13 results on '"Jihee L. Suh"'
Search Results
2. Liver transplant complications in hepatitis C infected recipients: recurrence versus rejection
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Daniel G. Maluf, Jihee L. Suh, Valeria R. Mas, and Ricardo C. Gehrau
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Genetic Markers ,Graft Rejection ,medicine.medical_specialty ,medicine.medical_treatment ,Disease ,Liver transplantation ,Diagnosis, Differential ,Predictive Value of Tests ,Recurrence ,Transplant complications ,medicine ,Humans ,Disease biomarker ,Biomarker discovery ,Intensive care medicine ,Hepatology ,business.industry ,Gastroenterology ,Hcv recurrence ,Hepatitis C ,medicine.disease ,Liver Transplantation ,Treatment Outcome ,Molecular Diagnostic Techniques ,Acute Disease ,Immunology ,Differential diagnosis ,business ,Biomarkers - Abstract
Despite improvement on outcomes post liver transplantation (LT), complications such as HCV recurrence (HCV-rec) and acute cellular rejection (ACR) continue to be a challenge for transplant physicians. Accurate diagnostic tools to better dissect between those complications post-LT are crucial for prompt and correct diagnosis and treatment. It is well known that the overlapping features of clinical and histo-pathological characteristics between these conditions turn difficult the appropriate differential diagnosis. Recently, new technological advances had supported the field of biomarker discovery in many diseases. Disease biomarkers capable to differentiate ACR versus HCV-rec post-LT is a long waited task in the transplant community. This editorial describes and discusses potential biomarkers of disease differentiation including recent reports in the field of genomics, proteomics, immunohistochemistry among other technologies.
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- 2014
3. The urine microRNA profile may help monitor post-transplant renal graft function
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Helen P. Cathro, Lorenzo Gallon, Mariano J. Scian, Jae K. Lee, Valeria R. Mas, Catherine I. Dumur, Kenneth L. Brayman, Ricardo C. Gehrau, Anne L. King, Daniel G. Maluf, and Jihee L. Suh
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Male ,Pathology ,Time Factors ,Biopsy ,Kidney ,Fibrosis ,Longitudinal Studies ,Prospective Studies ,Prospective cohort study ,Kidney transplantation ,Proteinuria ,microRNA ,medicine.diagnostic_test ,chronic allograft dysfunction ,Middle Aged ,3. Good health ,Treatment Outcome ,surgical procedures, operative ,medicine.anatomical_structure ,Nephrology ,Female ,medicine.symptom ,Adult ,Genetic Markers ,medicine.medical_specialty ,Urinalysis ,Urinary system ,Article ,urinary cell pellets ,Young Adult ,Predictive Value of Tests ,medicine ,Humans ,Genetic Testing ,Renal Insufficiency, Chronic ,Aged ,business.industry ,Gene Expression Profiling ,biomarkers ,Reproducibility of Results ,medicine.disease ,Kidney Transplantation ,MicroRNAs ,Case-Control Studies ,Atrophy ,business - Abstract
Noninvasive, cost-effective biomarkers that allow accurate monitoring of graft function are needed in kidney transplantation. Since microRNAs (miRNAs) have emerged as promising disease biomarkers, we sought to establish an miRNA signature in urinary cell pellets comparing kidney transplant patients diagnosed with chronic allograft dysfunction (CAD) with interstitial fibrosis and tubular atrophy and those recipients with normal graft function. Overall, we evaluated 191 samples from 125 deceased donor primary kidney transplant recipients in the discovery, initial validation, and the longitudinal validation studies for noninvasive monitoring of graft function. Of 1733 mature miRNAs studied using microarrays, 22 were found to be differentially expressed between groups. Ontology and pathway analyses showed inflammation as the principal biological function associated with these miRNAs. Twelve selected miRNAs were longitudinally evaluated in urine samples of an independent set of 66 patients, at two time points after kidney transplant. A subset of these miRNAs was found to be differentially expressed between groups early after kidney transplant before histological allograft injury was evident. Thus, a panel of urine miRNAs was identified as potential biomarkers for monitoring graft function and anticipating progression to CAD in kidney transplant patients.
