tbuckley/cabot-search huggingface dataset:
Remnant Lipoprotein-Induced Smooth Muscle Cell Proliferation Involves Epidermal Growth Factor Receptor Transactivation
Authors: Akio Kawakami, Akira Tanaka, Tsuyoshi Chiba, Katsuyuki Nakajima, Kentaro Shimokado, Masayuki Yoshida
Journal: Circulation (2003)

Background— Remnant lipoproteins (RLPs) have been shown to play a causative role during atherosclerosis. Furthermore, it is known that vascular smooth muscle cell (SMC) proliferation is crucial for the development of atherosclerosis and restenosis after percutaneous coronary intervention. We examined the direct effect of RLPs on the proliferation and signal transduction of SMCs. Methods and Results— Incubation in the presence of RLPs (20 mg cholesterol per dL) for 48 hours induced rat aortic SMC proliferation (2.3-fold over medium alone). RLPs also induced the phosphorylation of epidermal growth factor (EGF) receptor in SMCs, which was followed by the activation of mitogen-activated protein kinases. Moreover, the activation of protein kinase C (PKC) as well as the shedding of membrane-bound soluble heparin-binding EGF-like growth factor (HB-EGF) was observed after RLP treatment of SMCs, whereas PKC inhibitors and metalloprotease inhibitors inhibited RLP-induced EGF receptor transactivation and HB-EGF shedding in SMCs. Furthermore, anti-HB-EGF neutralizing antibody inhibited RLP-induced EGF receptor transactivation. Phosphorylation of EGF receptor and HB-EGF shedding were also observed in the aortas of apolipoprotein E–knockout mice but not in those of C57BL6 mice. Conclusions— These results suggest that RLPs transactivate EGF receptor via PKC and HB-EGF shedding from SMCs, resulting in SMC proliferation.
Fas and tumor necrosis factor receptor-mediated cell death: similarities and distinctions.
Authors: M V Clement, I Stamenkovic
Journal: The Journal of Experimental Medicine (1994)

Fas antigen and two tumor necrosis factor receptors (TNFR), p55 and p75, are implicated in the triggering of cell death upon stimulation by natural ligands and specific monoclonal antibodies. However, the relative efficiency of each receptor, the mechanisms that regulate their function and the signaling pathways they employ, remain to be elucidated. In this study, fusion proteins, composed of the extracellular domain of CD40 and the intracellular and transmembrane domains of Fas, TNFRp55 and TNFRp75, were stably expressed in a human melanoma cell line that is deficient in Fas and TNFR expression. Transfectants were stimulated by a soluble recombinant form of the CD40 ligand gp39, and the effect on cell viability determined. Engagement of all three fusion proteins by the gp39 ligand induced lethal signals, but the rate at which cell death occurred was distinct. Fas-derived signals were observed to have the most rapid effect, killing most cells within hours of stimulation, whereas TNFRp55- and TNFRp75-associated signals resulted in cell death within 2-3 d after engagement by ligand. It is interesting to note that optimal cell killing by all three fusion proteins was dependent on a critical, low to intermediate, cell surface expression level. High levels of fusion protein expression, on the other hand, were associated with inhibition of cell death. Our results provide a model to study Fas and TNFR-mediated cell death and suggest a novel mechanism for the regulation of death signals triggered by members of the TNFR family.
Laboratory Diagnosis of Polycythemia and Anemia
Authors: Thomas Hale Ham, William B. Castle, Frank H. Gardner, Geneva A. Daland
Journal: New England Journal of Medicine (1950)

In the following sections the various laboratory procedures to determine mechanism of red-cell destruction are outlined in order that the physician may study the problem of hemolytic anemias in an orderly fashion in view of present knowledge. These procedures have been found to be most useful as screening and specific tests. Although many other methods may be listed, those included herein have been used for several years and are considered most helpful. The more routine technics of enumerating blood values are not discussed.8. Detection of Sickle-Cell Phenomenon(1) Principle Hahn and Gillespie36 and others18,38–40 have shown that . . .
A Conflict of Interest “Revisited”: The Use of Stereotypes
Authors: Matthew Zucker
Journal: Annals of Internal Medicine (1994)

