Severe accidental colchicine poisoning by the autumn crocus: A case of successful treatment

AbstractBackgroundThe common garden plant autumn crocus contains colchicine and its derivatives. Colchicine poisoning causes abdominal cramps and diarrhea within hours. Several days later, multiorgan failure, pancytopenia, and cardiovascular collapse occur.1,2 Severe colchicine poisoning is associated with high mortality.Case reportA 63-year-old woman who accidentally ingested an autumn crocus, which contained ∼0.38 mg colchicine, had severe vomiting and was taken to an emergency center. She presented with symptoms of gastroenterocolitis within 1 hour of ingestion, and bone marrow hypoplasia with pancytopenia developed on the 3rd day after ingestion. We continued administration of granulocyte colony-stimulating factor (300 μg) for 5 days until we confirmed that the patient's white blood cell count was increasing. Also, there was focal and segmental intestinal ischemia and some cakes of charcoal remained in the intestinal tract. Therefore, we presumed that nonocclusive mesenteric ischemia was caused by hypotension with severe dehydration, although pseudo-obstruction due to the activated charcoal may have been a contributing factor. We were able to promptly intervene to treat paralytic ileus and gastrointestinal edema before anticipated worsening of abdominal compartment syndrome, by conducting open peritoneal drainage. Despite severe poisoning, our patient survived with intensive care. Conclusion: Colchicine intoxication may lead to a sudden and extreme critical course. Therefore, as there is no means to predict prognosis from initial severity of symptoms at onset, we suggest that all patients suspected of colchicine intoxication should be managed in hospital with continuous vital sign monitoring and frequent laboratory testing for at least a few days after ingestion

Gefitinib (IRESSA) sensitive lung cancer cell lines show phosphorylation of Akt without ligand stimulation

BACKGROUND: Phase III trials evaluating the efficacy of gefitinib (IRESSA) in non-small cell lung cancer (NSCLC) lend support to the need for improved patient selection in terms of gefitinib use. Mutation of the epidermal growth factor receptor (EGFR) gene is reported to be associated with clinical responsiveness to gefitinib. However, gefitinib-sensitive and prolonged stable-disease-defined tumors without EGFR gene mutation have also been reported. METHODS: To identify other key factors involved in gefitinib sensitivity, we analyzed the protein expression of molecules within the EGFR family, PI3K-Akt and Ras/MEK/Erk pathways and examined the sensitivity to gefitinib using the MTT cell proliferation assay in 23 lung cancer cell lines. RESULTS: We identified one highly sensitive cell line (PC9), eight cell lines displaying intermediate-sensitivity, and 14 resistant cell lines. Only PC9 and PC14 (intermediate-sensitivity) displayed an EGFR gene mutation including amplification. Eight out of the nine cell lines showing sensitivity had Akt phosphorylation without ligand stimulation, while only three out of the 14 resistant lines displayed this characteristic (P = 0.0059). Furthermore, the ratio of phosphor-Akt/total Akt in sensitive cells was higher than that observed in resistant cells (P = 0.0016). Akt phosphorylation was partially inhibited by gefitinib in all sensitive cell lines. CONCLUSION: These results suggest that Akt phosphorylation without ligand stimulation may play a key signaling role in gefitinib sensitivity, especially intermediate-sensitivity. In addition, expression analyses of the EGFR family, EGFR gene mutation, and FISH (fluorescence in situ hybridization) analyses showed that the phosphorylated state of EGFR and Akt might be a useful clinical marker of Akt activation without ligand stimulation, in addition to EGFR gene mutation and amplification, particularly in adenocarcinomas

Pds5 regulates sister-chromatid cohesion and chromosome bi-orientation through a conserved protein interaction module

Sister-chromatid cohesion is established by the cohesin complex in S phase and persists until metaphase, when sister chromatids are captured by microtubules emanating from opposite poles [1]. The Aurora-B-containing chromosome passenger complex (CPC) plays a crucial role in achieving chromosome bi-orientation by correcting erroneous microtubule attachment [2]. The centromeric localization of the CPC relies largely on histone H3-T3 phosphorylation (H3-pT3), which is mediated by the mitotic histone kinase Haspin/Hrk1 [3-5]. Hrk1 localization to centromeres depends largely on the cohesin subunit Pds5 in fission yeast [5]; however, it is unknown how Pds5 regulates Hrk1 localization. Here we identify a conserved Hrk1-interacting motif (HIM) in Pds5 and a Pds5-interacting motif (PIM) in Hrk1 in fission yeast. Mutations in either motif result in the displacement of Hrk1 from centromeres. We also show that the mechanism of Pds5-dependent Hrk1 recruitment is conserved in human cells. Notably, the PIM in Haspin/Hrk1 is reminiscent of the YSR motif found in the mammalian cohesin destabilizer Wapl and stabilizer Sororin, both of which bind PDS5 [6-12]. Similarly, and through the same motifs, fission yeast Pds5 binds to Wpl1/Wapl and acetyltransferase Eso1/Eco1, in addition to Hrk1. Thus, we have identified a protein-protein interaction module in Pds5 that serves as a chromatin platform for regulating sister-chromatid cohesion and chromosome bi-orientation