Identification of diagnostic evoked response potential segments in Alzheimer's disease.

Evoked response potentials (ERPs) to brief flashes of light were analyzed for constituent features that could be used to distinguish individuals with Alzheimer's disease (AD, n = 15) from matched control subjects (n = 17). Statistical k nearest-neighbor methods distinguished AD from control with a maximum sensitivity of 29% and false alarm rate of 12%. The comparable sensitivity/false-alarm values for a statistical projection pursuit method and an extended projection pursuit method, which selectively identify discriminative features for classification, were 75%/18% and 100%/6%, respectively.

Effect of penclomedine (NSC-338720) on telomere fusions, chromatin blebbing, and cell viability with and without telomerase activity and abrogated p53 function.

Telomeres, or chromosome ends, are essential in maintaining chromosomal integrity. Telomeres consist of a short hexameric sequence, 3'-TTAGGG-5', repeated in tandem arrays added to chromosomes by the ribonucleoprotein enzyme telomerase. In this study, we assessed whether penclomedine, a novel synthetic pyridine compound presently being evaluated in clinical trials for its anticancer activity, influences telomere fusions (chromosome end-to-end associations) and telomerase activity in cells in culture.

Biochemical pharmacology of penclomedine (NSC-338720).

Penclomedine (PEN) is a synthetic pyridine derivative that has been selected for clinical development based on its activity against human and mouse breast tumors implanted in mice. Its mechanism of action was unclear, and we were interested in determining its mechanism of cytotoxicity in vitro and in vivo. We found chromosome breaks, gaps, and exchanges in P388 ascites cells from BD2F1 mice treated with 200 mg/kg PEN.

Preclinical pharmacology of the natural marine product dolastatin 10 (NSC 376128).

The preclinical pharmacology and pharmacokinetics of the natural marine product dolastatin 10 were investigated. Pharmacokinetics of [3H]dolastatin 10 were determined in CD2F1 mice after intravenous, subcutaneous, and intraperitoneal routes of administration. After intravenous injection (0.

Degradation and inactivation of antitumor drugs.

Chemical methods for the degradation of 11 antineoplastic drugs [etoposide, teniposide, bleomycin, mitomycin C, cisplatin, cis-dichloro-trans-dihydroxy-bis(isopropylamine) platinum IV (CHIP), cyclophosphamide, ifosfamide, carmustine, lomustine, and methotrexate] were investigated. The success of the degradation procedures was assessed by HPLC and degree of biological inactivation by mutagenicity assays. The most widely applicable procedure was oxidation with potassium permanganate or 5.