Letters15 May 1994A Conflict of Interest “Revisited”: The Use of StereotypesMatthew Zucker, MDMatthew Zucker, MDNorth Miami Beach, FL 33169Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-10-199405150-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:You published a fictional essay [1] about lawyers, physicians, patients, and families who struggle to solve their problems. Named characters include attorneys Slattery and Prudhomme, Dr. Simpson, Allen Heath, Jennie Heath, and Mrs. Heath. Then there is attorney Isadore Lavinsky, described as “scum, a street fighter … He'll do anything … : perjury, bribery, witness tampering …” The only identifiable Eastern European Jew is the scummy lawyer, Iggie Lavinsky. Why give the Jewish name to the unsavory, unethical attorney? Everyone else gets a neutral “American” name. What is the message? Do the author and the editors really ...REFERENCE1. LaCombe MA. A conflict of interest. Ann Intern Med. 1993; 119:623-6. Google Scholar Author, Article, and Disclosure InformationAffiliations: North Miami Beach, FL 33169 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 May 1994Volume 120, Issue 10Page: 893-894KeywordsConflicts of interestForecastingJewish people Issue Published: 15 May 1994 CopyrightCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Response to Letter Regarding Articles, “Prevalence of Long QT Syndrome Gene Variants in Sudden Infant Death Syndrome,” “Cardiac Sodium Channel Dysfunction in Sudden Infant Death Syndrome,” and “Contribution of Long-QT Syndrome Genes to Sudden Infant Death Syndrome: Is It Time to Consider Newborn Electrocardiographic Screening?”
Authors: Peter J. Schwartz, Alfred L. George
Journal: Circulation (2007)
Society of Authors and its Medical Writers Group.
Authors: P MacLiesh, J H Baron
Journal: BMJ (1985)

and tireless on behalf of his less successful colleagues, put succinctly the need for such a society: When we begin writing, we are so poor and so busy that we have neither the time nor the means to defend ourselves against the commercial organisations which exploit us.When we become famous, we become famous suddenly, passing at one bound from the state in which we are, as I have said, too poor to fight our own battles, to a state in which our time is so valuable that it is not worth our while wasting any of it on lawsuits and bad debts.
A CASE OF DOUBLE UTERUS.
Authors: C. H. NEWTH
Journal: JAMA (1906)

I wish to report a case of double uterus. I first saw the patient one year ago, when called to determine whether she was pregnant or not. She had been married five years without becoming pregnant, but had not menstruated for five months and now thought she felt motion. She called me in because the tumor seemed to be all on the left side.  On making a vaginal examination, I found the vagina divided by a septum, and at the upper end of each side of the vagina a cervix and uterine cavity. As the patient was certainly pregnant, I could not use a sound. She was pregnant on the left side. The finger passed naturally up the right side and was with difficulty passed on the left side. I asked her if she knew that she was different from other women and she said no, but on further questioning
Impaired activation of adipocyte lipolysis in familial combined hyperlipidemia.
Authors: S Reynisdottir, M Eriksson, B Angelin, P Arner
Journal: Journal of Clinical Investigation (1995)

