tbuckley/cabot-search huggingface dataset:
Abstract 267: MYC maintains the self-renewal of cancer stem cells through the regulation of the glutathione redox system.
Authors: Bikul Das, Rika Tsuchida, Reza Bayat-Mokhtari, Jason R. Gotlib, Renee Reijo-Pera, Herman Yeger, Felsher W. Dean
Journal: Cancer Research (2013)

Abstract Cancer stem cells (CSCs) are a rare population of self-renewing cells that can persist even after extensive therapeutic intervention. The molecular mechanism of CSC self-renewal is not yet clear. Here we show that MYC is causally involved in CSC self-renewal through the regulation of glutathione (GSH) redox system. In a MYC-driven conditional transgenic mouse model of T-cell acute lymphoblastic leukemia (T-ALL), we identified Sca-1+ CSCs. We found that these CSCs express the glutathione (GSH) redox system related genes including glutamate cysteine ligase (GCL) and Pyruvate Dehydrogenase Kinase 1 (PDK1) but low levels of expression of the mitochondrial redox enzyme, Superoxide Dismutase 2 (SOD2). Even a brief period of MYC inactivation in the Sca1+ CSCs led to their apoptosis associated with the downregulation of GCL and PDK1, but the upregulation of SOD2, in turn resulting in ROS-generation and mitochondrial damage. Moreover, suppression of SOD2 by siRNA silencing or the use of the peroxide scavenger, ascorbic acid, prevented MYC inactivation from inducing apoptosis in the Sca-1+ CSCs. Finally, in human CSCs, including primary human Chronic Myeloid Leukemia (CML), and human colon cancers, we confirmed that MYC expression was required for high GCL, PDK1 and low SOD2. Even the brief inactivation of MYC in human CSCs resulted in the loss of their self-renewal, as well as the global chance in redox state by decrease in GCL, PDK1 and increase in SOD2. We conclude that high levels of continued MYC expression are essential for CSC self-renewal through regulation of redox state. Citation Format: Bikul Das, Rika Tsuchida, Reza Bayat-Mokhtari, Jason R. Gotlib, Renee Reijo-Pera, Herman Yeger, Felsher W. Dean. MYC maintains the self-renewal of cancer stem cells through the regulation of the glutathione redox system. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 267. doi:10.1158/1538-7445.AM2013-267 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
PRELIMINARY NOTE ON EXPERIMENTAL INVESTIGATIONS ON THE PITUITARY BODY
Authors: None Handelsmann, V. Horsley
Journal: BMJ (1911)

K50MEDICAL JOURNAL J anaesthetic even for proloniged periods.If cealnosis appears, this withholdin,g of tlhe anaesthetic is called for iml)eratively.i nee(d lhardly be said that wlien muorpliine is contraindicated on general principles it is better to avoid using scopolamine also, altlhougli this latter druo certainly renders the associated use of morph'nine more free froim danger.Tlle older method of emp)loying inorphlinie andl atrop)ine before chloroforim or etlher is-, I tlhink, less safe than the colmlbined use of sco)olanline, ifolrlliifo alnd atropine.Some surgeons hiave extolled this inijectioni ml-ethod as a p)relilllinary to the continuous inihalatioll of initrous oxide- oxygen for even prolonged operatiolns.The average doses alc scoL)olaflinl nOe grain, iiiorphine I graini, alnd atropine It,, grain, giveln one lhour befole the genieral anlaestlhetic.Sometim-les it is well to divide the dose.givilog lhalf an lhour before anid lhalf just before the inlhalatioll.It is conimiiiolnly tlhouglit that young clhildren are niot so suitable for this mlethod, anid I lhave little explerience of its use for tlheml.As to dosage, althoulgh the amouilts I lhave mentionied are usual, yet it is neces- sary), to miiodify theem according to tlle plhysique and state of the patienit.Some robust illeni ineed mllore, somle feeble persons requlire smaller (loses.A word mIusllt be said about the after-treatmenit of these cases.The patients usuially pass into a profouind slumber when tIme operation is tinislhed, and so lCedIlheedful watchinig for som0ie lhours, indeed
Use of anaesthesia. Care of the unconscious.
Authors: J M Horton
Journal: BMJ (1980)

