Accommodation: preventing injury in transplantation and disease.

Humoral immunity, as a cause of damage to blood vessels, poses a major barrier to successful transplantation of organs. Under some conditions, humoral immunity causes little or no damage to an organ graft. We have referred to this condition, in which a vascularized graft functions in the face of humoral immunity directed against it, as "accommodation.

B cell-dependent TCR diversification.

T cell diversity was once thought to depend on the interaction of T cell precursors with thymic epithelial cells. Recent evidence suggests, however, that diversity might arise through the interaction of developing T cells with other cells, the identity of which is not known. In this study we show that T cell diversity is driven by B cells and Ig.

Volumetric dimensional change of six direct core materials.

Objectives: This study evaluated the influence of water on the volumetric dimensional change of six direct placement core build-up materials by using Archimedes' principle.

Methods: The effect on dimensional change due to the setting reaction was determined through the use of a silicone oil storage medium. The materials used were two dual-cured resin composites (CoreStore and Build-It FR), two chemically activated resin composites (CorePaste and Ti-Core), one metal-reinforced glass ionomer cement (Ketac-Silver), and one resin-modified glass ionomer (Fuji II LC Core).

Cardiac xenotransplantation: future and limitations.

Despite improvements in pharmacological therapies, the outlook for patients with severe cardiac disease remains poor. At present, only transplantation can 'cure' end-stage cardiac failure. However, fewer than 5% of those who need a cardiac transplant receive one in the United States each year.

Pathways to acute humoral rejection.

Acute humoral rejection, also known as acute vascular rejection, is a devastating condition of organ transplants and a major barrier to clinical application of organ xenotransplantation. Although initiation of acute humoral or vascular rejection is generally linked to the action of antibodies and complement on the graft, other factors such as ischemia, platelets, T cells, natural killer cells, and macrophages have also been implicated. Central to any understanding of the pathogenesis of acute humoral rejection, and to developing means of preventing it, is to know whether these factors injure the graft independently or through one or few pathways.

Toll-like receptor-4 and allograft responses.

Signaling through toll-like receptors (TLRs) is believed to be the critical first step in the activation of antigen presenting cells and the initiation of adaptive immune responses. Of these receptors, TLR-4 particularly recognizes endogenous agonists and may be important for allograft responses. We tested this concept using mice with defective function and structure of TLR-4 as recipients of grafts across major and minor histocompatibility barriers.

Fusion of approaches to the treatment of organ failure.

Because organ transplantation is the preferred treatment for organ failure, the demand for human organs for transplantation is large and growing. From this demand, several fields based on new technologies for the replacement or repair of damaged tissues and organs have emerged. These fields include stem cell biology, cloning, tissue engineering and xenotransplantation.

Pulmonary xenotransplantation: rapidly progressing into the unknown.

As one approach to circumventing the dire shortage of human lungs for transplantation, a handful of investigators have begun to probe the possibility of pulmonary xenotransplantation. The immunologic and perhaps physiologic barriers encountered by these investigators are considerable and progress in pulmonary xenotransplantation has lagged behind progress in cardiac and kidney xenotransplantation. However, during the last few years there have been substantial advances in the field of pulmonary xenotransplantation including, most noticeably, significant progress in attenuating hyperacute dysfunction.

Spontaneous fusion of cells between species yields transdifferentiation and retroviral transfer in vivo.

Human cells can fuse with damaged or diseased somatic cells in vivo. Whether human cells fuse in vivo in the absence of disease and with cells of disparate species is unknown. Such a question is of current interest because blood exchanges between species through direct physical contact, via insect vectors or parasitism, are thought to underlie the transmission of zoonotic agents.

Inverse correlation between heparan sulfate composition and heparanase-1 gene expression in thyroid papillary carcinomas: a potential role in tumor metastasis.

Purpose: Heparanase-1 (HPR1) is an endoglycosidase that degrades the side chains of heparan sulfate proteoglycan (HSPG), a key component in cell surfaces, the extracellular matrix (ECM), and the basement membrane (BM). The purpose of this study was to evaluate HPR1 expression in thyroid neoplasms and its effect in degrading the HSPG substrates in the ECM and BM and to determine its role in thyroid tumor metastasis.

Experimental Design: HPR1 mRNA expression was analyzed by using in situ hybridization with a digoxigenin-labeled antisense RNA probe on paraffin-embedded tumor sections and reverse transcription-PCR (RT-PCR) in fresh tumor tissues.

Membrane pore size impacts performance of a xenogeneic bioartificial liver.

