Transforming growth factor-β: Recent advances on its role in immune tolerance

Transforming growth factor-β (TGF-β) is a key regulator of immune tolerance. In this paper, we will focus on T cells and natural killer (NK) cells, which are directly regulated by TGF-β in vivo. TGF-β controls T-cell activation and differentiation, and is involved in the suppressive function and generation of regulatory T cells. Recently, TGF-β has also been shown to directly inhibit NK cell activity. These studies demonstrate that TGF-β utilizes multiple mechanisms to ensure immune tolerance, which is critical in a variety of autoimmune and inflammatory disorders. We will also discuss recent advances on the role of TGF-β in immune-mediated diabetes, inflammatory bowel disease, arthritis, and systemic lupus erythematosus.     

Spinal Cord Protection in the Absence of Collateral Circulation: Meta-Analysis of Mortality and Paraplegia

A meta-analysis of paraplegia complicating aortic surgery on patients having neither intercostal nor spinal collaterals, epitomized by patients with acute traumatic aortic rupture, was done. Index Medicus and Medline were searched for all suitable English publications between 1972 and 1992. New paraplegia occurred in 9.9% of 1492 patients who underwent surgery. However, 19.2% of patients undergoing surgery with only simple aortic cross-clamping developed paraplegla, in contrast to 6.1% if distal aortic perfusion was augmented by either “passive” or “active” methods (p < 0.00001). The risk of paraplegia increased progressively as cross-clamp times lengthened if simple aortic cross-clamping was used (p < 0.00001), but only once did the cross-clamp time exceed 30 minutes (p < 0.05). Paraplegia occurred in 8.2% of patients with “passive” shunts from the ascending aorta (p < 0.001 vs simple cross-clamping). Shunts from the left ventricular apex, however, had an incidence of paraplegia of 26.1% and, therefore, did not decrease the risk of paraplegia. “Active” augmentation of distal perfusion had the lowest risk of paraplegia: 2.3% (p < 0.00001 vs simple cross-clamping or “passive” shunts). Mortality, however, was higher in these potentially polytraumatized patients when they were perfused distally using methods requiring full systemic heparinization (18.2%), compared to mortality with methods not requiring heparin (11.9%; p < 0.01). In conclusion, simple aortic cross-clamping has a high risk of paraplegia if the cross-clamp time extends beyond 30 minutes. “Active” modalities of augmenting distal perfusion provide optimal spinal protection. (J Card Surg 1994;9:685–691)     

The recovery of trust

Much of the social life of many animals depends on cooperation. It is argued that humans are no less reliant on each other. The pseudo‐biological view that social conflict is inevitable under all circumstances is rejected. However, warfare undoubtedly occurs and people certainly risk their lives in attacking others. Explanations must be sought at many different levels. Most indicate an implicit weighing of possible costs against likely benefits which might be performed by individuals or might result from the historical processes of cultural selection and Darwinian evolution. Whatever the processes might have been, their outcomes make no sense in a nuclear age since the benefits of warfare are likely to be non‐existent. Since little can be done to change the way we think, it becomes important to understand the conditions in which we are prepared to risk our lives. It is argued that the key lies in the breakdown of mutual trust and that it is possible to create the conditions in which trust can once again be recovered.