The pathophysiology of familial combined hyperlipidemia (FCHL) is unknown, but altered lipid turnover in peripheral tissues as well as hepatic overproduction of apolipoprotein B have been suggested as possible causes. In the present study, we explored whether a change in triglyceride breakdown by lipolysis in fat cells is present in FCHL. Lipolysis activation by catecholamines was examined in isolated subcutaneous adipocytes from 10 patients with FCHL and 22 healthy control subjects. Lipolysis rate was linear for at least 3 h in both groups. However, a marked (approximately 65%) decrease in the lipolytic response to noradrenaline was found in FCHL. This was also true when lipolysis was maximally stimulated at the receptor level with isoprenaline (nonselective beta-adrenergic agonist), at the adenylyl cyclase level with forskolin, or at the level of the protein kinase hormone-sensitive lipase complex with dibutyryl cAMP. The maximum enzymatic activity of hormone-sensitive lipase was decreased by approximately 40% in FCHL. On the other hand, the lipolytic sensitivity of alpha 2-, beta 1-, and beta 2-adrenoceptors was normal in this condition, as was the number and affinity of beta 1- and beta 2-adrenoceptors. Variations in the maximum lipolysis rate correlated significantly with the variations in hormone-sensitive lipase activity in the whole material, and with the serum values for triglycerides, HDL cholesterol and apoB lipoprotein within the control group, but the serum triglyceride values in FCHL were higher than this correlation predicted. In conclusion, the data demonstrate a marked resistance to the lipolytic effect of catecholamines in fat cells from patients with FCHL, in spite of normal adrenoceptor function. The lipolytic defect appears predominantly to be due to a defect in hormone-sensitive lipase, and may be of importance in the pathophysiology of FCHL.
Left Atrial Appendage “Stunning” After Electrical Cardioversion of Atrial Flutter: An Attenuated Response Compared With Atrial Fibrillation as the Mechanism for Lower Susceptibility to Thromboembolic Events
Authors: Richard A Grimm, William J Stewart, Kristopher L Arheart, James D Thomas, Allan L Klein
Journal: Journal of the American College of Cardiology (1997)
A missense mutation in hepatocyte nuclear factor-4 alpha, resulting in a reduced transactivation activity, in human late-onset non-insulin-dependent diabetes mellitus.
Authors: E H Hani, L Suaud, P Boutin, J C Chèvre, E Durand, A Philippi, F Demenais, N Vionnet, H Furuta, G Velho, G I Bell, B Laine, P Froguel
Journal: Journal of Clinical Investigation (1998)

Non-insulin-dependent diabetes mellitus (NIDDM) is a heterogeneous disorder characterized by hyperglycemia resulting from defects in insulin secretion and action. Recent studies have found mutations in the hepatocyte nuclear factor-4 alpha gene (HNF-4alpha) in families with maturity-onset diabetes of the young (MODY), an autosomal dominant form of diabetes characterized by early age at onset and a defect in glucose-stimulated insulin secretion. During the course of our search for susceptibility genes contributing to the more common late-onset NIDDM forms, we observed nominal evidence for linkage between NIDDM and markers in the region of the HNF-4alpha/MODY1 locus in a subset of French families with NIDDM diagnosed before 45 yr of age. Thus, we screened these families for mutations in the HNF-4alpha gene. We found a missense mutation, resulting in a valine-to-isoleucine substitution at codon 393 in a single family. This mutation cosegregated with diabetes and impaired insulin secretion, and was not present in 119 control subjects. Expression studies showed that this conservative substitution is associated with a marked reduction of transactivation activity, a result consistent with this mutation contributing to the insulin secretory defect observed in this family.
Effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora and bacterial translocation in rats with experimental cirrhosis
Authors: Maite Chiva, Germán Soriano, Isabelle Rochat, Carmen Peralta, Florence Rochat, Teresa Llovet, Beatriz Mirelis, Eduardo J. Schiffrin, Carlos Guarner, Joaquim Balanzó
Journal: Journal of Hepatology (2002)
Audit in general practice: factors influencing participation
Authors: R. Baker, N. Robertson, A. Farooqi
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To identify the factors influencing participation in a single topic audit initiated by a medical audit advisory group. <b>Design</b>: Interview and questionnaire survey of general practitioners who had been invited to take part in an audit of vitamin B-12. <b>Setting</b>: All 147 general practices in Leicestershire. <b>Main outcome measures</b>: Aspects of structure, attitude, and behaviour that influenced participation or non-participation. <b>Results</b>: 75 practices completed the audit, 49 withdrew after initial agreement,and 23 refused to take part at the outset. Participants were more likely than those who refused to view the advisory group as useful or a threat and to have positive thoughts about audit but less likely to have previously undertaken audit entailing implementation ofchange. Participants were more likely than those who withdrew to have positive thoughts about audit and to have discussed whether to take part within the practice but were less likely to view the advisory group as useful. The most common reason given for withdrawal was lack of time. <b>Conclusions</b>: Participation was influenced by attitudes towards audit in general and the advisory group in particular and by aspects of behaviour such as communication within the practice. Practical support and resources may help some practices undertake audit, but advisory groups must also deal with attitudes and unsatisfactory communication in practice teams.
Differences Between Out-of-Hospital Cardiac Arrest in Residential and Public Locations and Implications for Public-Access Defibrillation
Authors: Fredrik Folke, Gunnar H. Gislason, Freddy K. Lippert, Søren L. Nielsen, Peter Weeke, Morten L. Hansen, Emil L. Fosbøl, Søren S. Andersen, Søren Rasmussen, Tina K. Schramm, Lars Køber, Christian Torp-Pedersen
Journal: Circulation (2010)

