PubMed Health⌕ Search

Biomedical subjects

C Dickey

Publications and source records attributed to C Dickey.

30 records · Page 2Linked to original sources

Cigarette smoking related polycyclic aromatic hydrocarbon-DNA adducts in peripheral mononuclear cells.

Studies on cigarette smoking related polycyclic aromatic hydrocarbon-DNA adducts in blood have produced conflicting results. To determine whether a subset of specific white blood cells is a useful marker for monitoring exposure to cigarette smoke, blood was obtained from 63 heavy smokers and 27 non-smokers. Adduct levels were determined by competitive enzyme-linked immunosorbent assay with a polyclonal antiserum recognizing benzo[a]pyrene and structurally related diolepoxide-DNA adducts. Analysis of the lymphocyte plus monocyte fraction from smokers indicated 70% had detectable adducts with a mean of 4.38 +/- 4.29 adducts/10(8) nucleotides, while in non-smokers the corresponding values were 22% and 1.35 +/- 0.78/10(8) (P < 0.001). Plasma cotinine levels differed significantly in smokers (286 +/- 90 micrograms/l) compared to non-smokers (4.4 +/- 3.3 micrograms/l) (P < 0.001). However, cotinine was not correlated with self-reported smoking history in these heavy smokers. Nor were DNA adducts in smokers correlated with cigarettes per day, pack-years and plasma cotinine, indicating large interindividual variation in DNA adduct formation. These data demonstrate lymphocytes plus monocytes from smokers have elevated levels of polycyclic aromatic hydrocarbon diolepoxide-DNA adduct levels compared to non-smokers.

Adult↗

Combination chemotherapy in disseminated melanoma and other solid tumors in adults.

Eighty-eight patients with disseminated melanoma and 22 patients with various other solid tumors were treated with combination chemotherapy consisting of DTIC, at a fixed dose, with either adriamycin, CCNU, or hydroxyurea, at several dosages. An objective response rate of 20% was observed in 84 evaluable melanoma patients. The addition of the other agents to DTIC did not provide enhanced antitumor activity. Combination chemotherapy increased toxicity. Encouraging objective responses were observed in patients with synovial sarcoma (4/7) and teratocarcinoma of the testis (1/1) treated with the combination of adriamycin and DTIC.

Clinical Trials as Topic↗

A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease.

Vaccinations with amyloid-beta peptide (A beta) can dramatically reduce amyloid deposition in a transgenic mouse model of Alzheimer's disease. To determine if the vaccinations had deleterious or beneficial functional consequences, we tested eight months of A beta vaccination in a different transgenic model for Alzheimer's disease in which mice develop learning deficits as amyloid accumulates. Here we show that vaccination with A beta protects transgenic mice from the learning and age-related memory deficits that normally occur in this mouse model for Alzheimer's disease. During testing for potential deleterious effects of the vaccine, all mice performed superbly on the radial-arm water-maze test of working memory. Later, at an age when untreated transgenic mice show memory deficits, the A beta-vaccinated transgenic mice showed cognitive performance superior to that of the control transgenic mice and, ultimately, performed as well as nontransgenic mice. The A beta-vaccinated mice also had a partial reduction in amyloid burden at the end of the study. This therapeutic approach may thus prevent and, possibly, treat Alzheimer's dementia.

Aging↗

Polycyclic aromatic hydrocarbon-DNA adducts in white blood cells and urinary 1-hydroxypyrene in foundry workers.

In an ongoing comprehensive evaluation of biological markers, workers in or near an iron foundry with varying exposure to polycyclic aromatic hydrocarbons (PAH) were analyzed for molecular response to this exposure. Exposure to benzo(a)pyrene, determined by personal monitors worn by the workers (2 to 60 ng/m3), was considerably lower than in a previous study at this foundry (< 50 to 200 ng/m3) (F.P. Perera et al., Cancer Res., 48: 2288-2291, 1988). Two biomarkers, 1-hydroxypyrene in urine measured by high-performance liquid chromatography with fluorescence detection (a measure of internal dose) and PAH-DNA adducts in WBC measured by immunoassay (a measure of biologically effective dose) were assessed to demonstrate their relationship to the lowest exposures yet analyzed in foundry workers. In addition, these markers were analyzed for dose response and interindividual variability. Cigarette smoking, but not age or charbroiled food, influenced the level of 1-hydroxypyrene but not PAH-DNA adducts. When workers were classified into three exposure categories (low, medium, and high), mean 1-hydroxypyrene levels were 2.7, 1.8, and 3.6 mumol/mol creatinine, respectively. Comparisons by analysis of variance showed a significant difference between the groups after controlling for smoking (P = 0.02), but a trend test using multivariate linear regression analysis was not significant (r = 0.27; P = 0.07). Substantial interindividual variation was demonstrated by the 19- to 20-fold range in the values within each of the three exposure groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