Dendritic cells modulated by innate immunity improve collagen-induced arthritis and induce regulatory T cells in vivo

Dendritic cells (DCs) mediate interactions between innate and specific immunity and may induce regulatory mechanisms. We investigated the effects of modulated DCs in mice with collagen-induced arthritis (CIA) and tested the responses of cells to induced naturally occurring regulatory T cells. DCs were stimulated or not with DNA or lipopolysaccharide (LPS) for 24 hr. DC maturation was assayed, and then modulated DCs were intraperitoneally injected on day 14 into DBA/1 mice to treat CIA. In addition to arthritis scores and type 2 collagen (CII) response, the induction of CD4(+) CD25(+) T cells was analysed by flow cytometry in peripheral blood and the expression of Foxp3, transforming growth factor (TGF)-beta, interleukin (IL)-10 and cytotoxic T-lymphocyte antigen (CTLA)-4 was quantified. Finally, the expression of indoleamine-2,3-dioxygenase (IDO) was assayed in DCs. In comparison with LPS-stimulated DCs, plasmid-stimulated DCs expressed lower levels of major histocompatibility complex (MHC) class II, CD40, CD80 and CD86 molecules and secreted less IL-12p70, interferon (IFN)-gamma, IL-10 and TNF-alpha, displaying a semi-mature phenotype. Compared with non-stimulated DCs, stimulated DCs improved arthritis scores when injected after immunization, without modifying the T helper type 1 (Th1)/Th2 balance of the immune response against collagen. Stimulated DCs induced markers for regulatory T cells (Foxp3, TGF-beta1 and CTLA-4) in vivo. Only LPS-stimulated DCs expressed IDO, which may explain their better therapeutic efficacy. Regulatory mechanisms were induced using DCs modulated by innate immunity stimulators. Innate immunity mechanisms do not require the presence of the disease-causing antigen, even in T- and B-cell specific diseases. Our results have implications for the treatment of rheumatoid arthritis, an autoimmune disease whose triggering antigen has not been identified, and substantially clarify the role of regulatory T cells in CIA.     

Breast Cancer Treatment Delay in SafetyNet Health Systems,Houston Versus Southeast Brazil

BackgroundBreast cancer outcomes among patients who use safety-net hospitals in the highly populated Harris County, Texas and Southeast Brazil are poor. It is unknown whether treatment delay contributes to these outcomes.MethodsWe conducted a retrospective cohort analysis of patients with non-metastatic breast cancer diagnosed between January 1, 2009 and December 31, 2011 at Harris Health Texas and Unicamp’s Women’s Hospital, Barretos Hospital, and Brazilian National Institute of Cancer, Brazil. We used Cox proportional hazards regression to evaluate association of time to treatment and risk of recurrence (ROR) or death.ResultsOne thousand one hundred ninety-one patients were included. Women in Brazil were more frequently diagnosed with stage III disease (32.3% vs. 21.1% Texas; P = .002). Majority of patients in both populations had symptom-detected disease (63% in Brazil vs. 59% in Texas). Recurrence within 5 years from diagnosis was similar 21% versus 23%. Median time from diagnosis to first treatment defined as either systemic therapy (chemotherapy or endocrine therapy) or surgery, were comparable, 9.9 weeks versus 9.4 weeks. Treatment delay was not associated with increased ROR or death. Higher stage at diagnosis was associated with both increased ROR and death.ConclusionTime from symptoms to treatment was considerably long in both populations. Treatment delay did not affect outcomes.ImpactAccess to timely screening and diagnosis of breast cancer are priorities in these populations.     

