tbuckley/cabot-search huggingface dataset:
Ethanol enhances ADP-ribosylation of protein in rat hepatocytes
Authors: Emmanuel B. Akinshola, Savitri Sharma, James J. Potter, Esteban Mezey
Journal: Hepatology (1992)

Decreases in hepatocyte NAD + produced by ethanol are only partially explained by the increased conversion of NAD + to NADH and NADP +. The purpose of this study was to determine whether a mechanism for the ethanol-induced decrease in NAD + is its increased use in ADP-ribosylation. Exposure of hepatocytes in culture for 2 hr to 100 mmol/L ethanol increased the incorporation of 14 C-ribose from prelabeled NAD + into 14 C-ribosylated proteins. Poly (ADP-ribose) polymerase activity was increased by exposure of isolated hepatocytes to 100 mmol/L ethanol for 10 min. In hepatocyte culture, increases in poly (ADP-ribose) polymerase were not detected after exposure to 100 mmol/L ethanol for 10 min or 2 hr but rather occurred at 24 hr. Ethanol exposure of hepatocytes in culture for 2 hr, however, decreased the K m for NAD + of poly (ADP-ribose) polymerase. Both nicotinamide and 5-aminobenzamide, which are inhibitors of poly (ADP-ribose) polymerase, prevented the decrease in NAD + produced by 2-hr exposure of hepatocytes in culture to 100 mmol/L ethanol. The effect of ethanol in decreasing DNA synthesis on days 3 and 4 of culture was not reversed by the inhibitors of poly (ADP-ribose) polymerase. These results indicate that increased ADP-ribosylation of hepatocyte proteins is a mechanism for the effect of ethanol in decreasing NAD + (Hepatology 1992; 15:471-476).
Abstract 4905: Novel gene expression profiles of poorly differentiated lung cancer are enriched in stem cell factors and predictive of worse clinical outcome.
Authors: Marc Isaac Damelin, Wenyan Zhong, Veronica K. Diesl, Maximillian T. Follettie, Kenneth G. Geles
Journal: Cancer Research (2013)

Abstract Poorly differentiated non-small cell lung cancer (NSCLC) at the histopathological level has been associated with shorter patient survival. Analogously, at the cellular level, poorly differentiated tumor cells exhibit more aggressive phenotypes than their well-differentiated counterparts, including higher tumorigenic potential and higher metastatic capacity. Effective therapeutic targeting of the malignant undifferentiated cells will require a deeper understanding of their molecular drivers. To investigate the hierarchical basis of heterogeneous NSCLC tumors, we developed an improved method to study the undifferentiated and differentiated states of primary tumor cultures. The cultures were established in defined serum-free media from freshly resected tumors and were induced to differentiate either by culture in serum-containing media or by exposure to the air-liquid interface (ALI) in serum-free media with two variations. Gene expression profiles revealed similar patterns of change in all three conditions, which confirmed the undifferentiated state of the initial culture; however, differentiation in serum caused many extraneous changes in gene expression, which suggested that the ALI method represents a more physiologically relevant condition. Gene Set Enrichment Analysis demonstrated that the profile of the undifferentiated state was enriched in signatures of embryonic stem cell factors, metastasis and drug resistance. In addition, novel gene expression signatures of the undifferentiated state were predictive of shorter patient survival in a clinical dataset of NSCLC. These results establish a robust method for studying the cellular hierarchy in NSCLC that is independent of cell surface markers, and the data reveal several potential avenues for future therapeutic intervention. Citation Format: Marc Isaac Damelin, Wenyan Zhong, Veronica K. Diesl, Maximillian T. Follettie, Kenneth G. Geles. Novel gene expression profiles of poorly differentiated lung cancer are enriched in stem cell factors and predictive of worse clinical outcome. [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 4905. doi:10.1158/1538-7445.AM2013-4905
ABC of blood pressure reduction
Authors: L. Bannan
Journal: BMJ (1981)

About 0.5% of the middle-aged population have Middte-aged adults diastolic blood pressures of 130 mm Hg or more. If left untreated they have a prognosis worse than if they had cancer. A further 4% have diastolic t / °050/0 pressures of 110 to 129 mm Hg, and about 20% of these will die in five years if left untreated. The '7////!t gradient of risk extends to even lower pressures: people with diastolic pressures of 90 mm Hg have a z z;z ovvam _ shorter life expectancy than those with pressures 90 100 110 130 below this figure. A 35-year-old man with a pressure (mmHg) diastolic pressure of 100 mm Hg can expect a 16-year reduction in life expectancy and so is likely to die before he retires.
German politicians want a commissioner to investigate bribery of doctors
Authors: N. Stafford
Journal: BMJ (2009)

Health experts in Germany’s two biggest political parties have united to propose a new law that would create a commissioner in the federal health ministry to investigate allegations of bribery of doctors by hospitals and drug companies and of fraudulent billing.

