tbuckley/cabot-search huggingface dataset:
High Mobility Group A2 Potentiates Genotoxic Stress in Part through the Modulation of Basal and DNA Damage–Dependent Phosphatidylinositol 3-Kinase–Related Protein Kinase Activation
Authors: Lee Ming Boo, H. Helen Lin, Vincent Chung, Bingsen Zhou, Stan G. Louie, Michael A. O'Reilly, Yun Yen, David K. Ann
Journal: Cancer Research (2005)

Abstract The high mobility group A2 (HMGA2) protein belongs to the architectural transcription factor HMGA family, playing a role in chromosomal organization and transcriptional regulation. We and others have previously reported that ectopic HMGA2 expression is associated with neoplastic transformation and anchorage-independent cell proliferation. Here, we reported a correlation between increased HMGA2 expression and enhanced chemosensitivity towards topoisomerase II inhibitor, doxorubicin, in breast cancer cells. Using cells exhibiting differential HMGA2 expression and small interfering RNA technique, we showed that HMGA2 expression modulates cellular response to the genotoxicity of DNA double-strand breaks. Notably, HMGA2 enhances doxorubicin-elicited cell cycle delay in sub-G1 and G2-M and augments cell cycle dysregulation on cotreatment of doxorubicin and caffeine. We further reported that HMGA2 induces a persistent Ser139 phosphorylation of histone 2A variant X, analogous to the activation by doxorubicin-mediated genotoxic stress. Moreover, this HMGA2-dependent enhancement of cytotoxicity is further extended to other double-strand breaks elicited by cisplatin and X-ray irradiation and is not restricted to one cell type. Together, we postulated that the enhanced cytotoxicity by double-strand breaks in HMGA2-expressing cells is mediated, at least in part, through the signaling pathway of which the physiologic function is to maintain genome integrity. These findings should contribute to a greater understanding of the role of HMGA2 in promoting tumorigenesis and conveying (chemo)sensitivity towards doxorubicin and other related double-strand breaks.
Syndrome of Botulism in Infancy: Clinical and Electrophysiologic Study
Authors: Jackson Pickett, Bruce Berg, Edward Chaplin, Mary-Ann Brunstetter-Shafer
Journal: New England Journal of Medicine (1976)

Although botulism is characterized by weakness and hypotonicity, it is rarely considered in the diagnosis of the hypotonic infant. We report on two infants whose clinical course and electrophysiological findings were consistent with botulism and from whom botulinal toxin was identified in stool.Case ReportsCase 1. A two-month-old boy had diffuse weakness of short duration. He was the product of an unremarkable gestation, labor, and delivery. At birth, examination was normal; he had a vigorous suck. He was breast-fed and received only vitamin preparations. Growth and development were normal until he was six weeks old, when over a period . . .
Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine
Authors: H KIN, A ZATTA, M LOFYE, B AMERSON, M HALKOS, F KERENDI, Z ZHAO, R GUYTON, J HEADRICK, J VINTENJOHANSEN
Journal: Cardiovascular Research (2005)

Objective: This study tested the hypothesis that brief cycles of iterative ischemia–reperfusion at onset of reperfusion (termed "postconditioning", post-con) delays washout of intravascular adenosine and thereby increases endogenous adenosine receptor (AR) activation during the early moments of reperfusion (R).
Parkin reinvents itself to regulate fatty acid metabolism by tagging CD36
Authors: Nada A. Abumrad, Darren J. Moore
Journal: Journal of Clinical Investigation (2011)

Parkinson disease (PD) is a relatively common neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra. About 5%–10% of PD cases are inherited. Mutations in the Parkin gene, which encodes a protein that can function as an E3 ubiquitin ligase, are a common cause of familial PD. Such mutations act in a loss-of-function manner and impair the ability of the encoded protein to mediate substrate ubiquitination, although the subsequent molecular pathway that precipitates neuronal degeneration is poorly defined. In this issue of the JCI, Kim and colleagues describe painstaking evidence using a number of dissecting approaches in intact animals and cultured cells to functionally link Parkin and the class B scavenger receptor CD36, suggesting a novel and complex connection between PD and fatty acid metabolism.
Interrelationship between lung volume, expiratory flow, and lung transfer factor in fibrosing alveolitis.
Authors: J N Pande
Journal: Thorax (1981)

