Shedding of mutant tumor necrosis factor receptor superfamily 1A associated with tumor necrosis factor receptor-associated periodic syndrome: differences between cell types.

Objective: To investigate the effect of mutations in tumor necrosis factor receptor superfamily 1A (TNFRSF1A) on the ability of the receptors to be cleaved from the cell surface upon stimulation. The mutations we studied are associated with clinically distinct forms of TNF receptor-associated periodic syndrome (TRAPS). We also investigated different cell types within the same form of TRAPS.

Mutant forms of tumour necrosis factor receptor I that occur in TNF-receptor-associated periodic syndrome retain signalling functions but show abnormal behaviour.

Tumour necrosis factor (TNF)-receptor-associated periodic syndrome (TRAPS) is a hereditary autoinflammatory disorder involving autosomal-dominant missense mutations in TNF receptor superfamily 1A (TNFRSF1A) ectodomains. To elucidate the molecular effects of TRAPS-related mutations, we transfected HEK-293 cells to produce lines stably expressing high levels of either wild-type (WT) or single mutant recombinant forms of TNFRSF1A. Mutants with single amino acid substitutions in the first cysteine-rich domain (CRD1) were produced both as full-length receptor proteins and as truncated forms lacking the cytoplasmic signalling domain (deltasig).

Colorectal cancer cells induce lymphocyte apoptosis by an endothelial monocyte-activating polypeptide-II-dependent mechanism.

Endothelial monocyte-activating polypeptide-II (EMAP-II) was first isolated from cell growth medium conditioned by tumor cells, and is closely related or identical with the p43 component of the mammalian multisynthase complex. In its secreted form, EMAP-II has multiple cytokine-like activities in vitro, inducing procoagulant activity on the surface of endothelial cells, increasing expression of E- and P-selectins and TNF-R1, and directing migration of monocytes and neutrophils. EMAP-II has also been shown to induce apoptosis in endothelial cells, leading to the suggestion that it is a proinflammatory polypeptide with antiangiogenic activity.

Reactivation of Epstein-Barr virus in patients with systemic lupus erythematosus.

A link between Epstein-Barr Virus (EBV) and systemic lupus erythematosus (SLE) has been suggested. However, recent advances in molecular technology now permit more detailed analysis. Sera from SLE patients were tested for antibodies to several EBV antigens and had a significantly higher prevalence of immunoglobulin G antibodies against EBV early antigens than in normal or disease controls.

Symptomatic distress, hopelessness, and the desire for hastened death in hospitalized cancer patients.

Objective: This study evaluated the desire for hastened death (DHD) in cancer patients at varying stages of disease to determine its frequency and relationship to physical and psychological distress.

Methods: Two hundred twenty-four inpatients at Princess Margaret Hospital completed questionnaires assessing pain, physical symptoms, depression, hopelessness, and DHD.

Results: There was significant physical and psychological distress in this sample with a mean of nine physical symptoms reported by each subject.

Human autologous mixed lymphocyte reaction as an in vitro model for autoreactivity to apoptotic antigens.

Recent studies have indicated that cells undergoing apoptosis are the source of autoantigens which drive autoimmune responses in systemic lupus erythematosus (SLE). It has been recognized for many years that in vitro stimulation of T cells with irradiated major histocompatibility complex (MHC) class II-bearing autologous cells results in T-cell proliferation with immunological specificity and memory, namely the autologous mixed lymphocyte reaction (AMLR). The nature of the major stimulants in the AMLR is still unclear.