact of physical performance decline during the early posttransplantation period on survival and risk factors for this decline in LDLT recipients. METHODS: From national registry data, 2703 LDLT patients were divided into 2 groups based on the change in their Karnofsky performance status (KPS) between 1 and 6 mo posttransplantation: declined KPS (n = 188) and control (n = 2515). Multivariable analyses were conducted to control for confounders, including posttransplantation complications. RESULTS: Estimated 5-y patient survival rates were 91.6% in the declined KPS group and 96.3% in the control group, favoring the latter ( P = 0.003). The survival hazard of KPS decline was significant in a baseline covariates-adjusted Cox model (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.37-4.95) and an adjusted model accounting for posttransplantation complications (HR, 3.38; 95% CI, 1.70-6.72). In subgroup analyses, KPS decline independently reduced survival in patients without complications (HR, 3.95; 95% CI, 1.67-9.34), and the trend was similar in patients with complications, although significance was marginal (HR, 3.02; 95% CI, 0.98-9.27). We found that only posttransplantation complications, such as rejection, infection, bile duct complication, and vascular complication, were significant risk factors for KPS decline after LDLT. CONCLUSIONS: Physical performance decline during the early posttransplantation period independently reduced survival rates, and posttransplantation complications were the only significant risk factors for physical performance decline in LDLT recipients.
Subject(s)
Liver Transplantation , Humans , Liver Transplantation/adverse effects , Living Donors , Retrospective Studies , Graft Survival , Proportional Hazards Models , Treatment OutcomeABSTRACT
BACKGROUND: As the need for a nationwide organ-transplant registry emerged, a prospective registry, the Korean Organ Transplantation Registry (KOTRY), was initiated in 2014. Here, we present baseline characteristics and outcomes of the kidney-transplant cohort for 2014 through 2019. METHODS: The KOTRY consists of five organ-transplant cohorts (kidney, liver, lung, heart, and pancreas). Data and samples were prospectively collected from transplant recipients and donors at baseline and follow-up visits; and epidemiological trends, allograft outcomes, and patient outcomes, such as posttransplant complications, comorbidities, and mortality, were analyzed. RESULTS: From 2014 to 2019, there were a total of 6,129 registered kidney transplants (64.8% with living donors and 35.2% with deceased donors) with a mean recipient age of 49.4 ± 11.5 years, and 59.7% were male. ABO-incompatible transplants totaled 17.4% of all transplants, and 15.0% of transplants were preemptive. The overall 1- and 5-year patient survival rates were 98.4% and 95.8%, respectively, and the 1- and 5-year graft survival rates were 97.1% and 90.5%, respectively. During a mean follow-up of 3.8 years, biopsy-proven acute rejection episodes occurred in 17.0% of cases. The mean age of donors was 47.3 ± 12.9 years, and 52.6% were male. Among living donors, the largest category of donors was spouses, while, among deceased donors, 31.2% were expanded-criteria donors. The mean serum creatinine concentrations of living donors were 0.78 ± 0.62 mg/dL and 1.09 ± 0.24 mg/dL at baseline and 1 year after kidney transplantation, respectively. CONCLUSION: The KOTRY, a systematic Korean transplant cohort, can serve as a valuable epidemiological database of Korean kidney transplants.
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Data for Asian kidney transplants are very limited. We investigated the relative importance of prognostic markers in Asian kidney transplants by using Korean Organ Transplantation Registry (KOTRY) cohort. Prediction models were developed by data-driven variable selection approach. The relative importance of the selected predictors was measured by dominance analysis. A total of 4854 kidney transplant donor-recipient pairs were analyzed. Overall patient survival rates were 99.8%, 98.8%, and 91.8% at 1, 3, and 5 years, respectively. Death-censored graft survival rates were 98.4%, 97.0%, and 95.8% at 1, 3, and 5 years. Biopsy-proven acute rejection free survival rates were 90.1%, 87.4%, and 87.03% at 1, 3, and 5 years. The top 3 dominant predictors for recipient mortality within 1 year were recipient cardiovascular disease history, deceased donor, and recipient age. The dominant predictors for death-censored graft loss within 1 year were acute rejection, deceased donor, and desensitization. The dominant predictors to acute rejection within 1 year were donor age, HLA mismatched numbers, and desensitization. We presented clinical characteristics of patients enrolled in KOTRY during the last 5 years and investigated dominant predictors for early post-transplant outcomes, which would be useful for clinical decision-making based on quantitative measures.