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- 2014
4. Regulation of Molecular Pathways in Ischemia-Reperfusion Injury After Liver Transplantation
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Jihee L. Suh, Valeria R. Mas, Danielle E. Ladie, Samuel Luebbert, Daniel G. Maluf, Catherine I. Dumur, and Ricardo C. Gehrau
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Adult ,Graft Rejection ,Male ,Transcription, Genetic ,Biopsy ,Biology ,Bioinformatics ,Article ,Proinflammatory cytokine ,Young Adult ,microRNA ,Gene expression ,Humans ,Postoperative Period ,Gene ,Aged ,Regulation of gene expression ,Transplantation ,Gene Expression Profiling ,Middle Aged ,Cell cycle ,Liver Transplantation ,Gene expression profiling ,MicroRNAs ,Gene Expression Regulation ,Reperfusion Injury ,Cancer research ,Female ,DNA microarray ,Follow-Up Studies - Abstract
Background Ischemia-reperfusion (I/R) injury is a multifactorial phenomenon that occurs during the transplant event and frequently compromises early graft function after liver transplantation (LT). Current comprehension of molecular mechanisms and regulation processes of I/R injury lacks clarity. MicroRNA (miRNA) regulation results critical in several biological processes. Methods This study evaluated gene expression and miRNA expression profiles using microarrays in 34 graft biopsies collected at preimplantation (L1) and at 90 min postreperfusion (L2) from consecutives deceased-donor LT recipients. miRNA profiles were first analyzed. Data integration analysis (gene expression/miRNA expression) aimed to identify potential target genes for each identified miRNA from the L1/L2 differential gene expression profile. Results Pairwise comparison analyses identified 40 miRNAs and 3168 significantly differentially expressed genes at postreperfusion time compared with preimplantation time. Pathway analysis of miRNAs associated these profiles with antiapoptosis, inhibition of cellular proliferation, and proinflammatory processes. Target analysis identified an miRNA-associated molecular profile of 2172 genes involved in cellular growth and proliferation modulation by cell cycle regulation, cell death and survival, and proinflammatory and anti-inflammatory processes. miRNA-independent genes involved proinflammatory molecules. Conclusion We identified a miRNA profile involved in posttranscriptional regulatory mechanisms in I/R injury post-LT. A better understanding of these molecular processes involved in I/R may contribute to develop new strategies to minimize graft injury.
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- 2013
5. Donor Hepatic Steatosis Induce Exacerbated Ischemia-Reperfusion Injury through Activation of Innate Immune Response Molecular Pathways
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Helen P. Cathro, Valeria R. Mas, Ricardo C. Gehrau, Ashish Sharma, Daniel G. Maluf, Catherine I. Dumur, and Jihee L. Suh
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Male ,medicine.medical_treatment ,Biopsy ,Ischemia ,Biology ,Liver transplantation ,Real-Time Polymerase Chain Reaction ,Article ,Nitric oxide ,Proinflammatory cytokine ,chemistry.chemical_compound ,medicine ,Humans ,Transplantation ,Innate immune system ,Fatty liver ,Middle Aged ,medicine.disease ,Immunity, Innate ,Tissue Donors ,Liver Transplantation ,Fatty Liver ,chemistry ,Gene Expression Regulation ,Liver ,Reperfusion Injury ,Immunology ,Cytokines ,RNA ,Female ,Steatosis ,Reperfusion injury ,Biomarkers - Abstract
