In vivo anti-melanoma activities of the Melan-A/MART-1101–115 T CD4+ cell peptide

Malignant melanoma causes significant health problems. The identification of tumour-associated antigens has led to novel approaches to increase T cell mediated anti-tumour immune response. Melan-A/MART-1 has been use as target antigen for several T cell based immunotherapeutic treatments. More recently, the critical role of CD4+ T cells in inducing and maintaining anti-tumour immunity has been increasingly recognized. In order to optimize tumour immunotherapy, greater efforts have been concentrated on the identification of tumour antigens presented by MHC class II molecules to CD4+ T cells. In a publication, Tiwari et al. (2004) [1] have identified by a computational approach the 15-mer amino-acid sequence 101–115 (PPAYEKLSAEQSPPP) of the Melan-A/MART-1 as a good target for a vigorous and safe immunotherapy. Therefore, we have investigated the in vivo anti-tumour activity of this peptide in a murine melanoma model. For the prophylactic treatment, 20 μg or 50 μg peptide was subcutaneously injected in mice once a week during 3 weeks before tumour induction. Treatment with 50 μg peptide significantly affected tumour development. Thus, our preliminary data demonstrate potential in vivo prophylactic activity of the 101–115 peptide-based vaccine to control melanoma growth.     

Breast milk donors in France: a portrait of the typical donor and the utility of milk banking in the French breastfeeding context.

Although information regarding attitudes and characteristics of human blood donors has been researched, little is known about the motivations and demographic and personality characteristics of women who choose to donate their breast milk. Eight milk banks in France participated in a study examining donor characteristics, providing data on 103 women. The results showed that the donors were women of average childbearing age with strong support at home. Almost half did not work outside of the home, compared to the national average of 80% of women in this age group; similarly, a large number (currently working or not) were from the health and social services fields. Reasons for donation were largely altruistic, and a general optimistic attitude prevailed within the participants. The results of this study provide useful information for the recruitment of potential donors as well as information on how to facilitate and provide optimal service through milk donation.     

Contribution of molecular typing methods and antifungal susceptibility testing to the study of a candidemia cluster in a burn care unit.

We investigated a cluster of cases of Candida septicemia diagnosed in four burn patients. Twenty clinical isolates of Candida albicans and two of Candida parapsilosis, plus eight isolates of C. albicans recovered from nurses' clothes, were analyzed by antifungal susceptibility testing and three genotyping methods (restriction fragment length polymorphism analysis with EcoRI and HinfI, arbitrarily primed PCR, and karyotyping). The high MICs of the azoles for all of the C. albicans isolates tested suggest either a natural resistance of the endogenous flora or the transmission of isolates with acquired resistance. The genotyping methods demonstrated the involvement of four different strains, cross-infections with one C. albicans strain and one C. parapsilosis strain, and identity between some of the strains from the patients and nurses. The origins of the strains remain unclear. Our results show that the use of a combination of at least two different methods such as those used in the present study is recommended for C. albicans typing.     

The siderophore iron transporter of Candida albicans (Sit1p/Arn1p) mediates uptake of ferrichrome-type siderophores and is required for epithelial invasion

The human fungal pathogen Candida albicans contains a close homologue of yeast siderophore transporters, designated Sit1p/Arn1p. We have characterized the function of SIT1 in C. albicans by constructing sit1 deletion strains and testing their virulence and ability to utilize a range of siderophores and other iron complexes. sit1 mutant strains are defective in the uptake of ferrichrome-type siderophores including ferricrocin, ferrichrysin, ferrirubin, coprogen, and triacetylfusarinine C. A mutation of FTR1 did not impair the use of these siderophores but did affect the uptake of ferrioxamines E and B, as well as of ferric citrate, indicating that their utilization was independent of Sit1p. Hemin was a source of iron for both sit1 and ftr1 mutants, suggesting a pathway of hemin uptake distinct from that of siderophores and iron salts. Heterologous expression of SIT1 in the yeast Saccharomyces cerevisiae confirmed the function of Sit1p as a transporter for ferrichrome-type siderophores. The sit1 mutant was defective in infection of a reconstituted human epithelium as a model for human oral mucosa, while the SIT1 strain was invasive. In contrast, both sit1 and SIT1 strains were equally virulent in the mouse model of systemic infection. These results suggest that siderophore uptake by Sit1p/Arn1p is required in a specific process of C. albicans infection, namely epithelial invasion and penetration, while in the blood or within organs other sources of iron, including heme, may be used.     

