Search Results - (Author, Cooperation:C. D. James)

2011-08-20

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

*Aneuploidy ; Antigens, Nuclear/*genetics/*physiology ; Cell Cycle ; Cell Line ; Cell Line, Tumor ; Chromatids/physiology ; *Chromosomal Instability ; Chromosomes, Human, X/genetics ; Female ; Gene Deletion ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Gene Targeting ; Glioblastoma/*genetics ; Humans ; Karyotyping ; Male ; Melanoma/genetics ; Mutation ; Neoplasms/*genetics ; Polymorphism, Single Nucleotide ; Sarcoma, Ewing/genetics

2013-12-07

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

Animals ; Antineoplastic Agents/*therapeutic use ; Central Nervous System Neoplasms/*drug therapy/genetics ; DNA/genetics ; Drug Resistance, Neoplasm/*genetics ; Erlotinib Hydrochloride ; Glioblastoma/*drug therapy/genetics ; Humans ; Mice ; *Molecular Targeted Therapy ; Mutation ; Neoplasm Transplantation ; Protein Kinase Inhibitors/*therapeutic use ; Quinazolines/therapeutic use ; Receptor, Epidermal Growth Factor/antagonists & inhibitors/*genetics ; Single-Cell Analysis ; Tumor Cells, Cultured ; Withholding Treatment

2018-06-02

The American Association for Cancer Research (AACR)

1078-0432

1557-3265

Medicine

1365-2044

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Electronic Resource

1365-2044

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Electronic Resource

1365-2044

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Electronic Resource

1365-2044

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Aim : To assess the pharmacokinetics of alosetron, its effect on in vivo enzyme activities, and influence of demographic factors during repeated dosing.Methods : Thirty healthy men and women received 1 mg oral alosetron twice-daily for 29.5 days and a single oral dose of a metabolic probe cocktail before and on the last day of alosetron dosing. Serum alosetron concentrations were measured on days 1, 8, 15, 22 and 29. Probe-substrate and metabolite concentrations were measured after each cocktail dose.Results : Alosetron accumulation in serum was negligible. Exposure to alosetron did not alter probe-metabolite/substrate ratios associated with CYP2C19, 2E1, 2C9, or 3A4 activity, but modestly decreased those associated with CYP1A2 and N-acetyltransferase activity. Systemic exposure to alosetron was higher in women, positively correlated with age and body mass index, and negatively correlated with CYP1A2 activity. Incidence of constipation was higher in women, but not associated with alosetron concentration.Conclusions : Single dose data can reliably predict the pharmacokinetics of alosetron after repeated doses. Alosetron exhibits limited potential for inhibition of cytochrome P450-mediated metabolism. Interindividual differences in alosetron pharmacokinetics associated with demographic factors may be related to strong dependence on metabolism by CYP1A2.

Electronic Resource

1432-1939

Key words Biogeography ; Lizards ; Climate volume ; Regional diversity ; Sympatry

Springer Online Journal Archives 1860-2000

Biology

Abstract  Because Australian skinks of the genus Ctenotus display very high local species richness in arid-zone spinifex grasslands but not in mesic habitats, these lizards have been used as ”model organisms” to ask why ecologically similar taxa coexist under some circumstances but not others. Previous work has involved detailed studies within small areas, and has looked for differences in ecological processes between arid versus mesic habitats. We suggest a radically different explanation for the high species-richness of arid-zone Ctenotus, by shifting attention to a larger spatial scale: the regional species pool. Analyses of the geographic distributions of Ctenotus species confirm that more species coexist at sites in the arid-zone (mean =9.3 species per site) than in other climatic zones (means 2.4–7.6). However, the total number of species occurring within the arid-zone is actually lower, per km2 of habitat, than is the case in some other climatic zones. That is, arid-zone Ctenotus show a higher local (alpha) species diversity, but a lower regional (gamma) diversity, than their mesic-habitat congeners. This apparent paradox occurs because most arid-zone species occur over vast areas (mean =1,035,000 km2), whereas congeners from other climatic zones have smaller geographic ranges (200–373,000 km2). The broad distributions of arid-zone taxa reflect the great spatial homogeneity in climatic conditions in this zone. That is, the ”climate spaces” occupied are similar for Ctenotus species from all bioclimatic regions. Thus, a given amount of climatic space translates into a larger geographic distribution (and hence, more sympatry) in the arid-zone than in other areas. In summary, the high number of coexisting Ctenotus species in arid-zone habitats may simply reflect the facts that the arid zone is large (so that many species have evolved therein) and climatically homogeneous (so that any species evolving in that habitat type can disperse very widely, and thus overlap with many other species). Our approach explains much of the variance in local-assemblage species richness from regional to site scales; but explanations invoking biological attributes of the species concerned, the nature of their interactions with other species or with particular resources (such as prey or shelter) may still be significant at microhabitat scales. For lizard communities in Australia, species richness at a site may be determined more by continental biogeography rather than by ecological interactions.

Electronic Resource