Liver-specific deletion of augmenter of liver regeneration accelerates development of steatohepatitis and hepatocellular carcinoma in mice.

Background & Aims: Augmenter of liver regeneration (ALR, encoded by GFER) is a widely distributed pleiotropic protein originally identified as a hepatic growth factor. However, little is known about its roles in hepatic physiology and pathology. We created mice with liver-specific deletion of ALR to study its function.

Human dominant-negative class II transactivator transgenic pigs - effect on the human anti-pig T-cell immune response and immune status.

Swine leucocyte antigen (SLA) class II molecules on porcine (p) cells play a crucial role in xenotransplantation as activators of recipient human CD4(+) T cells. A human dominant-negative mutant class II transactivator (CIITA-DN) transgene under a CAG promoter with an endothelium-specific Tie2 enhancer was constructed. CIITA-DN transgenic pigs were produced by nuclear transfer/embryo transfer.

Fifty years later.

That concludes my remarks. If I have not made my purpose clear, let me summarize simply. I, like all others gathered here, have come to pay homage to Paul Terasaki, a man who bent in the winds of his time but never broke.

Upper-extremity transplantation using a cell-based protocol to minimize immunosuppression.

Objective: To minimize maintenance immunosuppression in upper-extremity transplantation to favor the risk-benefit balance of this procedure.

Background: Despite favorable outcomes, broad clinical application of reconstructive transplantation is limited by the risks and side effects of multidrug immunosuppression. We present our experience with upper-extremity transplantation under a novel, donor bone marrow (BM) cell-based treatment protocol ("Pittsburgh protocol").

Themes of liver transplantation.

Liver transplantation was the product of five interlocking themes. These began in 1958-1959 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor.

Kidney after nonrenal transplantation-the impact of alemtuzumab induction.

Background: Calcineurin inhibitor nephrotoxicity in nonrenal allograft recipients can lead to end-stage renal disease and the need for kidney transplantation. We sought to evaluate the role of alemtuzumab induction in this population.

Patients And Methods: We evaluated 144 patients undergoing kidney transplantation after nonrenal transplantation between May 18, 1998, and October 8, 2007.

Cholera toxin-sensitive GTP-binding protein-coupled activation of augmenter of liver regeneration (ALR) receptor and its function in rat kupffer cells.

Mitogenic effect of augmenter of liver regeneration (ALR), a protein produced and released by hepatocytes, on hepatocytes in vivo but not in vitro suggests that the effect is mediated by nonparenchymal cells. Since mediators produced by Kupffer cells are implicated in hepatic regeneration, we investigated receptor for ALR and its functions in rat Kupffer cells. Kupffer cells were isolated from rat liver by enzymatic digestion and centrifugal elutriation.

Complications of right lobe living donor liver transplantation.

Background/aims: Right lobar living donor liver transplantation (LDLT) has been controversial because of donor deaths and widely variable reports of recipient and donor morbidity. Our aims were to ensure full disclosure to donors and recipients of the risks and benefits of this procedure in a large University center and to help explain reporting inconsistencies.

Methods: The Clavien 5-tier grading system was applied retrospectively in 121 consecutive adult right lobe recipients and their donors.

The origin of clinical organ transplantation revisited.

A patient whose illness had begun with edema and hypertension was found to have extreme atrophy of both kidneys. Because of the steady worsening of the condition and the appearance of uremia with other unfavorable diagnostic signs, transplantation of 1 kidney from the patient's identical healthy twin brother was undertaken. Preparations included collection of evidence of monozygosity and experimental transplantation of a skin graft from the twin.

Successful salvage of mucormycosis infection of the forearm and osteomyelitis of the ulna.

A 6-month-old child developed cutaneous mucormycosis of the forearm 5 weeks after liver transplantation, which progressed to osteomyelitis of the proximal ulna. Aggressive treatment, which included serial radical debridements, intravenous administration of amphotericin B, and eventually split thickness skin graft coverage resulted in successful functional salvage of the forearm, wrist, and hand. Of the nine previously reported cases of mucormycosis affecting the forearm or hand in immunocompromised patients, all either required amputation of the hand or below elbow amputation, or resulted in the patient's death.

Alemtuzumab preconditioning with tacrolimus monotherapy-the impact of serial monitoring for donor-specific antibody.

Background: Antibody preconditioning with tacrolimus monotherapy has allowed many renal allograft recipients to be maintained on spaced weaning.

Methods: Of 279 renal allograft recipients transplanted between March 2003 and December 2004, 222 (80%) had spaced weaning (i.e.

Relative contribution of direct and indirect allorecognition in developing tolerance after liver transplantation.

The interaction of donor passenger leukocytes and host leukocytes in recipient secondary lymphoid tissues during the early posttransplantation period is crucial in directing host immune reactions toward allograft rejection or acceptance. Responsible T cell clones could be activated through the direct and indirect pathways of allorecognition. We examined the role of the indirect pathway in liver transplantation (LT) tolerance by depleting host antigen-presenting cells (APC) with phagocytic activity [e.

Augmenter of liver regeneration: an important intracellular survival factor for hepatocytes.

Background/aims: Augmenter of liver regeneration (ALR), a protein synthesized and stored in hepatocytes, is associated with mitochondria, and possesses sulfhydryl oxidase and cytochrome c reductase activities. We sought to determine the effects of ALR depletion in hepatocytes by antisense oligonucleotide transfection.

Methods: Rat hepatocytes in primary culture were transfected with antisense oligonucleotide for ALR mRNA (ALR-AS) or scrambled oligonucleotide.

Acquired immunologic tolerance: with particular reference to transplantation.

The first unequivocally successful bone marrow cell transplantation in humans was recorded in 1968 by the University of Minnesota team of Robert A. Good (Gatti et al. Lancet 2: 1366-1369, 1968).

World's longest surviving liver-pancreas recipient.

In July 1988, the liver and pancreas of a cadaveric donor were transplanted separately into a man with type 1 diabetes with end-stage chronic hepatitis B virus. Two features of the operation may help explain the patient's current status as the longest-lived liver-pancreas recipient. One was enteric drainage of pancreatic exocrine secretions.