CD59 expressed on a tumor cell surface modulates decay-accelerating factor expression and enhances tumor growth in a rat model of human neuroblastoma

It has been hypothesized that complement inhibitors expressed on the surface of tumor cells prevent effective immune-mediated clearance. Whereas there are in vitro data to support this hypothesis, the species-selective activity of complement inhibitors has been a hindrance to investigating the role of membrane-bound complement inhibitors in rodent models of human cancer. The CD59-positive LAN-1 human neuroblastoma cell line was significantly more sensitive to lysis by rat complement than by human complement, illustrating the species selectivity of endogenously expressed complement inhibitors. Transfection of LAN-1 cells with rat CD59, an inhibitor of the terminal cytolytic membrane attack complex, effectively protected the cells from lysis by rat complement in vitro. When LAN-1 cells stably expressing rat CD59 were inoculated into immune-deficient rats, the onset of tumor growth and the rate of tumor growth were significantly enhanced compared with those of control-transfected LAN-1 cells. These data show directly that the expression of a complement inhibitor on a tumor cell promotes tumor growth. Flow cytometric analysis revealed that the endogenous expression of decay-accelerating factor (DAF), an inhibitor of complement activation, was up-regulated on the surface of cells after in vivo growth. Of further interest, higher levels of DAF were present on CD59-transfected cells than on control-transfected cells derived from tumors. Increased DAF expression correlated with decreased complement deposition on the tumor cell surface. These results show that expression of complement inhibitors on a tumor cell has functional consequences with regard to complement deposition in vivo and indicate that CD59 can indirectly effect complement activation and C3 deposition in vivo via a link between CD59 and DAF expression.     

Effects of trilinolein on superoxide dismutase activity and mrna levels in aortic smooth muscle cells

1. Atherosclerotic cardiovascular disease is still the leading cause of death in Western countries. Oxygen free radicals are considered to be intimately involved in the development of atherosclerosis. Anti-oxidants may help to protect mammalian cells from the damage induced by these reactive oxygen species. Many reports have indicated that anti-oxidants used in the treatment or prevention of disease could modify the levels of superoxide dismutase (SOD). However, the effects of long-term anti-oxidant treatment on the levels of SOD in smooth muscle cells (SMC) is still unclear. In the present study, the effects of the lipophilic anti-oxidant trilinolein on the activity and gene expression of SOD in SMC were evaluated. 2. After 2 days incubation with 0.1 micromol/L trilinolein, the activity and mRNA levels of SOD were increased in rat aortic SMC (A7r5), but there was no significant change in these parameters with a higher concentration of 1 micromol/L trilinolein. 3. In contrast, after 7 days incubation with trilinolein, both the activity and mRNA levels of SOD were lowered in a dose-dependent manner. 4. These data emphasize the importance of choosing an optimal dosage for supplementation with anti-oxidants in humans for the scavenging of oxygen free radicals.     

Aconitine poisoning following the ingestion of Chinese herbal medicines: a report of eight cases

Background: Traditional Chinese medicines often contain 'chuanwu' and 'caowu', the roots of certain Aconitum species which are thought to have an anti-inflammatory effect in many conditions. Excessive amounts of these materials, which contain diterpene alkaloids particularly aconitine, can produce toxic effects and occasional fatalities.
Aims: This study was conducted to document the adverse effects related to these herbal medicines which resulted in hospital admission and to determine the outcome in these patients.
Methods: A retrospective survey was conducted of patients admitted to the Prince of Wales Hospital, Hong Kong with suspected adverse effects from Chinese herbal medicines containing chuanwu or caowu over a two year period from 1989 to 1991.
Results: Eight patients were identified with features of mild to moderate intoxication including nausea and vomiting, paraesthesiae or numbness in the mouth and extremities, hypotension and ventricular extrasystoles. The management of aconitine poisoning is essentially supportive and in-hospital observation with ECG monitoring should be continued for at least 24 hours because of the risk of cardiovascular collapse and ventricular arrhythmias. The medical profession and general public should be alerted to the potential toxicity of these herbs and their usage should be controlled by legislation in Hong Kong as it is in some other countries. (Aust NZ J Med 1993; 23: 268–271.)     

The effects of guanethidine, bretylium and debrisoquine on the accumulation of noradrenaline in constricted postganglionic sympathetic nerves in vitro

The accumulation of noradrenaline proximal to a constriction applied to cat hypogastric nerves in vitro has been studied in preparations treated with bretylium, guanethidine and debrisoquine. All three drugs reduced the accumulation of the amine. This was paralleled by a decrease in the accumulation of dense vesicles seen with the electron microscope. Evidence is presented which suggests that the drugs e xert a noradrenaline-depleting action upon the amine-storage vesichles. At leat 18 hrs' treatment with bretylium and debrisoquine were necessary before the amine-depleting action of these drugs was evident. It is suggested that the method employed is of value in the correlation of the ultrastructural and biochemical effects of drugs on sympathetic nerves.