Fifty patients with fibrosing alveolitis studied on 104 occasions exhibited significant direct correlations between vital capacity (VC), maximum mid-expiratory flow rate (MMFR), and transfer factor for carbon monoxide (TLCO). Forced expired volume in the first second (FEV1)/VC ratio bore a weak negative correlation with VC. Peak expiratory flow, MMFR, and maximum flow rates at 50% and 25% of VC were often reduced in patients with severe grades of pulmonary dysfunction. It appears that as the severity of the fibrotic process increases, the lung volumes shrink and the transfer factor for CO decreases. The total lung capacity decreases predominantly on account of reduction in VC. With a decrease in lung volume the MMFR also falls. Decrease in flow rates at low lung volumes is greater as compared to the fall in peak flow. The expiratory flow rates however were normal or even increased when related to absolute lung volume. Some patients exhibit disproportionate expiratory slowing as evidenced by a decrease in MMFR which is out of proportion to the reduction in VC. These patients also have a reduced FEV1/VC ratio. These changes are probably the consequence of associated peripheral airway narrowing.
EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-β1 signaling
Authors: Ankang Lu, Caojian Zuo, Yuhu He, Guilin Chen, Lingjuan Piao, Jian Zhang, Bing Xiao, Yujun Shen, Juan Tang, Deping Kong, Sara Alberti, Di Chen, Shenkai Zuo, Qianqian Zhang, Shuai Yan, Xiaochun Fei, Fei Yuan, Bin Zhou, Shengzhong Duan, Yu Yu, Michael Lazarus, Yunchao Su, Richard M. Breyer, Colin D. Funk, Ying Yu
Journal: Journal of Clinical Investigation (2015)

Pulmonary arterial hypertension (PAH) is commonly associated with chronic hypoxemia in disorders such as chronic obstructive pulmonary disease (COPD). Prostacyclin analogs are widely used in the management of PAH patients; however, clinical efficacy and long-term tolerability of some prostacyclin analogs may be compromised by concomitant activation of the E-prostanoid 3 (EP3) receptor. Here, we found that EP3 expression is upregulated in pulmonary arterial smooth muscle cells (PASMCs) and human distal pulmonary arteries (PAs) in response to hypoxia. Either pharmacological inhibition of EP3 or Ep3 deletion attenuated both hypoxia and monocrotaline-induced pulmonary hypertension and restrained extracellular matrix accumulation in PAs in rodent models. In a murine PAH model, Ep3 deletion in SMCs, but not endothelial cells, retarded PA medial thickness. Knockdown of EP3α and EP3β, but not EP3γ, isoforms diminished hypoxia-induced TGF-β1 activation. Expression of either EP3α or EP3β in EP3-deficient PASMCs restored TGF-β1 activation in response to hypoxia. EP3α/β activation in PASMCs increased RhoA-dependent membrane type 1 extracellular matrix metalloproteinase (MMP) translocation to the cell surface, subsequently activating pro–MMP-2 and promoting TGF-β1 signaling. Activation or disruption of EP3 did not influence PASMC proliferation. Together, our results indicate that EP3 activation facilitates hypoxia-induced vascular remodeling and pulmonary hypertension in mice and suggest EP3 inhibition as a potential therapeutic strategy for pulmonary hypertension.
Metastatic vs Bronchogenic Carcinoma
Authors: James R. Lisa
Journal: JAMA (1966)

<h3>To the Editor:—</h3> In his letter toThe Journal(<b>197:</b>300, 1966) Dr. John Steele takes issue with previous correspondence (<b>196:</b>459, 1966), on the frequency of solitary pulmonary metastases erroneously diagnosed as bronchogenic carcinoma. To document his allegations, Dr. Steele cites a study in which approximately 300 cases of bronchogenic carcinoma were followed for 2 1/2 to 6 years and none was ultimately found to be a pulmonary metastasis even though "In many cases autopsies were performed." In the quoted sentence lies the explanation for the apparent perfection in diagnostic accuracy. It is only by means of extensive and meticulous autopsy followup that it is possible to recognize the frequent pitfalls in the clinical, biopsy, and surgical diagnoses of bronchogenic carcinoma. Tumors of the kidney, adrenal, pancreas, prostate, etc, may never attain sufficient dimensions to produce characteristic clinical
Active expiratory glottic closure during permeability pulmonary edema in nonsedated lambs.
Authors: J P Praud, V Diaz, I Kianicka, D Dalle
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

