The role of soluble tumor necrosis factor receptor types I and II and tumor necrosis factor-alpha in malaria during pregnancy.

In a prospective study of rhesus monkeys inoculated with Plasmodium coatneyi or saline on an infection/gestational timeline, we determined the serum levels of tumor necrosis factor-alpha (TNF-alpha), soluble tumor necrosis factor receptor type I (sTNFR-I), and soluble tumor necrosis factor receptor type II (sTNFR-II) in peripheral blood throughout primigravid pregnancy, malaria infection, and a combination of the two. Our goal was to determine the association between levels of TNF-alpha and of its 2 soluble receptors and the course of pregnancy and/or malaria and infant outcome. We found that any detectable level of TNF-alpha was always associated with fetal death and that the sTNFRs may be important for fetal protection, possibly through neutralizing the toxic effects of TNF-alpha. Our findings also showed that increased levels of sTNFR-II were associated specifically with malaria and not with normal pregnancy or even pregnancy with low birth weight due to other causes. In contrast, increases in sTNFR-I levels during the later half of normal pregnancies indicate that sTNFR-I may be important in regulating TNF-alpha levels in preparation for normal labor and delivery.

Alterations in the profile of blood cell types during malaria in previously unexposed primigravid monkeys.

Malaria in nonimmune, primigravid women threatens both mother and fetus. We used the Plasmodium coatneyi/rhesus monkey model to examine factors associated with this. Clinical and immunologic responses during the blood stage of chronic malaria (4 months) were evaluated in 8 malaria-naive primigravid (PMI) and 8 age-matched nulligravid (NMI) infected monkeys, compared with those in 8 primigravid, noninfected control monkeys. Although parasitemia levels were similar, recrudescence was more frequent and prolonged, and anemia was more severe in PMI than in NMI monkeys. During infection, CD2+, CD4+, and CD8+ lymphocyte levels were higher in NMI than in PMI monkeys. Monocyte and neutrophil levels were lower in PMI than in NMI monkeys. During chronic, untreated malaria, NMI monkeys had a B lymphocyte count 23 times greater than that of PMI monkeys. Pregnancy-induced immunomodulation, defined as a lack of appropriate cellular responses to malaria, was indiscernible until the immune system was challenged by a pathogen.

Hematologic and lymphocyte immunophenotypic reference values for normal rhesus monkey (Macaca mulatta) umbilical cord blood; gravidity may play a role in study design.

Hematology and flow cytometry reference values for rhesus umbilical cord blood (UCB) were established in 17 healthy infant rhesus monkeys delivered by elective cesarean section 10 days preterm. The infants were born to age matched, singly caged primigravid or secundigravid dams. The hematology and flow cytometry values were determined by automated cell counter and by FACS. No significant differences were observed with respect to infant gender. With respect to gravida, the primigravid infants had a significantly higher percentage (P= 0.05) of CD20(+) B lymphocytes in UCB. These results provide useful reference values for future studies of maternal - fetal disease transmission, vaccine and drug evaluation in non-human primate pregnancy, as well as fetal programming and immune modulation, gene therapy and the use of UCB as a source of stem cells for research and transplantation. Importantly, our results suggest that maternal gravidity may be an important variable to consider.

Antibody responses and protection from pyelonephritis following vaccination with purified Escherichia coli PapDG protein.

PURPOSE: A critical early step in the establishment of Escherichia coli pyelonephritis is bacterial attachment via the tip protein of P fimbriae. This adhesin, PapG, binds to glycolipid receptors present on vaginal and kidney epithelial surfaces. In this study we investigated the efficacy of vaccination with purified PapDG protein complex in preventing pyelonephritis caused by E. coli. MATERIALS AND METHODS: Mature cynomolgus monkeys were intraperitoneally vaccinated with 100 microg purified PapDG protein. Following 3 identical boosters serum antibody titers to PapDG were measured by enzyme-linked immunosorbent assay. Vaccinated and unvaccinated animals were urethrally inoculated with 1 x 10 cfu of E. coli strain DS17, which was isolated from a child with acute pyelonephritis. The infection course was monitored by catheterized urine cultures, and by histological examination of the kidneys, bladder and kidney tissue culture 28 days after infection. RESULTS: Intraperitoneal administration of purified PapDG vaccine resulted in the development of specific antibody responses in cynomolgus monkeys. In contrast to control monkeys, vaccinated monkeys did not show histological evidence of pyelonephritis after subsequent urethral challenge with pyelonephritogenic E. coli expressing P fimbriae. CONCLUSIONS: Purified PapDG is a tractable vaccine candidate that in our small study demonstrated the ability to elicit adequate serum antibody levels to prevent E. coli mediated pyelonephritis.

Choline acetyltransferase and acetylcholinesterase activities in neocortex and hippocampus of squirrel monkey (Saimiri sciureus).

The activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were measured in five neocortical regions and in the hippocampal formation of one hemisphere in eight 30-day-old squirrel monkeys. Enzyme levels in the hippocampal formation (hippocampus, dentate gyrus, and subiculum) were higher than in any neocortical region. Within neocortex, ChAT activity was highest in superior temporal and precentral regions, intermediate in prefrontal and postcentral regions, and lowest in occipital cortex. AChE activity also varied across neocortical regions and correlated significantly, but imprecisely, with ChAT activity. The activity of overall neocortical ChAT, but not AChE, differed significantly among animals. The pattern of cholinergic innervation of neocortex in the lissencephalic squirrel monkey is highly similar to that reported in gyrencephalic Old World primates.