Home chaos: sociodemographic, parenting, interactional, and child correlates.

We conducted 2 studies to (a) establish the usefulness of the construct of home chaos, (b) investigate its correlates, and (c) determine the validity of the Confusion, Hubbub, and Order Scale (CHAOS) used to measure the construct in each study. Study 1 relied on a sample of European American preschoolers and their mothers and Study 2 on a sample of African American school-age children and their caregivers. Home chaos was associated with less effective parental discipline; elevated behavior problems, limited attentional focusing, and reduced ability to understand and respond to social cues in children; and reduced accuracy and efficiency in a cooperative parent-child interactional task, after controlling for potential confounds. It is concluded that (a) home chaos is not a proxy for adverse social or psychological circumstances but a useful construct in its own right; (b) home chaos is associated with multiple detrimental correlates in parents and children; and (c) the CHAOS scale provides an adequate and economical measure of home confusion and disorganization that should prove useful in clinical research with diverse populations.     

Mast cell–derived IL-13 downregulates IL-12 production by skin dendritic cells to inhibit the TH1 cell response to cutaneous antigen exposure

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Nucleated erythrocytes in maternal blood: quantity and quality of fetal cells in enriched populations

The discovery of nucleated erythrocytes in maternal circulationprovides a potential source for non-invasive prenatal diagnosis.We have evaluated the use of a three-stage procedure to determinethe number of cells that are of fetal rather than maternal origin.First, monoclonal antibodies specific for CD45 and CD14 wereused in conjunction with a magnetic (MACS) column to depleteunwanted leukocytes from maternal blood. This was followed bya positive MACS enrichment for nucleated erythrocytes, usingan anti-CD71 (transferrin receptor) monoclonal antibody. Todiscriminate between fetal nucleated erythrocytes and thoseof maternal origin, enriched fractions were simultaneously stainedwith an anti-fetal haemoglobin (HbF) antibody and hybridizedwith probes specific for X and Y chromosomes. Samples were thensubjected to blind analysis along with negative control samplesfrom non-pregnant volunteers. Using this dual analysis, we wereable to determine that less than one nucleated erythrocyte perml of maternal blood was of fetal origin. Small numbers of thesefetal cells were found in 87.5% of pregnancies, ranging from6 to 35 weeks gestational age. Comparison of HbF and X/Y probedata also suggests that the fetal cells are less suitable forfluorescence in-situ hybridization (FISH) analysis than similarpreparations from other sources. cell separation methods/fluorescence in-situ hybridization/hereditary diseases/polymerase chain reaction/pregnancy     

Role of IgG and complement component C5 in the initial course of experimental cryptococcosis.

Although cellular immunity has a crucial role during cryptococcosis, several in vitro studies have pointed out the importance of IgG anti-Cryptococcus neoformans antibodies and complement components during phagocytosis of the yeast by polymorphonuclear leucocytes and monocytes. We investigated the role of complement and specific antibodies in host defences against experimental cryptococcosis, using a monoclonal IgG1 antibody (E1) specific for cryptococcal capsular polysaccharide, and mice congenitally sufficient or deficient in the fifth component of complement (C5). During in vitro experiments, E1 and the normal mouse serum from C5-sufficient and -deficient mice were unable to inhibit the growth of C.neoformans. However, E1 was an efficient opsonin for the ingestion of C. neoformans by mouse peritoneal macrophages, acting in synergy with normal mouse serum. In vivo, E1 was protective in heavily infected C5-deficient mice (DBA/2) dying from an early acute pneumonia, but not in C5-sufficient mice (BALB/c) and in DBA/2 mice infected with a smaller inoculum dying from a late progressive meningo-encephalitis. Although protection against pneumonia is attributed to a local recruitment of phagocytes in C5-sufficient mice, this was not observed in C5-deficient mice protected with E1. In this case, IgG anti-C. neoformans antibodies seem to be an alternative for an efficient opsonization of the yeasts. Altogether, these data suggest that two main mechanisms may protect infected mice from an early fatal pneumonia: the efficient opsonization of the yeast by complement and the recruitment of phagocytes in infected tissues.