It has long been claimed that the active expiratory glottic closure observed in newborns, especially during hyaline membrane disease, is related to hypoxia. However, we recently showed that hypoxia does not lead to active expiratory glottic closure in nonsedated lambs. In this study, we test the hypothesis that glottic closure is related to an excess of lung water present at birth. We studied 17 nonsedated lambs after inducing a permeability pulmonary edema via intravenous of either oleic acid (8 lambs) or halothane (9 lambs). We recorded airflow via a facial mask and pneumotachograph, as well as the electromyographic activity (EMG) of the thyroarytenoid muscle (TA), a glottic adductor. Blood gases were measured in 8 lambs via a brachial artery catheter. We identified laryngeal expiratory airflow braking on the breath-by-breath computed flow-volume loop and TA expiratory EMG as evidence of active expiratory glottic adduction. After the injection of oleic acid or halothane, an active expiratory glottic closure was recorded in all lambs but 1, usually throughout the recording period (60 to 300 min). The active expiratory glottic closure was not inhibited after correction of the hypoxia. We conclude that, in nonsedated lambs, a permeability pulmonary edema induces an active expiratory glottic closure. We hypothesize that the expiratory glottic closure commonly observed in newborns could help to ameliorate the alveolocapillary gas exchange by reopening the flooded alveoli.
Actions of bretylium tosylate on the cardiovascular system of the dog
Authors: D. R. RICHMOND, J. A. ANGUS, A. H. GOODMAN, L. B. COBBIN
Journal: Cardiovascular Research (1973)

Bretylium tosylate produced an increase in myocardial contractility and heart rate in the dog. These actions were blocked by propranolol and by reserpine pretreatment. The drug also produced an initial transient vasodilatation which was blocked by atropine and was followed by a more sustained rise in blood pressure. This pressor response was partially blocked by phentolamine and reserpine pretreatment. It is concluded that the cardiac actions of this drug are indirect, due to catecholamine release.
A Randomized Trial Comparing Coronary Angioplasty with Coronary Bypass Surgery
Authors: Spencer B. King, Nicholas J. Lembo, William S. Weintraub, Andrzej S. Kosinski, Huiman X. Barnhart, Michael H. Kutner, Naomi P. Alazraki, Robert A. Guyton, Xue-Qiao Zhao
Journal: New England Journal of Medicine (1994)

The clinical benefit of percutaneous transluminal coronary angioplasty (PTCA) as compared with coronary-artery bypass grafting (CABG) for patients with multivessel coronary artery disease has not been established. To determine the outcomes of these treatments in patients referred for the first time for coronary revascularization, we conducted a three-year prospective, randomized trial comparing the two procedures.
Arsenic trioxide inhibits human cancer cell growth and tumor development in mice by blocking Hedgehog/GLI pathway
Authors: Elspeth M. Beauchamp, Lymor Ringer, Gülay Bulut, Kamal P. Sajwan, Michael D. Hall, Yi-Chien Lee, Daniel Peaceman, Metin Özdemirli, Olga Rodriguez, Tobey J. Macdonald, Chris Albanese, Jeffrey A. Toretsky, Aykut Üren
Journal: Journal of Clinical Investigation (2010)

The Hedgehog (Hh) pathway is activated in some human cancers, including medulloblastoma. The glioma-associated oncogene homolog (GLI) transcription factors are critical mediators of the activated Hh pathway, and their expression may be elevated in some tumors independent of upstream Hh signaling. Thus, therapies targeting GLI transcription factors may benefit a wide spectrum of patients with mutations at different nodal points of the Hh pathway. In this study, we present evidence that arsenic trioxide (ATO) suppresses human cancer cell growth and tumor development in mice by inhibiting GLI1. Mechanistically, ATO directly bound to GLI1 protein, inhibited its transcriptional activity, and decreased expression of endogenous GLI target genes. Consistent with this, ATO inhibited the growth of human cancer cell lines that depended on upregulated GLI expression in vitro and in vivo in a xenograft model of Ewing sarcoma. Furthermore, ATO improved survival of a clinically relevant spontaneous mouse model of medulloblastoma with activated Hh pathway signaling. Our results establish ATO as a Hh pathway inhibitor acting at the level of GLI1 both in vitro and in vivo. These results warrant the clinical investigation of ATO for tumors with activated Hh/GLI signaling, in particular patients who develop resistance to current therapies targeting the Hh pathway upstream of GLI.
Effects of Temperature, Na and K Concentration and Quinidine on Transmembrane Flux of K <sup>42</sup> and Incidence of Atrial Fibrillation
Authors: W. C. HOLLAND, R. L. KLEIN
Journal: Circulation Research (1958)