Subject(s)
Graft Survival , Kidney Transplantation , Graft Rejection , Humans , Registries , Republic of Korea/epidemiology , Tissue Donors , Treatment OutcomeABSTRACT
BACKGROUND: Although anastomosing hemangiomas are very rare and benign vascular neoplasms, these tumors are more common among patients with end-stage kidney disease. Incidental finding of these tumors in the kidney or adrenal gland has been reported. Herein, we describe a case in which an anastomosing hemangioma was misdiagnosed as a renal cell carcinoma before kidney transplant. CASE PRESENTATION: A 35-year-old woman with lupus nephritis was admitted to our emergency department for suspected uremic symptoms of nausea and general weakness. She had received hemodialysis due to end-stage kidney disease, and a living-donor kidney transplantation from her father was planned. On pre-operative contrast-enhanced computed tomography and magnetic resonance imaging, a 1.7 cm renal cell carcinoma was observed in the right kidney. On staining after radical nephrectomy, irregularly shaped vascular spaces of various sizes were observed, with these spaces having an anastomosing pattern. As the findings of the anastomosing hemangioma are similar to those of a renal cell carcinoma on imaging, histology examination was necessary to confirm the diagnosis of anastomosing hemangioma and to prevent delay in listing for kidney transplantation. Good kidney function was achieved after transplantation, with no tumor recurrence. CONCLUSION: Our case underlines the importance for prompt surgical resection of an enhancing renal mass to confirm diagnosis in patients scheduled for kidney transplantation to avoid any delay.
Subject(s)
Carcinoma, Renal Cell/diagnosis , Hemangioma , Kidney Failure, Chronic , Kidney Transplantation/methods , Kidney , Nephrectomy/methods , Adult , Diagnosis, Differential , Diagnostic Errors/prevention & control , Female , Hemangioma/diagnosis , Hemangioma/physiopathology , Hemangioma/surgery , Humans , Kidney/diagnostic imaging , Kidney/pathology , Kidney/surgery , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/surgery , Lupus Nephritis/complications , Lupus Nephritis/diagnosis , Magnetic Resonance Imaging/methods , Renal Dialysis/methods , Tomography, X-Ray Computed/methods , Treatment OutcomeABSTRACT
PURPOSE: Initial conservative treatment with selective endovascular or surgical intervention has shown successful outcomes in the treatment of spontaneous isolated superior mesenteric artery dissection (SISMAD). However, the benefits of antithrombotic therapy as a part of conservative treatment have not been clarified. This study aimed to investigate the clinical course of SISMAD patients and determine differences in clinical outcomes between the antithrombotic and no-antithrombotic groups. METHODS: We retrospectively reviewed 79 cases of SISMAD that were treated conservatively from January 2004 to December 2019 at Chonnam National University Hospital. Clinical outcomes, including the length of hospital stay, pain resolution time, image remodeling, and maximal remodeling time, were compared between the antithrombotic and no-antithrombotic groups. RESULTS: There were 30 patients in the no-antithrombotic group and 49 patients in the antithrombotic group. There was no significant difference in clinical characteristics between the 2 groups, except for dyslipidemia (P = 0.011). The follow-up period (32.6 months vs. 14.6 months, P = 0.009) and imaging follow-up period (31.6 months vs. 13.9 months, P = 0.011) were longer in the antithrombotic group than in the no-antithrombotic group. The length of hospital stay (5.1 days vs. 7.7 days, P = 0.002) was significantly shorter in the no-antithrombotic group than in the antithrombotic group because patients in the antithrombotic group required longer hospitalization for warfarin titration. CONCLUSION: In patients with SISMAD, conservative treatment without antithrombotic therapy may have clinical benefits such as decreased length of hospital stay compared with conservative treatment with antithrombotic therapy.