Background— The majority of out-of-hospital cardiac arrests (OHCAs) occur in residential locations, but knowledge about strategic placement of automated external defibrillators in residential areas is lacking. We examined whether residential OHCA areas suitable for placement of automated external defibrillators could be identified on the basis of demographic characteristics and characterized individuals with OHCA in residential locations. Methods and Results— We studied 4828 OHCAs in Copenhagen between 1994 and 2005. The incidence and characteristics of OHCA were examined in every 100×100-m (109.4×109.4-yd) residential area according to its underlying demographic characteristics. By combining ≥2 demographic characteristics, it was possible to identify 100×100-m (109.4×109.4-yd) areas with at least 1 arrest every 5.6 years (characterized by &gt;300 persons per area and lowest income) to 1 arrest every 4.3 years (characterized by &gt;300 persons per area, lowest income, low education, and highest age). These areas covered 9.0% and 0.8% of all residential OHCAs, respectively. Individuals with OHCA in residential locations differed from public ones in that the patients were older (70.6 versus 60.6 years; P &lt;0.0001), the ambulance response interval was longer (6.0 versus 5.0 minutes; P &lt;0.0001), arrests occurred more often at night (21.2% versus 11.2%; P &lt;0.0001), the patients had ventricular fibrillation less often (12.8% versus 38.1%; P &lt;0.0001), and the patients had a worse 30-day survival rate (3.2% versus 13.9%; P &lt;0.0001). Conclusions— On the basis of simple demographic characteristics of a city center, we could identify residential areas suitable for automated external defibrillator placement. Individuals with OHCA in residential locations were more likely to have characteristics associated with poor outcome compared with public arrests.
Limitations of Radionuclide Angiographic Assessment of Left Ventricular Systolic Function before Lung Transplantation
Authors: HERVÉ MAL, ANTOINE LEVY, THIERRY LAPERCHE, CHARLES SLEIMAN, JEAN LOUIS STIEVENART, ALAIN COHEN-SOLAL, OLIVIER BRUGIÈRE, GUY LESÈCHE, GILLES JEBRAK, MICHEL FOURNIER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

To evaluate the influence of increased right ventricular afterload on radionuclide assessment of the left ventricular ejection fraction (LVEF), we compared the preoperative and postoperative value of isotopic LVEF in 11 patients who underwent lung transplantation and had a preoperative LVEF value below 55% (normal value: 68 ± 8%). The underlying disease conditions were obstructive lung disease (n = 7) and pulmonary fibrosis (n = 4). The transplantation procedure was unilateral in 10 patients and bilateral in one. The mean value of isotopic LVEF prior to transplantation was 51 ± 3% (range: 49% to 55%). At 42 ± 13 mo postoperatively, isotopic LVEF increased significantly, to 65 ± 10% (p = 0.001), suggesting that intrinsic left ventricular systolic function was in fact normal in these patients. We hypothesize that the low preoperative isotopic LEVF was not related to intrinsic dysfunction of the left ventricle, but rather to right ventricular pressure overload, leading to bulging of the interventricular septum into the left ventricle and to subsequent geometric distortion of the left ventricle. We conclude that isotopic LVEF may underestimate intrinsic left-ventricular systolic function in patients with severe chronic lung disease. Candidates for lung transplantation should not be rejected on the basis of a low isotopic LVEF, provided echocardiographic examination does show apparently normal left ventricular contraction.
Variable anatomy of the right coronary artery supply to the left ventricle.
Authors: J Adams, T Treasure
Journal: Thorax (1985)

