Nursing Management of the Infant With a Congenital Malignancy

Care of the newborn diagnosed with a congenital malignancy is a challenge for the neonatal intensive-care unit nurse. Malignancies found in infants differ from those found in older children. Nursing care of the neonate suspected or diagnosed with a congenital malignancy includes standard practices and problem identification as well as interventions unique to the patient with cancer. This article reviews the incidence, diagnosis, treatment, and nursing management of neoplasms diagnosed in neonates.     

Direction and location of movement in kinesthetic judgements of extent

In unimanual kinesthetic judgements, larger ipsilateral extents felt equal to smaller contralateral ones. This was more likely to be due to a limb's general "intentional" tendencies towards its own ipsilateral hemispace than to e.g. differential attentional tendencies or the effects of muscular tension when crossing the midline. However hand asymmetries in this respect cannot account for the "pseudoneglect" phenomenon of setting the subjective midpoint of a felt rod slightly too far to the left. This phenomenon may instead be due to an asymmetric deployment of attentional and processing resources.     

High responsiveness of HLA-B57-restricted Gag-specific CD8+ T cells in vitro may contribute to the protective effect of HLA-B57 in HIV-infection

HLA-B57 has been shown to be associated with long-term asymptomatic HIV-1 infection. To investigate the biological mechanism by which the HLA-B57 allele could protect from HIV-1 disease, we studied both the number of CD8(+) T cells as well as CD8(+) T cell responsiveness directed to different HIV-1 Gag peptides presented by HLA-A2, -B8 or -B57. T cells specific for the HLA-B57 peptide KAFSPEVIPMF responded more readily and to a higher extend to antigenic stimulation in vitro than T cells specific for the HLA-A2 peptide SLYNTVATL or the HLA-B8 peptide EIYKRWII. This phenomenon was reproducible with T cells from individuals expressing HLA-B57 in combination with one or both of the other alleles and was persistent during long-term follow-up. Lower reactivity of A2- and B8-restricted T cells was not explained by mutations in the B8- or A2-restricted Gag-peptides. Moreover, no correlation between peptide mutation frequency and IFN-gamma production by the corresponding Gag-specific T cells was observed. In conclusion, functional differences were observed between T cells specific for HIV epitopes derived from the same protein presented by different HLA molecules. B57-restricted KAFSPEVIPMF-specific CD8(+) T cells have relatively high responsiveness, which could contribute to the protective effect of HLA-B57 in HIV infection.     

Use of turbidimetric growth curves for early determination of antifungal drug resistance of filamentous fungi

A previously described microbroth kinetic system (J. Meletiadis, J. F. Meis, J. W. Mouton, and P. E. Verweij, J. Clin. Microbiol. 39:478-484, 2001) based on continuous monitoring of changes in the optical density of fungal growth was used to describe turbidimetric growth curves of different filamentous fungi in the presence of increasing concentrations of antifungal drugs. Therefore, 24 clinical mold isolates, including Rhizopus oryzae, Aspergillus fumigatus, Aspergillus flavus, and Scedosporium prolificans, were tested against itraconazole, terbinafine, and amphotericin B according to NCCLS guidelines. Among various parameters of the growth curves, the duration of the lag phase was strongly affected by the presence of antifungal drugs. Exposure to increasing drug concentrations resulted in prolonged lag phases of the turbidimetric growth curves. The lag phases of the growth curves at drug concentrations which resulted in more than 50% growth (for itraconazole and terbinafine) and more than 75% growth (for amphotericin B) after 24 h of incubation for R. oryzae, 48 h for Aspergillus spp., and 72 h for S. prolificans were 4 h longer than the lag phases of the growth curves at the corresponding drug-free growth controls which varied from 4.4 h for R. oryzae, 6.5 h for A. flavus, 7.9 h for A. fumigatus, and 11.6 h for S. prolificans. The duration of the lag phases showed small experimental and interstrain variability, with differences of less than 2 h in most of the cases. Using this system, itraconazole and terbinafine resistance (presence of >50% growth) as well as amphotericin B resistance (presence of >75% growth) was determined within incubation periods of 5.0 to 7.7 h for R. oryzae (for amphotericin B resistance incubation for up to 12 h was required), 8.8 to 11.4 h for A. fumigatus, 6.7 to 8.5 h for A. flavus, and 13 to 15.6 h for S. prolificans while awaiting formal MIC determination by the NCCLS reference method.     

Dendritic cells pulsed with a recombinant chlamydial major outer membrane protein antigen elicit a CD4(+) type 2 rather than type 1 immune response that is not protective

