Acute humoral rejection in an ABO compatible combined liver-kidney transplant--the kidney is not always protected.

Combined liver-kidney transplantation has become a common practice for the treatment of patients with concurrent end-stage renal disease and end-stage liver disease. Liver transplantation in the setting of multiorgan transplantation is thought to have a protective effect against humoral rejection even when a positive crossmatch is obtained prior to surgery. In most centers, a pre liver-kidney transplant crossmatch is rarely performed because of the known immunoprotective effect of the liver allograft.

Viral fitness implications of variation within an immunodominant CD8+ T-cell epitope of HIV-1.

Cytotoxic T-lymphocyte (CTL) epitopes within the HIV genome are subject to negative and positive selective pressures, the balance of which influences CTL escape at a given epitope. We investigated whether viral fitness requirements dictate conservation of the HLA-A2 restricted immunodominant epitope SLYNTVATL (SL9). Viral clones incorporating changes throughout the SL9 epitope region were compared to consensus SL9 virus in terms of replication kinetics and relative viral fitness.

Stable complex formation between HIV Rev and the nucleosome assembly protein, NAP1, affects Rev function.

The Rev protein of HIV-1 is essential for HIV-1 proliferation due to its role in exporting viral RNA from the nucleus. We used a modified version of tandem affinity purification (TAP) tagging to identify proteins interacting with HIV-1 Rev in human cells and discovered a prominent interaction between Rev and nucleosome assembly protein 1 (Nap1). This interaction was also observed by specific retention of Nap1 from human cell lysates on a Rev affinity column.

Hepatitis A and B immunization for individuals with inherited bleeding disorders.

Hepatitis A and B vaccines are highly effective tools that can greatly reduce infection risk in the bleeding disorder population. Although hepatitis A and B immunization for individuals with bleeding disorders is universally recommended, various advisory bodies often differ with respect to many practical aspects of vaccination. To review the published literature and guidelines and form a practical, comprehensive and consistent approach to hepatitis A and B immunization for individuals with bleeding disorders.

Structural insights into immune recognition of the severe acute respiratory syndrome coronavirus S protein receptor binding domain.

The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) is responsible for host cell attachment and fusion of the viral and host cell membranes. Within S the receptor binding domain (RBD) mediates the interaction with angiotensin-converting enzyme 2 (ACE2), the SARS-CoV host cell receptor. Both S and the RBD are highly immunogenic and both have been found to elicit neutralizing antibodies.

Inhibition of HIV-1 gene expression by Sam68 Delta C: multiple targets but a common mechanism?

Two recent publications have explored the mechanisms by which a mutant of the host protein Sam68 blocks HIV-1 structural protein synthesis and expands its activity to encompass Nef. Although the two studies propose different mechanisms for the responses observed, it is possible that a common activity is responsible. Understanding how this Sam68 mutant discriminates among the multiple viral mRNAs promises to reveal unique properties of HIV-1 RNA metabolism.

Immune characterization of an individual with an exceptionally high natural killer T cell frequency and her immediate family.

Natural killer T cells (NKT) are a regulatory subset of T lymphocytes whose frequency in peripheral blood is highly variable within the human population. Lower than normal NKT frequencies are associated with increased predisposition to a number of diseases, including type 1 diabetes and some forms of cancer, raising the possibility that an increased frequency may be protective. However, there is little or no understanding of how high NKT frequencies arise or, most importantly, whether the potential exists to boost and maintain NKT levels for therapeutic advantage.

How does the journey affect the message(RNA)?

Research has determined that different RNAs within the cell (mRNA, snRNA, rRNA, tRNA) use distinct pathways to facilitate their movement from the nucleus to the cytoplasm. But does the nature of the pathway used affect the metabolism of the RNA? Recent studies have begun to address this question by examining the regulation of similar mRNAs exported by different pathways. We summarize the observations from several groups indicating that, in the case of HIV-1 mRNAs, the export pathway has dramatic effects on sensitivity to a translational inhibitor as well as the fate of the encoded proteins.

Mapping of determinants involved in the stimulation of HIV-1 expression by Sam68.

Control of HIV-1 RNA processing is central to the replication of the virus. Previously, we demonstrated that the cellular protein Sam68 enhances HIV-1 structural protein expression and RNA 3' end processing. In this report, we show that Sam68 interacts with unspliced HIV-1 RNA and that other members of the STAR/GSG protein family also promote viral RNA 3' end processing.

Procalcitonin versus C-reactive protein and immature-to-total neutrophil ratio as markers of infection after cardiopulmonary bypass in children.

Objective: To document concentrations of procalcitonin (PCT), C-reactive protein (CRP), and immature-to-total neutrophil ratio (ITR), postcardiopulmonary bypass (CPB), and to test the hypothesis that PCT is a more reliable marker of infection than CRP or ITR in the post-CPB child.

Design: Prospective cohort study.

Setting: Pediatric intensive care units at Royal Children's Hospital, Melbourne, Australia and Birmingham Children's Hospital, UK.

Selective translational repression of HIV-1 RNA by Sam68DeltaC occurs by altering PABP1 binding to unspliced viral RNA.

HIV-1 structural proteins are translated from incompletely spliced 9 kb and 4 kb mRNAs, which are transported to the cytoplasm by Crm1. It has been assumed that once in the cytoplasm, translation of incompletely spliced HIV-1 mRNAs occurs in the same manner as host mRNAs. Previous analyses have demonstrated that Sam68 and a mutant thereof, Sam68DeltaC, have dramatic effects on HIV gene expression, strongly enhancing and inhibiting viral structural protein synthesis, respectively.

