Anti-Kell (aa 55-713) polyclonal antibody

Based on dissolution profiles of three model drugs on spray layered beads with the same percentage of Aquacoat(R) coating, it was concluded that in vitro dissolution of oral controlled-release formulations should be performed in both gastric and intestinal media for ionizable drugs. Ketoprofen tweak acid, pK(a) 4.8), nicardipine HCl (salt of weak organic base, pK(a) 8.6), and acetaminophen (very weak organic acid, pK(a) 9.7 not ionized at physiologic pH) provided different dissolution characteristics in enzyme-free simulated gastric fluid (pH 1.4) and enzyme-free simulated intestinal fluid (pH 7.4), indicating that the rate of drug release was pH dependent and related to drug ionization even though the solubility of the coating (ethylcellulose) is pH independent. In acidic media, ketoprofen release from the beads containing low-level coating (3%) was slower than that of nicardipine HCl, with the opposite holding true in basic media. Acetaminophen was released at approximately the same rate in both acidic and basic media. A comparison of drug release profiles for nicardipine HCl nude beads was also investigated among three different dissolution methods: USP dissolution apparatus I (basket method, 50 rpm), USP dissolution apparatus II (paddle method, 50 rpm), and USP dissolution apparatus III (Bio-Dis(R), Van-Kel Industries, 5 and 10 dpm). Release profiles obtained from all methods were similar, indicating that the three dissolution methods were comparable.

Background: The Kell blood group system consists of at least 21 antigens. KEL6(Js(a)) is a low-incidence antigen that has an antithetical relationship with the high-incidence KEL7(Js(b)) antigen. The molecular basis of KEL6 that appears in less than 1.0 percent of the general population, but in up to 19.5 percent of African Americans, was unknown. Study Design and Methods: Nineteen exons of the Kell gene (KEL) were amplified by polymerase chain reaction (PCR) assays of genomic DNA obtained from individuals with K:6,-7 [Js(a+b-)] phenotype. The PCR products were sequenced. A comparison was made of the sequence of the PCR products and the sequence of K:-6,7, the common phenotype. Results: KEL from individuals with the K:6,-7 phenotype had two base substitutions in exon 17. One was a missense mutation (T-to-C base substitution) at nucleotide (nt) 1910, which predicts an amino acid change from leucine to proline; the other was a silent substitution (A-to-C) at nt 2019. The T-to-C substitution eliminated a restriction site for Mnl I, whereas the A-to-C substitution eliminated a Dde I site, Analyses of exon 17 in seven unrelated persons with K:6,-7 phenotype by Mnl I and Dde I enzymes showed the expected presence of restriction fragment length polymorphisms. Conclusion: The base substitutions T-to-C at nt 1910 and A-to-G at nt 2019 are unique to KEL6. The predicted Leu-->Pro change may disrupt the alpha-helical structure and thus form the epitope for KEL6.