It has been reported recently that granulocyte-colony stimulating factor (G-CSF) is degraded upon exposure to human neutrophil elastase (HNE), and this has a negative effect on the ability of the cytokine to promote the in vitro proliferation and maturation of CD34+ cells. This has important implications on the possible in vivo role of elastase in providing negative feedback to granulopoiesis by the direct antagonism of G-CSF. The cytokine used in that study was expressed in Escherichia coli [and was nonglycosylated (NG)], unlike the naturally occurring cytokine, which is an O-linked glycoprotein. As a Chinese hamster ovary-derived (glycosylated) cytokine is available, we compared the susceptibility of NG and glycosylated G-CSF to elastase degradation by incubating the cytokines with HNE and assessing its impact by sodium dodecyl sulfate gel electrophoresis and bioassay. We confirmed the ability of elastase to degrade NG G-CSF in a time- and concentration-dependent manner and found this was associated with a reduction in biological activity of the cytokine. Glycosylated G-CSF, however, was more resistant to elastase degradation, although prolonged exposure did lead to degradation and decreased biological activity. The significance of sugar residues on glycosylated G-CSF in providing protection against the effects of elastase was investigated using enzymatically deglycosylated G-CSF and a mutated form of the G-CSF molecule that was expressed in yeast but was NG. The possible role of HNE in serum-induced inactivation of NG G-CSF was also considered.
Objectives: The Baltic region, particularly Lithuania, was a politically vibrant area of Eastern Europe during the medieval and early modern period. To better understand the diet of Lithuanians during the late 14th to early 18th century, we examine stable carbon and nitrogen isotope ratios from bone and dentin samples from the site of Alytus. We investigate possible dietary differences based on sex, age, and religious practice, as well as dietary changes throughout an individual's lifetime, within the broader European milieu.Materials and methods: Stable carbon and nitrogen isotope analysis was conducted on bone (n = 35) and dentin (n = 38) collagen samples from a total of 39 individuals buried in the cemetery at Alytus (late 14th to early 18th centuries).Results: Results indicate individuals at Alytus consumed a C 3 terrestrial based diet. The δ 13 C and δ 15 N values are not significantly different between bone and dentin, and did not vary by sex.Discussion: The diet at Alytus was homogeneous between males and females and between tissue types. The lack of evidence indicating substantial consumption of fish is unexpected given widespread Catholic fasting practices and marine resource trade throughout Europe. Comparisons with other populations indicate that individuals from Alytus differ in diet from contemporaneous Polish-Lithuanian Commonwealth elites. Comparison of the diets of non-elite individuals in the Eastern Baltic region also reveals dietary variability.
K E Y W O R D SBaltic, collagen, dentin, paleodiet, stable isotope analysis
SUMMARYThe in-vivo clearance of Bordetella pertussis infections in murine models in naive mice and animals vaccinated with whole-cell vaccine is considered to be via a Th-1-dependent mechanism in which interleukin-12 (IL)-12 may play a prominent role. It has also been demonstrated clearly that the treatment of animals with macrophage-derived IL-12 administered with an acellular vaccine can increase the efficacy of this vaccine preparation to levels seen with the whole-cell vaccine. However, the effects of exogenously added IL-12 on immune responses in non-vaccinated B. pertussis -challenged mice remain unclear, with two studies giving contradictory findings. In this study we have treated mice with escalating doses of mIL-12 (0·1-10 m g/mouse) prior to challenge with B. pertussis (using an aerosol challenge model of infection). The ability of mice to clear infection was assessed in IL-12 treated and in phosphate buffered saline (PBS) control animals at days 6 and 13 post-challenge. Lymphoid cells were isolated from spleen and cell-mediated immune responses assessed at days 1, 6 and 13 post-challenge. In addition, the direct effects of high-dose IL-12 on challenged mice was assessed by checking natural killer (NK) activity from isolated lung and spleen lymphoid cells as well as interferon-g (IFN-g ) generation from isolated cells and serum at day 1 post-challenge. The results from this study show that bacterial colonization of the lungs is actually enhanced following treatment with high-dose IL-12. This is associated with impaired cellular immune responses. The mechanisms associated with the immunosuppressive effects of IL-12 are discussed.
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