Regulation of phosphoribosylpyrophosphate synthetase by endogenous purine and pyrimidine compounds and synthetic analogs in normal and leukemic white blood cells

Phosphoribosylpyrophosphate (PRPP) is essential for the formation of both purine and pyrimidine nucleotides as well as for the active nucleotide form of some chemotherapeutic agents. The formation of PRPP is catalyzed by by enzyme PRPP synthetase, and many different compounds are known to affect the activity of this enzyme. This report examines the effects of endogenous purine and pyrimidine nucleotides, nucleosides, and several analogs of these compounds on the activity of PRPP synthetase from different types of normal and leukemic white blood cells (i.e. normal lymphocytes, normal granulocytes, phytohemagglutinin-stimulated lymphocytes, and acute and chronic leukemic cells). Our results show that the effect varied with each individual compound, and the magnitude of the effect was dependent on the source of the enzyme. Since it appears possible to differentially affect PRPP synthetase activity from the different types of leukemic cells, this enzyme may be a potential target site in the chemotherapy of leukemia.     

Benign cementoblastoma. Case report

Benign cementoblastoma is a rare benign odontogenic tumour of mesenchymal origin. A case of a 24-year-old man with benign cementoblastoma is presented. The lesion manifested as a round, radiopaque mass attached to the root of the left first molar of the mandible. The tooth was extracted and the lesion was removed. A diagnosis of benign cementoblastoma was made microscopically. There has been no evidence of recurrence during the three-year follow-up period. A review of the literature and a discussion of the histologic feature of this case are included.     

Comparison of the immunogenicity of the human papillomavirus (HPV)-16/18 vaccine and the HPV-6/11/16/18 vaccine for oncogenic non-vaccine types HPV-31 and HPV-45 in healthy women aged 18-45 years

Protection against oncogenic non-vaccine types (cross-protection) offered by human papillomavirus (HPV) vaccines may provide a significant medical benefit. Available clinical efficacy data suggest the two licensed vaccines (HPV-16/18 vaccine, GlaxoSmithKline Biologicals (GSK), and HPV-6/11/16/18 vaccine, Merck & Co., Inc.) differ in terms of protection against oncogenic non-vaccine HPV types -31/45. The immune responses induced by the two vaccines against these two non-vaccine HPV types (cross-reactivity) was compared in an observer-blind study up to Month 24 (18 mo post-vaccination), in women HPV DNA-negative and seronegative prior to vaccination for the HPV type analyzed (HPV-010 [NCT00423046]). Geometric mean antibody titers (GMTs) measured by pseudovirion-based neutralization assay (PBNA) and enzyme-linked immunosorbent assay (ELISA) were similar between vaccines for HPV-31/45. Seropositivity rates for HPV-31 were also similar between vaccines; however, there was a trend for higher seropositivity with the HPV-16/18 vaccine (13.0-16.7%) versus the HPV-6/11/16/18 vaccine (0.0-5.0%) for HPV-45 with PBNA, but not ELISA. HPV-31/45 cross-reactive memory B-cell responses were comparable between vaccines. Circulating antigen-specific CD4+ T-cell frequencies were higher for the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (HPV-31 [geometric mean ratio [GMR] =2.0; p=0.0002] and HPV-45 [GMR=2.6; p=0.0092]), as were the proportion of T-cell responders (HPV-31, p=0.0009; HPV-45, p=0.0793). In conclusion, immune response to oncogenic non-vaccine HPV types -31/45 was generally similar for both vaccines with the exception of T-cell response which was higher with the HPV-16/18 vaccine. Considering the differences in cross-protective efficacy between the two vaccines, the results might provide insights into the underlying mechanism(s) of protection.