The proposed law would also create a new class of prosecutor in Germany’s 16 states who would specialise in healthcare fraud and provide so called whistleblower protection for hospital staff or others who report potential fraud.

The German Medical Association and regional doctors’ groups have publicly criticised the proposed law. They say that the current legal framework for investigations and prosecution is adequate as it regularly uncovers crimes for which doctors are prosecuted.

But Karl Lauterbach, professor of health economics and epidemiology at the University of Cologne and a health spokesman for the centre left Social Democratic Party (SPD) in …
Making consent patient centred
Authors: J. Bridson
Journal: BMJ (2003)

Taking the time to explore patients' objectives not only improves consent procedures but may avoid some interventions altogether 

Guidance on obtaining patients' consent for treatment encourages doctors to consider their needs and priorities when disclosing information.1 However, the focus on disclosure, which has arisen from the need to tell patients about risk, has meant not enough attention is given to patients' objectives. To make consent properly patient centred, clinicians need to ask patients what they want from treatment before they discuss treatment strategies.2 We believe this approach is essential, especially in the management of chronic illness. It should also help protect reticent patients, whose objectives may differ from the assumptions made by clinicians.

Several UK organisations have published guidance on improving procedures for consent in the past few years (box 1). Despite this, the BMA's working party on consent stated that “current awareness of the relevant ethical and legal principles relating to consent among the medical profession is largely inadequate.”3 Although other initiatives have sought to improve guidance, the working party emphasised the need to improve implementation of what was already recommended as best practice.

The BMA's view, that patients would benefit if more clinicians were familiar with guidance on consent, may be right. However, our experience suggests that even full compliance with current guidance may not prevent unnecessary procedures in some patients.6 Box 2 gives an example of one of the many patients at the National Refractory Angina Centre who conclude that coronary intervention is not necessary once they are given an opportunity to define their objectives and the risks are put in context. In this patient's case, only his first angioplasty was consistent with his objectives as it improved his chances of survival. The other procedures were aimed at relieving symptoms and may be …
Scientists call for moratorium on genetically modified foods
Authors: B. Christie
Journal: BMJ (1999)

A group of scientists from 13 countries has supported calls for a moratorium on the release of genetically modified foods after endorsing unpublished research that has raised fears of potentialhealth hazards

The British government has come under pressure to act after an announcement by the 22 scientists that research carried out by Dr Arpad Pusztai at the Rowett Research Institute in Aberdeen had found evidence of immune system changes and organ damage in rats fed on genetically modified potatoes

Dr Pusztai was suspended from his post last year after presenting details of his unpublished findings in a Granada Television World in Action documentary. Since then, totally opposing views have formed about the research, which was part of a £1.6m ($2.56m) project funded by the Scottish Office

The Rowett Research Institute carried out a review of Dr Pusztai's …
Abstract 4406: A monoclonal antibody targeting PAUF inhibits metastasis of pancreatic cancer
Authors: Yangsoon Lee, Su Jin Kim, Hye Jin Min, Kyung Sook Yu, Eun Hye Park, Sang Seok Koh
Journal: Cancer Research (2010)

