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A 53-year-old man with acute myeloid leukemia received an allogeneic hematopoietic cell transplant (HCT) from a matched unrelated donor. One month after his transplantation, he developed ARDS requiring initiation of VV-ECMO. He suffered from pancytopenia, managed with frequent transfusions, granulocyte-colony stimulating factor (G-CSF) and weekly thrombopoietin receptor agonist. On ECMO day 17, the patient developed severe hypotension after insertion of a chest tube for a large right-sided pneumothorax. CT angiography of the abdomen showed hemoperitoneum. Exploratory laparotomy revealed approximately 4 L of blood and a ruptured splenic hilum. A splenectomy was performed. Unfortunately, the patient continued to require multiple daily blood products and his condition continued to decline despite two reoperations. His family chose to discontinue ECMO and he passed away peacefully. Spontaneous splenic rupture after GM-CSF has never been reported in patients on VV-ECMO. This manuscript reviews the literature regarding the pathophysiology and clinical manifestation of this rare occurrence.

Atopic disorders are associated with an imbalanced THcell response biased toward a strong TH2 type, resulting in excessive production of IgE antibodies, eosinophil recruitment and activation, and mast cell degranulation. Restoring the TH1-TH2 balance by increasing the antigen-specific TH1 response has been pursued for specific allergy immunotherapy. Synthetic oligodeoxynucleotides containing unmethylated CG dinucleotides (CpG) are strong TH1 adjuvants and are being investigated for allergy immunotherapy.

The DNA damage induced by N‐hydroxy‐4‐acetylaminobiphenyl (N‐OH‐AABP), the proximate carcinogenic metabolite of the human bladder carcinogen 4‐aminobiphenyl (ABP), was examined in human transitional cell carcinoma (TCC) cells after exposure to the chemical in vitro. 32P‐postlabeling analysis of TCC cultures exposed to N‐OH‐AABP revealed a minor adduct identified as 3‐(deoxyguanosin‐N2‐yl)‐4‐acetylaminobiphenyl (dG‐N2‐AABP) based on comparison of the HPLC and TLC mobility of the product with the synthetic standard. An adduct with the same chromatographic properties was also detected on postlabeling analyses of calf thymus DNA bound to N‐OH‐AABP by incubation with horseradish peroxidase and hydrogen peroxide. Detection of dG‐N2‐AABP, which contains the acetyl moiety, suggests that N‐acetoxy‐4‐acetylamino‐biphenyl might be formed as a reactive intermediate and could conceivably arise by a free‐radical–mediated reaction of N‐OH‐AABP with endogenous peroxidases. The radical intermediates could also form reactive oxygen species (ROS). To test this possibility, TCC cultures were exposed to N‐OH‐AABP and the formation of ROS was measured using 2,7‐dichlorofluorescein (DCF) fluorescence assay. TCC cultures exposed to N‐OH‐AABP showed a dose‐dependent increase in the ratio of DCF/DNA fluorescence compared to the untreated controls. Formation of ROS was inhibited by butylated hydroxyanisole (BHA). Furthermore, oxidative DNA damage resulting from ROS was monitored by measurement of 8‐oxoguanine products by immunochemical staining and the TCC cells treated with N‐OH‐AABP revealed a characteristic staining. These results suggest that N‐OH‐AABP caused oxidative DNA damage as well as bulky covalent adducts in urothelial DNA, possibly involving endogenous peroxidases. These findings show that human uroepithelial cells, which are the target cell types in vivo for arylamine‐induced cancers, are metabolically capable of activating these proximate carcinogenic metabolites of arylamines, and these reactions might play a determinate role in the genotoxicity of these environmental carcinogens. Environ. Mol. Mutagen. 38:1–11, 2001 © 2001 Wiley‐Liss, Inc.

The global genomic repair of DNA adducts was examined in human papillary transitional cell carcinoma (TCC) cell lines after exposure to N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP), the proximate carcinogenic metabolite of the human bladder carcinogen 4-aminobiphenyl (ABP). 32P-post-labeling analysis of TCC cultures exposed to N-OH-AABP revealed a major adduct, identified as the 3′,5′-bisphosphate derivative of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP). The amount of adduct formation in TCC10 was dependent upon the dose and the duration of exposure and ranged between 1 and 5 adducts/107 nucleotides. To test if p53 regulates repair of the dG-C8-ABP adduct in genomic DNA, an isogeneic set of cell lines was obtained by infection of the TCC10 cultures with a retroviral construct expressing a trans-dominant mutant of p53, namely a Val→Ala mutation at codon 143. The TDM143-TCC10 line expressing the mutant form of p53 was selected. The rate of repair of dG-C8-ABP was compared between TCC10 and TDM143-TCC10 cultures after treatment with 15 μM N-OH-AABP. The rate of disappearance of the adduct was monitored over a period of time after chemical treatment. 32P-post-labeling analysis of dG-C8-ABP in parental TCC10 showed its rapid removal, the majority of adducts disappearing within 48 h. In contrast to TCC10, TDM143-TCC10 was relatively slower in removal of dG-C8-ABP. After 24 h DNA repair TDM143-TCC10 showed an ~3-fold greater amount of dG-C8-ABP compared with TCC10. These results imply that p53 plays a role in the repair of ABP adducts and that in p53 null cells the unrepaired DNA damage could cause accumulation of mutations, which might contribute to increased genomic instability and neoplastic progression.