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Sandy Feng

Publications and source records attributed to Sandy Feng.

35 records · Page 2Linked to original sources
PubMed2004

An uncomfortable silence em leader while we all search for a better reporter gene in adult stem cell biology.

The plasticity of bone marrow cells (BMCs) remains controversial. The present study found that persistent injury induces efficient trans-differentiation of BMCs into functional hepatocytes. Mice with liver cirrhosis induced by carbon tetrachloride were injected with 1 x 10(5) non-treated green fluorescent protein (GFP)-positive BMCs via the tail vein. In these mice, transplanted GFP-positive BMCs efficiently migrated into the peri-portal area of liver lobules after one day, repopulating 25% of the recipient liver by 4 weeks. In contrast, no GFP-positive BMCs were detected following transplantation into control mice with undamaged livers. BMCs trans-differentiated into functional mature hepatocytes via immature hepatoblasts. Serum albumin levels were significantly elevated to compensate for chronic liver failure in BMC transplantation. These results reveal that recipient conditions and microenvironments represent key factors for successful cell therapy using BMCs.

Comment↗
PubMed2004

Hepatitis C etiology of liver disease is strongly associated with early acute rejection following liver transplantation.

Although recurrent hepatitis C (HCV) occurs universally after liver transplantation (LT), its tempo and severity are variable and unpredictable. Diagnosis and treatment of early acute rejection (EAR) likely affect the course of recurrent HCV disease. We have studied a contemporary cohort of LT recipients to reexamine risk factors for EAR. We hypothesized that HCV etiology may represent a significant risk factor for EAR for many reasons. First, recurrent disease commonly causes biochemical abnormalities prompting allograft biopsy. Second, overlapping histologic features of acute rejection and recurrent HCV ambiguity may result in diagnostic ambiguity. Finally, the biology of hepatitis may precipitate an antidonor response in addition to an antiviral response. Records of 285 adult recipients undergoing primary LT for cirrhosis between January 1, 1999, and December 31, 2002, were retrospectively reviewed. EAR was defined as a biopsy-proven or an empirically treated episode within 6 months of LT. Cox proportional hazards analysis identified donor, recipient, transplant, and posttransplant characteristics associated with EAR; Kaplan-Meier analysis was used to assess rejection by etiology. HCV cirrhosis was the etiology for 51% of all LT recipients. There were 135 episodes of EAR (127 biopsy proven) in 117 recipients for an overall incidence of 41%. Patient groups with HCV and cholestatic / autoimmune disease groups exhibited the highest incidence of rejection at 49%. Recipient gender, ethnicity, etiology, LT year, and posttransplant immunosuppression levels were risk factors for EAR in univariate analysis; HCV etiology and female gender remained robust risk factors in multivariate analysis. Interferon-based therapy did not impact the incidence or timing of EAR. In conclusion, HCV etiology is strongly associated with EAR. HCV allograft reinfection may create an immunologic environment predisposed to EAR. Alternatively, the association of HCV and EAR may result from an increased frequency of allograft biopsy and may be further exacerbated by inability to accurately diagnose EAR in the setting of recurrent HCV.

Acute Disease↗
PubMed2004

Transplantation of islets transduced with CTLA4-Ig and TGFbeta using adenovirus and lentivirus vectors.

BACKGROUND: A major problem facing islet transplantation is immune destruction of grafts by transplant rejection and autoimmunity. Some success in prolonging graft rejection has been obtained by transducing islets prior to transplantation with adenoviral (Ad) vectors containing CTLA4-Ig and TGFbeta. The purpose of this study was to see if lentiviral (LV) vectors would provide superior results compared with adenoviral vectors. METHODS: Islets were isolated from Sprague-Dawley rats and transduced with Ad or LV vectors containing LacZ, CTLA4-Ig, CTLA4, and TGFbeta1 using various MOIs. Islets transduced with LV were healthy as judged by DNA and insulin content, and insulin secretion. Using the kidney capsule transplant site, 500 transduced rat islets were transplanted into streptozotocin diabetic B6AF1 mice. RESULTS: Maintenance of normoglycemia was prolonged in recipient mice carrying islets transduced with Ad vectors containing CTLA4-Ig, CTLA4, and TGFbeta1. Return of hyperglycemia in controls was 17-18 days while loss of function for the experimental groups occurred at 20-27 days. For the lentivirus transduced islets, rejection of controls was 20+/-1.6 days, for CTLA4-Ig was 42+/-21 days and for TGFbeta was 28+/-3.2 days. CONCLUSIONS: Although islets transduced with either adenovirus or lentivirus containing CTLA4-Ig, CTLA4, and TGFbeta1 could prolong graft survival in a rat to mouse transplantation model, with the conditions of this study lentivirus provided no advantage over adenovirus vectors.