Experimental data is presented and discussed on the effects of temperature, K and Na concentration, and quinidine on transmembrane ion fluxes and the incidence of fibrillation in isolated rabbit atria.
Etiology of Cor Pulmonale-Reply
Authors: Harold I. Palevsky
Journal: JAMA (1990)

In Reply.—  The three conditions suggested by Dr Shander are rather peripheral to the focus of our article on chronic cor pulmonale. The first two require an unconventional definition of cor pulmonale. We began our review by defining cor pulmonale in conventional terms, ie, as  descriptive term used to denote enlargement of the right ventricle, by either hypertrophy, dilatation, or both, as a consequence of disorders and diseases of the respiratory system. 1 According to this definition, chronic left ventricular failure and mitral valve stenosis, both of which may result in pulmonary hypertension and right-sided heart failure, were inappropriate for our discussion and, therefore, were omitted.  The third condition, chronic mountain sickness, is an uncommon disorder peculiar to life at a high altitude in which cor pulmonale and right ventricular failure may feature prominently because of chronic alveolar hypoventilation and alveolar hypoxia. 2 Although our article did not single
Breaker's Neck
Authors: Bertha Ramirez
Journal: JAMA (1984)

<h3>To the Editor.—</h3> To be added to the rapidly growing list of socially acquired injuries,<sup>1-4</sup>we report a case of traumatic cervical subluxation caused by a new dance technique. This technique, labeled "breaking" by its devotees, involves a modified head stand, in which the dancer, using his arms and hands for balance, spins rapidly on his head, neck, or shoulders to the rhythm of disco music. He then lowers his body to the floor and performs a series of rotational motions using his arms as a fulcrum. <h3>Report of a Case.—</h3> A 15-year-old boy was seen in our pediatric emergency room complaining that, on awakening two days previously, he felt a "snap" in his neck, followed by persistent neck stiffness. He reported having "danced on his head" the night prior to this incident. On physical examination, his head was tilted to the left with an inability to flex or
The Kidney and Erythropoiesis.
Authors: R. D. Lange
Journal: Annals of Internal Medicine (1962)

s1 April 1962The Kidney and Erythropoiesis.R. D. Lange, M.D., F.A.C.P., N. I. Gallagher, M.D.R. D. Lange, M.D., F.A.C.P.Search for more papers by this author, N. I. Gallagher, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-56-4-685_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe kidney has been linked to erythropoiesis by both clinical and experimental investigations. Our studies of this association are reported, and the significance of these findings in the pathogenesis of renal anemia and polycythemia is discussed.Jacobson and co-workers have postulated, from animal organ extirpation experiments, that the kidney is the source or "activator" of erythropoietin. Other studies, including our own, demonstrate that the kidney of the rabbit, at least, is not the sole source of erythropoietin. Thus, assays of plasma from nephrectomized rabbits produced a radioactive iron-RBC incorporation of 5 ± 0.3% in assayed animals, while plasma from nephrectomized... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: St. Louis, Mo. (CI) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1962Volume 56, Issue 4Page: 685-686KeywordsAnemiaBlood plasmaErythropoiesisErythropoietinKidneysPathogenesisPolycythemiaRabbits Issue Published: 1 April 1962 PDF DownloadLoading ...
New building at Guy's Hospital
Authors: R F Knight
Journal: BMJ (1994)

