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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.

Nine patients with an unusual and serious intraabdominal complication of the beta-adrenergic blocking agent practolol seen since 1973 are reported. The striking and bizarre peritoneal changes induced by the drug have distinctive features that are not shown by other forms of peritoneal disease. The cases presented with small bowel obstruction, usually chronic in type and often associated with profound weight loss and an abdominal mass. Characteristic radiological features were present. The abnormalities at laparotomy were impressive, with a gross proliferation of the visceral peritoneum which formed a dense white cocoon which encased, constricted and markedly shortened the small bowel, usually from the duodenojejunal flexure to the ileocaecal valve. The obstruction was relieved by mobilizing the small bowel from the ensheathing tissue. Restoration of alimentary function after surgery was delayed but the long term result was satisfactory with full relief of symptoms and the absence of recurrent obstruction during the follow-up period. This complication may arise after treatment with the drug has been stopped, and although long term oral therapy has been discontinued, further cases will almost certainly present for some time to come.

I. Results of 298 nitrogen balance studies from experiments with male cross-bred lambs, ranging in weight from 3 to 38 kg, which had been either fasted, or fed entirely on liquid diets of varying protein content at various energy intakes up to ad lib. intake, were used to quantitatively describe the effects of the amount and quality of absorbed protein, energy intake and live weight on N balance and total N requirement of lambs.2. When N intake was less than the amount required, N balance was independent of energy intake, but linearly related to absorbed N and metabolic body-weight (live eight""^). In the fitted relationship, the coefficient of absorbed N was shown to be an estimate of the biological value of absorbed protein and the coefficient of metabolic body-weight was an estimate of the loss of endogenous N in both urine and faeces. For the milk-based diets used in the experiment biological value was 0'72 and the total endogenous N loss in urine and faeces was 148 mg N/kg075 per d. 3.When N intake was in excess of the amount required, N balance in lambs of a constant live weight increased linearly with metabolizable energy (ME) intake, at a rate that decreased with increasing live weight. Similarly at constant ME intake, N balance was a curvilinear decreasing function of metabolic body-weight. When N balance was expressed per unit metabolic body-weight, it was constant for lambs of all weights when ME intake was about 0.23 M J/kg0'76 per d, but it decreased linearly with increasing metabolic body-weight for ME intakes above this level.4. N balance of fasted lambs was several times less than predicted by either of the relationships established for fed animals, and was found to be linearly related to metabolic bodyweight.G . The effects of enerm intake and live weight on the total N requirement of lambs were -_ -determined. When total N requirement was expressed per unit of energy intake, it was found to be constant at 0-9 g N/MJ ME for all lambs irrespective of live weight when ME intake was 0.23 MJ/kg@75 per d. However, as ME intake/unit metabolic body-weight was raised above this level, N requirement/unit ME intake increased for lambs weighing less than c. 23 kg, but decreased for heavier animals.

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.

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