Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys

We transplanted kidneys from alpha 1,3-galactosyltransferase knockout (GalT-KO) pigs into six baboons using two different immunosuppressive regimens, but most of the baboons died from severe acute humoral xenograft rejection. Circulating induced antibodies to non-Gal antigens were markedly elevated at rejection, which mediated strong complement-dependent cytotoxicity against GaIT-KO porcine target cells. These data suggest that antibodies to non-Gal antigens will present an additional barrier to transplantation of organs from GaIT-KO pigs to humans.

Generalized Maugis-Dugdale Model of an Elastic Cylinder in Non-Slipping Adhesive Contact with a Stretched Substrate

We have recently developed a generalized JKR model for non-slipping adhesive contact between an elastic cylinder and a stretched substrate where both tangential and normal tractions are transmitted across the contact interface. Here we extend this model to a generalized Maugis-Dugdale model by adopting a Dugdale-type adhesive interaction law to eliminate the stress singularity near the edge of the contact zone. The non-slipping Maugis-Dugdale model is expected to have a broader range of validity in comparison with the non-slipping JKR model. The solution shares a number of common features with experimentally observed behaviors of cell reorientation on a cyclically stretched substrate.

Improved suppression of circulating complement does not block acute vascular rejection of pig-to-rhesus monkey cardiac transplants

At present, acute vascular rejection (AVR) remains a primary obstacle inhibiting long-term graft survival in the pig-to-non-human primate transplant model. The present study was undertaken to determine whether repetitive injection of low dose Yunnan-cobra venom factor (Y-CVF), a potent complement inhibitor derived from the venom of Naja kaouthia can completely abrogate hemolytic complement activity and subsequently improve the results in a pig-to-rhesus monkey heterotopic heart transplant model. Nine adult rhesus monkeys received a heterotopic heart transplant from wild-type pigs and the recipients were allocated into two groups: group 1 (n = 4) received repetitive injection of low dose Y-CVF until the end of the study and group 2 (n = 5) did not receive Y-CVF. All recipients were treated with cyclosporine A (CsA), cyclophosphamide (CyP) and steroids. Repetitive Y-CVF treatment led to very dramatic fall in CH50 and serum C3 levels (CH50 < 3 units/C3 remained undetectable throughout the experiment) and successfully prevented hyperacute rejection (HAR), while three of five animals in group 2 underwent HAR. However, the continuous suppression of circulating complement did not prevent AVR and the grafts in group 1 survived from 8 to 13 days. Despite undetectable C3 in circulating blood, C3 deposition was present in these grafts. The venular thrombosis was the predominant histopathologic feature of AVR. We conclude that repetitive injection of low dose Y-CVF can be used to continuously suppress circulating complement in a very potent manner and successfully prevent HAR. However, this therapy did not inhibit complement deposition in the graft and failed to prevent AVR. These data suggest that using alternative pig donors [i.e. human decay accelerating factor (hDAF)-transgenic] in combination with the systemic use of complement inhibitors may be necessary to further control complement activation and improve survival in pig-to-non-human primate xenotransplant model.

Indentation of power law creep solids by self-similar indenters

For creep solids obeying the power law under tension proposed by Tabor, namely sigma = b(epsilon) over dot(m), it has been established through dimensional analysis that for self-similar indenters the load F versus indentation depth h can be expressed as F(t) = bh(2)(t)[(h) over dot(t)/h(t)](m)Pi(alpha) where the dimensionless factor Pi(alpha) depends on material parameters such as m and the indenter geometry. In this article, we show that by generalizing the Tabor power law to the general three dimensional case on the basis of isotropy, this factor can be calculated so that indentation test can be used to determine the material parameters b and m appearing in the original power law. Hence indentation test can replace tension test. This could be a distinct advantage for materials that come in the form of thin films, coatings or otherwise available only in small amounts. To facilitate application values of this constant are given in tabulated form for a range of material parameters. (C) 2010 Elsevier B.V. All rights reserved.