Abstract Pancreatic cancer is one of the deadliest human tumors and, due to lack of effective therapeutic agents and diagnostic tools, has a poor prognosis with approximately a five-year survival rate of less than 5%. This disease is characterized by early metastatic spread but the process of tumor cell dissemination is largely unknown. Recently, we have shown that a novel soluble protein named PAUF (Pancreatic Adenocarcinoma Up-regulated Factor) plays an important role in the metastasis and progression of the disease. The expression of CXCR4 is induced by PAUF, implicating a role of PAUF in the organ specific metastasis of pancreatic cancer. The tumorigenic and metastatic activity of PAUF suggests that PAUF could be a target for pancreatic cancer immunotherapy. To examine the therapeutic potential of PAUF, a human monoclonal antibody against PAUF (8F3) has been generated. The 8F3 antibody exerted inhibition of migration, invasion, adhesion and proliferation of pancreatic cancer cells in vitro. In combination with gemcitabine, 8F3 showed additive effect on reduction of cell growth. In orthotopically xenografted mouse model, these anti-tumor activities of 8F3 converted to growth retardation and repression of metastasis. The level of PAUF in tumor and serum from 8F3 treated mouse was lower than that of control mouse. The immunohistochemical analysis revealed that the treatment of 8F3 inhibited the proliferation and CXCR4 expression in both primary and metastasized tumors. The 8F3 antibody also alters intracellular signaling which was induced by PAUF. We will also discuss about the effect of 8F3 in tumor microenvironment, especially recruitment of immune cells. Collectively, these findings indicate that PAUF has a therapeutic potential for treatment of human pancreatic cancer and the 8F3 antibody can be developed for therapeutic agent for this disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4406.
Sympathetically Mediated Hypertension in Autonomic Failure
Authors: John R. Shannon, Jens Jordan, Andre Diedrich, Bojan Pohar, Bonnie K. Black, David Robertson, Italo Biaggioni
Journal: Circulation (2000)

Approximately 50% of patients with primary autonomic failure have supine hypertension. We investigated whether this supine hypertension could be driven by residual sympathetic activity.In patients with multiple system atrophy (MSA) or pure autonomic failure (PAF), we studied the effect of oral yohimbine on seated systolic blood pressure (SBP), the effect of ganglionic blockade (with trimethaphan) on supine SBP and plasma catecholamine levels, and the effect of alpha(1)-adrenoreceptor blockade (phentolamine) on supine SBP. The SBP response to yohimbine was greater in patients with MSA than in those with PAF (area under the curve, 2248+/-543 versus 467+/-209 mm Hg. min; P=0.022). MSA patients with a higher supine SBP had a greater response than those with a lower supine SBP (3874+/-809 versus 785+/-189 mm Hg. min; P=0. 0017); this relationship was not seen in PAF patients. MSA patients had a marked depressor response to low infusion rates of trimethaphan; the response in PAF patients was more variable. Plasma norepinephrine decreased in both groups, but heart rate did not change in either group. At 1 mg/min, trimethaphan decreased supine SBP by 67+/-8 and 12+/-6 mm Hg in MSA and PAF patients, respectively (P<0.0001). Cardiac index and total peripheral resistance decreased in MSA patients by 33.4+/-5.8% and 40.7+/-9.5%, respectively (P=0. 0015). Patients having a depressor response to trimethaphan also had a depressor response to phentolamine. In MSA patients, the pressor response to yohimbine and the decrease in SBP with 1 mg/min trimethaphan were correlated (r=0.98; P=0.001).Residual sympathetic activity drives supine hypertension in MSA. It contributes to, but does not completely explain, supine hypertension in PAF.
AMPKα2 Deletion Causes Aberrant Expression and Activation of NAD(P)H Oxidase and Consequent Endothelial Dysfunction In Vivo
Authors: Shuangxi Wang, Miao Zhang, Bin Liang, Jian Xu, Zhonglin Xie, Chao Liu, Benoit Viollet, Daoguang Yan, Ming-Hui Zou
Journal: Circulation Research (2010)