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OBJECTIVES: No data are available regarding different prognostic values of Tc-99m diethylenetriaminepentaacetic acid (DTPA) renal scan in kidney transplantation (KT) recipients according to two distinct donor types: deceased donor KT (DDKT) and living donor KT (LDKT). We evaluated whether the interpretation of Tc-99m DTPA renal scan should be different by the donor type in predicting acute renal allograft rejection (AR). METHODS: One hundred and seven KT recipients (61 DDKT and 46 LDKT) were included in this study. Tc-99m DTPA renal scan was performed 1 week after KT. AR was defined as pathological evidence of renal allograft rejection during the first 6 months of KT. Clinical factors and Tc-99m DTPA renal scan findings were compared between patients with and without AR. To further analyze the effect of the donor type, they were again compared within DDKT and LDKT recipients, respectively. RESULTS: AR occurred in 15 patients (7 DDKT and 8 LDKT recipients). Among all patients, time to peak uptake (TTP) of the cortex (TTPCX) measured by Tc-99m DTPA renal scan was independently predictive of AR. Moreover, TTPKD (TTP of the whole transplanted kidney) and TTPCX were the only predictors of AR among DDKT recipients. The most accurate predictors were TTPCX and kidney area on renal scan for DDKT and LDKT, respectively. However, these parameters could not predict AR for the opposite donor type. CONCLUSIONS: AR could be effectively predicted by Tc-99m DTPA renal scan obtained at 1 week post-KT. Different parameters should be applied according to the donor type in the prediction of AR.
Subject(s)
Allografts , Graft Rejection/diagnosis , Kidney Transplantation/adverse effects , Kidney/diagnostic imaging , Living Donors , Technetium Tc 99m Pentetate , Adult , Female , Graft Rejection/diagnostic imaging , Humans , Kidney Transplantation/methods , Male , Middle Aged , Prognosis , Retrospective StudiesABSTRACT
Coil migration is an extremely rare but hazardous complication of aneurysmal coil embolization. Only 1 case report has described coil migration following endovascular exclusion to gastrointestinal (GI) tract. We report the experience of a case of colon penetration caused by embolization coil placed for internal iliac aneurysm. A 66-year-old man visited the Emergency Department for hematochezia that had persisted for 3 months. Stent insertion and coil embolization of left internal iliac artery aneurysm had been performed on the patient 18 months ago. Colonoscopy was performed. It suggested penetration of sigmoid colon by embolization coil and diverticulum. Angiography revealed extravasation of contrast media at left internal iliac artery. Covered stent deployment was done in the left internal iliac artery. One week after the stent insertion, the patient underwent anterior resection, aneurysm resection, and coil removal. The patient recovered without complications. He was discharged at 2 weeks after the operation.
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PURPOSE: To evaluate patients who underwent surgical or endovascular treatment after vascular injury related to posterior lumbar disc surgery. MATERIALS AND METHODS: We retrospectively reviewed seven cases of vascular injuries (four lacerations, one arteriovenous fistula [AVF], and two pseudoaneurysms) related to lumbar disc surgery by a posterior approach from January 1997 to December 2016 at Chonnam National University Hospital. Information of patient characteristics, diagnosis, treatment strategies, and outcomes were analyzed. RESULTS: Five out of seven cases were inhospital cases. In three laceration cases, each patient instantly became hypotensive and a life-threatening arterial injury was suspected. Therefore, the patient was immediately turned to the supine position and surgical repair was performed. The patients with pseudoaneurysm and AVF were treated by endovascular intervention. Remaining two were referred cases under the impression of vascular injuries. One laceration case of them was in preshock condition, and the left common iliac artery was surgically repaired. The other referred patient showed pseudoaneurysm which was treated with stent graft insertion. There was no surgery or endovascular intervention related death and none of the patients suffered any sequela related to vascular injury. CONCLUSION: Vascular injury associated with posterior lumbar disc surgery is not common, but can be fatal. Early recognition, diagnosis, and prompt treatment are essential to prevent fatal outcomes. Recently, endovascular intervention is increasingly and preferably used because of its low morbidity and mortality. However surgery is still the best option for the patients with unstable vital sign and endovascular approach can be applied to stable patients.
