David K. Manchester

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The authors briefly review the current potential and limitations of molecular epidemiology. This approach uses biomarkers to measure the internal and bioeffective dose of toxicants, early biologic effects likely to be predictive of cancer, and variations in individual susceptibility. The most frequent application of biomarkers has been in assessment of(More)
Mutations in the GLI3 zinc-finger transcription factor gene cause Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS), which are variable but distinct clinical entities. We hypothesized that GLI3 mutations that predict a truncated functional repressor protein cause PHS and that functional haploinsufficiency of GLI3 causes GCPS. To(More)
Germline mutations in the tumour suppressor gene PTEN have been implicated in two hamartoma syndromes that exhibit some clinical overlap, Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRR). PTEN maps to 10q23 and encodes a dual specificity phosphatase, a substrate of which is phosphatidylinositol 3,4,5-triphosphate, a phospholipid in the(More)
Vici syndrome is a recessively inherited multisystem disorder characterized by callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency and hypopigmentation. To investigate the molecular basis of Vici syndrome, we carried out exome and Sanger sequence analysis in a cohort of 18 affected individuals. We identified recessive mutations in EPG5(More)
Over the last two decades, the importance of executive functions in successful adaptive living has been increasingly recognized. Hence, investigation of executive functioning has become a core component of neuropsychological assessment. At present, correct identification is seen as crucial to ensuring adequate treatment, compensation and support. It is(More)
Industrialized regions in Poland are characterized by high ambient pollution, including polycyclic aromatic hydrocarbons (PAHs) from coal burning for industry and home heating. In experimental bioassays, certain PAHs are transplacental carcinogens and developmental toxicants. Biologic markers can facilitate evaluation of effects of environmental PAHs on the(More)
This study investigated the relationship in human placenta between polycyclic aromatic hydrocabon (PAH)-DNA adduct levels and two biomarkers of cytochrome P4501A1 (CYP1A1): gene induction evidenced by CYP1A1 mRNA, and a genetic polymorphism, the CYP1A1 MspI RFLP. CYP1A1 codes for an inducible enzyme system that catalyzes the bioactivation of PAHs. Prior(More)
Tobacco smoking and indoor smoky coal combustion emissions lead to exposures to complex environmental mixtures that have been associated with increased lung cancer mortality rates in the USA and Xuan Wei County, China, respectively. Human exposures to benzo[a[pyrene (BaP) present in smoky coal emissions are 20-200 times greater than exposure to BaP from(More)
The in vitro oxidation of 7-ethoxyresorufin was studied in placental microsomes from 47 full-term pregnancies. Placental activities were compared in four groups formed on the basis of maternal smoking history as follows: nonsmokers (n = 12), passive smokers (n = 16), 1 to 20 cigarettes/day (n = 13), and 20+ cigarettes/day (n = 5). Passive smoking was(More)
The dystrophin-based membrane cytoskeleton of muscle fibers has emerged as a critical multiprotein complex which seems to impart structural integrity on the muscle fiber plasma membrane. Deficiency of dystrophin causes the most common types of muscular dystrophy, Duchenne and Becker muscular dystrophies. Muscular dystrophy patients showing normal(More)