Anti-My-26: a monoclonal antibody inhibiting human phagocyte chemiluminescence

Anti-My-26, a mouse monoclonal IgG1 antibody, was raised against human granulocytes and has been shown to inhibit luminol-enhanced, glucose-independent chemiluminescence (CL) of human granulocytes (or monocytes) responding to the soluble secretagogues A23187 or ionomycin (calcium ionophores) and phorbol myristate acetate (PMA). Anti-My-26 inhibition of CL was reversible and was dependent on both secretatogue and monoclonal antibody concentration. This inhibition appeared to be directed at the component of granulocyte CL that is independent of NAD(P)H-oxidase-catalyzed formation of superoxide anion, because neither opsonized zymosan-stimulated CL nor the PMA-induced decrease in NAD (P)H-associated autofluorescence was affected by anti-My-26. In addition, ionomycin, over a wide concentration range, failed to generate any decrease in granulocyte autofluorescence. The A23187-induced CL inhibited by anti-My-26 was correlated with its depression of oxygen consumption. Furthermore, anti-My-26 was not cytotoxic and did not itself induce oxidative metabolism when used as a stimulant. Binding of anti-My-26 to phagocytic cells was not decreased by pre-exposure of cells to either A23187 or PMA. Evidence is presented to suggest that the binding of anti-My-26 to the granulocyte surface inhibits the oxidative response to calcium ionophore and PMA by blocking a common pathway(s) stimulated by these different secretagogues.     

Gentamicin and amikacin repress the growth of Plasmodium falciparum in culture, probably by inhibiting a parasite acid phospholipase

Human erythrocytes were loaded with either gentamicin or amikacin and subsequently infected with the human malarial parasite Plasmodium falciparum and grown in culture. Parasite invasion of erythrocytes was unaffected by the drugs, but subsequent development was retarded. The digestion of host cell cytosol in ring-stage parasites was inhibited by the drugs. A substantial acid, Ca2+-independent phospholipase activity could be monitored in parasite cytosol and was found to be inhibited by the drugs. These results imply that phospholipases are involved in the feeding mechanism of the parasite and that gentamicin and amikacin exert their inhibitory activity by affecting these enzymes.     

Methoxyindoles of the retina

Melatonin and other 5-methoxyindoles are compounds usually associated with the pineal gland. Research is expanding from studies of pineal melatonin to studies of extrapineal organs and of other 5-methoxyindoles besides melatonin. Research in recent years has shown that the retina also contains and synthetises 5-methoxyindoles. The biochemical modes of action are still unclear. Nevertheless, they seem to have physiological roles in the pineal gland and the retina. These compounds are thought to participate in the regulation of the cyclic metabolism of the retina. Melatonin and other 5-methoxyindoles are often classified as neuromodulators.     

Environmental factors affecting seasonal variation in immunity of clinically normal dogs

A whole blood lymphocyte stimulation test, an in vitro corollary of in vivo cell mediated immunity, was done with blood collected monthly from eleven dogs for a period of three years (August, 1977 through August, 1980). Seasonal variations in immunity were observed to occur. These fluctuations were analyzed for possible association with 22 environmental, solar, and meteorological parameters. Of the six independent variables significantly entering the predictive regression equations, sunspot activity (monthly mean daily number of sunspots) was most prominent, showing a significant negative correlation in 10 of the 11 dogs. This suggests that solar activity might be associated with some activity on earth, e.g., geomagnetism which in turn might affect immune response.     

Influence of chronic antigen exposure on the metabolism of PGH2 by microsomal preparations of airway and parenchymal tissues in the sheep

The effects of repeated antigen exposure on the synthesis of mediators by lung tissues are not well understood. To investigate the influence of antigen challenge on the synthesis of prostaglandins by central airway and peripheral lung tissues, fourteen sensitive sheep underwent biweekly exposure to aerosolized $\text{Ascaris suu}$ antigen (7) or saline (7). Following the fifth exposure, microsomal and high speed supernatant fractions were prepared from trachealis muscle and lung parenchyma. Synthesis of thromboxane (TX) A₂, prostaglandin (PG) D₂ and PGI₂ from the PG endoperoxide intermediate, PGH₂, was assayed over a range of substrate concentrations from 3–200 uM. Synthesis of PGI₂ by trachealis microsomes was approximately 5-fold greater than that of TXA₂. PGI₂ and TXA₂ production was identical in tracheal preparations from Ascaris- and saline-exposed animals. In parenchymal tissues, where TXA₂ production predominated over PGI₂ by 9-fold, preparations from Ascaris- exposed animals synthesized 50% more TXA₂ than controls at PGH₂ concentrations of 25 uM and above, whereas synthesis of PGI₂ and PGD₂ were similar in preparations from both groups of animals. The density of pulmonary mast cells was decreased by 21% in the Ascaris group, whereas polymorphonuclear leukocyte density was unchanged. These results demonstrate the differential synthesis of TXA₂ and PGI₂ in central airways and peripheral lung regions of the sheep. They further indicate that repeated exposure of the airways to antigen selectively enhances TXA₂ synthesis in the lung periphery of sensitized animals. The site of this increased enzymatic activity, whether in resident cells or newly-infiltrated cells, has not been determined.     

Comparison of estrogen priming effects with body weight restoration effects on the gonadotropin pattern of patients with anorexia nervosa

Plasma estradiol (E2), serum LH and FSH, and the gonadotropin response to two consecutive LHRH administrations (10 and 100 micrograms with an interval of 2 h) were determined in 19 patients with anorexia nervosa (AN) at the emaciation phase, before and after estradiol benzoate (E2B) injections (3 micrograms/kg/day for 7 days). The same investigations were repeated after weight restoration in 9 AN patients who remained amenorrheic. Both at the emaciation phase and after weight restoration, E2B enhanced the second LH response to LHRH and decreased serum FSH, suggesting that the functional capacities of the pituitary gonadotrophs are normal in AN. Unlike E2B injections, weight restoration increased all the hormone values, suggesting that the weight restoration effects on the abnormal gonadotropin secretory pattern of AN depend on another mechanism than the E2 lowering. That mechanism is probably a disorder of the hypothalamic LHRH secretion, the consequences of which could be reinforced by the low E2 levels.