Normal conscious behaviour means awareness of self and the environment and depends on intact brain function.'Changes in the level of consciousness reflect an abnormal function of the brain.The degree, depth, and duration of altered consciousness may vary from drowsiness to brain death, and "coma" or un- consciousness is best defined as an inability to obey commands, utter recognisable words, or open the eyes.2Pathological conditions associated with this state are brain injury from trauma; cerebrovascular accidents; hypoxia; hypotension (low perfusion states); uncontrolled epilepsy; and disorders of metabolism, such as hepatic and renal failure and drug overdose.As well as managing the primary cause of the coma, energetic treatment is needed to prevent the complications of unconscious- ness, the most serious of which are hypoxia and hypotension.All unconscious patients run the risk of an obstructed airway from the tongue falling back into the oropharynx.The inability to cough or swallow leads to an accumulation of secretions in the mouth, pharynx, trachea, and bronchi.Vomit and regurgitated gastric contents may be inhaled giving rise to the acid-aspiration (Mendelson's) syndrome in the lungs.The already damaged brain cannot withstand any further insults that may occur from inadequate cerebral oxygenation and perfusion due to a low arterial Po2 or low blood pressure.3The unconscious patient may need total care for days, weeks, or months, the problems being those of maintaining vital functions (adequate ventilation, circulation, and nutrition) and general nursing care.Anaesthesia is a pharmacologically induced state of uncon- sciousness and the well-trained anaesthetists of today, with their skill in care of the airway, endotracheal intubation, intravenous cannulation, ventilator management, and knowledge of applied pharmacology and respiratory physiology, are particularly able to care for these patients.The skills and lessons learnt in the operating theatre have enabled them to take part in the development, organisation, and management of patients in immediate care schemes and intensive treatment units and to teach these skills to other doctors, nurses, paramedical staff, and ambulance men.
Biopsy of Cervical Node
Authors: James Patterson Browder
Journal: JAMA (1979)

<h3>To the Editor.—</h3> The article concerning the diagnosis of lymphadenopathy in primary care practice by Sheldon Greenfield, MD, and M. Colin Jordan, MD (240:1388, 1978), correctly states that in the workup of persistent enlarged lymph nodes, "after local lesions have been effectively excluded, other systemic conditions must be pursued by biopsy of the enlarged node." Head and neck surgeons have found through experience that "partial surgical removal of a mass for diagnostic purposes is always objectionable and should be avoided if there is any alternative procedure."<sup>1</sup>This was convincingly reaffirmed by McGuirt and McCabe,<sup>2</sup>who retrospectively analyzed the data from 64 patients who had had a cervical node biopsy before diagnosis and definitive treatment. The complications of wound necrosis and local cervical recurrence were substantially higher in these patients than in those who had had either no cervical node biopsy or a node biopsy only at the time
Endobronchial Ultrasound–guided Transbronchial Needle Aspiration versus Cervical Mediastinoscopy: Case Selection Is Needed to Maintain Cost Benefits
Authors: Sushil Agarwal, Nawaid Ahmad
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Funded by a grant to N.N. and S.M.J. from the UK Medical Research Council. S.M.J. is a Wellcome Trust Senior Research Fellow in Clinical Science. This study was undertaken at UCLH/UCL, which received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme (N.N., S.M.J.).



Author disclosures are available with the text of this letter at www.atsjournals.org.
Effectiveness of Right Heart Catheterization: Time for a Randomized Trial-Reply
Authors: Alfred F. Connors
Journal: JAMA (1997)

In Reply.  —In our prospective observational cohort study of RHC, we adjusted for treatment selection bias using a multivariable propensity score. The adjustment was done using 2 standard techniques: multivariable analysis in all 5735 patients, which should yield the best estimate of the treatment effect, and matched-pair analysis in 2016 patients, which is less powerful but more easily understood. As reported, the results were essentially identical.  Dr Baxter and colleagues and Drs Jackson, Lewis, Punch, and Kaufman express several concerns about the generalizability of our results. We agree that surgical patients and patients with acute MI, head injury, and subarachnoid hemorrhage are not well represented in this analysis. We do not recommend applying our results to these populations. While our population represented the sickest patients in the ICUs at the 5 study hospitals (hence, the high mortality), we contend that this is the appropriate population for an analysis of the procedure. Right
Determinants of outcome in ANCA-associated glomerulonephritis: A prospective clinico-histopathological analysis of 96 patients
Authors: Herbert A. Hauer, Ingeborg M. Bajema, Hans C. Van Houwelingen, Franco Ferrario, Laure-Hélène Noël, Rüdiger Waldherr, David R.W. Jayne, Niels Rasmussen, Jan A. Bruijn, E. Christiaan Hagen
Journal: Kidney International (2002)
The Cry of Wolf
Authors: William R. Barclay
Journal: JAMA (1979)