Abatacept↗
PubMed2004

Organ donors with malignant gliomas: an update.

The escalating shortage of organs motivates frequent reconsideration of concepts that guide the decision to accept or decline organs from donors with central nervous system (CNS) malignancy. Currently, a minority of patients who die annually of CNS malignancies are organ donors. Specifically, the organs of less than 0.5% of the 13 000 patients dying from glioma are procured and transplanted every year in the United States. This review seeks to clarify the risk of cancer transmission from transplantation of organs from donors with glioma. After considering historical precedence, we will systematically outline the clinical features of a potential organ donor with glioma that might reflect upon the risk of cancer transmission. We will then present recent knowledge regarding basic glioma biology that speaks to their metastatic potential and suggest rational strategies for the post-transplant management of recipients of organs from donors with glioma.

Brain Neoplasms↗
PubMed2004

Early graft function after living donor kidney transplantation predicts rejection but not outcomes.

Poor early graft function (EGF) after deceased donor kidney transplantation (DDKT) has been intensely studied. Much less is known about poor EGF after living donor kidney transplantation (LDKT). Data were collected on 469 LDKTs performed between 1/1/97 and 12/31/01 to determine risk factors for and outcomes associated with poor EGF, defined as either delayed or slow graft function (DGF or SGF). The incidence of DGF and SGF were 4.7% and 10.7%, respectively. Diabetic etiology (OR 2.22; p = 0.021) and warm ischemia time (WIT) (OR 1.05 per min increment; p = 0.0025) emerged as independently associated with poor EGF. Neither functional graft survival nor 1-year graft function differed among the EGF groups. However, DGF and SGF strongly predisposed to acute rejection (AR), which compromised functional graft survival (p = 0.0007) and 1-year graft function. Therefore, we conclude that diabetic etiology of renal disease and WIT are the dominant risk factors for poor EGF after LDKT. Poor EGF did not directly compromise functional graft survival but strongly predisposed to AR. We suggest that immunosuppression should be intensified in the poor EGF setting to maximize LDKT longevity, as AR does impair functional graft survival.

Diabetes Mellitus↗
PubMed2004

National conference to assess antibody-mediated rejection in solid organ transplantation.

The process of humoral rejection is multifaceted and has different manifestations in the various types of organ transplants. Because this process is emerging as a leading cause of graft loss, a conference was held in April 2003 to comprehensively address issues regarding humoral rejection. Though humoral rejection may result from different factors, discussion focused on a paradigm caused by antibodies, typically against donor HLA antigens, leading to the term 'antibody-mediated rejection' (AMR). Conference deliberations were separated into four workgroups: The Profiling Workgroup evaluated strengths and limitations of different methods for detecting HLA reactive antibody, and created risk assessment guidelines for AMR; The Diagnosis Workgroup reviewed clinical, pathologic, and serologic criteria for assessing AMR in renal, heart and lung transplant recipients; The Treatment Workgroup discussed advantages, limitations and possible mechanisms of action for desensitization protocols that may reverse AMR; and The Basic Science Workgroup presented animal and human immunologic models for humoral rejection and proposed potential targets for future intervention. This work represents a comprehensive review with contributions from experts in the fields of Transplantation Surgery, Medicine, Pathology, Histocompatibility, Immunology, and clinical trial design. Immunologic barriers once considered insurmountable are now consistently overcome to enable more patients to undergo organ transplantation.

Antibodies↗
PubMed2003

Sirolimus delays recovery of rat kidney transplants after ischemia-reperfusion injury.

