Phosphorylation regulates Myc expression via prolonged activation of the mitogen-activated protein kinase pathway.

We previously showed that prolonged and strong ERK phosphorylation induced by Compound 5 (Cpd 5), a Cdc25A protein phosphatase inhibitor, was involved in its mechanism of cell growth inhibition. To study the relationship between ERK phosphorylation and cell growth inhibition, we used Cpd 5 as a tool to investigate ERK-regulated c-Myc expression in Hep3B hepatoma cells. We found that ERK phosphorylation caused by Cpd 5 induced c-Myc phosphorylation, but suppressed c-Myc expression at the mRNA and protein levels.

Monitoring immune function during tacrolimus tapering in small bowel transplant recipients.

Long term use of immunosuppressants impacts the cardiovascular system and increases the risk of infection and malignancy. To effectively reduce immunosuppression in a transplant recipient a tool is needed to directly monitor the level of immune function. The Cylex(R) Immune Cell Function Assay, approved by the FDA for the assessment of cell-mediated immunity, shows promise as an objective measure of a transplant recipient's immune function.

Cdc25A and ERK interaction: EGFR-independent ERK activation by a protein phosphatase Cdc25A inhibitor, compound 5.

Extracellular signal-regulated kinase (ERK) plays a central role in regulating cell growth, differentiation, and apoptosis. We previously found that 2-(2-mercaptoethanol)-3-methyl-1,4-napthoquinone or Compound 5 (Cpd 5), is a Cdc25A protein phosphatase inhibitor and causes prolonged, strong ERK phosphorylation which is triggered by epidermal growth factor receptor (EGFR) activation. We now report that Cpd 5 can directly cause ERK phosphorylation by inhibiting Cdc25A activity independently of the EGFR pathway.

Biliverdin protects the functional integrity of a transplanted syngeneic small bowel.

Background & Aims: Heme oxygenase-1 (HO-1) protects against inflammation in many disease models. By degrading heme, HO-1 generates carbon monoxide (CO), iron and biliverdin. We investigated whether biliverdin would protect rat syngeneic small intestinal transplants (SITx) against damage and, if so, by what mechanism.

Hypophosphatemia after 95 right-lobe living-donor hepatectomies for liver transplantation is not a significant source of morbidity.

Background: Hypophosphatemia appears to be a universal event after right hepatic lobectomy for live-donor adult liver transplantation according to one report. Because hypophosphatemia appears to contribute to increased postoperative complications, routine hyperalimentation with supratherapeutic levels of phosphorus was advocated.

Methods: From July 2000 to May 2002, we performed 95 right-lobe living-donor hepatectomies for 95 adult liver-transplant recipients, the largest single institutional experience.

Minimal evidence of transdifferentiation from recipient bone marrow to parenchymal cells in regenerating and long-surviving human allografts.

Liver, small intestine, and heart allografts in residence for 4 days to 16 years were analyzed by simultaneous XY fluorescent in situ hybridization to search for evidence of the recently described process of transdifferentiation of recipient bone marrow stem cells to allograft parenchymal cells. These studies were carried out in an effort to find conditions associated with maximal levels of engraftment or expansion of the recipient parenchymal cells. Despite prolonged survival up to 16 years, regeneration after severe preservation injury or use of split livers, only rare, isolated and tentatively identified recipient hepatocytes were detected in liver allografts.

Impact of anti-hepatitis Bc-positive grafts on the outcome of liver transplantation for HBV-related cirrhosis.

Background: The present scarcity of organ donors requires consideration of grafts from sources not previously used. Several studies have addressed the use of grafts from donors who have antibodies to the hepatitis B core antigen (anti-HBc+). The aim of this study was to evaluate the impact of the use of anti-HBc+ grafts in patients transplanted for hepatitis B virus (HBV)-related cirrhosis.

Hepatic artery chemoembolization for advanced stage HCC: experience of 650 patients.

Unlabelled: Hepatic artery chemotherapy using cisplatin in various protocols was examined in 650 patients. Overall objective tumor response rate (PR) was 65%. Average survival was 7.

The effect of cytokine gene polymorphisms on pediatric heart allograft outcome.

Background: Cytokines play a major role in the inflammatory and immune responses that mediate allograft outcome. Several studies have shown that the production of cytokines varies among individuals and these variations are determined by genetic polymorphisms, most commonly within the regulatory region of the cytokine gene. The aim of this study was to assess the effect of these allelic variations on acute rejection after pediatric heart transplantation.

Use of a high-risk alcohol relapse scale in evaluating liver transplant candidates.

Background: Methods to improve assessment, selection, and monitoring of patients with alcoholic cirrhosis who pursue liver transplantation are sought continuously. We chose to investigate the use of the High-Risk Alcohol Relapse (HRAR) scale in our transplant population in the hope that it would improve our ability to identify and follow patients at highest risk for alcohol relapse.

Methods: Detailed alcohol histories of 207 patients evaluated for liver transplantation were collected and graded for severity by using the HRAR.

Effects of donor bone marrow infusion in clinical lung transplantation.

Background: We have demonstrated that donor cell chimerism is associated with a lower incidence of obliterative bronchiolitis (OB) in lung recipients, and that donor chimerism is augmented by the infusion of donor bone marrow (BM). We herein report the intermediate results of a trial combining the infusion of donor BM and lung transplantation.

Methods: Clinical and in vitro data of 26 lung recipients receiving concurrent infusion of donor bone marrow (3.

A clinical trial combining donor bone marrow infusion and heart transplantation: intermediate-term results.

Background: Donor chimerism (the presence of donor cells of bone marrow origin) is present for years after transplantation in recipients of solid organs. In lung recipients, chimerism is associated with a lower incidence of chronic rejection. To augment donor chimerism with the aim to enhance graft acceptance and to reduce immunosuppression, we initiated a trial combining infusion of donor bone marrow with heart transplantation.

Hepatic hemangioendothelioma: clinical experience and management strategy.

Purpose: This study sought to define management strategies based on clinical experience in treating infantile hepatic hemangioendothelioma.

Methods: A retrospective analysis of patients with hemangioendothelioma presenting to a tertiary liver transplantation center between 1989 and 1997 was performed.

Results: Thirteen patients (median age, 14 days) with hemangioendothelioma were identified.

Role of splenectomy in human liver transplantation under modern-day immunosuppression.

Between January 1987 and October 1991, 1466 patients underwent consecutive Orthotopic Liver Transplantation (OLTx) at the University of Pittsburgh. Forty of these patient's had concomitant splenectomy with OLTx. These patients were compared to 147 randomly selected OLTx patients without splenectomy within the same time period.

The inhibitory effect of interleukin 1beta on rat hepatocyte DNA synthesis is mediated by nitric oxide.

Interleukin 1beta (IL-1beta) and nitric oxide (NO) have potent growth-regulatory effects on different cell types. We found that epidermal growth factor-induced DNA synthesis in primary cultures of adult rat hepatocytes was inhibited by NO when it was provided by addition to the cultures of S-nitroso-N-acetyl-penicillamine (SNAP), an NO donor, as well as by addition of IL-1beta in a dose-dependent manner. IL-1beta also induced NO production and inducible NO synthase (iNOS) gene expression.