BACKGROUND Severe liver steatosis is a known risk factor for increased ischemia-reperfusion injury (IRI) and poor outcomes after liver transplantation (LT). This study aimed to identify steatosis-related molecular mechanisms associated with IRI exacerbation after LT. METHODS Paired graft biopsies (n = 60) were collected before implantation (L1) and 90 minutes after reperfusion (L2). The LT recipients (n = 30) were classified by graft macrosteatosis: without steatosis (WS) of 5% or less (n = 13) and with steatosis (S) of 25% or greater (n = 17). Plasma samples were collected at L1, L2, and 1 day after LT (postoperative [POD]1) for cytokines evaluation. Tissue RNA was isolated for gene expression microarrays. Probeset summaries were obtained using robust multiarray average algorithm. Pairwise comparisons were fit using 2-sample t test. P values 0.01 or less were significant (false discovery rate
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- 2015
6. Transcriptome at the time of hepatitis C virus recurrence may predict the severity of fibrosis progression after liver transplantation
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Amiee Potter, Valeria R. Mas, Federico G. Villamil, Kellie J. Archer, Jihee L. Suh, Ricardo C. Gehrau, Daniel G. Maluf, and Valeria Descalzi
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Transplantation ,medicine.medical_specialty ,Pathology ,Hepatology ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Hepatitis C virus ,Immunosuppression ,Histology ,Liver transplantation ,medicine.disease ,medicine.disease_cause ,Gastroenterology ,Transcriptome ,Fibrosis ,Internal medicine ,Liver biopsy ,Gene expression ,Medicine ,Surgery ,business - Abstract
Allograft gene expression analysis may provide insights into the mechanisms involved in liver damage during hepatitis C virus recurrence (HCVrec) after orthotopic liver transplantation (OLT) and allow the identification of patients who have a higher risk of developing severe disease. Forty-three OLT recipients with hepatitis C virus (HCV) were evaluated. Genomewide gene expression analysis was performed with formalin-fixed, paraffin-embedded (FFPE) liver biopsy samples obtained from 21 OLT recipients with HCV at the time of clinical HCVrec, which was defined as increased alanine aminotransferase levels and detectable HCV RNA levels in serum. Patients were classified into 3 groups according to the severity of the fibrosis in the liver biopsies at 36 months post-OLT : group 1 (G1) for mild fibrosis (F0-F1), group 2 for moderate fibrosis (F2), and group 3 (G3) for severe fibrosis (F3-F4). No significant differences were observed between the groups with respect to donor age, histology during HCVrec, treated episodes of acute cellular rejection, or immunosuppression therapy. The results were validated in the remaining 22 OLT recipients with HCV using quantitative real-time polymerase chain reaction. Fifty-seven beadtypes showed significantly different expression (P < 0.001) between the groups during HCVrec. In G3, the gene expression of interleukin-28RA (IL-28RA), IL-28, and angiotensin-converting enzyme was up-regulated. Samples from G1 and G3 were used to determine whether a multigenetic classifier could be derived to predict the group class. The final model included the intercept and 9 bead types. Pairwise scatter plots of these 9 bead types revealed that G1 and G3 were well separated with respect to each gene. Our analysis has demonstrated the utility of a set of molecular markers indicating HCVrec severity early after OLT. Liver Transpl 17:824-835, 2011. © 2011 AASLD.
