Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2,3 dioxygenase

Murine dendritic cells (DCs) expressing indoleamine 2,3 dioxygenase (IDO) catabolize tryptophan and can suppress T cell responses elicited in vivo. Here, we identify specific subsets of splenic (CD11c+) dendritic cells competent to mediate IDO-dependent T cell suppression following CTLA4-mediated ligation of B7 molecules. IDO-competent DC subsets acquired potent and dominant T cell suppressive properties as a consequence of IDO up-regulation, as they blocked the ability of T cells to respond to other stimulatory DCs in the same cultures. Soluble CTLA4 (CTLA4-Ig) and cloned CTLA4+ regulatory T cells (Tr1D1) up-regulated IDO selectively in DC subsets co-expressing B220 or CD8alpha. The ability of Tr1D1 T cells to suppress CD8+ T cell responses was completely dependent on their ability to induce tryptophan catabolism in DCs. Selective IDO up-regulation in DCs did not inhibit T cell activation, but prevented T cell clonal expansion due to rapid death of activated T cells. T cell responses were restored by genetic or pharmacologic inhibition of IDO enzyme activity, or by adding excess tryptophan. DCs from interferon gamma (IFNgamma)-receptor-deficient mice were effective in promoting IDO-dependent T cell suppression following CTLA4-Ig exposure in vivo, indicating that IFNgamma signaling was not necessary for IDO up-regulation in this model. These findings suggest that IDO-competent DCs provide a regulatory bridge, mediated by CTLA4-B7 engagement, between certain regulatory T cell subsets and naive responder T cells.     

The prevalence of Echinococcus granulosus in stray dogs in Iraq.

The present paper records the prevalence of Echinococcus granulosus in stray dogs of Al-Tamim (northern Iraq), Diala (mid Iraq) and Theqar province (southern Iraq), where many people are infected with hydatid disease. Of 150 dogs examined in three provinces in Iraq, 57 (38%) were infected with E. granulosus. The prevalence of the worm was higher in the dogs of Theqar province (56%) than in those of Al-Tamim (20%) and Diala Provinces (38%). Infections were light (1-200 worms) in eight (14%) of the infected dogs, medium (201-1000 worms) in 14 (24.6%) and high (over 1000 worms) in 35 (61.4%). The mean worm burden was 1844 and the maximum number of worms was 15,182 recorded in a male dog from Theqar province. The reasons for such a high rate of infection in the dogs are discussed.     

Mitochondrial complex I and NAD(P)H oxidase are major sources of exacerbated oxidative stress in pressure-overloaded ischemic-reperfused hearts

We tested the hypothesis that pressure overload exacerbates oxidative stress associated with augmented mitochondrial permeability transition (MPT) pore opening and cell death in ischemic-reperfused hearts. Pressure overload decreased the level of reduced glutathione but increased nitrotyrosine and 8-hydroxydeoxyguanosine levels in ischemic-reperfused hearts. The activity of catalase, but not superoxide dismutase (SOD), was lower in ischemic-reperfused hearts perfused at higher pressure. Mitochondria from ischemic-reperfused hearts subjected to higher perfusion pressure displayed significantly greater [³H]-2-deoxyglucose-6-P entrapment suggestive of greater MPT pore opening and consistent with greater necrosis and apoptosis. Tempol (SOD mimetic) reduced infarct size in both groups but it remained greater in the higher pressure group. By contrast, uric acid (peroxynitrite scavenger) markedly reduced infarct size at higher pressure, effectively eliminating the differential between the two groups. Inhibition of xanthine oxidase, with allopurinol, reduced infarct size but did not eliminate the differential between the two groups. However, amobarbital (inhibitor of mitochondrial complex I) or apocynin [inhibitor of NAD(P)H oxidase] reduced infarct size at both pressures and also abrogated the differential between the two groups. Consistent with the effect of apocynin, pressure-overloaded hearts displayed significantly higher NAD(P)H oxidase activity. Furthermore, pressure-overloaded hearts displayed increased nitric oxide synthase activity which, along with increased propensity to superoxide generation, may underlie uric acid-induced cardioprotection. In conclusion, increased oxidative and nitrosative stress, coupled with lack of augmented SOD and catalase activities, contributes importantly to the exacerbating impact of pressure overload on MPT pore opening and cell death in ischemic-reperfused hearts.     

Low levels of breast cancer risk awareness in young women: an international survey

At least a fifth of breast cancer cases in Western countries are likely to be due to modifiable lifestyle factors. Previous work has found that while women in Western countries are aware that breast cancer can be hereditary, their knowledge of the influence of lifestyle is poor. This survey investigated on the awareness of breast cancer risk factors in university students from 23 countries between 1999 and 2001. Data were collected on awareness of links with heredity, alcohol use, exercise, obesity, stress, smoking and diet. Almost a third of women were not aware that any of these factors influenced breast cancer. Just 57% were aware of the genetic link and fewer than 1 in 20 women correctly identified alcohol, exercise or obesity as factors influencing breast cancer. Stress and smoking were the most commonly chosen lifestyle risk factors although current data suggest that they have little actual impact on breast cancer risk. There was considerable international variation, with highest levels of awareness in students in the United States of America (USA). Knowledge of risk in this sample was poorer than previously observed in older women. Health messages concerning cancer in general may be more relevant for this age group, because of the lower salience of breast cancer for younger women.     

Prenatal attachment: using measurement invariance to test the validity of comparisons across eight culturally diverse countries

Studies in high-income countries (HICs) have shown that variability in maternal-fetal attachment (MFA) predict important maternal health and child outcomes. However, the validity of MFA ratings in low- and middle-income countries (LMICs) remains unknown. Addressing this gap, we assessed measurement invariance to test the conceptual equivalence of the Prenatal Attachment Inventory (PAI: Muller, 1993) across eight LMICs. Our aim was to determine whether the PAI yields similar information from pregnant women across different cultural contexts. We administered the 18-item PAI to 1181 mothers in the third trimester (Mean age = 28.27 years old, SD = 5.81 years, range = 18–48 years) expecting their first infant (n = 359) or a later-born infant (n = 820) as part of a prospective birth cohort study involving eight middle-income countries: Ghana, Jamaica, Pakistan, Philippines, Romania, South Africa, Sri Lanka and Vietnam. We used Multiple Group Confirmatory Factor Analyses to assess across-site measurement invariance. A single latent factor with partial measurement invariance was found across all sites except Pakistan. Group comparisons showed that mean levels of MFA were lowest for expectant mothers in Vietnam and highest for expectant mothers in Sri Lanka. MFA was higher in first-time mothers than in mothers expecting a later-born child. The PAI yields similar information about MFA across culturally distinct middle-income countries. These findings strengthen confidence in the use of the tool across different settings; future studies should explore the use of the PAI as a screen for maternal behaviour that place children at risk.