Rational : AMP-activated protein kinase (AMPK) is an energy sensor and ubiquitously expressed in vascular cells. Recent studies suggest that AMPK activation improves endothelial function by counteracting oxidative stress in endothelial cells. How AMPK suppresses oxidative stress remains to be established. Objective : The aim of this study is to examine the effects of AMPK in regulating NAD(P)H oxidase, oxidative stress, and endothelial function. Methods and Results : The markers of oxidative stress, NAD(P)H oxidase subunit expression (gp91 phox , p47 phox , p67 phox , NOX1 to -4), NAD(P)H oxidase–mediated superoxide production, 26S proteasome activity, IκBα degradation, and nuclear translocation of nuclear factor (NF)-κB (p50 and p65) were examined in cultured human umbilical vein endothelial cells and mouse aortas isolated from AMPKα2 deficient mice. Compared to the wild type, acetylcholine-induced endothelium-dependent relaxation was significantly impaired in parallel with increased production of oxidants in AMPKα2 −/− mice. Further, pretreatment of aorta with either superoxide dismutase (SOD) or tempol or apocynin significantly improved acetylcholine-induced endothelium-dependent relaxation in AMPKα2 −/− mice. Analysis of aortic endothelial cells from AMPKα2 −/− mice and human umbilical vein endothelial cells expressing dominant negative AMPK or AMPKα2-specific siRNA revealed that loss of AMPK activity increased NAD(P)H oxidase subunit expression (gp91 phox , p47 phox , p67 phox , NOX1 and -4), NAD(P)H oxidase–mediated superoxide production, 26S proteasome activity, IκBα degradation, and nuclear translocation of NF-κB (p50 and p65), whereas AMPK activation by AICAR or overexpression of constitutively active AMPK had the opposite effect. Consistently, we found that genetic deletion of AMPKα2 in low-density lipoprotein receptor knockout (LDLr −/− ) strain markedly increased 26S proteasome activity, IκB degradation, NF-κB transactivation, NAD(P)H oxidase subunit overexpression, oxidative stress, and endothelial dysfunction, all of which were largely suppressed by chronic administration of MG132, a potent cell permeable proteasome inhibitor. Conclusions : We conclude that AMPKα2 functions as a physiological suppressor of NAD(P)H oxidase and ROS production in endothelial cells. In this way, AMPK maintains the nonatherogenic and noninflammatory phenotype of endothelial cells.
Clinician-Discoverers — Marshall, Warren, and<i>H. pylori</i>
Authors: Julie Parsonnet
Journal: New England Journal of Medicine (2005)

In 2002, Barry Marshall — the cowinner with Robin Warren of this year's Nobel Prize in Physiology or Medicine for their discovery of Helicobacter pylori — edited a book entitled Helicobacter Pioneers.1 In it, he collected papers by and about the many physicians who had seen spiral bacteria in the stomach but whose work had languished or been erased from scientific memory. Indeed, the century preceding the publication of Marshall and Warren's first article on H. pylori was peppered with reports from investigators who described seeing helicobacters in human and mammalian gastric mucosa and even curing peptic ulcer disease . . .
Experience of a public education programme on early detection of cutaneous malignant melanoma.
Authors: V. R. Doherty, R. M. MacKie
Journal: BMJ (1988)

A public education campaign is described which aimed at encouraging earlier self recognition and thus treatment of cutaneous malignant melanoma. The unique aspect of this campaign was that the changes in the numbers of referrals of patients with melanomas and the changes in the hospital workload associated with this programme were quantified. In the calendar year of the campaign and the following year a statistically significant rise was seen in the percentage of thin melanomas with a good prognosis that were treated and a concomitant significant fall in the proportion of thick lesions with a poor prognosis.
Global Chromatin State Analysis Reveals Lineage-Specific Enhancers during the Initiation of Human T helper 1 and T helper 2 Cell Polarization
Authors: R. David Hawkins, Antti Larjo, Subhash K. Tripathi, Ulrich Wagner, Ying Luu, Tapio Lönnberg, Sunil K. Raghav, Leonard K. Lee, Riikka Lund, Bing Ren, Harri Lähdesmäki, Riitta Lahesmaa
Journal: Immunity (2013)
896 SUCCESSFUL HCV ERADICATION DUE TO ANTIVIRAL THERAPY IS ASSOCIATED WITH IMPROVED LONG TERM OUTCOME OF PATIENTS WITH CHRONIC HEPATITIS C
Authors: K. Rutter, A.F. Stättermayer, P. Ferenci, S. Beinhardt, T.M. Scherzer, R. Strassl, P. Steindl-Munda, M. Trauner, H. Hofer
Journal: Journal of Hepatology (2013)
Fibula Stress Fracture and Confounding Myositis Ossificans
Authors: Stephen J. Morris, Joseph Trieu, Raymond Chin, Kevin Allman, Hans Van Der Wall
Journal: Clinical Nuclear Medicine (2004)

A 26-year-old man presented with left lower leg pain after a skiing injury. Plain radiography was initially reported as normal at the site of the suspected fracture but revised after the bone scan. An additional area of calcification was described adjacent to the proximal fibula without a conclusive diagnosis. A fibula fracture was easily apparent on Tc-99m bone scintigraphy, and the more proximal focus of uptake in the soft tissues was thought to be an area of myositis ossificans, subsequently confirmed on ultrasound. The patient provided a history of trauma to the area 1 year previously. The typical correlative imaging features of confounding myositis ossificans and a stress fracture are outlined.
1131-147 Thoracic aorta atherosclerosis burden index predicts coronary artery disease in patients undergoing transesophageal echocardiography
Authors: Alexandra A Frogoudaki, John Barbetseas, Constadina Aggeli, Demosthenes Panagiotakos, Christos Pitsavos, Pavlos Toutouzas, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2004)
Pathology of Atherosclerosis
Authors: Sheldon C. Sommers
Journal: JAMA (1983)