Initial results of primary device closure of large muscular ventricular septal defects in early infancy using perventricular access.

Objectives: To report our experience with the use of the Amplatzer muscular ventricular septal defect (VSD) occluder, using direct right ventricle free wall puncture for primary closure of muscular VSDs in infants.

Background: Young infants with heart failure due to large or multiple muscular VSDs often require intervention at a stage when percutaneous device closure is impractical due to delivery system limitations. There are considerable benefits to avoiding bypass in these infants.

Surgical treatment of congenital mitral valve disease: midterm results of a repair-oriented policy.

Objective: Management of congenital mitral valve disease is challenging because of a wide morphologic spectrum, frequent associated lesions, and small patient size. We evaluated the results of a repair-oriented policy.

Methods: All consecutive patients with congenital mitral valve disease who underwent surgery between 1996 and 2006 were studied retrospectively.

Modulating HIV-1 RNA processing and utilization.

Expression of the integrated HIV-1 provirus is achieved by overcoming multiple barriers to the processing, transport and utilization of the viral RNA. Some of the strategies involve viral encoded proteins (i.e.

Long-distance transport of critically ill children on extracorporeal life support in Australia.

Background: The Royal Children's Hospital, Melbourne, Victoria, provides extracorporeal life support (ECLS) for infants and children from all around Australia. Since 2003, we have offered a mobile ECLS service to retrieve critically ill children whose condition is too unstable for conventional transport. The retrieval team comprises a paediatric intensive care unit specialist, an ECLS nurse specialist, a perfusionist and a cardiac surgeon.

Increased rejection rates in cardiac transplant associated with dexamethasone.

Background: Peri-operative immunosuppression in cardiac transplantation includes the use of intravenous methylprednisolone. During a national shortage, intravenous dexamethasone was substituted for methylprednisolone at standard equivalencies. Methylprednisolone and dexamethasone are used interchangeably in many clinical settings; however, their equivalency has not been demonstrated.

HIV-1-infected CD8+CD4+ T cells decay in vivo at a similar rate to infected CD4 T cells during HAART.

Objectives: To investigate the potential for CD4+CD8+ T cells [CD8 double positive (CD8 DP)] T cells to form a reservoir of HIV-1 following HAART through measurement of the rate of decay of infected CD4/CD8 DP T cells.

Methods: HIV-1 proviral loads in highly pure CD4 and CD8 DP T cells were determined for study subjects before and after 200-400 days of therapy and HIV-1 DNA decay rates were calculated.

Results: Before therapy, HIV-1 proviral load in CD8 DP correlated negatively with CD4 cell count.

Acceptance versus distraction: brief instructions, metaphors and exercises in increasing tolerance for self-delivered electric shocks.

The current study compared the effects of an acceptance versus distraction rationale on coping with experimentally induced pain. Eighty participants were randomly assigned to one of five conditions: Full-Acceptance, Full-Distraction, Instruction-only-Acceptance, Instruction-only-Distraction and No-Instructions. Participants completed a simple matching task and were intermittently given the choice either to receive an electric shock and continue, or to avoid the shock and terminate the task.

The Fontan procedure: contemporary techniques have improved long-term outcomes.

Background: To determine whether patients undergoing the lateral tunnel and extracardiac conduit modifications of the Fontan procedure have better outcomes than patients undergoing a classical atriopulmonary connection.

Methods And Results: Between 1980 and 2000, 305 consecutive patients underwent a Fontan procedure at our institution. There were 10 hospital deaths (mortality: 3%) with no death after 1990.

Virus immunocapture provides evidence of CD8 lymphocyte-derived HIV-1 in vivo.

Objectives: To demonstrate that HIV-1 immunocapture with an antibody against CD8 specifically captures virions derived from infected CD8 T cells, and to determine the proportion of HIV-1 derived from CD8 lymphocytes in plasma samples from HIV-infected individuals.

Methods: A virus capture method was developed to enable the detection of HIV-1 virions based upon the presence of certain cell-specific host-derived proteins (CD8, CD3, CD36) within the viral envelope. HIV-1 virions were captured using antibodies against these proteins and levels of bound virus were determined by quantitative reverse transcriptase-polymerase chain reaction.

Surgical strategy for the bicuspid aortic valve: tricuspidization with cusp extension versus pulmonary autograft.

Objective: The congenitally bicuspid aortic valve is the most common etiologic factor associated with clinically significant aortic stenosis and/or regurgitation in pediatric patients. Beyond infancy, surgical intervention typically involves valve repair with cusp thinning and commissurotomy or valve replacement, primarily with pulmonary autograft in the current era. An aortic valve repair technique using tricuspidization with cusp extension was introduced in 1999.

hnRNP E1 and E2 have distinct roles in modulating HIV-1 gene expression.

Pre-mRNA processing, including 5' end capping, splicing, and 3' end cleavage/polyadenylation, are events coordinated by transcription that can influence the subsequent export and translation of mRNAs. Coordination of RNA processing is crucial in retroviruses such as HIV-1, where inefficient splicing and the export of intron-containing RNAs are required for expression of the full complement of viral proteins. RNA processing can be affected by both viral and cellular proteins, and in this study we demonstrate that a member of the hnRNP E family of proteins can modulate HIV-1 RNA metabolism and expression.