Between December 1996 and September 1998, 13 patients with advanced recurrent malignant brain tumors (9 with glioblastoma multiforme, 1 with gliosarcoma, and 3 with anaplastic astrocytoma) were treated with a single intratumoral injection of 2 x 10(9), 2 x 10(10), 2 x 10(11), or 2 x 10(12) vector particles (VP) of a replication-defective adenoviral vector bearing the herpes simplex virus thymidine kinase gene driven by the Rous sarcoma virus promoter (Adv.RSVtk), followed by ganciclovir (GCV) treatment. The VP to infectious unit ratio was 20:1. Our primary objective was to determine the safety of this treatment. Injection of Adv.RSVtk in doses <==2 x 10(11) VP, followed by GCV, was safely tolerated. Patients treated with the highest dose, 2 x 10(12) VP, exhibited central nervous system toxicity with confusion, hyponatremia, and seizures. One patient is living and stable 29.2 months after treatment. Two patients survived >25 months before succumbing to tumor progression. Ten patients died within 10 months of treatment, 9 from tumor progression and 1 with sepsis and endocarditis. Neuropathologic examination of postmortem tissue demonstrated cavitation at the injection site, intratumoral foci of coagulative necrosis, and variable infiltration of the residual tumor with macrophages and lymphocytes.

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Significant differences in the rates and patterns of discharge of GPe and GPi neurons exist in DYS and PD. The findings are discussed with reference to the current model of the functional connections of the basal ganglia.

The repair enzyme 8-oxoguanine glycosylase/ apyrimidinic/apurinic lyase (OGG) removes 8-hydroxy-2'deoxyguanosine (oh8dG) in human cells. Our goal was to examine oh8dG-removing activity in the cell nuclei of male C57BL/6 mouse brains treated with either forebrain ischemia-reperfusion (FblR) or sham operations. We found that the OGG activity in nuclear extracts, under the condition in which other nucleases did not destroy the oligodeoxynucleotide duplex, excised oh8dG with the greatest efficiency on the oligodeoxynucleotide duplex containing oh8dG/dC and with less efficiency on the heteroduplex containing oh8dG/dT, oh8dG/dG, or oh8dG/dA. This specificity was the same as for the recombinant type 1 OGG (OGG1) of humans. We observed that the OGG1 peptide and its activity in the mouse brain were significantly increased after 90 min of ischemia and 20-30 min of reperfusion. The increase in the protein level and in the activity of brain OGG1 correlated positively with the elevation of FblR-induced DNA lesions in an indicator gene (the c-fos gene) of the brain. The data suggest a possibility that the OGG1 protein may excise oh8dG in the mouse brain and that the activity of OGG1 may have a functional role in reducing oxidative gene damage in the brain after FblR.

To assess differences and trends in personal chemical exposure, volunteers from 14 communities in Africa (Senegal, South Africa), North America (United States (U.S.)) and South America (Peru) wore 262 silicone wristbands. We analysed wristband extracts for 1530 unique chemicals, resulting in 400 860 chemical data points. The number of chemical detections ranged from 4 to 43 per wristband, with 191 different chemicals detected, and 1339 chemicals were not detected in any wristband. No two wristbands had identical chemical detections. We detected 13 potential endocrine disrupting chemicals in over 50% of all wristbands and found 36 chemicals in common between chemicals detected in three geographical wristband groups (Africa, North America and South America). U.S. children (less than or equal to 11 years) had the highest percentage of flame retardant detections compared with all other participants. Wristbands worn in Texas post-Hurricane Harvey had the highest mean number of chemical detections (28) compared with other study locations (10–25). Consumer product-related chemicals and phthalates were a high percentage of chemical detections across all study locations (36–53% and 18–42%, respectively). Chemical exposures varied among individuals; however, many individuals were exposed to similar chemical mixtures. Our exploratory investigation uncovered personal chemical exposure trends that can help prioritize certain mixtures and chemical classes for future studies.