<h3>Introduction</h3> A standard terminology is required for the chronic symptoms that may occur after pelvic radiotherapy (RT) as this will ensure that patients are treated not only for GI symptoms but are also referred when required for bladder and sexual problems, pain, nerve/bone/vascular damage, lymphoedema and mental health. ICD coding indicates radiation proctitis/colitis should be standard terms - however the ’-itis’ suffix indicates localised inflammation and fails to acknowledge the complex co-existing ischaemic and fibrotic pathology of radiation-induced damage which is mainly submucosal. <h3>Methods</h3> The Pelvic Radiation Disease Association polled visitors to the BSG2019 exhibition by showing them a choice of answers to “What do you call GI symptoms caused by pelvic radiotherapy?”. <h3>Results</h3> Respondents (n=164) were physicians (61%), nurses and other professions (39%). The majority diagnosed GI disorders after pelvic radiotherapy. Many chose more than one response (Table 1). Radiation proctitis, enteritis and colitis were the most commonly chosen. 37 respondents chose ‘Pelvic Radiation Disease’ and 30 chose ‘radiation enteropathy’. <h3>Conclusions</h3> The terminology for radiation damage is not standardised. This may impact on investigation and treatment choices by clinicians, and provides no incentive to address the spectrum of issues that may arise, and which seriously impact on quality of life. Chronic GI problems after pelvic radiotherapy are increasingly prevalent so gastroenterologists may see more of these patients than other specialists. The term ‘Pelvic Radiation Disease’ was coined<sup>1</sup> so that radiation-induced chronic toxicity is seen as a disease, rather than a constellation of vague and poorly defined symptoms. Use of this term allows prevalence to be measured, a holistic approach to be developed towards patients, a better definition of optimal therapy<sup>2</sup> and facilitation of research. Further work and debate are needed to reach consensus on this issue. <h3>References</h3> 1. Andreyev HJN et al. Defining pelvic-radiation disease for the survivorship era. Lancet Oncology. 2010;11(4):310-2. 2. Andreyev HJN et al. The practical management of the gastrointestinal symptoms of pelvic radiation disease. Frontline Gastroenterol 2015;6(1):53-72.
Submicroscopic bone marrow involvement in isolated extramedullary relapses in childhood acute lymphoblastic leukemia: a more precise definition of “isolated” and its possible clinical implications, a collaborative study of the Resistant Disease Committee of the International BFM study group
Authors: Nikola Hagedorn, Cécile Acquaviva, Eva Fronkova, Arend von Stackelberg, Andrea Barth, Udo zur Stadt, André Schrauder, Jan Trka, Nathalie Gaspar, Karl Seeger, Günter Henze, Hélène Cavé, Cornelia Eckert
Journal: Blood (2007)
Eusol: the continuing controversy
Authors: J L Burton
Journal: BMJ (1992)

fore based on self reports and hearsay.People may have many reasons for informing the police, correctly or incorrectly, about their own or others' HIV status, Such data are inaccurate: there is no justification for using them either in relation to individual HIV status or to population prevalences.Our investigations into the prevalence of HIV 1 infection among prostitutes throughout London over the past six years have included street based interviews and HIV testing with the consent of participants.We have found much lower preva- lences of HIV infection than those quoted by the police.7 Unfortunately, such research does not have the same impact on the press as police reports confirming prejudiced views of prostitutes as the major reservoir of venereal disease.Reports of the prevalence of HIV infection in tabloid newspapers clearly do not have the same rigorous peer review as your own journal, but they may have a greater impact on the lives of those concerned.Prostitutes suspected of being infected with HIV have been the target of violence and abuse.
Aspirin, Statins, or Both Drugs for the Primary Prevention of Coronary Heart Disease Events in Men: A Cost–Utility Analysis
Authors: Michael Pignone, Stephanie Earnshaw, Jeffrey A. Tice, Mark J. Pletcher
Journal: Annals of Internal Medicine (2006)

Background: Aspirin and statins are both effective for primary prevention of coronary heart disease (CHD), but their combined use has not been well studied. Objective: To perform a cost–utility analysis of the effects of aspirin therapy, statin therapy, combination therapy with both drugs, and no pharmacotherapy for the primary prevention of CHD events in men. Design: Markov model. Data Sources: Published literature. Target Population: Middle-aged men without a history of cardiovascular disease at 6 levels of 10-year risk for CHD (2.5%, 5%, 7.5%, 10%, 15%, and 25%). Time Horizon: Lifetime. Perspective: Third-party payer. Interventions: Low-dose aspirin, a statin, both drugs as combination therapy, or no therapy. Outcome Measure: Cost per quality-adjusted life-year gained. Results of Base-Case Analysis: For 45-year-old men who do not smoke, are not hypertensive, and have a 10-year risk for CHD of 7.5%, aspirin was more effective and less costly than no treatment. The addition of a statin to aspirin therapy produced an incremental cost–utility ratio of $56 200 per quality-adjusted life-year gained compared with aspirin alone. Results of Sensitivity Analysis: Excess risk for hemorrhagic stroke and gastrointestinal bleeding with aspirin, risk for CHD, the cost of statins, and the disutility of taking medication had important effects on the cost–utility ratios. Limitations: Several input parameters, particularly adverse event rates and utility values, are supported by limited empirical data. Results are applicable to middle-aged men only. Conclusions: Compared with no treatment, aspirin is less costly and more effective for preventing CHD events in middle-aged men whose 10-year risk for CHD is 7.5% or higher. The addition of a statin to aspirin therapy becomes more cost-effective when the patient's 10-year CHD risk before treatment is higher than 10%.