Carfilzomib [(2S)-N-[(S)-1-[(S)-4-methyl-1-[(R)-2-methyloxiran-2-yl]-1-oxopentan-2-ylcarbamoyl]-2-phenylethyl]-2-[(S)-2-(2-morpholinoacetamido)-4-phenylbutanamido]-4-methylpentanamide, also known as PR-171] is a selective, irreversible proteasome inhibitor that has shown encouraging results in clinical trials in multiple myeloma. In this study, the pharmacokinetics, pharmacodynamics, metabolism...

Division of Molecular Toxicology (R.A.M., M.O., M.I.-S.) and Unit of Genetic Toxicology (A.-K.A., A.R.), Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden, National Institute for Working Life, 171 84 Solna, Sweden (A.-K.A., A.R.), The Wallenberg Laboratory and Astra Draco AB, 221 00 Lund, Sweden (J.S.), and C 123 Riyadh Armed Forces Hospital, Riyadh 11159, Kin...

From the ‡Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, the §Department of Medicine, Karolinska Institute, 171 77 Stockholm, Sweden, the ¶Department of Microbiology and Immunology, Stanford University, Stanford, California 94305, ‡‡Swedish Institute for Infectious Disease Control, 171 82 Solna, Sweden, and §§AstraZeneca Re...

Adaptive Mutation: How Growth under Selection Stimulates Lac Reversion by Increasing Target Copy Number John R. Roth* and Dan I. Andersson Microbiology Section, University of California, Davis, Davis, California 95616, and Department of Bacteriology, Swedish Institute for Infectious Disease Control, S-171 82 Solna, and Microbiology and Tumour Biology Center, Karolinska Institute, S-171 77, Soln...

Primary clinical features Retinitis pigmentosa (rod-cone dystrophy) Obesity Polydactyly Hypogonadism Intellectual disability/cognitive impairment Renal abnormalities Secondary clinical features Diabetes mellitus type II Cardiovascular problems Hearing loss Speech deficiency Behavioral problems Craniofacial dysmorphism Short stature Hepatic involvement Eye abnormalities Ataxia Dental and palatal...

PURPOSE Patients with adult acute myeloid leukemia (AML) with intermediate cytogenetics remain a heterogeneous group with highly variable individual prognoses. New molecular markers could help to refine cytogenetic stratification. EXPERIMENTAL DESIGN We assessed P-glycoprotein (Pgp) activity and Flt3 internal tandem duplication (ITD+) because of their known prognostic value and because they m...