B-chronic lymphocytic leukemia cells and other B cells can produce granzyme B and gain cytotoxic potential after interleukin-21-based activation

B cells currently are not viewed as being capable of producing granzyme B or being cytotoxic. We found that B-chronic lymphocytic leukemia (B-CLL) cells treated with interleukin-21 (IL-21) produce low levels of granzyme B. The addition of either CpG oligodeoxynucleotide (ODN) or anti-B-cell-receptor antibody (anti-BCR) to IL-21 results in enhanced production of functional granzyme B by B-CLL cells. B-CLL cells treated with IL-21 and CpG ODN undergo apoptosis and are able to induce apoptosis of untreated bystander B-CLL cells. This effect can be inhibited by anti-granzyme B antibody. Benign human B cells, Epstein-Barr virus (EBV)-transformed lymphoblasts, and many standard lymphoma cell lines produce high levels of granzyme B in response to IL-21 and anti-BCR. Our results suggest that the ability to induce production of functional granzyme B by B cells could open new approaches to the therapy of B-CLL and other B-cell malignancies. Our findings also have significant implications for our understanding of the role of B cells for immune regulation and for a variety of immune phenomena, including cancer immunity, autoimmunity, and infectious immunity.     

Developing antenatal classes for women with HIV infection

As numbers of new HIV infections rise, innovative means of healthcare delivery for this patient group are being sought. This article describes the running of antenatal classes for pregnant women with HIV infection in a south-east London hospital, which aim to reduce mother-to-child HIV transmission. Led by a community-based clinical nurse specialist, the initiative adopts a multidisciplinary team approach.     

Calcium-pterin suppresses mitogen-induced tryptophan degradation and neopterin production in peripheral blood mononuclear cells

Antitumor activity of a calcium-pterin suspension has been described in vitro and in animal model systems. Recent studies provide some evidence that this effect involves immune-mediated mechanisms. We investigated the influence of calcium-pterin on freshly isolated human peripheral blood mononuclear cells (PBMC) stimulated with the mitogens phytohaemagglutinin and concanavalin A in vitro. Influence of calcium-pterin on tryptophan-degrading enzyme indoleamine (2,3)-dioxygenase (IDO) and on neopterin production was monitored in supernatants of cells. Increased neopterin concentrations as well as accelerated tryptophan degradation have been found to predict poor prognosis in patients with cancer, and both these immunobiochemical pathways are induced by the pro-inflammatory cytokine interferon-γ.

Compared to unstimulated cells, mitogens induced degradation of tryptophan and formation of neopterin in PBMC, and upon addition of calcium-pterin, both biochemical results were suppressed in a dose-dependent way. Thus, calcium-pterin suppresses immunological pathways in vitro that in patients with malignant diseases characterize an unfavorable prognosis. The effect of the compound to suppress IDO activity could be of considerable relevance for the antitumoral effect of the compound because activation of the enzyme is considered as an immune-escape mechanism of tumor cells.     

Neurolisteriosis mimicking herpes simplex encephalitis in an immunocompromized patient

Brain MRI was performed in an immunocompromized febrile and lethargic patient, revealing an asymmetric bilateral temporal lobe involvement, strongly suggestive of herpetic encephalitis. Nevertheless, PCR in CSF for Listeria monocytogens was positive. This case implies that Listeria might be considered in patients with clinical and imaging suspicion of herpetic encephalitis.     

