Residual bone marrow damage (RBMD) persists for years following exposure to radiation and is believed to be due to decreased self-renewal potential of radiation-damaged hematopoietic stem cells (HSC). Current literature has examined primarily sub-lethal doses of radiation and time points within a few months of exposure. In this study, we examined RBMD in mice surviving lethal doses of total body ionizing irradiation (TBI) in a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome (H-ARS). Survivors were analyzed at various time points up to 19 months post-TBI for hematopoietic function. The competitive bone marrow (BM) repopulating potential of 150 purified c-Kit+ Sca-1+ lineage- CD150+ cells (KSLCD150+) remained severely deficient as long as 16months post-TBI compared to KSLCD150+ cells from non-TBI age-matched controls. The minimal engraftment from these TBI HSC is predominantly myeloid, with minimal production of lymphocytes both in vitro and in vivo. All classes of blood cells as well as BM cellularity were significantly decreased in TBI mice, especially at later time points as mice aged. Primitive BM hematopoietic cells (lin-, KSL, KSLCD150+) displayed significantly increased cell cycling in TBI mice at all time points, which may be a physiological attempt to maintain HSC numbers in the post-irradiation state. Taken together, these data suggest that the increased cycling among primitive hematopoietic cells in survivors of lethal radiation may contribute to long-term HSC exhaustion and subsequent RBMD, exacerbated by the added insult of aging at later time points.

Experimental and clinical evidence suggests that long chain n-3 fatty acids may protect against sudden cardiac death, the leading cause of mortality in hemodialysis patients. Here we investigated whether long chain n-3 fatty acids have a protective relationship with sudden cardiac death in 100 patients who died of sudden cardiac death during the first year of starting hemodialysis and 300 patients who survived. Individuals were selected from a nationally representative cohort of over 1000 U.S. hemodialysis units in 2004–2005. The odds of sudden cardiac death were calculated by quartile of long chain n-3 fatty acids levels over the first year. There was a significant inverse relationship between long chain n-3 fatty acids and the risk of sudden cardiac death even after adjusting for relevant co-morbid conditions, biochemical values, and dietary fats. The odds of sudden cardiac death at 1 year for the second, third, and fourth quartile groups of long chain n-3 fatty acids were 0.37, 0.22, and 0.20, respectively, compared to the lowest quartile. This significant inverse relationship was maintained even during the highest-risk first few months on hemodialysis. Thus, long chain n-3 fatty acids are strongly and independently associated with a lower risk of sudden cardiac death in hemodialysis patients throughout the first year of hemodialysis.

Summary Background Childhood asthma is often characterized by recurrent wheezing, airway hyper-reactivity, atopy, and altered immune characteristics; however, our understanding of the development of these relationships from early in life remains unclear. The aim of our study was to evaluate whether atopy, cytokine production by peripheral blood mononuclear cells (PBMCs), and airway responsiveness, assessed in infants and toddlers, are associated with asthma and airway responsiveness at 4-years of age. Methods Infants with eczema (N = 116), enrolled prior to wheezing, were assessed at entry (mean age of 10.7 months), at 1-year follow-up (N = 112), and at 4-years of age (N = 94). Total serum IgE, specific IgE to allergens, and cytokines produced by stimulated PBMCs, were assessed at entry and 1-year follow-up. Spirometry was obtained at all 3-visits, while airway reactivity to methacholine was assessed at entry and 1-year follow-up, and bronchodilator (BD) responsiveness, as well as current asthma was assessed at 4-years of age. Results We found that pre-school children with asthma had lower spirometry and a greater BD-response. Serum IgE, particularly to egg and/or milk, and altered cytokine production by PBMCs at entry to the study were associated with asthma, lower spirometry, and greater airway responsiveness at 4-years of age. In addition, we found that airway responsiveness, as well as spirometry, tracked from infancy to 4-years of age. Conclusions While spirometry and airway responsiveness track longitudinally from early in life, atopy and cytokine production by PBMCs are associated not only with an increased risk of pre-school asthma, but also lower spirometry and increased airway responsiveness.

Although preliminary, our findings raise the hypothesis that IL-8 and MCP-1 may be involved in the pathogenesis of FM. If replicated in a larger study, IL-8 and MCP-1 may assist in determining prognosis and in monitoring of treatment response.

BACKGROUND. The objective of this study was to evaluate the effect of pericyte coverage (PC) of differentiated tumor microvessels on the prognosis of patients with clear cell renal cell carcinoma (CCRCC). METHODS. Samples from 2 cohorts of patients with CCRCC (101 Asian patients and 524 US patients) were prepared using 2 different histologic approaches: routine sectioning versus tissue microarray. Then, the samples were immunohistochemically doubled-stained for a pericyte marker (alpha smooth muscle actin [a-SMA]) and a differentiated vessel marker (cluster of differentiation 34 [CD34]), followed by multispectral image capturing and computerized image analyses to quantify the microvessel density (MVD) and the PC of differentiated vessels. The correlations of PC and the MVD:PC ratio with clinicopathologic characteristics were analyzed. RESULTS. There was an inverse correlation between differentiated MVD and PC. Higher PC correlated with more aggressive clinicopathologic characteristics of CCRCC in both cohorts, including more advanced T-classification, higher pathologic grades, and the occurrence of tumor necrosis. The MVD:PC ratio was an independent favorable prognostic factor for overall and recurrence-free survival in the Asian cohort and for recurrence-free survival in the US cohort. PC also was an independent prognostic factor, with higher PC predicting a poorer outcome. The combination of PC and MVD was better at distinguishing the outcome of patients with CCRCC. PC combined with differentiated MVD or with the MVD:PC ratio provided additional, independent prognostic information to the Leibovich risk model, and that information was used to generate improved risk models. CONCLUSIONS. The authors consistently observed that higher PC was correlated with more aggressive clinicopathologic characteristics. PC was an independent unfavorable prognostic factor. The authors concluded that pericytes should be considered for therapeutic targeting. Cancer 2013;119:313-34.