fable The Boy Who Cried Wolf (no pun intended) is familiar to all.  hero, or should we say villain, of the story falsely raised the specter of imminent hazard to draw attention to himself. Such seems to be the case with the propoxyphene inquiry, the latest in a series of alarms raised over the dangers of some pharmaceutical products. This new sortie follows the action against phenformin, which was the first drug to be removed from the market under the imminent hazard rule.  Now, it is perfectly proper and even desirable that society, through its political structure, should exercise some control over medical care; however, such control should be directed at cost and access and should not involve scientific issues for which political officials are not trained or in which they are not experienced in dealing.  laws of science are not established by majority vote of a
Correlation of plasma oxidized low-density lipoprotein levels to vascular complications and human serum paraoxonase in patients with type 2 diabetes
Authors: Sachie Tsuzura, Yukio Ikeda, Tadashi Suehiro, Kikuko Ota, Fumiaki Osaki, Kaoru Arii, Yoshitaka Kumon, Kozo Hashimoto
Journal: Metabolism (2004)
Project seeks to improve dancers' health
Authors: J. Wise
Journal: BMJ (2008)

A new research project aims to discover why dancers have such a high rate of injuries and to examine ways to keep them fit and healthy.

Matthew Wyon, reader in performance science at the University of Wolverhampton, said, “Dancers have a huge injury occurrence: 80% of dancers incur at least one injury a year that affects their ability to perform.” In comparison, he said, footballers or rugby players have an injury rate of 20%. “And dance isn’t even a contact sport. We need to look properly at why this is.”

The dancers’ health pilot scheme has been devised by Dance UK in partnership with the Olympic Medical Institute, the …
Book: "To Improve the Evidence of Medicine": The 18th Century British Origins of a Critical Approach Knowledge and Practice in English Medicine 1550-1680
Authors: A. K Banerjee
Journal: BMJ (2001)

Ulrich Tröhler Royal College of Physicians of Edinburgh, £10, pp 147 Andrew Wear Cambridge University Press, £16.95, pp 496 ISBN: 0 521 55827 1 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img>; ![Graphic][5]</img>![Graphic][6]</img>![Graphic][7]</img> To future medical historians, the last decade of the millennium will be perhaps most noteworthy for the remarkable renaissance in articles and books on evidence based medicine. In the first monograph here, Ulrich Tröhler, a distinguished Swiss physician and medical historian, reminds us that evidence based medicine is not a new concept and can be traced back to 18th century British origins. The title of the book is taken from … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif [5]: /embed/inline-graphic-5.gif [6]: /embed/inline-graphic-6.gif [7]: /embed/inline-graphic-7.gif
RAD51 Up-regulation Bypasses <i>BRCA1</i> Function and Is a Common Feature of <i>BRCA1</i>-Deficient Breast Tumors
Authors: Richard W. Martin, Brian J. Orelli, Mitsuyoshi Yamazoe, Andy J. Minn, Shunichi Takeda, Douglas K. Bishop
Journal: Cancer Research (2007)

