Radiation-induced cell death and dendritic cells: potential for cancer immunotherapy?

Dendritic cells are key orchestrators of the immune system. There is considerable interest in their use for treating cancer. Whether they initiate an effective cytotoxic response against antigen-bearing cells, or produce tolerance, depends on the context in which those antigens are presented. Ionising radiation, and the cell death it causes, has several properties that may facilitate such an effective response. A range of in-vitro and in-vivo data supports this, although potential problems exist that may require concurrent strategies.     

Genetic and behavioral aspects of pharmacologically induced arousal

Summary Previously reported studies have shown clear differences among strains of inbred mice in response to a variety of novel situations and to certain pharmacologic agents. The purpose of the present study was to test the tenability of the hypothesis that such behavioral differences between genetically distinct groups may be a function of arousal system differences. To achieve this objective while using a pharmacologic method, the investigators assumed: (1) that the state of arousal of the organism is isomorphic to the effects of certain depressant and excitatory drugs; and (2) that a direct relation exists between quantitative differences in overt behavior and the cumulative effects of the drug. Four drugs were selected which could produce measurable changes on an arousal continuum from sleep (pentobarbital), through quiescence (chlorpromazine) and alertness (amphetamine), to convulsions (pentylenetetrazol). Similarly, four strains of mice were selected which show related differences in normal activity: BALB/c, C3H/An, DBA/2, and C57BL/6.Although significant strain differences appeared in base-activity levels as well as in the responses to the standard doses of the drugs and of the placebo, only the responses to pentobarbital and amphetamine were entirely consistent with an arousal hypothesis. The duration of the effect of pentylenetetrazol was also consistent but the latency of that effect was not. At best, the effect of chlorpromazine was that of a mild stimulant, contrary to the justification for its inclusion in this study. Clearly the rigid adherence to any one theoretical orientation in the interpretation of strain-activity phenomena is premature.This research was supported by an AEC contract, No. AT (40-1)-2186, with Vanderbilt University, Nashville, Tenn.     

Contaminant Exposure and Reproductive Success of Ospreys (<Emphasis Type="Italic">Pandion haliaetus</Emphasis>) Nesting in Chesapeake Bay Regions of Concern

Abstract:The Chesapeake Bay osprey population has more than doubled in size since restrictions were placed on the production and use of DDT and other toxic organochlorine contaminants in the 1970s. Ospreys are now nesting in the most highly polluted portions of the Bay. In 2000 and 2001, contaminant exposure and reproduction were monitored in ospreys nesting in regions of concern, including Baltimore Harbor and the Patapsco River, the Anacostia and middle Potomac rivers, and the Elizabeth River, and a presumed reference site consisting of the South, West, and Rhode rivers. A sample egg from each study nest was collected for contaminant analysis, and the fate of eggs remaining in each nest (n = 14–16/site) was monitored at 7- to 10-day intervals from egg incubation through fledging of young. Ospreys fledged young in regions of concern (observed success: 0.88–1.53 fledglings/active nest), although productivity was marginal for sustaining local populations in Baltimore Harbor and the Patapsco River and in the Anacostia and middle Potomac rivers. Concentrations of p,p-DDE and many other organochlorine pesticides or metabolites, total PCBs, some arylhydrocarbon receptor-active PCB congeners and polybrominated diphenyl ether congeners, and perfluorooctanesulfonate were often greater in sample eggs from regions of concern compared to the reference site. Nonetheless, logistic regression analyses did not provide evidence linking marginal productivity to p,p-DDE, total PCBs, or arylhydrocarbon receptor-active PCB congener exposure in regions of concern. In view of the moderate concentrations of total PCBs in eggs from the reference site, concerns related to new and emerging toxicants, and the absence of ecotoxicological data for terrestrial vertebrates in many Bay tributaries, a more thorough spatial evaluation of contaminant exposure in ospreys throughout the Chesapeake may be warranted.     

Folic acid reduces nuclear translocation of beta-catenin in rectal mucosal crypts of patients with colorectal adenomas

We have demonstrated that folic acid inhibits cell proliferation and epidermal growth factor receptor (EGFR) activation in colon cancer cell lines. We examined the effect of one year supplemental folic acid (5 mg/day) on the rectal mucosal expression of beta-catenin and pGSK3beta, known to be affected by EGF-R, in patients with colorectal adenomas. Folic acid treatment significantly reduced nuclear expression of beta-catenin (P < 0.05) and cellular expression of pGSK3beta (P < 0.01) when compared to placebo. Folic acid may exert its chemopreventive effect, at least in part, through inhibition of nuclear translocation of beta-catenin.     

Use of RT-PCR and DNA microarrays to characterize RNA recovered by non-invasive tape harvesting of normal and inflamed skin

We describe a non-invasive approach for recovering RNA from the surface of skin via a simple tape stripping procedure that permits a direct quantitative and qualitative assessment of pathologic and physiologic biomarkers. Using semi-quantitative RT-PCR we show that tape-harvested RNA is comparable in quality and utility to RNA recovered by biopsy. It is likely that tape-harvested RNA is derived from epidermal cells residing close to the surface and includes adnexal structures and present data showing that tape and biopsy likely recover different cell populations. We report the successful amplification of tape-harvested RNA for hybridization to DNA microarrays. These experiments showed no significant gene expression level differences between replicate sites on a subject and minimal differences between a male and female subject. We also compared the array generated RNA profiles between normal and 24 h 1% SLS-occluded skin and observed that SLS treatment resulted in statistically significant changes in the expression levels of more than 1,700 genes. These data establish the utility of tape harvesting as a non-invasive method for capturing RNA from human skin and support the hypothesis that tape harvesting is an efficient method for sampling the epidermis and identifying select differentially regulated epidermal biomarkers.     

Aging,physical activity,and cognitive processing: an examination of P300

Physical activity appears to attenuate the decline of cognitive function typically observed in older men and women. The P300 component of the event-related potential (ERP) is particularly affected by aging and allows for basic neurobiological assessment of cognitive function. Three aspects of the P300 component (i.e. latency, amplitude, and area under the curve (AUC)), elicited by an oddball task, were derived to assess cognitive function in young and older participants (N=73) who were further classified as high- and low-active. The low-active elderly participants exhibited larger AUC values than those observed in all other groups which were undifferentiated. That is, the high-active elderly and the young participants exhibited smaller AUC values than the low-active older group. In conclusion, higher levels of physical activity in the elderly may be associated with a reduction in the neural resources allocated in response to simple cognitive challenge. This interpretation is consistent with the concept of psychomotor efficiency proposed by Hatfield and Hillman [The psychophysiology of sport: a mechanistic understanding of the psychology of superior performance. In: Singer RN, Hausenbias HA, Janelle CM, editors. Handbook of sport psychology. 2nd ed. New York: Wiley; 2001, p. 362-88].