Fluence response relationships for the induction of DNA damage in the skin of I \ -irradiali-«!Xiphophorus fish were obtained by quantitative gel electrophoresis of unlabeled DNA following extraction and treatment with an enzyme preparation that makes single strand breaks next to cyclobutane pyrimidine dimers. A buffer containing 7 M urea minimized the degradation of DNA during extraction and ...

BACKGROUND Treatment options that improve overall symptoms of irritable bowel syndrome with constipation (IBS-C) are lacking. AIM A prespecified further analysis to evaluate the efficacy and safety of linaclotide, a guanylate cyclase C agonist, in patients with IBS-C, based on efficacy parameters prespecified for European Medicines Agency (EMA) submission. METHODS Two randomised, double-bli...

The solvent extraction of Fe from aqueous chloride solution by bis-(2,4,4-trimethylpentyl) monothiophosphinic acid (Cyanex 302, H2A2) dissolved in kerosene has been investigated over a wide range of aqueous acidity as a function of phase contact time, concentrations of Fe, H and Cl in the aqueous phase, Cyanex 302 concentration in the organic phase and temperature. The equilibration time is 50 ...

Objective: To define the prevalence of auto antibodies (Ab) to different organs in young patients with type 1 diabetes (type 1DM). Methods: Ab to thyroid, celiac and adrenal disease was analyzed in 831 type 1 DM patients. Results: Hundred twenty-three (14.8%) had positive thyroid Ab. The risk of developing thyroid Ab was increased in girls (HR 2.3; 95% CI 1.6 3.2, p < 0.0001). Thirty-three (3.9...

Arp 302, a luminous infrared source (LIR = 4.2× 10 11 L⊙), consisting of two spiral galaxies (VV340A and VV340B) with nuclear separation of ∼ 40, has the highest CO luminosity known. Observations with the BIMA array at 5 ×7 resolution reveal that the CO emission is extended over 23.0 kpc in the edge-on spiral galaxy, VV340A, corresponding to 6.7× 10 M⊙ of H2. In the companion face-on galaxy, VV...

Angiogenesis is a critical step during tumor progression. Anti-angiogenic therapy has only provided modest benefits in delaying tumor progression despite its early promise in cancer treatment. It has been postulated that anti-angiogenic therapy may promote the emergence of a more aggressive cancer cell phenotype by generating increased tumor hypoxia-a well-recognized promoter of tumor progressi...

[This corrects the article on p. 302 in vol. 52.].

PURPOSE The objectives of this phase 1, first-in-human study were to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), safety, pharmacokinetics, and preliminary activity of the hypoxia-activated prodrug TH-302 in patients with advanced solid tumors. EXPERIMENTAL DESIGN TH-302 was administered intravenously over 30 to 60 minutes in two regimens: three times weekly dos...

Pancreatic ductal adenocarcinomas are desmoplastic and hypoxic, both of which are associated with poor prognosis. Hypoxia-activated prodrugs (HAPs) are specifically activated in hypoxic environments to release cytotoxic or cytostatic effectors. TH-302 is a HAP that is currently being evaluated in a Phase III clinical trial in pancreatic cancer. Using animal models, we show that tumor hypoxia ca...