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- 2011
7. Molecular Pathways Differentiate Hepatitis C Virus (HCV) Recurrence from Acute Cellular Rejection in HCV Liver Recipients
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Ngoc Le, Kellie J. Archer, Valeria R. Mas, Richard T. Stravitz, Daniel G. Maluf, Ricardo C. Gehrau, and Jihee L. Suh
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Oncology ,Graft Rejection ,medicine.medical_specialty ,Hepatitis C virus ,medicine.medical_treatment ,Liver transplantation ,medicine.disease_cause ,Sensitivity and Specificity ,Article ,Diagnosis, Differential ,Text mining ,Postoperative Complications ,Recurrence ,Internal medicine ,Positive predicative value ,Genetics ,medicine ,Cluster Analysis ,Humans ,Molecular Biology ,ARG2 ,Genetics (clinical) ,Oligonucleotide Array Sequence Analysis ,business.industry ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Reproducibility of Results ,Molecular medicine ,Hepatitis C ,Liver Transplantation ,Gene expression profiling ,Liver ,Acute Disease ,Molecular Medicine ,Analysis of variance ,business - Abstract
Acute cellular rejection (ACR) and hepatitis C virus (HCV) recurrence (HCVrec) are common complications after liver transplantation (LT) in HCV patients, who share common clinical and histological features, making a differential diagnosis difficult. Fifty-three liver allograft samples from unique HCV LT recipients were studied using microarrays, including a training set (n = 32) and a validation set (n = 19). Two no-HCV-ACR samples from LT recipients were also included. Probe set intensity values were obtained using the robust multiarray average method (RMA) method. Analysis of variance identified statistically differentially expressed genes (P ≤ 0.005). The limma package was used to fit the mixed-effects models using a restricted maximum likelihood procedure. The last absolute shrinkage and selection operator (LASSO) model was fit with HCVrec versus ACR as the dependent variable predicted. N-fold cross-validation was performed to provide an unbiased estimate of generalization error. A total of 179 probe sets were differentially expressed among groups, with 71 exclusive genes between HCVrec and HCV-ACR. No differences were found within ACR group (HCV-ACR vs. no-HCV-ACR). Supervised clustering analysis displayed two clearly independent groups, and no-HCV-ACR clustered within HCV-ACR. HCVrec-related genes were associated with a cytotoxic T-cell profile, and HCV-ACR-related genes were associated with the inflammatory response. The best-fitting LASSO model classifier accuracy, including 15 genes, has an accuracy of 100% in the training set. N-fold cross-validation accuracy was 78.1%, and sensitivity, specificity and positive and negative predictive values were 50.0%, 90.9%, 71.4% and 80.0%, respectively. Arginase type II (ARG2), ethylmalonic encephalopathy 1 (ETHE1), transmembrane protein 176A (TMEM176A) and TMEM176B genes were significantly confirmed in the validation set. A molecular signature capable of distinguishing HCVrec and ACR in HCV LT recipients was identified and validated.
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- 2011
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8. Evaluation of Molecular Profiles in Calcineurin Inhibitor Toxicity Post-Kidney Transplant: Input to Chronic Allograft Dysfunction
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Catherine I. Dumur, Kenneth L. Brayman, J. K. Lee, Lorenzo Gallon, Jihee L. Suh, Daniel G. Maluf, Helen P. Cathro, Valeria R. Mas, and Anne L. King
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Adult ,Graft Rejection ,Male ,Pathology ,medicine.medical_specialty ,Calcineurin Inhibitors ,Gastroenterology ,Kidney transplant ,Article ,Postoperative Complications ,Histological diagnosis ,Internal medicine ,Immunology and Allergy ,Medicine ,Humans ,Pharmacology (medical) ,Longitudinal Studies ,Prospective Studies ,Prospective cohort study ,Kidney transplantation ,Oligonucleotide Array Sequence Analysis ,Transplantation ,Kidney ,business.industry ,Gene Expression Profiling ,Calcineurin inhibitor toxicity ,Middle Aged ,medicine.disease ,Allografts ,Prognosis ,Kidney Transplantation ,Calcineurin ,medicine.anatomical_structure ,Cross-Sectional Studies ,Area Under Curve ,Toxicity ,Disease Progression ,Kidney Failure, Chronic ,Female ,business ,Biomarkers ,Follow-Up Studies - Abstract