BACKGROUND: Sirolimus (SRL) seems to impair renal recovery from ischemic injury in animal models and delayed graft function after clinical renal transplantation. This study determined the impact of SRL on renal recovery after ischemia-reperfusion injury in a rat kidney transplant model. METHODS: Syngeneic kidneys were preserved in University of Wisconsin solution before transplantation into bilaterally nephrectomized rats. Recipients received vehicle or SRL targeting for whole-blood trough levels of 10 to 20 ng/mL as measured by high-performance liquid chromatography. Renal function was assessed by animal survival or daily serum creatinine. Tissue samples were collected for histologic examination. RESULTS: Median SRL whole-blood concentrations were 16.6 +/- 1.6 ng/mL on postoperative day (POD) 1 and 12.0 +/- 0.9 ng/mL on POD 3. Transplantation of kidneys after 39 hr of cold storage resulted in 30% survival in the SRL-treated group compared with 100% survival in the control group (P=0.002). Transplantation of kidneys after 24 hr of cold storage resulted in no survival differences, but there were significant differences in renal function. Daily serum creatinine (PODs 1-4) was higher in the SRL-treated group compared with the control group (P<0.05 at all time points). Grafts from SRL-treated animals showed more severe tubular necrosis compared with control animals. CONCLUSIONS: When given at therapeutic immunosuppressive doses, SRL compromises renal function after ischemia-reperfusion injury in a rat kidney transplant model. The antiproliferative effect of SRL may translate into impairment of tubular repair and regeneration necessary for recovery after such injury.

Adenosine↗
PubMed2003

Excellent short-term results with steroid-free maintenance immunosuppression in low-risk simultaneous pancreas-kidney transplantation.

HYPOTHESIS: Steroid avoidance is possible in simultaneous pancreas-kidney transplantation with the use of newer immunosuppressive agents and induction therapy. DESIGN: A retrospective consecutive case review. SETTING: A university tertiary referral center. PATIENTS: Medical records of 40 consecutive patients who underwent pancreas-kidney transplantation from November 2000 to July 2002 were reviewed. INTERVENTION: The immunosuppression protocol used in this series of patients consisted of Thymoglobulin induction combined with mycophenolate mofetil, tacrolimus, and sirolimus for maintenance immunosuppression. Steroids were used as pretreatment only, given with Thymoglobulin, and were typically discontinued by postoperative week 1. MAIN OUTCOME MEASURES: Graft and patient survival rates, rejection rates of the kidney or pancreas, infection rates, and surgical complication rates. RESULTS: Patient, kidney, and pancreas survival rates were 95.0%, 92.5%, and 87.5%, respectively. Biopsy-proven pancreas rejection rates at 1 and 3 months' posttransplantation were 2.5%. Kidney rejection rates at 1 and 3 months were 2.5%. Steroids were given only to patients with documented transplant rejection. Surgical and medical complications were no different from earlier protocols. CONCLUSIONS: Immunosuppression protocols that do not include maintenance steroids have shown minimal rejection in the first 3 months and equivalent patient and graft survival rates compared with protocols that use steroids. The potential beneficial long-term impact of steroid avoidance will require further study.

Adult↗
PubMed2003

Sirolimus prolongs recovery from delayed graft function after cadaveric renal transplantation.

Sirolimus, lacking known nephrotoxicity, appeared to be an ideal immunosuppressive agent in the setting of delayed graft function (DGF) after renal transplantation. Coincident with our use of sirolimus however, we noticed prolongation of DGF. To investigate possible causes of prolonged DGF, extensive donor, recipient, transplant, and post-transplant data were collected on 132 consecutive cases of DGF at the University of California, San Francisco between 1/1/97 and 6/30/01. Cox proportional hazards analysis of time to graft function was used in univariate and multivariate models to identify factors that prolong DGF. Sirolimus had a large and highly significant effect on time to graft function (hazard ratio 0.48, p = 0.0007). The hazard ratio indicates that a recipient on sirolimus is half as likely to resolve DGF or twice as likely to remain on dialysis as a recipient without sirolimus. Two other factors had less potent but still significant association with DGF duration: recipient sensitization (hazard ratio 0.66, p = 0.037), and Novartis score (hazard ratio 0.93 per 1.0 increase; p = 0.034). Sirolimus retained its profound negative association with time to graft function in all multivariate models. Because sirolimus appears to prolong DGF, it may not be the optimal immunosuppressive choice in the DGF setting.

Adult↗
PubMed2003

Death from donor-transmitted malignancy despite emergency liver retransplantation.

