Cytokine-driven loss of plasmacytoid dendritic cell function in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of CD5(+)CD19(+) B cells in the peripheral blood, and in primary and secondary lymphoid organs. A major complication associated with CLL is severe recurrent infections, which are often fatal. Vulnerability to infection is due to a wide variety of immunological defects, yet the initiating events of immunodeficiency in CLL are unclear. Using CLL patient samples and a mouse model of CLL, we have discovered that plasmacytoid dendritic cells (pDCs), which underpin the activity of effector immune cells critical for anti-viral immunity and anti-tumor responses, are reduced in number and functionally impaired in progressive CLL. As a result, the levels of interferon alpha (IFNα) production, a cytokine critical for immunity, are markedly reduced. Lower pDC numbers with impaired IFNα production was due to the decreased expression of FMS-like tyrosine kinase 3 receptor (Flt3) and Toll-like receptor 9 (TLR9), respectively. Reduced Flt3 expression was reversed using inhibitors of TGF-ß and TNF, an effect correlating with a reduction in tumor load. Defects in pDC numbers and function offer new insight into mechanisms underpinning the profound immunodeficiency affecting CLL patients and provide a potentially novel avenue for restoring immunocompetency in CLL.

Linkages between common wheat yields and climate in Morocco (1982-2008).

In Morocco, wheat production shows a high inter-annual variability due to uncertain rainfall. In view of the importance of this resource to the country's economy, it is important to gain a better understanding of the natural large-scale climate oscillation governing this variability. In this study, we analyzed de-trended (1) time series of common wheat yields (1983-2008) from 11 agricultural provinces that account for 80% of national wheat production; (2) monthly rainfall and 10-day temperature from ten meteorological stations; (3) 10-day normalized difference vegetation index (NDVI) from the AVHRR sensor; (4) monthly atmospheric climate indices [North Atlantic Oscillation (NAO) and Scandinavian Pattern (SCA)] and monthly 500 hPa geopotentials fields; and (5) monthly sea surface temperature (SST) fields and indices (NIÑO3, Tropical North Atlantic and Tropical South Atlantic). The relationship between rainfall and temperature during tillering in early winter and grain filling in early spring and wheat yields already observed at the plot scale was also found to be significant at the provincial scale. The linkages between wheat yields and large scale climate have been analyzed for the first time over Morocco. In agreement with previous studies, results show a complex and competing influence of different climate phenomena. The NAO is found to be significantly related to yields during the early stage of wheat growth in December, whereas the SCA correlates with yields later in the season, in January and February. Interesting lagged correlations with higher lead time are also highlighted, with the leading modes of SST variability in the equatorial Atlantic during October (the "Atlantic Niño" mode) and in the North Atlantic (the "Atlantic tripole" mode) in February. Our conclusion is that regional climate indices and variables represent valuable information with which to increase lead time and skill regarding wheat yield predictions in Morocco.

Genetic polymorphism of KIR2DL4 (CD158d), a putative NK cell receptor for HLA-G, does not influence susceptibility to asthma.

Human leukocyte antigen (HLA)-G is upregulated on the bronchial epithelium of asthma patients and genetic polymorphism affecting expression of HLA-G has been reported to influence susceptibility to asthma. As the NK cell receptor KIR2DL4 has been reported to induce interferon gamma (IFNγ) secretion when ligated with HLA-G, we postulated that the 9A/10A genetic polymorphism of KIR2DL4 which influences receptor structure may influence susceptibility to asthma. KIR2DL4 genotypes were determined in two cohorts of children (n = 219 and n = 1356) in whom total serum IgE, allergen-specific IgE, atopy, bronchial reactivity and asthma symptoms had been studied between birth and 14 years. No reproducible associations with KIR2DL4 genotype were identified, leading us to conclude that the KIR2DL4 9A/10A polymorphism has no influence on susceptibility to asthma.

[Therapeutic management and survival of gastric adenocarcinoma in the province of Finistère between 1984 and 1989]. / Prise en charge thérapeutique et survie de l'adénocarcinome gastrique dans le département du Finistère entre 1984 et 1989.

OBJECTIVES: The aim of this study was to analyze the evolution of treatment regimens and survival rates of stomach adenocarcinoma recorded in the Finistère cancer registry from 1984 to 1989. METHODS: In a population of 838,627 inhabitants, 1,280 patients with a gastric cancer were registered; 1,164 patients (693 males and 471 females) had an adenocarcinoma. Survival rates were estimated by the actuarial method, and compared using the logrank test and the Cox model. RESULTS: Surgical resection was the main treatment for 661 patients (57%). The frequency of curative resection increased from 25% between 1984 and 1986 to 35% after 1986. Among the other patients, 39 (3%) were treated by chemotherapy and/or radiotherapy, and 53 patients (4%) by endoscopy alone; 253 patients had only symptomatic treatment. The survival rates of all patients were 43% at 1 year and 20% at 5 years. The median survival was 9.2 +/- 0.6 months. In patients with cancer managed surgically, the factors associated with a better prognosis were young age, long duration of symptoms before diagnosis, ulcerated macroscopic aspect, limited tumour extension and curative surgical resection. In other patients, 2 factors were associated a with better prognosis: the absence of metastases and an endoscopic palliative treatment. CONCLUSIONS: Surgical resection is the main treatment of gastric adenocarcinoma. Although the frequency of surgery increased, the prognosis of gastric adenocarcinoma did not improve within this 6-year period.