Maternal serum concentrations of BDNF and depression in the perinatal period

There is accumulating evidence that a deficiency in brain-derived neurotrophic factor (BDNF) plays a critical role in the pathophysiology of depression. This is in line with the postulate that low BDNF levels in serum are associated with depression. However, the regulation of maternal BDNF serum levels in the perinatal period, and its relationship to maternal depression is unknown. In this study, serum BDNF concentrations were measured in 40 pregnant (follow-up: 30th and 37th week of gestation, 1 week and 8 weeks after childbirth) and 40 non-pregnant women (20-40 years old). The Edinburgh Postnatal Depression Scale (EPDS) was assessed in all subjects at all time points. Maternal serum levels of BDNF were markedly decreased, both before and after childbirth (median: <30% of non-pregnant controls). BDNF correlated with decreased Serotonin (5-HT) levels in serum (r>0.6 and p<0.001 at all time points). In contrast, there was no association with altered estrogen, progesterone, dehydroepiandrosterone or cortisol concentrations in serum. There were significantly higher cortisol levels in cases of maternal depression (EPDS scores>9 points) than in cases without depression. There was a trend to a decrease of BDNF and 5-HT levels in cases of maternal depression (as compared to cases without depression), but this was not significant. In conclusion, we demonstrate that women display markedly decreased BDNF serum levels before and after childbirth. This phenomenon might reflect an increased risk for the development of mood disorders in the perinatal period. However, the individual serum concentration of BDNF alone did not predict maternal depression in our study.     

Moderately increased alcohol consumption is associated with higher pressure wave reflections and blood pressure in men

Background and aimsIncreased alcohol consumption has been associated with CVD risk. Subclinical arterial damage (SAD) precedes the onset of cardiovascular disease (CVD), and allows early identification and study of the pathophysiology of CVD. Reliable, noninvasive vascular biomarkers are available for the early detection of SAD and reclassification of CVD risk. To investigate the association of alcohol consumption with multiple SAD biomarkers and central hemodynamics in a large sample of Greek adults with CVD risk factors.Methods and resultsThis cross-sectional study was conducted with 938 participants (43.5% men) and collected data on SAD biomarkers, central hemodynamics, and dietary intake. Multiple linear regression analysis was performed according to sex after adjusting for several confounders. In men, alcohol consumption of 20–30 g/d was positively associated with mean, diastolic, and peripheral systolic blood pressure (BP). The consumption of >30 g/d was positively associated with the augmentation index. In women, no statistically significant associations were found between alcohol consumption and BP or SAD indices. No statistically significant associations were found between alcohol consumption and arterial compliance or distensibility in both sexes.ConclusionIn men even a small deviation from the current recommendation for alcohol consumption is associated with both higher BP indices and pressure wave reflections. The absence of association in women might be due to very low alcohol intake, even in the high consumption group. More studies are needed to verify our findings and establish the above associations in each sex.     

First blood: the endothelial origins of hematopoietic progenitors

Angiogenesis - Hematopoiesis in vertebrate embryos occurs in temporally and spatially overlapping waves in close proximity to blood vascular endothelial cells. Initially, yolk sac hematopoiesis...     

Obesity Risk Assessment Tool for Low-Income Spanish Speaking Immigrant Parents with Young Children: Validity with BMI and Biomarkers of Obesity

Children of Hispanic origin bear a high risk of obesity. Child weight gain trajectories are influenced by the family environment, including parent feeding practices. Excessive body fat can result in unhealthful metabolic and lipid profiles and increased risk of metabolic diseases. The objective was to estimate criterion validity of an obesity risk assessment tool targeting Spanish-speaking families of Mexican origin using anthropometric measures and blood values of their young children. A cross-sectional study design with five data collection sessions was conducted over an eight-week period and involved 206 parent/child dyads recruited at Head Start and the Special Supplemental Nutrition Program for Women, Infants and Children in Northern California. Main outcome measures were criterion validity of Niños Sanos, a pediatric obesity risk assessment tool, using anthropometric measures and blood biomarkers. Niños Sanos scores were inversely related to child BMI-for-age percentiles (p = 0.02), waist-for-height ratios (p = 0.05) and inversely related to blood biomarkers for the metabolic index (p = 0.03) and lipid index (p = 0.05) and positively related to anti-inflammatory index (p = 0.047). Overall, children with higher Niños Sanos scores had more healthful lipid, metabolic and inflammatory profiles, as well as lower BMI-for-age percentiles and waist-to height ratios, providing evidence for the criterion validity of the tool. Niños Sanos can be used by child obesity researchers, by counselors and medical professionals during clinic visits as a screening tool and by educators as a tool to set goals for behavior change.