The molecular basis of calcineurin inhibitor toxicity (CNIT) in kidney transplantation (KT) and its contribution to chronic allograft dysfunction (CAD) with interstitial fibrosis (IF) and tubular atrophy (TA) were evaluated by: (1) identifying specific CNIT molecular pathways that associate with allograft injury (cross-sectional study) and (2) assessing the contribution of the identified CNIT signature in the progression to CAD with IF/TA (longitudinal study). Kidney biopsies from well-selected transplant recipients with histological diagnosis of CNIT (n = 14), acute rejection (n = 13) and CAD with IF/TA (n = 10) were evaluated. Normal allografts (n = 18) were used as controls. To test CNIT contribution to CAD progression, an independent set of biopsies (n = 122) from 61 KT patients collected at 3 and ~12 months post-KT (range = 9-18) were evaluated. Patients were classified based on 2-year post-KT graft function and histological findings as progressors (n = 30) or nonprogressors to CAD (n = 31). Molecular signatures characterizing CNIT samples were identified. Patients classified as progressors showed an overlap of 7% and 22% with the CNIT signature at 3 and at ~12 months post-KT, respectively, while the overlap was
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- 2014
9. Identification of biomarkers to assess organ quality and predict posttransplantation outcomes
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Kenneth L. Brayman, Stephen D. Turner, Kellie J. Archer, Krystle G. David, Anne L. King, Daniel G. Maluf, Marc P. Posner, Mariano J. Scian, Jihee L. Suh, and Valeria R. Mas
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Oncology ,medicine.medical_specialty ,Renal function ,Biology ,Bioinformatics ,CXCR4 ,Article ,Transcriptome ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Kidney transplantation ,Oligonucleotide Array Sequence Analysis ,Proportional Hazards Models ,Transplantation ,Proportional hazards model ,medicine.disease ,Kidney Transplantation ,Fold change ,Tissue Donors ,Gene expression profiling ,Biomarkers ,Glomerular Filtration Rate ,Signal Transduction - Abstract
UNLABELLED The increased disparity between organ supply and need has led to the use of extended criteria donors and donation after cardiac death donors with other comorbidities. METHODS We have examined the preimplantation transcriptome of 112 kidney transplant recipient samples from 100 deceased-donor kidneys by microarray profiling. Subject groups were segregated based on estimated glomerular filtration rate (eGFR) at 1 month after transplantation: the GFR-high group (n=74) included patients with eGFR 45 mL/min per 1.73 m(2), whereas the GFR-low group (n=35) included patients with eGFR 45 mL/min or less per 1.73 m(2). RESULTS Gene expression profiling identified higher expression of 160 probe sets (140 genes) in the GFR-low group, whereas expression of 37 probe sets (33 genes) was higher in the GFR-high group (P
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- 2012
10. Reduced expression of inflammatory genes in deceased donor kidneys undergoing pulsatile pump preservation
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Kenneth L. Brayman, Daniel G. Maluf, Catherine I. Dumur, Anne L. King, Kellie J. Archer, Julie A. Straub, Mariano J. Scian, Marc P. Posner, Valeria R. Mas, Megan E. Wardius, and Jihee L. Suh
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Male ,Pathology ,genetic structures ,Biopsy ,030232 urology & nephrology ,Pulsatile flow ,lcsh:Medicine ,030230 surgery ,Kidney ,Expanded Criteria Donor ,Cohort Studies ,0302 clinical medicine ,Prospective Studies ,lcsh:Science ,Kidney transplantation ,Multidisciplinary ,medicine.diagnostic_test ,Organ Preservation ,Genomics ,Middle Aged ,medicine.anatomical_structure ,Transplant Surgery ,Nephrology ,Medicine ,Female ,Research Article ,Adult ,medicine.medical_specialty ,Clinical Research Design ,Immunology ,Delayed Graft Function ,Cold storage ,Young Adult ,03 medical and health sciences ,Cadaver ,medicine ,Humans ,Biology ,Aged ,Inflammation ,Deceased donor ,urogenital system ,business.industry ,Gene Expression Profiling ,lcsh:R ,Immunity ,Kidney metabolism ,medicine.disease ,Kidney Transplantation ,Gene Expression Regulation ,Clinical Immunology ,Surgery ,lcsh:Q ,Genome Expression Analysis ,business - Abstract
