BACKGROUND: Blood group antigens are physiologically important differentiation markers in embryogenesis and development. Monoclonal antibody (MoAb) B2 recognizes a transient antigen expressed on late sympathoadrenal neuroendocrine precursors and early sympathetic neuroblasts. It has been suggested that MoAb B2 may recognize a globo-series glycosphingolipid (GSL) related to the P blood group family.STUDY DESIGN AND METHODS: MoAb B2 and two anti-LKE MoAbs, MC813-70 and RM1, were screened against a panel of GSL standards and isolated red blood cell (RBC) GSLs by high-performance thin layer chromatography (HPTLC) immunostaining. The ability of all three MoAbs to bind intact RBCs and two LKE+ renal cell carcinoma cell lines (A498, ACHN) were examined by flow cytometry and hemagglutination.RESULTS: MoAbs B2, MC813-70, and RM1 all specifically recognized monosialogalactosylgloboside (MSGG) on HPTLC immunostaining. Only MoAb MC813-70 bound intact RBC by flow cytometry and hemagglutination. Differential staining was observed between the three antibodies and two renal cell carcinoma cell lines.CONCLUSION: MoAb B2 recognizes MSGG or LKE antigen, suggesting that LKE may play a role in neuroendocrine differentiation from neural crest cells. Although MoAb B2 is not suitable for RBC phenotyping, it may be a useful immunologic reagent for the identification of human embryonic stem cells and renal cell and embryonic carcinoma.

Objective. Oral mucositis (OM) is a common toxicity of ionizing radiation (IR), which is used as treatment for head and neck cancer. Ceramide-mediated apoptosis may contribute to the pathogenesis of mucositis. In response to IR or other cellular stresses, ceramide production occurs either by the hydrolytic action of sphingomyelinase (SMase) or de novo via ceramide synthase.Study design. Male golden Syrian hamsters (10 per group) exposed to a single dose of 40 Gy ionizing radiation (day 0) were treated with subcutaneous 0.2 mL injections of either neutral SMase, acidic SMase, or ceramide synthase inhibitor (5 mmol/L glutathione, 5 mu mol/L desipramine, or 1 mu mol/L fumonisin B-1, respectively) from day -1 to day 16. A control group was treated with saline. Two blinded examiners assessed clinical OM development from day 6 to day 26. Two animals per group were killed on days 3, 10, and 16 for immunohistochemical detection of ceramide expression in both the epithelium and in the connective tissue.Results. The group exposed to fumonisin 131 exhibited a statistically significant reduction in mean daily weight gain, mean mucositis score, duration of mucositis, and expression of ceramide in the epithelium on day 3 as well as in the connective tissue on days 10 and 16 relative to control. Immunohistologic analysis also revealed significant differences in ceramide expression on days 3 and 16 for animals treated with glutathione in both the epithelial and connective tissue when compared to the control.Conclusions. These results suggest that IR triggers early de novo ceramide production and that inhibition of this process attenuates OM on a clinical level.

Platelets express ABH antigens, which can adversely effect platelet transfusion recovery and survival in ABH-incompatible recipients. To date, there has been no large, comprehensive study comparing specific donor factors with ABH expression on platelet membranes and glycoconjugates. We studied ABH expression in 166 group A apheresis platelet donors by flow cytometry, Western blotting, and thin layer chromatography relative to donor age, sex, A1/A2 subgroup, and Lewis phenotype. Overall, A antigen on platelet membranes, glycoproteins, and glycosphingolipids was linked to an A1 red blood cell (RBC) phenotype. Among A1 donors, platelet ABH varied significantly between donors (0%-87%). Intradonor variability, however, was minimal, suggesting that platelet ABH expression is a stable, donor-specific characteristic, with 5% of A1 donors typing as either ABH high- or low-expressers. Group A2 donors, in contrast, possessed a Bombay-like phenotype, lacking both A and H antigens. Unlike RBCs, ABH expression on platelets may be determined primarily by H-glycosyltransferase (FUT1) activity. Identification of A2 and A1 low expressers may increase the availability and selection of crossmatched and HLA-matched platelets. Platelets from group A2 may also be a superior product for patients undergoing A/O major mismatch allogeneic progenitor cell transplantation.

This study describes the extent of cross-resistance and interactions for selected inhibitors of human cytomegalovirus (HCMV) DNA synthesis and DNA processing. HCMV isolates resistant to the benzimidazole d-ribonucleoside viral DNA processing inhibitors TCRB and BDCRB were sensitive to BAY 38-4766, a non-nucleoside inhibitor of viral DNA processing. This indicates that these two drug types have distinct interactions with the products of HCMV genes UL56 and UL89 required for viral DNA cleavage and packaging. These virus isolates also were sensitive to ganciclovir (GCV) but slightly resistant to the l-benzimidazole ribonucleoside viral DNA synthesis inhibitor 1263W94. Virus resistant to 1263W94 remained sensitive to BDCRB, GCV, and BAY 38-4766. Examination of drug–drug interactions in cell culture assays measuring inhibition of HCMV replication revealed strong synergism for the combination of BDCRB with 1263W94, and for combinations of 1263W94 with cidofovir (CDV) and foscarnet (PFA), but not with GCV. Combinations of GCV with CDV and PFA were synergistic as well. The combination of GCV with 1263W94 showed additive antiviral interactions, whereas, a combination of BAY 38-4766 with GCV showed antagonism. Interaction of BDCRB with BAY 38-4766 showed a mixed pattern of synergy and antagonism. The antiviral synergy observed between GCV and PFA or CDV serves to validate clinical combination therapies for these drugs. Antagonism seen for BAY 38-4766 with GCV indicates that these two drugs are unlikely to be useful for combination therapies. Notably, 1263W94 demonstrated greater synergy in combination with PFA or CDV than did GCV, suggesting some promise for this benzimidazole l-riboside in such combination therapies.