Background: We have developed a novel bioartificial liver (BAL) composed of porcine hepatocyte spheroids in a reservoir design. A semipermeable membrane is used to protect the spheroids from immune-mediated damage. This study was designed to assess the influence of membrane pore size on performance of the spheroid reservoir BAL.

High temperature characteristics and solidification microstructures of dental metallic materials part I: silver-palladium-copper-gold alloy.

Ag-Pd-Cu-Au alloy was subjected to a Thermo-Mechanical Analyzer to investigate high temperature properties up to its liquidus temperature. Microstructural examination and elemental analysis with EPMA were also conducted in the solid/liquid mixture region. The following conclusions were obtained.

Direct measurement of lymphocyte receptor diversity.

The ability to mount an immune defense against infectious microorganisms and their products, and against tumors is believed to be a direct function of lymphocyte diversity. Because the diversity of lymphocyte receptor genes is >1000-fold more diverse than the entire genome and varies between genetically identical individuals, measuring lymphocyte diversity has been a daunting challenge. We developed a novel technique for measuring lymphocyte diversity directly using gene chips.

Natural mechanisms for evading graft rejection: the fetus as an allograft.

Most primitive multicellular animals mount allogeneic immune responses to protect themselves from invasion by foreign organisms. The reproductive success of eutherian mammals, in which the maternal immune system is in direct contact with the semi-allogeneic fetus, depends on the ability to control allogeneic immune responses. Multiple, overlapping mechanisms exist to prevent maternal allogeneic immune responses towards the fetus while maintaining the capacity to mount a defense against infectious organisms.

The role of antibodies and von Willebrand factor in discordant pulmonary xenotransplantation.

Pulmonary xenotransplantation is one potential solution to the paucity of donors but is currently limited by rapid failure of the graft. Unlike cardiac and renal xenotransplants, pulmonary xenografts release large quantities of swine von Willebrand factor (vWF). Swine vWF binds xenoreactive antibodies and is capable of activating primate platelets.

Activation of mammalian Toll-like receptors by endogenous agonists.

Toll-like receptors activate innate and adaptive immune systems in mammals. This ancient family of receptors has been evolving since before the taxonomic split between the plant and animal kingdoms. The discovery of the mammalian Toll-like receptors was heralded as confirmation of a predicted biological system explicitly designed to detect exogenous molecules from micro-organisms.

Three different methods to evaluate microleakage of packable composites in Class II restorations.

This in vitro study compared three different methods to evaluate detectable levels of microleakage in Class II restorations placed with five commercially available packable resin composites: Alert, Glacier, Pyramid, Solitaire 2 and SureFil. A flowable resin composite, Flow-It, was used to line all packable composites. The hybrid resin composite Z100 was also included.

Accommodation in ABO-incompatible kidney allografts, a novel mechanism of self-protection against antibody-mediated injury.

To elucidate the mechanism of self-protection against anti-donor blood-group antibody known as accommodation, we studied 16 human ABO-incompatible living-donor kidney transplant recipients at 3 and 12 months post transplantation. Both circulating anti-blood-group antibody and the target blood-group antigen in the graft were demonstrable in all patients after transplantation. Thirteen of 16 grafts had normal renal function and histology, while three grafts with prior humoral rejection demonstrated significant glomerulopathy and thus did not meet the criterion for accommodation.

The effect on shear bond strength of rewetting dry dentin with two desensitizers.

The difficulty related to achieving a balance between wet and dry dentin makes the dentin bonding technique extremely sensitive. This study evaluated the effect of rewetting dried dentin with two commercial desensitizing agents (Protect and HurriSeal) on the dentin shear bond strength of three total-etch dentin bonding agents (Syntac Single-Component, OptiBond Solo Plus and Prime & Bond NT) and compared both to applying these same bonding agents to moist dentin and dry dentin. Each bonding agent was paired with an appropriate resin composite from the same manufacturer (Table 1).

Propagation and control of T cell responses by heparan sulfate-bound IL-2.

IL-2, a cytokine produced by T cells, is a key regulator of immune responses and T cell homeostasis. Controlling the availability of IL-2 is consequently of significant import to the immune system. Like other cytokines, IL-2 is thought to function as a soluble agonist, transiently present when secreted in response to appropriate stimuli.

ABO-incompatible kidney transplantation using both A2 and non-A2 living donors.

Background: Given the scarcity of cadaveric organs, efforts are intensifying to increase the availability of living donors. The current study assessed the feasibility of using ABO-incompatible living-donor kidneys to expand the donor pool.

Methods: The authors performed 18 ABO-incompatible living-donor kidney transplants between May 1999 and April 2001.