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Biomedical subjects

N K Bell

Publications and source records attributed to N K Bell.

14 recordsLinked to original sources

Use of porcine tumor necrosis factor receptor 1-Ig fusion protein to prolong xenograft survival.

BACKGROUND: Delayed rejection of xenografts is a major hurdle that needs to be addressed to achieve long-term engraftment in the pig-to-primate transplant setting. Both vascular and avascular xenografts are susceptible to a delayed rejection process that comprises humoral and cellular responses. Tumor necrosis factor (TNF) is believed to play a role in this process by promoting cell activation, apoptosis and the recruitment of inflammatory cells. To address this problem, we engineered the donor cell in such a way that it could block both human and porcine TNF. METHODS: We produced a recombinant fusion protein containing the extracellular domain of the porcine TNF-Receptor 1 and an IgG Fc moiety (pTNFR1Ig). We first evaluated by flow cytometry the pTNFR1Ig capacity to prevent TNF alpha-induced expression of SLAI, SLAII, VCAM-1, ICAM-1 and E-selectin on the cell surface of porcine aortic endothelial cells (PAEC). The effect on TNF alpha-mediated cell death was also assessed by propidium iodide staining after incubating PAEC with TNF alpha plus cycloheximide for 24 h. PAEC and porcine fibroblasts were subsequently engineered by retroviral infection to express and secrete pTNFR1Ig and their resistance to the TNF alpha effects was tested in vitro. Finally, we transplanted mock-control and pTNFR1Ig-expressing PAEC under the kidney capsule of BALB/c mice in the absence of immunosuppression and examined the degree of rejection at 2 and 3 weeks post-transplantation. RESULTS: Treatment with pTNFR1Ig resulted in a very potent blockade of human, porcine and murine TNF alpha activity on porcine cells. It inhibited the upregulation of all cell surface markers of activation tested as well as the TNF alpha-mediated cell death. Moreover, pTNFR1Ig-expressing PAEC showed prolonged engraftment in a pig-to-mouse xenotransplant model. CONCLUSIONS: Incorporation of strategies that block TNF may prove useful in the development of xenografts resistant to delayed rejection.

Animals↗

Social/sexual norms and AIDS in the South. Ethics and the politics of aids: lessons for small cities and rural areas throughout the U.S.

No one denies that the face of AIDS (the "AIDS profile") is changing, and it is clear that we are entering a new phase in our understanding of this disease. As the AIDS profile changes, however, we are seeing a change in attitudes about prevention. In this stage of the epidemic there seems to be a move toward adopting more coercive strategies for breaking the chain of transmission. One concern, obviously, is that newly HIV-infected persons will find that they have little capacity to demand recognition of their rights to consent, to be treated, to confidentiality, to move about freely in society, to work, and so on. Unfortunately, this bodes ill for newly infected persons in previously low-incidence areas. Two very recent studies suggest that rates of high-risk sexual behavior among homosexual/bisexual men in smaller cities and rural areas in the South are much higher than rates now reported for gay men in large city epicenters. This paper attempts to examine the implications of differences in social and sexual behavior norms in the South for the spread of AIDS/HIV and to suggest morally appropriate primary prevention strategies for working within them.

Acquired Immunodeficiency Syndrome↗

Ethical dilemmas in trauma nursing.

For someone seeking to understand the ethical dimensions of trauma nursing, it quickly becomes apparent that there is a uniquely complex set of issues to be examined in this context. Many of these issues are made more difficult by the fact that the provider/patient relationship that undergirds the moral dimension of patient care in other contexts is necessarily truncated or absent in the trauma unit. This article seeks to explore some of these issues and the moral ambivalence they create.

Acquired Immunodeficiency Syndrome↗

What is wrong with 'wrongful life' cases?

'Wrongful life' torts raise a number of interesting and perplexing philosophical issues. In a suit for 'wrongful life', the plaintiff (usually an infant) brings an action (usually against a physician) claiming that some negligent action has caused the plaintiff's life, say by not informing the parents of the likely prospect that their child would be born with severe defects. The most perplexing feature of this is that the plaintiff is claiming that he would have been better off if he had never been born. A number of arguments have appeared which purport to show that "wrongful life' claims should not be allowed, either because it is senseless to claim that one would be better off if one had not existed or that it is impossible to assess the extent to which someone has been damaged by being brought into existence. In our paper we rebut these arguments and suggest a procedure for determining damages in 'wrongful life cases'.

California↗