Optimal T-cell activation requires both an antigen-specific signal delivered through the T-cell receptor and a costimulatory signal which can be delivered through the CD28 molecule. CD28 costimulation induces the expression of multiple lymphokines, including interleukin 2 (IL-2). Because the c-Rel transcription factor bound to and activated the CD28 response element within the IL-2 promoter, we focused our study on the mechanism of CD28-mediated regulation of c-Rel in human peripheral blood T cells. We showed that CD28 costimulation accelerated the kinetics of nuclear translocation of c-Rel (and its phosphorylated form), p50 (NFKB1), and p65 (ReIA). The enhanced nuclear translocation of c-Rel correlated with the stimulation of IL-2 production and T-cell proliferation by several distinct anti-CD28 monoclonal antibodies. This is explained at least in part by the long-term downregulation of IKBax following CD28 signalling as opposed to phorbol myristate acetate alone. Furthermore, we showed that the c-Rel-containing CD28-responsive complex is enhanced by, but not specific to, CD28 costimulation. Our results indicate that c-Rel is one of the transcription factors targeted by CD28 signalling.Antigenic stimulation of T cells requires both recognition by the T-cell receptor (TCR) of the major histocompatibility complex-antigen complex and the interactions of other cell surface molecules (reviewed in reference 59). One such interaction occurs between the accessory molecule CD28 on T cells and its cognate ligands B7-1 (CD80/B7 [33]), B7-2 (2, 16), and B7-3 (BB-1 [7]) on antigen-presenting cells. The CD28 molecule (for reviews, see references 26, 34, and 48) is constitutively expressed as a 44-kDa homodimer which is present on 95% of CD4' T cells and on approximately 50 to 70% of CD8' T cells. Blocking CD28 function during T-cell activation with an antigen can drive the T cells into a long-lasting antigen-specific anergic state (18,53). Conversely, anergy induced by suboptimal stimulation of TCRs can be prevented by ligation of CD28 molecules with anti-CD28 monoclonal antibody (MAb) (23). The CD28 signalling pathway is distinct from the TCR-CD3 signalling pathway (26), as shown by the inability of the immunosuppressant cyclosporin A to block CD28 signalling (5, 27) while completely blocking TCR-CD3 signalling.CD28 signalling as mimicked by MAbs can cooperate with anti-CD2, anti-CD3, phytohemagglutinin (PHA), and phorbol myristate acetate (PMA) to upregulate T-cell responsiveness. It synergizes with these signals to induce proliferation of T cells and secretion of multiple lymphokines such as interleukin 1 (IL-1), IL-2, IL-3, IL-4, IL-5, gamma interferon (IFN--y), granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha (34, 55). The combination of anti-CD28 and anti-CD2 MAbs (but not anti-CD3) can both enhance and prolong IL-2 receptor at-chain (IL-2Ra) gene expression (8). Anti-CD28 MAb cooperates with anti-CD3 in the induction of the human immunodeficiency virus type 1 (HIV-1) long terminal repe...
Simultaneous sampling for airborne particulate matter was carried out at four Los Angeles locations for one year. A composite for the year at each site was extracted and analyzed for polynuclear aromatic hydrocarbons (PAH) and lead. The yields of total particulate mass, benzene solubles, lead, and coronene paralleled the estimated traffic densities at the four sites. A number of PAH, other than coronene, did not parallel traffic density. The PAH patterns, normalized to coronene, were similar for three sites and to a fair degree, resembled patterns for auto exhaust previously published. The fourth site had a distinctly different pattern, reflecting local sources of nonautomotive PAH. Absolute levels of PAH are much below those found before imposition of stationary source emission controls, but have not changed much further since the late 1950's.Polynuclear aromatic hydrocarbons (PAH) associated with airborne particles are believed to arise mainly as products of combustion (Badger, 1962). Their concentrations in the air may be high in areas where coal and fuel oil are used for space heating and power generation (Sawicki et al., 1962), but they are also observed in automobile exhaust (Hoffman and Wynder, 1962). Since no coal is used in Los Angeles and much of the heat and power are derived from natural gas, it was of interest to compare the atmospheric PAH patterns at several locations there with those in auto exhaust. PAH have been measured previously in Los Angeles and several other cities (Kotin et al., 1954;Sawicki et al., 1962). A current study was also of interest for comparison with the earlier work. A program of large-volume air sampling for carcinogenesis studies offered an opportunity for this comparison.
After extraction of benzene solubles from airborne particulate matter collected at four Los Angeles sites, a still larger fraction can be extracted with methanol. This contains mostly inorganic materials. Qualitative tests, Kjeldahl titration, 2,4-xylenol nitrate determination, and infrared spectra show it to be principally ammonium nitrate. This salt comprises approximately 10-15% of the total airborne particles in composite samples collected over the year 1971-72.
The area surrounding the Colorado Department of Transportation Materials Testing Laboratory in Denver was the subject of intense investigation, involving the collection of thousands of ground water, soil-gas, and indoor air samples in order to investigate indoor air impacts associated with a subsurface release of chlorinated solvents. The preremediation portion of that data set is analyzed and reduced in this work to ground water-to-indoor air attenuation factors (a gw ¼ the ratio of the measured indoor air concentration to the soil-gas concentration predicted to be in equilibrium with the local ground water concentration). The empirical a gw values for this site range from about 10 -6 to 10 -4 with an overall average of 3 3 10 -5 (lg/L indoor air)/(lg/L soil gas). The analysis of this data set highlights the need for a thorough data review and data screening when using large data sets to derive empirical relationships between subsurface concentrations and indoor air. More specifically, it is necessary to identify those parts of the data that contain a strong vapor intrusion pathway signal, which generally will require concentrations well above reported detection levels combined with spatial or temporal correlation of subsurface and indoor concentrations.
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