Transplantation of organs procured from donors with malignancies identified subsequent to implantation presents a significant dilemma regarding the optimal management strategy to simultaneously minimize the risk for cancer transmission and recipient morbidity. In this report, we present a patient who underwent orthotopic liver transplantation for hepatitis B cirrhosis. The donor had no previous history of cancer. On autopsy, enlarged mediastinal lymph nodes led to the discovery of a 1-cm lung tumor. Histological examination showed pulmonary adenocarcinoma with metastatic mediastinal disease. Despite urgent retransplantation within 7 days, the recipient developed metastatic pulmonary adenocarcinoma diagnosed 11 months after transplantation and died soon thereafter. Analysis of short tandem repeat regions of chromosomal DNA from the recipient, the 2 liver donors, and the posttransplantation tumor corroborates that the first donor was the source of the malignancy. This case of donor-transmitted malignancy underscores the need for vigilance by the procuring surgeon in identifying potential malignancy during organ retrieval and use of a full autopsy on selected donors after organ procurement.

Adenocarcinoma↗
PubMed2003

Management of lymphoceles after renal transplantation: laparoscopic versus open drainage.

PURPOSE: Laparoscopic surgery has become widely accepted for the treatment of lymphoceles following kidney transplantation. In this single center study we retrospectively reviewed our results of the surgical management of post-transplant lymphoceles, assessing indication and outcome of laparoscopic versus open drainage. MATERIALS AND METHODS: The records of 60 patients who underwent surgical treatment for a symptomatic lymphocele following kidney transplantation or combined kidney/pancreas transplantation were retrospectively reviewed. RESULTS: Between 1995 and 2002, 1,836 patients received a kidney transplant at the University of California San Francisco. In 60 patients (3.3%) a symptomatic lymphocele developed and either laparoscopic (20) or open drainage (40) was completed. The conversion rate from laparoscopic to open drainage was 16.5%. The most common indications for open lymphocele drainage were noninfectious wound complications (13 patients) and a high risk of vessel or ureter injury (8) due to proximity of the lymphocele to hilar structures. Additional surgery on the graft was required in 5 patients. Intraoperative blood loss was significantly lower in the laparoscopy group. Median hospital stay was 1 day in the laparoscopy group versus 4 days in the open drainage group. No perioperative complications were observed in either group. After a median followup of 38 months, 2 patients in each treatment group had a symptomatic recurrence. CONCLUSIONS: Although both surgical approaches are safe and effective, laparoscopic drainage should remain the method of choice for the treatment of post-transplant lymphocele. However, open drainage should be performed in patients with wound complications and in those with a small lymphocele adjacent to vital renal structures.

Adult↗
PubMed2002

Targeted gene therapy with CD40Ig to induce long-term acceptance of liver allografts.

BACKGROUND: The purpose of this study was to modulate the immune response of rat liver transplant recipients by adenovirus-mediated gene transfer of CD40Ig, a secretable fusion protein designed to block the CD40-CD154 T-cell costimulation pathway. METHODS: CD40Ig complementary DNA was created by joining the reverse transcriptase-polymerase chain reaction complementary DNA products for the extracellular domain of murine CD40 to the Fc portion of murine IgG2a. AdCD40Ig and AdSIg (IgG2a-Fc control) recombinant adenoviruses were used to transduce donor liver grafts before nonarterialized orthotopic rat liver transplantation. Donor specific unresponsiveness was examined with skin transplants. RESULTS: All rats (n = 6) that received liver allografts transduced with AdCD40Ig survived >100 days with normal liver histology. Serum levels of CD40Ig at 10, 30, 60, and 100 days after transplantation ranged from 100 to 500, 100 to 250, 5 to 40, and 2 to 10 microg/mL, respectively. Mean survival of rats (n = 4) that received liver allografts transduced with AdSIg control adenovirus was 9.25 +/- 2.9 days. Long-term survivors were rechallenged with skin grafts 100 days after liver transplantations. Survival was 72, >100 (x4) days for donor specific allogeneic skin grafts and 14, 14, 18, 19, and 21 days for third-party allogeneic skin grafts. CONCLUSIONS: Adenovirus-mediated gene transfer of CD40Ig into cold-preserved liver allografts before transplantation results in high levels of transgene expression with resultant long-term survival of hepatic allografts and donor specific unresponsiveness.

Adenoviridae↗
PubMedDate not supplied

Magnetic resonance imaging of hepatocellular carcinoma mimicking focal nodular hyperplasia: a potential pitfall in patients with cirrhosis?

The magnetic resonance imaging findings in 2 cases of pathologically proven hepatocellular carcinoma that mimicked focal nodular hyperplasia are presented. Both cases were found in patients with cirrhosis, a condition in which focal nodular hyperplasia is unlikely to occur. Recognition that hepatocellular carcinoma may mimic focal nodular hyperplasia in patients with cirrhosis may prevent misdiagnosis and allow for earlier intervention.

Aged↗