A Case of Bowen’s Disease and Small-Cell Lung Carcinoma: Long-Term Consequences of Chronic Arsenic Exposure in Chinese Traditional Medicine

Chronic arsenic toxicity occurs primarily through inadvertent ingestion of contaminated water and food or occupational exposure, but it can also occur through medicinal ingestion. This case features a 53-year-old lifetime nonsmoker with chronic asthma treated for 10 years in childhood with Chinese traditional medicine containing arsenic. The patient was diagnosed with Bowen’s disease and developed extensive-stage small-cell carcinoma of the lung 10 years and 47 years, respectively, after the onset of arsenic exposure. Although it has a long history as a medicinal agent, arsenic is a carcinogen associated with many malignancies including those of skin and lung. It is more commonly associated with non–small-cell lung cancer, but the temporal association with Bowen’s disease in the absence of other chemical or occupational exposure strongly points to a causal role for arsenic in this case of small-cell lung cancer. Individuals with documented arsenic-induced Bowen’s disease should be considered for more aggressive screening for long-term complications, especially the development of subsequent malignancies

The cardiomyocyte "redox rheostat": Redox signalling via the AMPK-mTOR axis and regulation of gene and protein expression balancing survival and death.

Reactive oxygen species (ROS) play a key role in development of heart failure but, at a cellular level, their effects range from cytoprotection to induction of cell death. Understanding how this is regulated is crucial to develop novel strategies to ameliorate only the detrimental effects. Here, we revisited the fundamental hypothesis that the level of ROS per se is a key factor in the cellular response by applying different concentrations of H2O2 to cardiomyocytes. High concentrations rapidly reduced intracellular ATP and inhibited protein synthesis. This was associated with activation of AMPK which phosphorylated and inhibited Raptor, a crucial component of mTOR complex-1 that regulates protein synthesis. Inhibition of protein synthesis by high concentrations of H2O2 prevents synthesis of immediate early gene products required for downstream gene expression, and such mRNAs (many encoding proteins required to deal with oxidant stress) were only induced by lower concentrations. Lower concentrations of H2O2 promoted mTOR phosphorylation, associated with differential recruitment of some mRNAs to the polysomes for translation. Some of the upregulated genes induced by low H2O2 levels are cytoprotective. We identified p21Cip1/WAF1 as one such protein, and preventing its upregulation enhanced the rate of cardiomyocyte apoptosis. The data support the concept of a "redox rheostat" in which different degrees of ROS influence cell energetics and intracellular signalling pathways to regulate mRNA and protein expression. This sliding scale determines cell fate, modulating survival vs death

Relative value to surgical patients and anesthesia providers of selected anesthesia related outcomes

BACKGROUND: Anesthesia side effects are almost inevitable in most situations. In order to optimize the anesthetic experience from the patient's viewpoint, it makes intuitive sense to attempt to avoid the side effects that the patient fears the most. METHODS: We obtained rankings and quantitative estimates of the relative importance of nine experiences that commonly occur after anesthesia and surgery from 109 patients prior to their surgery and from 30 anesthesiologists. RESULTS: Pain was the most important thing to avoid, and subjects allocated a median of $25 of an imaginary$100 to avoiding it. Next came vomiting ($20), nausea ($10), urinary retention ($5), myalgia ($2) and pruritus ($2). Avoiding blood transfusion, an awake anesthetic technique or postoperative somnolence was not given value by the group as a whole. Anesthesiologists valued perioperative experiences in the same way as patients. CONCLUSIONS: Our results are comparable with those of previous studies in the area, and suggest that patients can prioritize the perioperative experiences they wish to avoid during their perioperative care. Such data, if obtained in the appropriate fashion, would enable anesthetic techniques to be compared using decision analysis

Emergence of CD26+ cancer stem cells with metastatic properties in colorectal carcinogenesis

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Three Level Thoracolumbar Spondylectomy for Recurrent Giant Cell Tumour of the Spine: A Case Report

Giant cell tumour (GCT) is a benign tumour but can be locally aggressive and with the potential to metastasise especially to the lungs. Successful treatments have been reported for long bone lesions; however, optimal surgical and medical treatment for spinal and sacral lesions are not well established. In treating spinal GCTs, the aim is to achieve complete tumour excision, restore spinal stability and decompress the neural tissues. The ideal surgical procedure is an en bloc spondylectomy or vertebrectomy, where all tumour cells are removed as recurrence is closely related to the extent of initial surgical excision. However, such a surgery has a high complication rate, such as dura tear and massive blood loss. We report a patient with a missed pathological fracture of T12 treated initially with a posterior subtraction osteotomy, who had recurrence three years after the index surgery and subsequently underwent a three level vertebrectomy and posterior spinal fusion

T Cells Recognizing a Peptide Contaminant Undetectable by Mass Spectrometry

Synthetic peptides are widely used in immunological research as epitopes to stimulate their cognate T cells. These preparations are never completely pure, but trace contaminants are commonly revealed by mass spectrometry quality controls. In an effort to characterize novel major histocompatibility complex (MHC) Class I-restricted β-cell epitopes in non-obese diabetic (NOD) mice, we identified islet-infiltrating CD8+ T cells recognizing a contaminating peptide. The amount of this contaminant was so small to be undetectable by direct mass spectrometry. Only after concentration by liquid chromatography, we observed a mass peak corresponding to an immunodominant islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)206-214 epitope described in the literature. Generation of CD8+ T-cell clones recognizing IGRP206-214 using a novel method confirmed the identity of the contaminant, further underlining the immunodominance of IGRP206-214. If left undetected, minute impurities in synthetic peptide preparations may thus give spurious results