Lymphocyte Cyclic AMP Levels Antepartum and Postpartum as an Indirect Assessment of the Immune System During Pregnancy

ABSTRACT: The literature dealing with the immunological state of the pregnant woman has been conflicting. The concentrations and activity of a number of hormones and proteins which modify lymphocytic activity have been measured both in vivo and in vitro during pregnancy. Most of the differences between reported studies can be reconciled to technical or experimental variations. In some instances, the purported suppressive effects of embryonic proteins such as HCG have actually been caused by the impurity of the preparation studied. We have attempted to approach the question of whether or not the pregnant woman is immunosuppressed by studying a regulatory material in the lymphocytes. It is known that cAMP is a mirror of lymphocytic activity and that low levels of cAMP may indicate a high degree of reactivity, while high levels are present when lymphocyte reactivity is low. In an initial study, ten women volunteered to have blood drawn in the last trimester and two months postpartum. Cyclic AMP was extracted from lymphocyte-enriched leukocytes and stored until all samples were available from all patients so that the analysis could be made simultaneously. Five samples were obtained from healthy nonpregnant women in the same age range. Postpartum and nonpregnant women were found to have significantly elevated levels of cAMP as compared to the lymphocytes obtained in the third trimester of pregnancy. The experiments were then repeated using seven more patients. The same significant increase in postpartum lymphocyte cAMP concentrations were found. The precise reason(s) for this is not known, but may be due to increased suppressor cell activity.     

Comparative Toxicity of the Hematinic MDL 80,478--Effects on the Liver and Adrenal Cortex of the Dog, Rat and Monkey

Comparative Toxicity of the Hematinic MDL 80,478 — Effectson the Liver and Adrenal Cortex of the Dog, Rat and Monkey.Yarrington, J. T., Huffman, K.W., Leeson, G.A., Sprinkle, D.J.,Loudy, D.E., Hampton, C., Wright, G.J. and Gibson, J.P. (1983).Fundam. Appl. Toxicol.. 3:86-94. The ferrocene hematinic MDL80,478 was administered orally at dosages ranging from 0 to500 mg/kg/day to dogs (2 weeks), monkeys (6 weeks), and rats(6 weeks). Rats given 500 mg/kg/day had distended abdomens dueto enlarged livers while the high-dose (250 mg/kg/day) dogsand monkeys demonstrated the following signs: emesis, depression,ataxia, anorexia and a high number of deaths. Increase in serumtotal bilirubin, alkaline phosphatase, and glutamic-pyruvictransaminase, indicators of hepatocellular injury, were detectedin these high-dose dogs and monkeys prior to their deaths. Necropsyexamination revealed yellowish discoloration of the abdominalfat of the rat and enlarged yellow livers of all three species.In the rat, increasing the dose of 25 to 250 mg/kg/day resultedin significantly (P < 0.05) elevated levels of plasma MDL80, 478 following longterm administration. At the highest dosagefor each test animal drug-related microscopic lesions occurredin the livers as diffuse, Prussian blue positive, brown pigmentation(rats), fatty degeneration (dogs), and centrolobular necrosis(monkeys) and the adrenals with focal to diffuse cortical vacuolardegeneration (all three species). Ultrastructural evaluationof rat tissue demonstrated iron storage and hypertrophy of smoothendoplasmic reticulum (SER) of the liver and mild vacuolar degenerationof the mitochondria and lipid droplet accumulation of the adrenalcortex. In addition to increased SER, the parent compound causedin the liver of the rat increased hepatic activity of ethylmorphineN-demethylase and aniline hydroxylase with no change in cytochromeP-450 or microsomal protein, findings suggestive of mild drug-relatedinduction of the monoxygenase system.     

Molecular and serological characteristics of the glutathione S-transferases of Schistosoma japonicum and Schistosoma mansoni

When aqueous extracts of Schistosoma japonicum and S. mansoni adult worms are passed over columns of glutathione-conjugated agarose, two molecular species of Mr 26,000 and Mr 28,000 are detected in eluates as analysed by SDS-PAGE, these eluates having glutathione S-transferase (GST) activity. The molecules, termed Sj26 and Sj28 from S. japonicum and Sm26 and Sm28 from S. mansoni, can be immunogenic in rabbits or mice and appear not to be linked together as subunits of GST heterodimers. The elution profile of SjGST (Sj26+Sj28) from glutathione columns resembles that of SmGST (Sm26+Sm28) and, by peptide mapping, radioiodinated Sj26 and Sm26 are related as are the two Mr 28,000 molecules. Similarities between radioiodinated Sj28 and Sm28 are also obvious on two-dimensional gel electrophoresis with some differences being observed between Sj26 and Sm26. The Mr 28,000 molecules are more prominent than the Mr 26,000 molecules and, although Sj28 and Sm28 is a poor immunogen in mice, immunological cross-reactivity between Sj28 and Sm28 is generally more readily detected than that between Sj26 and Sm26. Whether experimental vaccination against schistosomiasis japonica and schistosomiasis mansoni reported with cloned GSTs can be improved by incorporation of both Mr 28,000 and Mr 26,000 species into the vaccine remains to be determined. On this point, the present data suggest that vaccination of mice with Sj26 plus Sm28 should be a useful means of increasing antibody responses to the GSTs of S. japonicum.