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PURPOSE: To introduce a nation-based endovascular aneurysm repair (EVAR) registry in South Korea and to analyze the anatomical features and early clinical outcomes of abdominal aortic aneurysms (AAA) in patients who underwent EVAR. MATERIALS AND METHODS: The Korean EVAR registry (KER) was a template-based online registry developed and established in 2009. The KER recruited 389 patients who underwent EVAR from 13 medical centers in South Korea from January 2010 to June 2010. We retrospectively reviewed the anatomic features and 30-day clinical outcomes. RESULTS: Initial deployment without open conversion was achieved in all cases and procedure-related 30-day mortality rate was 1.9%. Anatomic features showed the following variables: proximal aortic neck angle 48.8±25.7° (mean±standard deviation), vertical neck length 35.0±17.2 mm, aneurysmal sac diameter 57.2±14.2 mm, common iliac artery (CIA) involvement in 218 (56.3%) patients, and median right CIA length 34.9 mm. Two hundred and nineteen (56.3%) patients showed neck calcification, 98 patients (25.2%) had neck thrombus, and the inferior mesenteric arteries of 91 patients (23.4%) were occluded. CONCLUSION: Anatomical features of AAA in patients from the KER were characterized as having angulated proximal neck, tortuous iliac artery, and a higher rate of CIA involvement. Long-term follow-up and ongoing studies are required.
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This study was designed to evaluate the efficacy and safety of CT-guided embolization of internal iliac artery aneurysm (IIAA) after repair of abdominal aortic aneurysm by transretroperitoneal approach using the lidocaine injection technique to iliacus muscle, making window for safe needle path for three patients for whom CT-guided embolization of IIAA was performed by transretroperitoneal approach with intramuscular lidocaine injection technique. Transretroperitoneal access to the IIAA was successful in all three patients. In all three patients, the IIAA was first embolized using microcoils. The aneurysmal sac was then embolized with glue and coils without complication. With a mean follow-up of 7 months, the volume of the IIAAs remained stable without residual endoleaks. Transretroperitoneal CT-guided embolization of IIAA using intramuscular lidocaine injection technique is effective, safe, and results in good outcome.
Subject(s)
Embolization, Therapeutic , Iliac Aneurysm/therapy , Lidocaine , Postoperative Complications/therapy , Radiography, Interventional/methods , Aged, 80 and over , Anesthetics, Local , Aortic Aneurysm, Abdominal/therapy , Female , Follow-Up Studies , Humans , Iliac Aneurysm/diagnostic imaging , Iliac Artery/diagnostic imaging , Injections, Intramuscular , Male , Middle Aged , Pain/prevention & control , Postoperative Complications/diagnostic imaging , Retroperitoneal Space/diagnostic imaging , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
PURPOSE: We investigated whether suprarenal and infrarenal aortic angles change after the endovascular aneurysm repair (EVAR) procedure and during follow-up, and investigated the correlation between infrarenal aortic angle after EVAR and type Ia endoleaks. METHODS: Data collected on 70 EVAR procedures for a fusiform infrarenal aortic aneurysm performed between May 2006 and December 2012 were supplemented with a retrospective review of charts and radiographs. RESULTS: The greater the preoperative infrarenal aortic angle, the greater the suprarenal aortic angle (r = 0.72, P < 0.001). The infrarenal aortic angle decreased after the EVAR procedure and continued to decrease slowly thereafter (all P < 0.001). Suprarenal aortic angle decreased immediately after the EVAR procedure and continued to decrease during the first month (P < 0.001). No differences in angulation were observed based on stent graft type. Type Ia endoleaks occurred with significantly greater incidence in patients with a larger post EVAR infrarenal angle (P = 0.037). CONCLUSION: The infrarenal aortic angle decreased significantly immediately after the EVAR procedure and continued to decrease slowly thereafter. Suprarenal aortic angle decreased immediately after the EVAR procedure and continued to decrease during the first month. We found a correlation between infrarenal and suprarenal aortic angle. Type Ia endoleaks occurred with greater incidence in patients with a larger infrarenal angle immediately after EVAR.