Chlamydia trachomatis is an obligate intracellular bacterium that infects the oculogenital mucosae. C. trachomatis infection of the eye causes trachoma, the leading cause of preventable blindness. Infections of the genital mucosae are a leading cause of sexually transmitted diseases. A vaccine to prevent chlamydial infection is needed but has proven difficult to produce by using conventional vaccination approaches. Potent immunity to vaginal rechallenge in a murine model of chlamydial genital infection has been achieved only by infection or by immunization with dendritic cells (DC) pulsed ex vivo with whole inactivated organisms. Immunity generated by infection or ex vivo antigen-pulsed DC correlates with a chlamydia-specific interleukin 12 (IL-12)-dependent CD4(+) Th1 immune response. Because of the potent antichlamydial immunizing properties of DC, we hypothesized that DC could be a powerful vehicle for the delivery of individual chlamydial antigens that are thought to be targets for more conventional vaccine approaches. Here, we investigated the recombinant chlamydial major outer membrane protein (rMOMP) as a target antigen. The results demonstrate that DC pulsed with rMOMP secrete IL-12 and stimulate infection-sensitized CD4(+) T cells to proliferate and secrete gamma interferon. These immunological properties implied that rMOMP-pulsed DC would be potent inducers of MOMP-specific CD4(+) Th1 immunity in vivo; however, we observed the opposite result. DC pulsed ex vivo with rMOMP and adoptively transferred to naive mice generated a Th2 rather than a Th1 anti-MOMP immune response, and immunized mice were not protected following infectious challenge. We conclude from these studies that the immunological properties of ex vivo pulsed DC are not necessarily predictive of the immune response generated in vivo following adoptive transfer. These findings suggest that the nature of the antigen used to pulse DC ex vivo influences the Th1-Th2 balance of the immune response in vivo.     

New alleles in the B44 family including B*44022, B*44032, B*4411, B*4420, B*4421, B*4424, and B*8301

Seven new HLA-B locus alleles have been described. B*44022 and B*44032 are silent substitutions altering known alleles. B*4411 carries a unique Bw4-like epitope. B*4420, B*4421, and B*4424 carry new combinations of motifs previously observed in other alleles. B*8301 appears to be the result of the replacement of exon 2 from B*4402 with exon 2 from B*5603.     

Sequence variation within botulinum neurotoxin serotypes impacts antibody binding and neutralization

The botulinum neurotoxins (BoNTs) are category A biothreat agents which have been the focus of intensive efforts to develop vaccines and antibody-based prophylaxis and treatment. Such approaches must take into account the extensive BoNT sequence variability; the seven BoNT serotypes differ by up to 70% at the amino acid level. Here, we have analyzed 49 complete published sequences of BoNTs and show that all toxins also exhibit variability within serotypes ranging between 2.6 and 31.6%. To determine the impact of such sequence differences on immune recognition, we studied the binding and neutralization capacity of six BoNT serotype A (BoNT/A) monoclonal antibodies (MAbs) to BoNT/A1 and BoNT/A2, which differ by 10% at the amino acid level. While all six MAbs bound BoNT/A1 with high affinity, three of the six MAbs showed a marked reduction in binding affinity of 500- to more than 1,000-fold to BoNT/A2 toxin. Binding results predicted in vivo toxin neutralization; MAbs or MAb combinations that potently neutralized A1 toxin but did not bind A2 toxin had minimal neutralizing capacity for A2 toxin. This was most striking for a combination of three binding domain MAbs which together neutralized >40,000 mouse 50% lethal doses (LD(50)s) of A1 toxin but less than 500 LD(50)s of A2 toxin. Combining three MAbs which bound both A1 and A2 toxins potently neutralized both toxins. We conclude that sequence variability exists within all toxin serotypes, and this impacts monoclonal antibody binding and neutralization. Such subtype sequence variability must be accounted for when generating and evaluating diagnostic and therapeutic antibodies.     

Characterization of the antibody response to the receptor binding domain of botulinum neurotoxin serotypes A and E

Clostridium botulinum neurotoxins (BoNTs) are the most toxic proteins for humans. The current clostridial-derived vaccines against BoNT intoxication have limitations including production and accessibility. Conditions were established to express the soluble receptor binding domain (heavy-chain receptor [HCR]) of BoNT serotypes A and E in Escherichia coli. Sera isolated from mice and rabbits immunized with recombinant HCR/A1 (rHCR/A1) from the classical type A-Hall strain (ATCC 3502) (BoNT/A1) and rHCR/E from BoNT serotype E Beluga (BoNT/E(B)) neutralized the homologous serotype of BoNT but displayed differences in cross-recognition and cross-protection. Enzyme-linked immunosorbent assay and Western blotting showed that alpha-rHCR/A1 recognized epitopes within the C terminus of the HCR/A and HCR/E, while alpha-rHCR/E recognized epitopes within the N terminus or interface between the N and C termini of the HCR proteins. alpha-rHCR/E(B) sera possessed detectable neutralizing capacity for BoNT/A1, while alpha-rHCR/A1 did not neutralize BoNT/E. rHCR/A was an effective immunogen against BoNT/A1 and the Kyoto F infant strain (BoNT/A2), but not BoNT serotype E Alaska (BoNT/E(A)), while rHCR/E(B) neutralized BoNT/E(A), and under hyperimmunization conditions protected against BoNT/A1 and BoNT/A2. The protection elicited by rHCR/A1 to BoNT/A1 and BoNT/A2 and by rHCR/E(B) to BoNT/E(A) indicate that immunization with receptor binding domains elicit protection within sub-serotypes of BoNT. The protection elicited by hyperimmunization with rHCR/E against BoNT/A suggests the presence of common neutralizing epitopes between the serotypes E and A. These results show that a receptor binding domain subunit vaccine protects against serotype variants of BoNTs.