Effect of the growth hormone-secreting tumor StW5 on pituitary and adrenal gland function in rats

A growth hormone-secreting tumor (StW5 was implanted into male rats and resulted in a tripling of adrenal weight concomitant with a 30% decrement in pituitary weight. Plasma concentrations of corticosterone in tumor-bearing (TB) rats were significantly elevated at rest or after ACTH injections or the stress of either anesthesia. The rise in plasma concentrations of corticosterone was due mainly to the large increment in adrenal size although a significant increase in adrenal responsiveness to ACTH was demonstrated in vitro. In addition, plasma corticosterone concentrations were higher in TB rats despite both a doubling of the blood volume and a 50% increase in liver capacity to metabolize corticosterone. Pituitary ACTH content was significantly lower in TB rats, but these pituitary glands could still release near-normal quantities of ACTH as shown both by in vitro incubations and adrenal corticosterone output following ether stress.     

Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons

Insulin appears in the developing mouse pancreas at embryonic day 12 (e12). Transgenic mice harboring three distinct hybrid genes utilizing insulin gene regulatory information first express the transgene product two days earlier, at e10, in a few cells of the pancreatic bud. Throughout development and postnatal life, all of the insulin-producing (beta) cells coexpress the hybrid insulin gene. In addition, islet cells containing glucagon, somatostatin, pancreatic polypeptide, and the neuronal enzyme tyrosine hydroxylase coexpress the transgene when they first arise. Similarly, coexpression of these normally distinct islet cell markers occurs during differentiation of the four endocrine cell types. The transgene product also appears transiently during embryogenesis in cells of the neural tube and in neural crest. The results suggest a common precursor for the endocrine cells of the pancreas. Moreover, they imply a relationship between neural and pancreatic endocrine tissue.     

The CD40 agonist antibody CP-870,893 enhances dendritic cell and B-cell activity and promotes anti-tumor efficacy in SCID-hu mice

CD40 is a member of the TNF family of receptors that has been shown to play a crucial role in enhancing dendritic cell activity and fostering anti-tumor immune responses. In this study, we demonstrate the in vitro properties and in vivo efficacious activity of the CD40 agonist antibody, CP-870,893. CP-870,893 is a fully human, IgG2 antibody that selectively interacts with CD40 at a site distinct from its ligand-binding region with a KD of 0.4?nM. It enhances the expression of MHC class II, CD54, CD86, and CD23 on human B cells in vitro. CP-870,893 also enhances dendritic cell activity as evidenced by cytokine secretion (IL-12, IL-23, IL-8), the upregulation of CD86 and CD83, and the ability to prime T cells to secrete IFNγ. In SCID-beige mice, a single parenteral injection of CP-870,893 was therapeutically effective against several CD40(pos) human tumors (B-cell lymphoma, breast, colon, and prostate) indicating direct effects on tumor cell survival and/or growth. When mice were co-implanted with human T cells and dendritic cells, the activity of CP-870,893 against CD40(pos) tumors increased, and efficacy was also observed against CD40(neg) and CD40(low) tumors demonstrating the ability of CP-870,893 to enhance anti-tumor immune function in vivo. These studies suggest that CP-870,893 has the potential to be efficacious against a wide range of tumor types through both direct and immune-mediated effects.     

Association of Leisure-Time Physical Activity to Cardiovascular Disease Prevalence in Relation to Smoking among Adult Nevadans

It is well known that cigarette smoking and physical activity have significant impacts on cardiovascular disease (CVD) mortality and morbidity. Meanwhile, it is of interest to understand whether physical activity protects against CVD for smokers in a similar manner as it does for non-smokers. The present study examined how leisure-time physical activity (LTPA) is associated with the prevalence of CVD in relation to smoking status among adult Nevadans, using data from the 2010 Nevada Behavioral Risk Factor Surveillance System. Of the 3,913 survey respondents, 8.5% self-reported that they had ever been diagnosed with CVD. People with a history of CVD were significantly less likely to engage in LTPA than those with no history of CVD (p < 0.05). After adjusting for common sociodemographic variables, it was revealed that people with CVD were twice more likely to not engage in LTPA than their counterparts independent of smoking status. Without taking LTPA into account, the odds of having CVD for current and former smokers was 1.87–2.25 times higher than the odds for non-smokers. Interestingly, however, if LTPA was accounted for, there was no significant difference in the odds of having CVD between current and non-smokers. These results indicate that LTPA is inversely associated with the prevalence of CVD independent of smoking status, and that regular physical activity may protect against CVD for smokers as well as for non-smokers. Physical activity, along with smoking cessation, should be promoted to better prevent and control CVD among smokers.     

Clonal integration increases performance of ramets of the fern Diplopterygium glaucum in an evergreen forest in southeastern China

Physiological integration is a major ecological advantage of clonal growth in angiosperms. Clonal growth is also common in pteridophytes, but almost no study has tested whether clonal integration increases performance in ramets of pteridophytes in natural populations. To test this hypothesis and also whether the positive effect of integration is greater on smaller ramets, we severed the connecting rhizomes of individual ramets of the common, understory fern Diplopterygium glaucum in an evergreen, broadleaf forest in southeastern China. In another experiment, we severed rhizomes around the edges of small plots each containing several ramets. After 19.5 weeks, survival was 100% in intact individual ramets but only 27% in severed ones. Among surviving ramets, final dry mass and lamina mass were also less in severed than in intact ramets, though stalk, rhizome, and root mass and maximum quantum yield of PSII (F_v/F_m) were not reduced. Individual ramets with fewer stalk nodes had lower dry mass but were not more affected by severing than ramets with more stalk nodes. Severance around the edge of plots did not significantly affect the combined final mass of the ramets within a plot. We conclude that clonal integration can have significant positive effects on both survival and growth of individual ramets of ferns in natural populations.     

ADCC Develops Over Time during Persistent Infection with Live-Attenuated SIV and Is Associated with Complete Protection against SIVmac251 Challenge

Live-attenuated strains of simian immunodeficiency virus (SIV) routinely confer apparent sterilizing immunity against pathogenic SIV challenge in rhesus macaques. Understanding the mechanisms of protection by live-attenuated SIV may provide important insights into the immune responses needed for protection against HIV-1. Here we investigated the development of antibodies that are functional against neutralization-resistant SIV challenge strains, and tested the hypothesis that these antibodies are associated with protection. In the absence of detectable neutralizing antibodies, Env-specific antibody-dependent cell-mediated cytotoxicity (ADCC) emerged by three weeks after inoculation with SIVΔnef, increased progressively over time, and was proportional to SIVΔnef replication. Persistent infection with SIVΔnef elicited significantly higher ADCC titers than immunization with a non-persistent SIV strain that is limited to a single cycle of infection. ADCC titers were higher against viruses matched to the vaccine strain in Env, but were measurable against viruses expressing heterologous Env proteins. In two separate experiments, which took advantage of either the strain-specificity or the time-dependent maturation of immunity to overcome complete protection against SIV_mac251 challenge, measures of ADCC activity were higher among the SIVΔnef-inoculated macaques that remained uninfected than among those that became infected. These observations show that features of the antibody response elicited by SIVΔnef are consistent with hallmarks of protection by live-attenuated SIV, and reveal an association between Env-specific antibodies that direct ADCC and apparent sterilizing protection by SIVΔnef.