Abstract The breast cancer susceptibility gene BRCA1 encodes a large protein thought to contribute to a variety of cellular processes, although the critical determinants of BRCA1-deficient tumorigenesis remain unclear. Given that BRCA1 is required for cell proliferation, suppressor mutations are believed to modify BRCA1 phenotypes and contribute to the etiology of BRCA1-deficient tumors. Here, we show that overexpression of the homologous recombinase RAD51 in a DT40 BRCA1Δ/Δ mutant rescues defects in proliferation, DNA damage survival, and homologous recombination (HR). In addition, epistasis analysis with BRCA1 and the DNA end-joining factor KU70 indicates that these factors operate independently of one another to repair double-strand breaks. Consistent with this genetic finding, cell synchronization studies show that the ability of BRCA1 to promote radioresistance is restricted to the late S and G2 phases of the cell cycle, as predicted for genes whose function is specific to homology-mediated repair rather than nonhomologous end-joining. Notably, retrospective analyses of microarray expression data reveal elevated expression of RAD51 and two of its late-acting cofactors, RAD54 and RAD51AP1, in BRCA1-deficient versus sporadic breast tumors. Taken together, our results indicate that up-regulation of HR provides a permissive genetic context for cells lacking BRCA1 function by circumventing its requirement in RAD51 subnuclear assembly. Furthermore, the data support a model in which enhanced HR activity contributes to the etiology of BRCA1-deficient tumors. [Cancer Res 2007;67(20):9658–65]
Points: Medical indemnity
Authors: R. Jandoo
Journal: BMJ (1984)

known inhibitors of the enzyme-for example, isoniazide.Isoniazide interferes with the ALA- synthase coenzyme, pyridoxal phosphate, and, chronically administered, has a potent inhibitory effect on the hepatic enzyme in guinea pigS.2 3 I know of no trial concerning the effect of the drug in acute porphyria, either clinical or experimental.
Routine Serum Magnesium Analysis
Authors: CHARLES E. JACKSON
Journal: Annals of Internal Medicine (1968)

Serum magnesium levels were determined by atomic absorption spectrometry on 5,100 consecutive patients seen at a diagnostic clinic. The average value was 1.78 ± 0.15 mEq/liter with 90% of the values between 1.53 and 1.99 mEq/liter. The prevalence of various clinical conditions found in those patients with abnormal serum magnesium levels was compared with their prevalence in 500 randomly selected patients with magnesium levels between 1.53 and 1.99 mEq/liter. Hypo- and hypermagnesemia were more frequently encountered in seriously ill patients requiring hospitalization than in ambulatory patients. Diabetes mellitus was the most common condition associated with hypomagnesemia. Hypomagnesemia was also observed in increased frequency in patients on diuretic therapy. Hypermagnesemia with values above 2.08 mEq/liter was encountered in uremic patients and in patients receiving magnesium therapy, usually in the form of antacids.
The role of allergen‐specific T cells in the allergic immune response: relevance to allergy vaccination
Authors: Rjj Van Neerven
Journal: Allergy (1999)

Recent research has elucidated many of the immunologic mechanisms that underlie atopic allergies. In particular, it has become clear that the role of CD4+ allergen-specific T cells is crucial for the induction of IgE and eosinophilia, factors that mediate the immediate hypersensitivity reaction and late-phase responses, respectively. Therefore, the reactivity patterns and activation requirements of allergen-specific T cells are important parameters for understanding and manipulating the allergic immune response. This review addresses these issues and discusses their relevance to the further development of allergy vaccines.
TRAUMATIC RUPTURE OF THE PERICARDIUM WITH RESULTING DEXTROCARDIA COMPLICATED BY RUPTURE OF THE DIAPHRAGM AND LIVER
Authors: J. F. Doughty
Journal: JAMA (1923)

This type of injury to the pericardium is unusual; the resulting dextrocardia is particularly interesting. I was able to find in the literature only one case of rupture of the pericardium due to trauma,<sup>1</sup>but many due to gunshot wounds. Miss M. H., aged 35, was knocked down by an automobile as she was stepping off a street car. She came under our observation four days later, complaining of dyspnea on lying down. She maintained the sitting posture constantly. Eating caused a feeling of fulness in the left hypochondrium and was frequently accompanied by a choking sensation. Orthopnea was present. The cardiac pulsation was not visible on the left side, but the apical beat was observed in the sixth right interspace 4 cm. to the right of the midsternal line. The left border of the heart, determined by percussion, was 2 cm. to the left of the midsternal line,
Low-Grade Albuminuria and the Risks of Hypertension and Blood Pressure Progression
Authors: Thomas J. Wang, Jane C. Evans, James B. Meigs, Nader Rifai, Caroline S. Fox, Ralph B. D’Agostino, Daniel Levy, Ramachandran S. Vasan
Journal: Circulation (2005)

