Heterotopic heart transplantation in the rat receiving FK-506 alone or with cyclosporine.

In rats, FK significantly prolonged heterotopic heart graft survival over a wide dose range when given for 2 weeks starting on the day of the operation. Brief courses of FK for one to four days preoperatively, and especially beginning four days postoperatively, allowed long subsequent survival of heart grafts in otherwise untreated recipients. The seeming acceptance of the grafts with postoperative FK treatment was largely but not exclusively donor specific when tested eight days after the last FK dose by second grafts from the same donor v third-party donor grafts. FK in minimally therapeutic doses was synergistic with suboptimal doses of CyA

Platelet-activating factor and hyperacute rejection: The effect of a platelet-activating factor antagonist, sri 63-441, on rejection of xenografts and allografts in sensitized hosts

The pathogenesis of hyperacute transplantation reactions includes the activation of a cascade of nonspecific inflammatory reactions that precipitates the destruction of the target organ. Platelet-activating factor (PAF) represents an important component of these inflammatory cascades, and we have examined the influence of a specific PAF receptor antagonist (SRI 63-441) on the inhibition of hyperacute rejection in two experimental models, the rejection of rat cardiac allografts by presensitized recipients and guinea pig-to-rat and mouse-to- rat cardiac xenografts. Our results demonstrate that inhibition of PAF function by SRI 63-441 has a variable effect on the survival of cardiac allografts in presensitized rat recipients. In the ACI to sensitized BN cardiac allograft model, the use of SRI 63-441 alone, or in combination with CsA, FK506, or prostaglandin E2(PGE2), does not prolong graft survival. As we have previously reported, SRI 63-441 does act as a single agent to prolong the survival of ACI to sensitized LEW grafts, and this survival effect is synergistic when combined with CsA. Here we extend these results to demonstrate that this survival is also extended when FK506 is used in the ACI-to-LEW model. Concordant mouse-to- rat cardiac xenografts are also relatively resistant to prolongation of graft survival following treatment with SRI 63-441 alone or in combination with CsA or FK506. Discordant xenografts appear to be more susceptible to inhibition of the rejection reaction with SRI 63-441. When either donor or recipient animals were treated with SRI 63-441 alone, or in combination with CsA or FK506, there was significant prolongation of guinea pig-to-rat cardiac xenograft survival. These results are consistent with our earlier description of the effectiveness of SRI 63-441 in preventing the rejection of cat- to-rabbit kidney xenografts. We believe that these resuits demonstrate that the use of the SRI 63-441 to specifically interfere with the function of PAF has the effect of prolonging graft survival in those systems in which preformed antibody and/or complement activation are important components of the hyperacute reaction. This synthetic drug is representative of a family of compounds whose structure can be modified to balance their therapeutic and toxicity activities, and may prove to be important components of a polytherapeutic approach to the control of graft rejection in sensitized patients or following discordant xenografting. © 1990 by Williams and Wilkins

The role of inflammatory reactions in xenotransplantation

Since the original description of hyperacute rejection of the kidney, numerous experimental and clinical studies have attempted to define the precise mechanism(s) of this process. While our interpretation of HAR has advanced, one must recognize this phenomenon as multifactorial and the product of a complex immune/inflammatory reaction. The non-specific effector inflammatory cascade that ensues once an antigen-antibody reaction has initiated hyperacute rejection serves as the target for therapeutic intervention by various modalities. Classically, the platelet-coagulation system has been considered to be the most important and has received the greatest attention. These therapeutic modalities have included heparin, aspirin, dextran, citrate, defibrinating agents, cobra and venom factor, induction of thrombocytopenia by antibodies, and various prostaglandins. All these approaches have been either too toxic or the results too inconclusive to be accepted for generalized use. The difficulty in overcoming the inflammatory process in hyperacute rejection and in explaining the discrepancies in the therapeutic results rest not only in the complexity of the biological reactions, but also in their resiliency and redundancy. That is, there are numerous alternative mediator pathways that can back up the same set of functions. Thus, the inhibition of one arm of an inflammatory reaction can easily be replaced by the release of other inflammatory autocoids with complete mediation of the disease process

OH spectral evolution of oxygen-rich late-type stars

We investigated the main-line spectral evolution with shell thickness of oxygen rich AGB stars. The study is based on a sample of 30 sources distributed along the IRAS colour-colour diagram. The sources were chosen to trace the Miras with thick shells and the whole range of OH/IR stars. The Miras exhibit a 1665 MHz emission strength comparable to that at 1667 MHz. Even though the Miras of the study have quite thick shells, their spectral characteristics in both main lines attest to a strong heterogeneity in their OH shell with, in particular, the presence of significant turbulence and acceleration. The expansion velocity has been found to be about the same at 1665 and 1667 MHz, taking into account a possible velocity turbulence of 1-2km/s at the location of the main-line maser emission. An increase in the intensity ratio 1667/1665 with shell thickness has been found. A plausible explanation for such a phenomenon is that competitive gain in favour of the 1667 MHz line increases when the shell is getting thicker. There is an evolution in the spectral profile shape with the appearance of a substantial inter-peak signal when the shell is getting thicker. Also, inter-peak components are found and can be as strong as the external standard peaks when the shell is very thick. This trend for an increase of the signal in between the two main peaks is thought to be the result of an increase of the saturation with shell thickness. All sources but two - a Mira and an OH/IR star from the lower part of the colour-colour diagram - are weakly polarized. The strong polarization observed for those two particular objects is thought to be the result of perturbations in their shells.Comment: 19 pages, 12 figures, accepted for publication in A&

Polarization properties of OH masers in AGB and post-AGB stars

Context: Ground-state OH maser emission from late-type stars is usually polarized and remains a powerful probe of the magnetic field structure in the outer regions of circumstellar envelopes if observed with high angular and spectral resolutions. Observations in all four Stokes parameters are quite sparse and this is the most thorough, systematic study published to date. Aims: We aim to determine polarization properties of OH masers in an extensive sample of stars that show copious mass loss and search for candidate objects that are well-suited for high angular resolution studies. Methods: Full-polarization observations of the OH 1612 and 1667 MHz maser transitions were carried out for a sample of 117 AGB and post-AGB stars. Several targets were also observed in the 1665 MHz line. Results: Polarized features occur in more than 75% of the sources in the complete sample and there is no intrinsic difference in the occurrence of polarized emission between the three classes of objects of different infrared characteristics. The highest fractional polarization occurs for the post-AGB+PN and the Mira+SR classes at 1612 and 1667 MHz, respectively. Differences in the fractional polarization between the sources at different evolutionary stages appear to be related to depolarization caused by blending. The alignment of the polarization angles at the extreme sides of the shell implies a regular structure of the magnetic field of a strength of 0.3-2.3 mG. Conclusions: Polarized OH maser features are widespread in AGB and post-AGB stars. The relationship between the circular and linear fractional polarizations for a representative sample are consistent with the standard models of polarization for the Zeeman splitting higher than the Doppler line width, whereas the polarized features are the sigma components.Comment: Accepted for publication in Astronomy and Astrophysics. A version with appendices (Tab. A.1 and Fig. B.1) can be downloaded from http://paulo.astro.uni.torun.pl/~pw/arXiv_