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.     

Regulatory role of interleukin-10 in experimental group B streptococcal arthritis

Intravenous inoculation of CD-1 mice with 10(7) CFU of type IV group B Streptococcus (GBS) results in a high incidence of diffuse septic arthritis, associated with high levels of systemic and local production of interleukin-1beta (IL-1beta) and IL-6. In this study, the role of the anti-inflammatory cytokine IL-10 in the evolution of GBS systemic infection and arthritis was evaluated. IL-10 production was evident in sera and joints of GBS-infected mice. Neutralization of endogenous IL-10 by administration of anti-IL-10 antibodies (1 mg/mouse) at the time of infection resulted in worsening of articular lesions and 60% mortality associated with early sustained production of IL-6, IL-1beta, and tumor necrosis factor alpha (TNF-alpha). The effect of IL-10 supplementation was assessed by administering IL-10 (100, 200, or 400 ng/mouse) once a day for 5 days, starting 1 h after infection. Treatment with IL-10 had a beneficial effect on GBS arthritis, and there was a clear-cut dose dependence. The decrease in pathology was associated with a significant reduction in IL-6, IL-1beta, and TNF-alpha production. Histological findings showed limited periarticular inflammation and a few-cell influx in the articular cavity of IL-10-treated mice, confirming clinical observations. In conclusion, this study provides further information concerning the role of IL-10 in regulating the immune response and inflammation and calls attention to the potential therapeutic use of IL-10 in GBS arthritis.     

Dependence of 2,3-DPG and oxygen affinity of haemoglobin on sex and pregnancy in the guinea-pig

Oxygen half-saturation of blood (P50), 2,3-diphosphoglycerate concentration (2,3-DPG) and Bohr effect were determined in male, and nonpregnant and pregnant female guinea pigs, according to a randomized block design. P50 was significantly higher in the female group (26.3 Torr plus or minus 0.22 SEM) than in the male group (24.8 Torr plus or minus 0.26 SEM) and was significantly lower in both these groups than in the pregnant group (27 Torr plus or minus 0.35 SEM). This difference in oxygen affinity was explained by differences in 2,3-DPG: 1.08 plus or minus 0.02 SEM in males, 1.24 plus or minus 0.03 in non-pregnant females and 1.34 plus or minus 0.03 mol/mol HB in pregnant females P50, 2,3-DPG and haemoglobin concentrations were significantly correlated for the ensemble of the 3 groups. There was no significant difference in Bohr effect between the 3 groups.     

Chromogranin A activates diverse pathways mediating inducible nitric oxide expression and apoptosis in primary microglia

Chromogranin A (CgA) is associated with microglial activation cascades implicated in neurodegeneration in Alzheimer's, Pick's and Parkinson's diseases. In primary rat microglia, CgA-mediated inducible nitric oxide (iNOS) expression, nitric oxide (NO) production, mitochondrial depolarisation and apoptosis were inhibited by PP2 (Src kinase inhibitor). CgA-mediated iNOS expression and NO production were also inhibited by U0126 (MEK inhibitor), but mitochondrial depolarisation and apoptosis were not. PP2 inhibited ERK phosphorylation; therefore, Src mediates CgA-induced ERK phosphorylation leading to iNOS expression and NO production. Glutamate release induced by CgA was independent of both pathways. These findings provide insights into the way microglia are activated by CgA and the microglial signalling mechanisms associated with neurological disorders such as Alzheimer's disease.     

Nocardia ignorata, a new agent of human nocardiosis isolated from respiratory specimens in Europe and soil samples from Kuwait

Nocardia ignorata is a recently described species identified on the basis of a single isolate of unknown origin. Here we describe the epidemiological, phenotypic, and phylogenetic characteristics of this new species, based on five new clinical and soil isolates.     

In Healthy Adults,Biological Activity of Vitamin D,as Assessed by Serum PTH,Is Largely Independent of DBP Concentrations

