No abstract

SummarySurface lymphotoxin (LT) is a heteromeric complex of LT-c~ and LT-[3 chains that binds to the LT-I3 receptor (LT-I3-R), a member of the tumor necrosis factor (TNF) family of receptors. The biological function of this receptor-ligand system is poorly characterized. Since signaling through other members of this receptor family can induce cell death, e.g., the TNF and Fas receptors, it is important to determine if similar signaling events can be communicated via the LT-13-tL. A soluble form of the surface complex was produced by coexpression of LT-c~ and a converted form of LT-[3 wherein the normally type II LT-[3 membrane protein was changed to a type I secreted form. Recombinant LT-oq/[32 was cytotoxic to the human adenocarcinoma cell lines HT-29, WiDr, MDA-MB-468, and HT-3 when added with the synergizing agent interferon (IFN) y. When immobilized on a plastic surface, anti-LT-[3-tL monoclonal antibodies (mAbs) induced the death of these cells, demonstrating direct signaling via the LT-I3-R. Anti-LT-[3-R mAbs were also identified that inhibited ligand-induced cell death, whereas others were found to potentiate the activity of the ligand when added in solution. The human WiDr adenocarcinoma line forms solid tumors in immunocompromised mice, and treatment with an anti-LT-~-R, antibody combined with human IFN-~/arrested tumor growth. The delineation of a biological signaling event mediated by the LT-I3-R opens a window for further studies on its immunological role, and furthermore, activation of the LT-I3-R may have an application in tumor therapy.T he TNF family ofligands and receptors is a set of regulatory elements in the immune system (t). TNF was discovered as a cytolytic agent circulating in the blood of endotoxin-stimulated animals (2-4). Originally cloned in the expectation that TNF would be a novel antitumor agent, it was later shown that its primary physiologic function lies in initiating the inflammatory cascade underlying the host's immediate defensive response to infection or stress. More complex immunological functions have been described (5,6). Lymphotoxin (LT) 1 e~ (also called TNF-I3) is a similar cytokine secreted by activated lymphocytes (7) and was originally characterized as having the same functions as TNF. Later, activated T and B cells were found to display LT-c~ on their surfaces in an unusual form compIexed with another member of the TNF family called LT-13 in an . A complex with an apparent 1 Abbreviations used in this paper: LT, lymphotoxin; LT-I3-1L, LT-[3 receptor; MTT, 3-(4,5-dimethylthiazol-2-yl) 2,5 diphenyltetrazolium bromide; TUNEL, terminal deoxynucleotidyl transferase UTP nick-end labeling; VCAM, vascular cell adhesion molecule.LT-c~2/I31 stoichiometry is also present, but only in minor amounts on human lymphocytes. The major LT-cq/f3 z form does not bind to the known TNF receptors, referred to here as TNF-R55 and TNF-R.75, but rather interacts with another receptor in the TNF family called the LT-[3 receptor 14).Currently, the function of the LT system is poorly character...

In a survey of dogs in Sydney, mastocytomas (16.1%) and histiocytomas (14.0%) were the most common in a total of 1,000 skin neoplasms. The basal cell and appendage group provided 25.5% of the neoplasms. The prevalence of the various neoplasms, the age of affected dogs, the proportion in the sexes, the common sites of occurrence and prevalence in the different breeds were broadly similar to findings in surveys in other countries, except that in the Syndeny dogs there was a greater prevalence of histiocytomas and haemangiopericytomas, a more common occurrence of histiocytomas in mature dogs, an occurrence of histiocytomas in similar numbers on the head, trunk and limbs, and a remarkably common development of squamous cell carcinomas in Dalmatians.

Summary Catalytic epidemic models are concerned with the age distribution at attack of infectious disease. A catalytic linear infection model, in which it is assumed that the force of infection acting on an individual is a linear function of age, is developed and applied to measles. The model is fitted to measles incidence data in England and Wales for the period 1956–69. Trends in time and differences between populations in estimated parameter values are discussed. In particular, it is observed that the (estimated) mean age at attack has decreased linearly with time over that period. It is hypothesized that the introduction of large‐scale vaccination programmes may alter the age distribution of attack among the remaining susceptibles.

These findings demonstrate that disability is a stronger predictor of depressive symptoms than depressive symptoms are of disability. In addition, the prior existence of a health condition will lead to further deterioration of health conditions and that they often coexist.