Background The use of expanded criteria donor kidneys (ECD) had been associated with worse outcomes. Whole gene expression of pre-implantation allograft biopsies from deceased donor kidneys (DDKs) was evaluated to compare the effect of pulsatile pump preservation (PPP) vs. cold storage preservation (CSP) on standard and ECD kidneys. Methodology/Principal Findings 99 pre-implantation DDK biopsies were studied using gene expression with GeneChips. Kidneys transplant recipients were followed post transplantation for 35.8 months (range = 24–62). The PPP group included 60 biopsies (cold ischemia time (CIT) = 1,367+/−509 minutes) and the CSP group included 39 biopsies (CIT = 1,022+/−485 minutes) (P
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- 2012
11. Pretransplant Transcriptome Profiles Identify among Kidneys with Delayed Graft Function Those with Poorer Quality and Outcome
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Thomas F. Mueller, Marc P. Posner, Anne L. King, Krystle G. David, Daniel G. Maluf, Valeria R. Mas, Jihee L. Suh, Kellie J. Archer, Qing Ren, Todd W.B. Gehr, and Mariano J. Scian
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Adult ,Male ,medicine.medical_specialty ,Pathology ,Adolescent ,medicine.medical_treatment ,Biopsy ,Urology ,Renal function ,Delayed Graft Function ,Biology ,Kidney ,Real-Time Polymerase Chain Reaction ,Transcriptome ,Cohort Studies ,Young Adult ,Genetics ,medicine ,Humans ,Young adult ,Molecular Biology ,Genetics (clinical) ,Dialysis ,Aged ,Demography ,medicine.diagnostic_test ,Gene Expression Profiling ,Kidney metabolism ,Reproducibility of Results ,Articles ,Middle Aged ,Molecular medicine ,Kidney Transplantation ,medicine.anatomical_structure ,Treatment Outcome ,Gene Expression Regulation ,Creatinine ,Molecular Medicine ,Female ,Biomarkers ,Glomerular Filtration Rate ,Signal Transduction - Abstract
Robust biomarkers are needed to identify donor kidneys with poor quality associated with inferior early and longer-term outcome. The occurrence of delayed graft function (DGF) is most often used as a clinical outcome marker to capture poor kidney quality. Gene expression profiles of 92 preimplantation biopsies were evaluated in relation to DGF and estimated glomerular filtration rate (eGFR) to identify preoperative gene transcript changes associated with short-term function. Patients were stratified into those who required dialysis during the first week (DGF group) versus those without (noDGF group) and subclassified according to 1-month eGFR of45 mL/min (eGFR(hi)) versus eGFR of ≤45 mL/min (eGFR(lo)). The groups and subgroups were compared in relation to clinical donor and recipient variables and transcriptome-associated biological pathways. A validation set was used to confirm target genes. Donor and recipient characteristics were similar between the DGF versus noDGF groups. A total of 206 probe sets were significant between groups (P0.01), but the gene functional analyses failed to identify any significantly affected pathways. However, the subclassification of the DGF and noDGF groups identified 283 probe sets to be significant among groups and associated with biological pathways. Kidneys that developed postoperative DGF and sustained an impaired 1-month function (DGF(lo) group) showed a transcriptome profile of significant immune activation already preimplant. In addition, these kidneys maintained a poorer transplant function throughout the first-year posttransplant. In conclusion, DGF is a poor marker for organ quality and transplant outcome. In contrast, preimplant gene expression profiles identify "poor quality" grafts and may eventually improve organ allocation.
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- 2011
12. Molecular Mechanisms Associated With Hepatitis C Recurrence Severity Post Liver Transplantation
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Jihee L. Suh, V. Mas, B. Kane, D. Maluf, Kenneth L. Brayman, Ricardo C. Gehrau, and Shawn J. Pelletier
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Transplantation ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine.medical_treatment ,medicine ,Hepatitis C ,Liver transplantation ,medicine.disease ,business ,Gastroenterology - Published
- 2014
13. Epigenetic in Kidney Transplantation: Characteristic Paired Donor-Recipient DNA Methylation Patterns Correlate With Long-Term Graft Function
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D. Ladie, V. Mas, Jihee L. Suh, Lorenzo Gallon, J. Lee, D. Maluf, Kenneth L. Brayman, and Ricardo C. Gehrau
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Transplantation ,business.industry ,DNA methylation ,medicine ,Cancer research ,Epigenetics ,medicine.disease ,business ,Graft function ,Kidney transplantation ,Term (time) - Published
- 2014
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