Role of Antilipopolysaccharide Antibodies in Serum Bactericidal Activity against Salmonella enterica Serovar Typhimurium in Healthy Adults and Children in the United States

Recent observations from Africa have rekindled interest in the role of serum bactericidal antibodies in protecting against systemic infection with Salmonella enterica serovar Typhimurium. To determine whether the findings are applicable to other populations, we analyzed serum samples collected from healthy individuals in the United States. We found that all but 1 of the 49 adult samples tested had robust bactericidal activity against S. Typhimurium in a standard in vitro assay. The activity was dependent on complement and could be reproduced by immunoglobulin G (IgG) purified from the sera. The bactericidal activity was inhibited by competition with soluble lipopolysaccharide (LPS) from S. Typhimurium but not from Escherichia coli, consistent with recognition of a determinant in the O-antigen polysaccharide. Sera from healthy children aged 10 to 48 months also had bactericidal activity, although it was significantly less than in the adults, correlating with lower levels of LPS-specific IgM and IgG. The lone sample in our collection that lacked bactericidal activity was able to inhibit killing of S. Typhimurium by the other sera. The inhibition correlated with the presence of an LPS-specific IgM and was associated with decreased complement deposition on the bacterial surface. Our results indicate that healthy individuals can have circulating antibodies to LPS that either mediate or inhibit killing of S. Typhimurium. The findings contrast with the observations from Africa, which linked bactericidal activity to antibodies against an S. Typhimurium outer membrane protein and correlated the presence of inhibitory anti-LPS antibodies with human immunodeficiency virus infection.     

Fatal Hepatic Coma Complicating Oxymetholone Therapy in Multiple Myeloma

Fatal hepatic coma complicating oxymetholone therapy in multiple myeloma. G. P. Young, P. S. Bhathal, J. R. Sullivan, A. J. Wall, D. J. Fone and T. H. Hurley, Aust. N.Z. J. Med, 1977,7, pp. 47–51. Two patients with multiple myeloma died in acute liver failure. Both had been treated with the anabolic steroid oxymetholone and both subsequently developed severe cholestatic hepatitis. In one the histological lesion progressed despite cessation of oxymetholone therapy. Myeloma infiltration of the liver and peliosis hepatis were not seen. As a fatal outcome from cholestatic hepatitis due to oxymetholone is rare it is possible that an unknown potentiating factor is present in multiple myeloma that can lead to a fatal outcome. If oxymetholone therapy is to be used in such patients then close clinical and laboratory assessment of liver function should be carried out in an attempt to prevent this unusual and fatal complication.     

Human burst-forming units-erythroid need direct interaction with stem cell factor for further development

To understand the factors that regulate the early growth and development of immature erythroid progenitor cells, the burst-forming units-erythroid (BFU-E), it is necessary to have both highly purified target cells and a medium free of serum. When highly purified human blood BFU-E were cultured in a serum-free medium adequate for the growth of later erythroid progenitors, BFU-E would not grow even with the addition of recombinant human interleukin-3 (rIL-3), known to be essential for these cells. However, the addition of recombinant human stem cell factor (rSCF), which supports germ cell and pluripotential stem cell growth, stimulated BFU-E to grow equally well in serum-free as in serum-containing medium. Limiting dilution studies showed that rSCF acts directly on the BFU-E that do not require accessory cells for growth. Furthermore, rSCF was necessary for BFU-E development during the initial 7 days of culture, until these cells reached the stage of the late progenitors, the colony-forming units-erythroid (CFU-E). These studies indicate that early erythropoiesis is dependent on the direct action of SCF that not only affects early stem cells but is continually necessary for the further development of committed erythroid progenitor cells until the CFU-E stage of maturation.     

Antibody response to varicella-zoster virus after natural or vaccine-induced infection

The development of serum and nasopharyngeal antibody responses to varicella-zoster virus (VZV) was studied in groups of children after naturally acquired varicella or after immunization with the Oka strain of live attenuated VZV vaccine administered in varying doses via respiratory inhalation or subcutaneous injection. Natural infection, subcutaneous immunization, and respiratory inhalation of large doses of VZV vaccine consistently resulted in the development of VZV-specific IgG antibody responses in serum. Although the serum IgG antibody responses persisted for at least eight to 12 months (to date) after either form of infection, the antibody activity appeared to be four- to eight-fold higher after natural infection than after immunization. Transient IgG antibody responses were observed in serum after respiratory inhalation of smaller doses of VZV vaccine. Natural infection, but not VZV vaccine, was associated with the development of serum and nasopharyngeal IgA responses to VZV in most subjects.     

Hematopoietic stem cell donor registry strategies for assigning search determinants and matching relationships

Registries and cord blood banks around the world collect and store the HLA types of volunteers in order to identify matched unrelated donors for patients requiring hematopoietic stem cell transplantation. This task is complicated by the many formats in which HLA types are provided by the testing laboratories (types obtained by serology vs by DNA-based methods; high vs intermediate vs low resolution) and by the need to identify which of these diverse types are most likely to match the HLA assignments of a searching patient as closely as possible. Conversion of the assignments to 'search determinants' may be included within the algorithm used to select and prioritize a list of potentially suitable donors, either as an aid to matching or as a tool to optimize the performance of comparisons within large data files. The strategies used by registries to create search determinants are described. A set of search determinants, utilized by the National Marrow Donor Program, is provided as an example and is intended to initiate further discussion aimed at understanding the process used by each registry with the possibility of developing a standard process among registries worldwide.