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An 18-year-old woman reported that after exposure to cold temperatures her fingers appeared blue and her hands and feet felt cold. Secondary Raynaud's phenomenon (RP) associated with peripheral vascular disease was suspected. Technetium (Tc)-99m-labeled RBC hand scintigraphy after cold change showed decreased blood pool activity in her fingers. The patient's symptoms improved after she received sarpogrelate HCL (200 mg/day) and nifedifine (40 mg/day). Follow-up scintigraphy performed 7 months after the patient started treatment showed paradoxically increased blood pool activity in her fingers after cold challenge. To the best of our knowledge, this is the first case report of a patient with secondary RP showing paradoxical change on scintigraphy after she received medication that improved her symptoms.
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Ingestion of foreign bodies is common in gastroenterology practice. Most of them are spontaneously passed through gastrointestinal tract. However, ingestion of multiple magnets can cause serious complications, because magnets attract each other and they hold the gastrointestinal wall. Here, we describe a patient who ingested multiple magnets that attracted each other between distal esophagus, and a part of them was impacted into the esophageal wall. In general, impacted magnetic foreign bodies should be removed by surgical intervention because of a high perforation risk. But, in this case, we used an insulated-tip knife for endoscopic submucosal dissection technique to make an incision to expose the impacted magnetic foreign bodies, and removed them successfully without surgery. With this report, we hope to encourage gastroenterologists to consider this new technique as one of procedures for difficult cases, including impacted foreign bodies.
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Endoscopy, Gastrointestinal/instrumentation , Esophagogastric Junction/surgery , Foreign Bodies/surgery , Magnets , Child, Preschool , Endoscopy, Gastrointestinal/methods , Humans , MaleABSTRACT
PURPOSE: This study demonstrated that apoptosis induced by mycophenolic acid (MPA) is mediated by mitochondrial membrane potential transition (MPT) changes in Jurkat cells. METHODS: Cell viability and MPT changes were measured by flow cytometry. Western blotting was performed to evaluate the expression of Bcl-2 family proteins, Bid, truncated Bid (tBid), cytochrome c, voltage dependent anion channel (VDAC), poly ADP-ribose polymerase (PARP), and protein kinase C-δ (PKC-δ). The catalytic activity of caspase-9 and -3 was also measured. RESULTS: Cell viability was decreased in time- and dose-dependent manners. Bcl-2 protein expression was decreased, but Bax protein expression was identified. A decreased Bcl-X(L) /Bcl-X(S) ratio was also noted. The expression of tBid protein also increased in a time-dependent manner in Jurkat cells treated with MPA. While normal MPT appeared as orange fluorescence, abnormal MPT corresponded to green fluorescence. Green fluorescence increased as orange decreased in the MPA-treated cells. Significantly increased concentrations of MPA induced the release of cytosolic cytochrome c. MPA also augmented the catalytic activity of caspase-9 and caspase-3 in Jurkat cells. Our findings demonstrated that MPA-induced apoptosis is mediated by MPT changes accompanied by decreased Bcl-XL expression and the appearance of tBid protein. The release of cytosolic cytochrome c from mitochondria and increased catalytic activity of caspase-9 and caspase-3 were observed in MPA-treated Jurkat cells. CONCLUSION: These results suggest that mitochondrial dysfunction caused by MPA induces human T lymphocyte apoptosis.
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All-trans retinoic acid (ATRA) affects on the function of antigen presenting cells with somewhat controversies. We investigated the effects of ATRA on differentiation, maturation and function of human monocyte-derived dendritic cells (DCs). Low dose (10(-14)M) or high dose (10(-6)M) of ATRA was added either when monocytes were differentiated into immature DCs (imDCs) or mature DCs (mDCs) were induced. Apoptotic cell populations were dramatically increased in imDCs or mDCs with increasing concentration of ATRA. The productions of IL-12p40 and IL-12p70 were significantly suppressed in imDCs or mDCs induced by the addition of ATRA in the dose-dependent manner, whereas IL-10 was increased. DCs cultured with ATRA induced the differentiation of naïve T cells towards a helper T cell type 2 (Th2) response and expansion of CD4(+)CD25(+)Foxp3(+) regulatory T cells. Allostimulatory capacity of DCs was suppressed with increasing concentration of ATRA. These findings suggest that ATRA inhibits the effects on the differentiation, maturation and function of human monocyte-derived DCs in vitro and also enhance the differentiation of naïve T cell toward the Th2 type.