Role of the CTLA-4 receptor in t cell activation and immunity

Costimulatory molecules of the B7 family regulate the activation of T lymphocytes. T cell activation is promoted by binding of B7 molecules to CD28 and inhibited by binding to CTLA-4 (CD152). The balance between positive signals through CD28 and negative signals through CTLA-4 is critical for the fate of the T cell and is subject to tight regulation. Recent in vitro and in vivo studies have significantly advanced our understanding of the function of the CTLA-4 receptor. The results of these experiments suggest that CTLA-4 is critical for the induction of self-tolerance, and that it may have distinct signaling functions in resting and activated T cells. In resting T cells, CTLA-4 crosslinking leads to cell-cycle arrest, whereas in activated T cells, CTLA-4 crosslinking induces apoptosis. In this article, we will review the physiologic functions of the CTLA-4 receptor.     

Holographic interferometry forIn Vitro investigation of bioprosthetic valves

Dysfunction of heart valve prostheses—mechanical as well as biological—is a common problem in cardiac surgery. The reasons for the valve failures are still not well understood. Biological valves especially have an unsatisfactory durability; degeneration and calcification very often lead to the failure of the valves. In our opinion, hidden defects present in the valve material prior to implantation of the valves is a plausible explanation for the dysfunction. Hitherto there has been no technique to detect these defects without destructing the specimen. Holographic interferometry proved to be applicable forin vitro evaluation of mechanical heart valve prostheses. In the present paper we describe application of this method to biological valves. Nine porcine bioprostheses and four fresh porcine aortic valves were investigated by means of holographic interferometry. In eight of nine bioprostheses, the results showed irregularities of the leaflet structure which depend on anomalies of the connective tissue of the leaflets of the valves. To make sure that these findings are not due to normal variations of the morphology, the investigations were carried out with fresh and unfixated porcine aortic valves. In the latter, no such anomalies of the structure were detected. The results obtained confirm the above hypothesis on the origin of the later valve dysfunction. Thus, holographic interferometry tests of bioprostheses prior to their implantation prevent the use of potentially dysfunctional valves.Presented at the 35th World Congress, International College of Angiology, Copenhagen, Denmark, July 1993     

Papillitis and vasculitis of the arteria spinalis anterior as complications of hepatitis C reinfection after liver transplantation

It is well known that hepatitis C virus (HCV)-related chronic liver disease may be associated with various immunological disorders including mixed cryoglobulinemia, which is accompanied by cutaneous vasculitis, arthralgias, membranoproliferative glomerulonephritis, and neuropathy in association with cryoprecipitable immune complexes in serum. We describe here the first case of central nervous system HCV infection with evidence of the virus in the cerebrospinal fluid in association with cryoglobulinemia in a patient who developed recurrent episodes of papillitis and vasculitis of the arteria spinalis anterior after liver transplantation. Received: 3 September 1996 Received after revision: 13 November 1996 Accepted: 6 December 1996     

Severe ciguatera poisoning in Madagascar: A case report

In a single outbreak on the East coast of Madagascar, more than 500 people, 98 of whom died, were poisoned by the flesh of a shark, Carcharhinus amboinensis. From clinical symptoms it can be concluded that this poisoning is due to ciguatera toxins. It is the first case of a severe outbreak caused by a shark, and it is the first case with a mortality rate of 20%.     

Paramecium calcium channels are blocked by a family of calmodulin antagonists.

Although the voltage-sensitive Ca channel present in Paramecium has been subjected to detailed physiological and genetic analysis, no organic ligands have been described that block this channel with high affinity and that ultimately can be used to identify channel components. Based on a previous observation that the naphthalene sulfonamide calmodulin antagonist W-7 can block Paramecium Ca channels at high concentration, we have synthesized analogs of W-7 that block these channels at concentrations of less than 1 microM. The effectiveness of these compounds was tested both by a sensitive behavioral assay and on Ca channels that had been incorporated into planar lipid bilayers. Despite the fact that these compounds are effective Paramecium calmodulin antagonists, two independent lines of evidence suggest that W-7 and its analogs block the Ca channel by a mechanism that is independent of their action on calmodulin. In addition, the sensitivity to W-7 or dihydropyridines of Ca channels present in a number of eukaryotic phyla has been used to identify similarities in Ca channels from widely diverse organisms. It appears that the pharmacological specificity provides a means to group Ca channels.