Vitamin D insufficiency, as measured by 25‐hydroxyvitamin D (25[OH]D) levels, has been associated with important health outcomes. The majority of vitamin D in circulation is bound to vitamin D–binding protein (DBP) and albumin, and recent genetic studies have demonstrated that serum DBP is a major determinant of 25(OH)D concentrations in adults. The impact of circulating DBP levels on vitamin D's biologic action, is unclear, but is of particular relevance to vitamin D epidemiology, because a lack of control for DBP levels could strongly influence the association of vitamin D with disease. Serum parathyroid hormone (PTH) levels can act as a biological readout of 25(OH)D activity. We therefore assessed the relationship between serum total and free 25(OH)D and PTH with and without adjusting for DBP, in 2073 subjects of European descent. Total 25(OH)D levels correlated positively (r = 0.19, p = 1.8 × 10^?17) with DBP, whereas the free 25(OH)D correlated negatively (r = ?0.14, p = 5.0 × 10^?12). Total and free 25(OH)D levels correlated negatively with PTH (r = ?0.29, p = 1.3 × 10^?39; r = ?0.26, p = 1.9 × 10^?33, respectively). Including age, body mass index (BMI), sex, estimated glomerular filtration rate, calcium, and season of blood draw as covariates, total 25(OH)D levels were significantly associated with log‐transformed PTH (lnPTH) levels (linear term: β = ?0.010, p < 0.0001, squared term: β = 0.00004, p < 0.0001) and this association was not changed by adjusting for DBP. These findings provide evidence that in a largely vitamin D–sufficient cohort, the biological effect of vitamin D on PTH levels is mainly independent of DBP concentration. Accordingly, this study may provide useful information for studies investigating the relationship between vitamin D, DBP, and disease. © 2014 American Society for Bone and Mineral Research.     

Prospectively measured 10-year changes in health-related quality of life and comparison with cross-sectional estimates in a population-based cohort of adult women and men

Purpose

To prospectively assess changes in health-related quality of life (HRQOL) over 10 years, by age and sex, and to compare measured within-person change to estimates of change based on cross-sectional data.

Methods

Participants in the Canadian Multicentre Osteoporosis Study completed the 36-item short form (SF-36) in 1995/1997 and 2005/2007. Mean within-person changes for domain and summary components were calculated for men and women separately, stratified by 10-year age groups. Projected changes based on published age- and sex-stratified cross-sectional data were also calculated. Mean differences between the two methods were then estimated, along with the 95 % credible intervals of the differences.

Results

Data were available for 5,569/9,423 (59.1 %) of the original cohort. Prospectively collected 10-year changes suggested that the four physically oriented domains declined in all but the youngest group of men and women, with declines in the elderly men exceeding 25 points. The four mentally oriented domains tended to improve over time, only showing substantial declines in vitality and role emotional in older women, and all four domains in older men. Cross-sectional estimates identified a similar pattern of change but with a smaller magnitude, particularly in men. Correspondence between the two methods was generally high.

Conclusions

Changes in HRQOL may be minimal over much of the life span, but physically oriented HRQOL can decline substantially after middle age. Although clinically relevant declines were more evident in prospectively collected data, differences in 10-year age increments of cross-sectional data may be a reasonable proxy for longitudinal changes, at least in those under 65 years of age. Results provide additional insight into the natural progression of HRQOL in the general population.     

Effects of water soaking and/or sodium polystyrene sulfonate addition on potassium content of foods

In this study, we determined, by atomic absorption spectrophotometry, the potassium amount leached by soaking or boiling foods identified by children suffering from chronic renal failure as “pleasure food” and that they cannot eat because of their low-potassium diet, and evaluated whether addition of sodium polystyrene sulfonate resin (i.e. Kayexalate®) during soaking or boiling modulated potassium loss. A significant amount of potassium content was removed by soaking (16% for chocolate and potato, 26% for apple, 37% for tomato and 41% for banana) or boiling in a large amount of water (73% for potato). Although Kayexalate® efficiently dose-dependently removed potassium from drinks (by 48% to 73%), resin addition during soaking or boiling did not eliminate more potassium from solid foods. Our results therefore provide useful information for dietitians who elaborate menus for people on potassium-restricted diets and would give an interesting alternative to the systematic elimination of all potassium-rich foods from their diet.     

Molecular characterization of yam virus X,a new potexvirus infecting yams (Dioscorea spp) and evidence for the existence of at least three distinct potexviruses infecting yams

The genome of yam virus X (YVX), a new member of the genus Potexvirus from yam (Dioscorea trifida), was completely sequenced. Structural and phylogenetic analysis showed that the closest relative of YVX is nerine virus X. A prevalence study found YVX only in plants maintained in Guadeloupe and showed that it also infects members of the complex D. cayenensis rotundata. This study provides evidence for the existence of two additional potexviruses, one of which infects D. nummularia in Vanuatu and the other, D. bulbifera and D. rotundata in Haiti and D. trifida and D. rotundata in Guadeloupe. This work also shows that existing potexvirus-specific degenerate primers targeting the ORF1-encoded polymerase domain are well suited for the identification of the three potexviruses reported here.