Abstract. Controlled bench scale pulverized coal combustion studies were performed, demonstrating that inorganic particles play a critical role as carriers of organic species. Two commonly-used aerosol mass spectrometry techniques were applied to characterize fine particle formation during coal combustion. It was found that the organic species in coal combustion aerosols have mass spectra similar to those generated by biomass combustion. Ambient measurements in Shanghai, China confirm the presence of these species in approximately 29–38% of the sampled particles. With the absence of major biomass sources in the Shanghai area, it is suggested that coal combustion may be the main source of these particles. This work indicates there is a significant potential for incorrect apportionment of coal combustion particles to biomass burning sources using widely adopted mass spectrometry techniques.

Immune responses against lung-associated self-antigens (self-Ags) are hypothesized to play a role in the development of chronic lung graft rejection. We determined whether immune responses to lung self-Ags, K-alpha-1-tubulin (Kα1T) and Collagen V (Col-V) in the absence of alloimmunity, could promote airway inflammation and fibrosis. Following syngeneic murine orthotopic lung transplantation (LTx) we administered antibodies (Abs) to either Kα1T or Col-V or in combination to both of these self-Ags. As compared to recipients of isotype control Abs Kα1T Abs and/or Col-V Abs-treated recipients had marked lung graft cellular infiltration and bronchiolar fibrosis, This inflammation was also associated the accumulation of Kα1T and Col-V specific IFN-γ+ and IL-17+ T cells. Notably, the administration of Abs to Kα1T led to cellular and humoral immune responses to Col-V prior to development of fibrosis, and vice versa, indicating that epitope spreading can occur rapidly in an alloantigen independent manner. Collectively, these data support a model of chronic lung transplant rejection where the progressive loss of self-tolerance through epitope spreading promotes airway fibrosis. Strategies that target autoreactive Abs may be useful to inhibit chronic rejection of lung grafts.

No abstract

SUMMARYDeficiency of the complement protein C2 (C2D), one of the most common genetic deficiencies of the complement system, is associated with rheumatological disorders and increased susceptibility to infection. Two types of C2D have been recognized, each in the context of specific major histocompatibility complex (MHC ) haplotypes; type I, a deletion, frameshift and premature stop codon resulting in absence of detectable C2 protein synthesis, and type II, missense mutations resulting in a block in secretion of C2 proteins. Analysis of C2 expression in a child with C2 deficiency, a MHC haplotype different from those associated with type I or II C2D, and recurrent infections revealed additional molecular heterogeneity among C2 deficient patients. No detectable C2 protein was synthesized in the child's fibroblasts under conditions supporting C2 synthesis and secretion in normals and the child's C2 mRNA was reduced to 42% of normal. Nucleotide sequencing of RT-PCR fibroblast mRNA and genomic DNA revealed a type I C2 deficiency (28 base-pair deletion) on one allele and a previously unrecognized two base-pair deletion in exon 2 on the other. Expression of the closely linked factor B gene was markedly decreased (Bf mRNA 25% of normal ), though Bf was up-regulated appropriately by interferon-c and the flanking sequence containing the Bf promoter was normal in this C2-deficient patient. Moreover, the concentration of Bf protein was normal in the patient's plasma.

had cirrhosis with Child-Pugh score <8. The prescribed dose was 40 Gy in four fractions. Dose reduction was permitted for normal organ dose constrains. The bile duct (BD) was delineated from the common bile duct to the first bifurcation of left and right intrahepatic duct. In addition, the central hepatobiliary tract (cHBT) was defined by a 10 or 15 mm expansion of the portal vein from the splenic confluence to the first bifurcation of left and right portal veins. We analyzed the clinical and dosimetric parameters, including multiple dose-volume histogram endpoints: D max (the maximum point dose), D mean (the mean dose), V 40Gy (volume of cHBT that received 40 Gy), V 37Gy , V 34Gy. Receiver operator curves (ROC) defined optimal dosimetric thresholds for analysis. HB toxicities were graded according to Common Terminology Criteria for Adverse Events version 4.0 and we defined grade 3+ HB toxicity as a severe HB toxicity. Results: Median follow-up duration was 9.9 months after SABR. Eight out of 28 patients (28.6%) experienced severe HB toxicity. Among clinical and dosimetric parameters, V 40Gy of cHBT with 10 mm expansion were highly associated with severe HB toxicity: V 40Gy >40 cm 3 (relative risk [RR] Z 3.2, P < 0.011). However, clinical or other dosimetric factors, D max or D mean of BD and cHBT, did not have predictive value. The risk of severe HB toxicity for V 40Gy 20 cm 3 , > 20 cm 3 , > 30 cm 3 , and > 40 cm 3 are 8.3% (n Z 1/12), 41.2% (n Z 7/17), 46.2% (n Z 6/13), and 54.5% (n Z 6/11), respectively. Conclusion: SABR to the central liver lesions should be used with caution due to the risk of HB toxicity. Radiation doses to cHBT are associated with development of severe HB toxicity. We suggest that V 40Gy <20 cm 3 as a potential dose constraint for cHBT when delivered in four fractions.