The right coronary artery is "dominant" (contributing to the supply of the left ventricular muscle) in 90% of people. Although the most common pattern is for the right coronary artery to bifurcate at the crux giving the posterior descending (posterior interventricular) artery, a branch may arise before the crux, either as an aberrant acute marginal artery or as an early posterior descending artery, crossing the diaphragmatic surface of the right ventricle. Recognition of this possibility may be important if surgical revascularisation is to be complete. To establish the frequency of these different patterns of blood supply, 22 hearts were studied in the dissecting room, and 100 consecutive coronary angiograms and 100 consecutive operative drawings were reviewed. A vessel arising before the crux contributed to the supply of the left ventricle in one third of cases.
Early Insulin Therapy in Very-Low-Birth-Weight Infants
Authors: Kathryn Beardsall, Sophie Vanhaesebrouck, Amanda L. Ogilvy-Stuart, Christine Vanhole, Christopher R. Palmer, Mirjam van Weissenbruch, Paula Midgley, Michael Thompson, Marta Thio, Luc Cornette, Iviano Ossuetta, Isabel Iglesias, Claire Theyskens, Miranda de Jong, Jag S. Ahluwalia, Francis de Zegher, David B. Dunger
Journal: New England Journal of Medicine (2008)

Studies involving adults and children being treated in intensive care units indicate that insulin therapy and glucose control may influence survival. Hyperglycemia in very-low-birth-weight infants is also associated with morbidity and mortality. This international randomized, controlled trial aimed to determine whether early insulin replacement reduced hyperglycemia and affected outcomes in such neonates.
“Doctor, Is My Sugar Normal?”
Authors: Ronald A. Arky
Journal: New England Journal of Medicine (2005)

We live in an era in which the public interest in medical matters is high. When so much information and misinformation are available on the Internet, many patients devote a fair share of time to matching their most recent laboratory results with the “normal” values cited in health-related Web sites or even in the advertisements for their medication. It seems reasonable for patients to strive to achieve the best possible results from medication or other treatments, and patients' requests for information about the desired goals of treatment are to be commended.Frequently, as physicians, we are asked, “Are my laboratory . . .
Prolyl Hydroxylase Domain Protein 2 Silencing Enhances the Survival and Paracrine Function of Transplanted Adipose-Derived Stem Cells in Infarcted Myocardium
Authors: Wei Eric Wang, Dezhong Yang, Liangpeng Li, Wei Wang, Yulan Peng, Caiyu Chen, Peng Chen, Xuewei Xia, Hongyong Wang, Jiahui Jiang, Qiao Liao, Yuan Li, Ganfeng Xie, Haiyun Huang, Yanli Guo, Linda Ye, Dayue Darrel Duan, Xiongwen Chen, Steven R. Houser, Chunyu Zeng
Journal: Circulation Research (2013)

Transplantation of stem cells into damaged hearts has had modest success as a treatment for ischemic heart disease. One of the limitations is the poor stem cell survival in the diseased microenvironment. Prolyl hydroxylase domain protein 2 (PHD2) is a cellular oxygen sensor that regulates 2 key transcription factors involved in cell survival and inflammation: hypoxia-inducible factor and nuclear factor-κB.We studied whether and how PHD2 silencing in human adipose-derived stem cells (ADSCs) enhances their cardioprotective effects after transplantation into infarcted hearts.ADSCs were transduced with lentiviral short hairpin RNA against prolyl hydroxylase domain protein 2 (shPHD2) to silence PHD2. ADSCs, with or without shPHD2, were transplanted after myocardial infarction in mice. ADSCs reduced cardiomyocyte apoptosis, fibrosis, and infarct size and improved cardiac function. shPHD2-ADSCs exerted significantly more protection. PHD2 silencing induced greater ADSC survival, which was abolished by short hairpin RNA against hypoxia-inducible factor-1α. Conditioned medium from shPHD2-ADSCs decreased cardiomyocyte apoptosis. Insulin-like growth factor-1 (IGF-1) levels were significantly higher in the conditioned medium of shPHD2-ADSCs versus ADSCs, and depletion of IGF-1 attenuated the cardioprotective effects of shPHD2-ADSC-conditioned medium. Nuclear factor-κB activation was induced by shPHD2 to induce IGF-1 secretion via binding to IGF-1 gene promoter.PHD2 silencing promotes ADSCs survival in infarcted hearts and enhances their paracrine function to protect cardiomyocytes. The prosurvival effect of shPHD2 on ADSCs is hypoxia-inducible factor-1α dependent, and the enhanced paracrine function of shPHD2-ADSCs is associated with nuclear factor-κB-mediated IGF-1 upregulation. PHD2 silencing in stem cells may be a novel strategy for enhancing the effectiveness of stem cell therapy after myocardial infarction.