Papillary Thyroid Carcinoma in Mexican Patients: Clinical Aspects and Prognostic Factors

Abstract. The present study characterizes papillary thyroid carcinoma (PTC) in a Mexican patient sample and evaluates potential prognostic factors for recurrence. Clinical records of 229 patients with PTC were analyzed. Surgical specimens were rereviewed and DNA ploidy determined. Cox logistic regression was used to explore prognostic factors. Mean age ± SD of the patients was 42 ± 16 years, with a male/female ratio of 24:205. A thyroid mass was the initial manifestation in 99%. Extrathyroid invasion occurred in 45% and nodal metastases in 38%. Mean size ± SD of the tumors was 3 ± 2 cm. By flow cytometry 88% of the tumors were DNA euploid and 12% aneuploid. Complete tumor resection was achieved in 83% with an operative mortality of 0.4%. Postoperative hormone suppression was administered in 65% and remnant ¹³¹ I thyroid ablation in 84%. The 10-year recurrence-free survival was 85%. In the group of patients with tumors totally removed and without distant metastases, none of the 14 evaluated variables demonstrated statistical significance as an independent prognostic factor for recurrence. However, the group of patients in whom a combination of the following factors was present—age ≥ 40 years, tumor size ≥ 3 cm, local invasion, and lymph node metastases—showed a higher incidence of tumor recurrence.     

Validation of self-reported proximity to agricultural crops in a case-control study of neural tube defects

Self-reported perinatal exposures to chemicals or pollutant sources in case-control studies of birth defects may be inaccurate due to misreporting among mothers. In a case-control study of neural tube defects delivered in California in 1987-1988, mothers of case and control infants were asked whether they lived within 0.25 mile (400 m) of agricultural crops. Responses were compared against a gold standard derived from historical agricultural land-use survey maps. The odds ratio for self-reported proximity to any crops (1.62, 95% confidence interval: 1.08, 2.43) appeared to be positively biased compared with the estimate for map-based proximity (1.17, 95% confidence interval: 0.79, 1.71). This pattern was also observed for proximity to specific crops such as nonpermanent and orchard crops. For vineyards, however, we observed an increased risk associated with map-based proximity (odds ratio=2.45, 95% confidence interval: 1.08, 5.58) but not with self-reported proximity (1.09, 95% confidence interval: 0.51, 2.34). The sensitivity of self-reported proximity to any crops was greater for case (65.7%) than control mothers (50.0%) while specificity was about the same for case and control mothers (87.5 vs. 89.3%), suggesting that control mothers under-reported proximity to crops. Differential reporting was also observed between geographic regions, urban and rural residents, and across levels of maternal employment and education. These results suggest differential reporting between case and control mothers as well as an influence from maternal demographic characteristics on reporting accuracy.     

The effect of bariatric surgery on adipocytokines, renal parameters and other cardiovascular risk factors in severe and very severe obesity: 1-year follow-up

AIMS: To evaluate the effect of weight loss after bariatric surgery (BS) on peripheral adipocytokines, renal parameters and other cardiovascular risk factors (CVRFs). METHODS: A total of 70 (41 women) extremely obese adults were prospectively studied before and 12 months after surgery. Controls: 24 (15 women) normal-weight adults. Anthropometric, biochemical and renal parameters were recorded. RESULTS: Presurgery, adiponectin (ADPN) was lower, whereas leptin, insulin resistance, C-reactive protein, creatinine clearance and albuminuria were higher in patients than controls (P<0.001). All parameters improved postsurgery. Changes in ADPN correlated negatively with leptin, insulin resistance, albumin, C-reactive protein, and creatinine clearance. Multiple regression analysis: using changes in ADPN as the dependent variable, only changes in insulin resistance (P=0.005) and albumin (P=0.019) were significant independent determinants for changes in ADPN. No statistical differences were found in relation to the degree of obesity. CONCLUSION: Patients changed to obesity type I after surgery. This implies a substantial improvement of CVRFs including ADPN, creatinine clearance and albuminuria. Changes in plasma ADPN correlated negatively with insulin resistance and with albuminemia but not with renal parameters. The lack of differences between different degrees of obesity suggests that the relationship between weight and CVRFs no longer exists when obesity becomes very extreme.