This monograph, addressed particularly to pathologists in training, is crisply written, thoughtful, judicious, rather witty, and very well illustrated and produced. The author appears to be relatively young, scholarly, and experimentally oriented, and he describes the mainstream of present knowledge of atherosclerosis and its development. The book is a considerable intellectual accomplishment and should reward those readers who have a particular interest in the basic biomedical science of this field. Atherosclerosis is particularly a burden of aged people of developed countries. It is anatomically multifocal, not generalized, and particularly affects the aorta, large and mediumsized extravisceral arteries, and epicardial coronary branches. Experience with many gross autopsies shows how notably atherosclerosis may regress in wasting diseases like cancer or in starvation. Poorly nourished people of undeveloped countries who have little means of transportation except their legs manifest it less. Davies wrote that among African natives only the butcher has atherosclerosis because
Access to infertility investigations and treatment in couples infected with HIV: questionnaire survey
Authors: A. Apoola, J. tenHof, P S Allan
Journal: BMJ (2001)

Life expectancy among patients infected with HIV has increased since combination anti-HIV therapies were introduced. This has led to calls for infertility in people with HIV to be treated in an identical way to that in patients with other chronic medical conditions.1

Two broad groups of patients infected with HIV are likely to request infertility treatment. The first group consists of couples in which only one partner is infected with HIV (serodiscordant couples) who would like to have children but who wish to avoid the transmission of the virus to the uninfected partner; they may not be subfertile. The second group consists of serodiscordant couples who are subfertile and have tried to conceive spontaneously (with the attendant risks) without success and subfertile couples in which both partners are infected with HIV who would like to have children. We determined whether couples presenting to infertility clinics …
Mutations in GNAL cause primary torsion dystonia
Authors: Tania Fuchs, Rachel Saunders-Pullman, Ikuo Masuho, Marta San Luciano, Deborah Raymond, Stewart Factor, Anthony E Lang, Tsao-Wei Liang, Richard M Trosch, Sierra White, Edmond Ainehsazan, Denis Hervé, Nutan Sharma, Michelle E Ehrlich, Kirill A Martemyanov, Susan B Bressman, Laurie J Ozelius
Journal: Nature Genetics (2012)
Structural correlates of cross-reactive and individual idiotypic determinants on murine antibodies to alpha-(1 leads to 3) dextran.
Authors: B Clevinger, J Schilling, L Hood, J M Davie
Journal: The Journal of Experimental Medicine (1980)

For the first time V-region amino acid sequence differences have been correlated with the expression of cross-reactive and individual idiotypes through an analysis of 12 dextran-binding proteins. This correlation has been possible because of the apparent sequence identity of the corresponding lambda chains. Expression of a cross-reactive idiotype was localized to two residues and/or a carbohydrate in the second hypervariable region of the heavy chain. Two individual idiotypes correlate with the two amino acids within the third hypervariable region that comprises the D segment of the dextran-binding proteins. These results demonstrate that idiotype reagents can recognize two amino acid differences within V and D segments of classical variable regions. In anti-dextran antibodies, cross-reactive idiotypes involve V-region determinants, whereas individual idiotype determinants correlate with D-segment variation.
Pitfalls in Diagnosis
Authors: Harvey J. Blumenthal
Journal: JAMA (1975)

<h3>To the Editor.—</h3> "To err in the diagnosis of a relievable disorder is a tragedy," is Dr. Aring's initial statement in his editorial comment (229:1879, 1974) on recent articles<sup>1-3</sup>emphasizing the pitfalls in diagnosis of lesions about the junction of medulla and spinal cord. Dr. Boshes, discussing a case inThe Journal(229:1518, 1974) of a middle-aged woman with chronic neurologic findings, failed to mention a treatable lesion at the foramen magnum in his differential diagnosis. The limited clinical description indicated no cranial nerve abnormality except a vague history of visual disturbance "ten years ago, the details of which she could not recall." The chorioretinitis described could be responsible. All the other neurological findings of tremor, weakness, pyramidal signs, unilateral proprioceptive loss, and neurogenic bladder could result from a high spinal lesion. The weight loss, fever, anemia, and other constitutional symptoms may be the sequelae of chronic urinary infection;