28 research outputs found
Validation of an Immunoassay for anti-thymidine phosphorylase antibodies in patients with MNGIE treated with enzyme replacement therapy
Erythrocyte encapsulated thymidine phosphorylase is recombinant Escherichia coli thymidine phosphorylase encapsulated within human autologous erythrocytes and is under development as an enzyme replacement therapy for the ultra-rare inherited metabolic disorder mitochondrial neurogastrointestinal encephalomyopathy. This study describes the method validation of a two-step bridging electrochemiluminescence immunoassay for the detection of anti-thymidine phosphorylase antibodies in human serum according to current industry practice and regulatory guidelines. The analytical method was assessed for screening cut point, specificity, selectivity, precision, prozone effect, drug tolerance, and stability. Key findings were a correction factor of 129 relative light units for the cut-point determination; a specificity cut point of 93% inhibition; confirmed intra-assay and inter-assay precision; assay sensitivity of 356 ng/mL; no matrix or prozone effects up to 25,900 ng/mL; a drug tolerance of 156 ng/mL; and stability at room temperature for 24 hr and up to five freeze-thaws. Immunogenicity evaluations of serum from three patients who received erythrocyte encapsulated thymidine phosphorylase under a compassionate treatment program showed specific anti-thymidine phosphorylase antibodies in one patient. To conclude, a sensitive, specific, and selective immunoassay has been validated for the measurement of anti-thymidine phosphorylase antibodies; this will be utilized in a phase II pivotal clinical trial of erythrocyte encapsulated thymidine phosphorylase
PSY32 - CLAIMS-BASED ANALYSIS OF HOMOCYSTEINE TESTING, ELEVATED HOMOCYSTEINE LEVELS, AND HOMOCYSTINURIA DIAGNOSIS IN THE U.S.
PSY31 - COMPARISON OF THE ESTIMATED PREVALENCE OF DIAGNOSED HOMOCYSTINURIA AND PHENYLKETONURIA IN THE UNITED STATES
Amylase in Pecten maximus (mollusca, bivalve): protein and cDNA characterization
International audienc
Stable isotopic composition of Anguilliform leptocephali and other food web components from west of the Mascarene Plateau
Leptocephali are the poorly-understood transparent larvae of elopomorph fishes that live in the ocean surface layer throughout the world's tropical and subtropical oceans. Their feeding ecology has been difficult to understand because they appear to primarily feed on particulate organic material (POM), which contains few identifiable objects, and there have been few studies on their diets or trophic positions. This study presents the first comparative results on the stable isotope ratios of 7 families of leptocephali in relation to the ratios of 30 taxa of other marine animals and POM samples. The carbon and nitrogen stable isotope ratios were analyzed using 50 specimens of leptocephali, 354 specimens of mesozooplankton, cephalopods, fishes, and POM collected west of the Mascarene Plateau in the western Indian Ocean. Nitrogen and carbon isotopic ratio analyses indicated that the 12 taxa of DNA barcoded leptocephali (>= 15 species) could be separated into 2 groups of species with either higher (Group 1: 9 taxa of 7 families, 25-91 mm) or lower (Group 2: 3 taxa of 2 families, 43-275 mm) delta N-15 ranges. Group 2 exclusively included species that reach much larger sizes of >150-200 mm (Nemichthys and Avocettina, 3 species of Ariosoma-type), whereas Group 1 included Anguilla bicolor bicolor, Serrivomeridae, Muraenidae, Congridae (3 species), Chlopsidae, Ophichthidae (2 species), and Thalassenchelys. Differences in feeding depths, the types of POM ingested by preference or because of different jaw morphology, or the transport of larvae from other regions with different isotopic signatures are possible reasons for the differences between the two groups. The isotopic signatures of 14 taxa of copepods had higher but slightly overlapping delta N-15 and delta C-13 signatures compared to leptocephali and most crustaceans and other mezozooplankton, cephalopods and mesopelagic fish taxa had even higher values. The delta N-15 and delta C-13 signatures and composition of POM were variable spatially and with depth and may have been influenced by particulates originating from the shallow banks of the Mascarene Plateau. The two apparent isotopic groups of leptocephali should be examined in relation to their consumption of POM, which can include various proportions of prokaryotes, phytoplankton, protozoans, discarded appendicularian houses and other materials, by conducting further studies in different regions and using a variety of techniques