Secreted phospholipase A2 (sPLA2) regulates a variety of cellular functions. The present investigation was undertaken to elucidate the potential role of sPLA2 in endothelial cell (EC) migration. Bovine aortic endothelial cells (BAECs) exposed to sPLA2 placed in the lower compartment of a modified Boyden chamber displayed increased migration compared to cells exposed to vehicle. The effect of sPLA2 on EC migration was time and dose dependent. Migration of BAECs was observed at 30 minutes, increased over 1 to 2 hours, and declined thereafter. At 2 hours of stimulation, sPLA2 (0.01-2 μmol/L) induced 1.2- to 3-fold increased cell migration compared with media alone. Among the different sPLA2s tested, bee venom, Naja naja, and porcine and human pancreatic PLA2s all evoked a migratory response in ECs. Moreover, human synovial fluid, obtained from patients with arthritis and containing sPLA2 activity, induced EC migration. Migration of ECs was significantly reduced after exposure to a catalytic site mutant of pancreatic sPLA2with decreased lipolytic activity as compared to wild-type sPLA2. Similarly, pretreatment of human synovial fluid withp-bromophenacyl bromide, an irreversible inhibitor of sPLA2, markedly decreased the ability of human synovial fluid to stimulate EC migration. Moreover, migration of ECs was stimulated on exposure to hydrolytic products of sPLA2activity including arachidonic acid, lysophosphatidic acid, and lysophosphatidylcholine. These findings suggest that sPLA2plays a physiologic role in induction of EC migration. Moreover, the effects of sPLA2 on EC migration are mediated, at least in part, by its catalytic activity.
Many reports over the years have indicated an association between alcohol consumption and infectious illness among chronic heavy drinkers; however, many patients in these studies have been chronically ill. Thus the question of whether alcohol can appreciably influence immunity in humans and affect the incidence of infectious diseases remains largely unanswered. For this study over 1,100 undergraduate students from a general education course at a large midwestern university were surveyed. Students were asked about their drinking habits and acute health problems. Analyses of their self-reports showed no increase in acute health problems or upper respiratory infections in students drinking between one and 21 drinks per week. However, students drinking 28 or more alcoholic drinks per week had significantly more health problems in the aggregate and those drinking more than 22 drinks per week had more upper respiratory infections than other students including nondrinkers. It was concluded that excessive alcohol intake increased the risk of respiratory infections and acute illnesses in these students, but more moderate alcohol consumption had little effect on the risk for these health problems.
SUMMARY High-dose intravenous methylprednisolone therapy has previously been shown to be efficacious in the treatment of renal lupus erythematosus. The present report presents 2 patients with life-threatening, nonrenal lupus erythematosus. One patient had coma and seizures, while the other had severe thrombocytopenia and anaemia. Both had failed to respond to oral corticosteroid therapy in high doses but had dramatic clinical responses with intravenous methylprednisolone given in 'pulses.' Possible mechanisms of clinical improvement are discussed.High-dose intravenous methylprednisolone given in 'pulses' has become an established therapy for the prevention of acute renal graft rejection.' 2 Each pulse consists of an intermittent large dose of intravenous methylprednisolone given over several days. This form of therapy has also been tried in severe glomerulonephritis3 and in proliferative lupus nephritis46 with improvement in clinical and laboratory parameters of renal disease activity.While previous reports have shown reversal of deteriorating renal function in lupus erythematosus,46 little is known about the effects of pulse therapy in life-threatening, nonrenal manifestations of systemic lupus erythematosus (SLE). We report 2 cases of patients with life-threatening, nonrenal complications of SLE, one with central nervous system (CNS) involvement and one with haemolysis and thrombocytopenia, in which large doses of intravenous methylprednisolone were given after clinical failure with large doses of oral prednisone. Patients and materials CASE IA 23-year-old white female was admitted to hospital in December 1977 with a 4-month history of fever, myalgias, arthralgias, alopecia, and facial rash. The patient had previously been in good health except
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