It has been postulated that glomerular hyperfiltration and endothelial dysfunction are early features of essential hypertension that may antedate blood pressure elevation. Microalbuminuria, a marker of glomerular hyperfiltration and endothelial dysfunction, has been described in individuals with established hypertension, but its role as a biomarker of preclinical stages of this disease has not been investigated prospectively.We examined the association between urinary albumin excretion and the risks of hypertension and blood pressure progression in 1499 nonhypertensive individuals (58% women) without diabetes. During a mean follow-up of 2.9 years, 230 participants (15%) developed hypertension and 499 (33%) progressed to a higher blood pressure category (defined by the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure). In multivariable logistic regressions that adjusted for known risk factors, the urine albumin-creatinine ratio (UACR) was a significant predictor of incident hypertension (adjusted OR 1.20, 95% CI 1.01 to 1.44, per 1-SD increment in log UACR). Compared with those in the lowest UACR quartile, participants in the highest quartile (men: >6.66 mg/g; women: >15.24 mg/g) had an approximately 2-fold risk of developing hypertension (adjusted OR 1.93, P=0.006) and 1.5-fold risk of blood pressure progression (adjusted OR 1.45, P=0.03).Urinary albumin excretion predicts blood pressure progression in nondiabetic, nonhypertensive individuals incrementally over established risk factors and at levels well below the conventional threshold for microalbuminuria. UACR may be a useful biomarker for identifying individuals most likely to develop hypertension.
The Variously Quoted Stanza Again.
Authors: W. S. Caldwell
Journal: JAMA (1897)

<h3>To the Editor:</h3> —Many years ago I picked up in London an old volume of medical rhymes published in the last century, and in this "God and the doctor" ran thus: " God and the doctor we alike adore, Only when in danger, not before, The danger o'er both are alike requited, God is forgotten and the doctor slighted." This is certainly another verse than any quotation so far given in theJournal.
Toll-like receptor 2-mediated innate immune response in human nonparenchymal liver cells toward adeno-associated viral vectors
Authors: Marianna Hösel, Mathias Broxtermann, Hanna Janicki, Knud Esser, Silke Arzberger, Pia Hartmann, Sonja Gillen, Jörg Kleeff, Dirk Stabenow, Margarete Odenthal, Percy Knolle, Michael Hallek, Ulrike Protzer, Hildegard Büning
Journal: Hepatology (2011)

Adeno-associated viral vectors (rAAV) are frequently used in gene therapy trials. Although rAAV vectors are of low immunogenicity, humoral as well as T cell responses may be induced. While the former limits vector reapplication, the expansion of cytotoxic T cells correlates with liver inflammation and loss of transduced hepatocytes. Because adaptive immune responses are a consequence of recognition by the innate immune system, we aimed to characterize cell autonomous immune responses elicited by rAAV in primary human hepatocytes and nonparenchymal liver cells. Surprisingly, Kupffer cells, but also liver sinusoidal endothelial cells, mounted responses to rAAV, whereas neither rAAV2 nor rAAV8 were recognized by hepatocytes. Viral capsids were sensed at the cell surface as pathogen-associated molecular patterns by Toll-like receptor 2. In contrast to the Toll-like receptor 9-mediated recognition observed in plasmacytoid dendritic cells, immune recognition of rAAV in primary human liver cells did not induce a type I interferon response, but up-regulated inflammatory cytokines through activation of nuclear factor κB.Using primary human liver cells, we identified a novel mechanism of rAAV recognition in the liver, demonstrating that alternative means of sensing rAAV particles have evolved. Minimizing this recognition will be key to improving rAAV-mediated gene transfer and reducing side effects in clinical trials due to immune responses against rAAV.
A strategy for fabrication of a three-dimensional tissue construct containing uniformly distributed embryoid body-derived cells as a cardiac patch
Authors: Chieh-Cheng Huang, Chen-Kang Liao, Mei-Ju Yang, Chun-Hung Chen, Shiaw-Min Hwang, Yi-Wen Hung, Yen Chang, Hsing-Wen Sung
Journal: Biomaterials (2010)
Evaluation of Simpson.
Authors: R Ballantine
Journal: BMJ (1970)

escaping initially due to its high level of parasympathetic tone.' Ileus has for many years been known to occur as the result of a variety of condi- tions, many of them remote from the gastrointestinal tract, and I would submit that the patients described as suffering from pseudo-obstruction of the large bowel were in reality suffering from paralytic ileus.-I