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Previous research and therapy in renal transplantation largely focused on the cellular arm of the adaptive immune response. Evidence is emerging that innate immune mechanisms, particularly complement, play a greater role in inflammatory and immune responses against the graft than has been preciously recognized. Alternative complement pathway activation appears to mediate renal ischaemia/reperfusion injury, and proximal tubular cells maybe both the source and the site of attack of complement components in this setting. Locally produced complement also plays a role in the development of both cellular and antibody-mediated immune responses against the graft. C4d staining has emerged as a useful marker of humoral rejection both in the acute and in the chronic setting and led to renewed interest in the significance of anti-donor antibody formation. A number of therapies are in development which inhibit complement or reduce local synthesis, and may lead to an improved clinical outcome following renal transplantation. Keywords: Complement in renal transplantation; Allograft rejection, C4d proximal tubular cell [ABSTRACT FROM AUTHOR]

Using DNA probes in a structural study of the antithrombin III gene locus we found no evidence of gene deletion in two British kindreds with inherited antithrombin III deficiency. However, linkage analysis between a common DNA polymorphism and the antithrombin III deficiency trait showed that the defect lies at or close to the antithrombin III structural gene. The lod score for linkage within the larger Scottish kindred was 3.1 (theta = 0). These results are consistent with previously published data suggesting that mutation of the antithrombin III structural gene is the cause of inherited antithrombin III deficiency in some families. [ABSTRACT FROM PUBLISHER]

An investigation into the mechanisms of failure of current Björk-Shiley cardiac valve prostheses is reported. Two failed valves, one apparently unfailed but defective valve, and one unused valve, were examined by scanning electron microscopy and metallographic section. In the first two valves (removed 12 and 23 months after implantation) fracture was associated with the welds joining the short strut to the valve ring. The fracture surfaces in all cases were heavily faceted and showed branching cracks. Extensive wear had occurred on one fracture surface in the first case, suggesting that one leg of the short strut had failed before the other, though this had been clinically undetectable. The third valve was removed owing to failure of the suturing (24 months after implantation) but one leg of the short strut was found to be completely fractured. The other leg showed extensive cracking and porosity in the weld region. A metallographic section taken through the weld region of the fourth (unused) valve illustrated several sizable defects directly attributable to the welding process. It is suggested that the valves failed by fatigue and that these problems could be overcome if the complete valve cage were machined as a single piece. [ABSTRACT FROM PUBLISHER]

Local synthesis of complement components may play a crucial role in the pathogenesis of renal disease. Previous reports have shown that a number of complement components are produced by renal tissue both in vitro and in disease states. In the present study, we focused on the topographical distribution of components of the alternative and classical activation pathways in normal human kidney. As a whole, the normal renal cortex has the capacity to express the genes corresponding to most components of both complement pathways. There appears to be relatively high expression of transcripts for factor D and properdin in glomeruli, whilst factor B expression is greater within the medulla. Components C2, C3, and C4 and factor H are expressed predominantly in cortical tubule-rich fractions, and C1q is similarly expressed in all fractions. These results suggest that there may be differing emphasis on the alternative and classical pathways of complement activation in different regions within normal kidney. [ABSTRACT FROM AUTHOR]

Fracture of the short strut of the latest series of Björk-Shiley mitral valve prostheses occurred 12 months after implantation. The patient died despite emergency surgery to excise and replace the prosthesis. Björk-Shiley 29-33 mm valves with a 60 degree opening angle manufactured between February 1981 and March 1982 have a predicted strut fracture rate of 0.3% (three times greater than that of valves produced outside these dates). Unimplanted valves from this batch have now been recalled by the manufacturers. [ABSTRACT FROM PUBLISHER]