tbuckley/cabot-search huggingface dataset:
Endothelin-1 and Endothelin-3 Promote Invasive Behavior via Hypoxia-Inducible Factor-1α in Human Melanoma Cells
Authors: Francesca Spinella, Laura Rosanò, Valeriana Di Castro, Samantha Decandia, Maria Rita Nicotra, Pier Giorgio Natali, Anna Bagnato
Journal: Cancer Research (2007)

Abstract Endothelin (ET) B receptor (ETBR), which is overexpressed in human cutaneous melanomas, promotes tumorigenesis upon activation by ET-1 or ET-3, thus representing a potential novel therapeutic target. Hypoxia-inducible factor-1α (HIF-1α) is the transcriptional factor that conveys signaling elicited by hypoxia and growth factor receptors. Here, we investigated the interplay between ET axis and hypoxia in primary and metastatic melanoma cell lines. We report that under normoxic conditions, ETBR activation by ET-1/ET-3 enhances vascular endothelial growth factor (VEGF) up-regulation, cyclooxygenase (COX)-1/COX-2 protein expression and COX-2 promoter activity, prostaglandin E2 (PGE2) production, and do so to a greater extent under hypoxia. Moreover, COX-1/COX-2 inhibitors block ET-induced PGE2 and VEGF secretion, matrix metalloproteinase (MMP) activation, and cell invasion, indicating that both enzymes function as downstream mediators of ET-induced invasive properties. The ETBR selective antagonist BQ788 or transfection with ETBR small interfering RNA (siRNA) block the ET-mediated effects. ETs also increase HIF-1α expression under both normoxic and hypoxic conditions and its silencing by siRNA desensitizes COX-2 transcriptional activity, PGE2 and VEGF production, and MMP activation in response to ET-3, implicating, for the first time, HIF-1α/COX as downstream targets of ETBR signaling leading to invasiveness. In melanoma xenografts, specific ETBR antagonist suppresses tumor growth, neovascularization, and invasiveness-related factors. Collectively, these results identify a new mechanism whereby ET-1/ET-3/ETBR axis can promote and interact with the HIF-1α–dependent machinery to amplify the COX-mediated invasive behavior of melanoma. New therapeutic strategies using specific ETBR antagonist could provide an improved approach to the treatment of melanoma by inhibiting tumor growth and progression. [Cancer Res 2007;67(4):1725–34]
Primary Cilium Formation Requires von Hippel-Lindau Gene Function in Renal-Derived Cells
Authors: Mallory S. Lutz, Robert D. Burk
Journal: Cancer Research (2006)

Abstract Biallelic inactivation of the von Hippel-Lindau tumor suppressor gene, VHL, occurs in the majority of renal clear cell carcinomas (RCC). VHL's function, regulating the degradation of hypoxia-inducible factor α (HIFα) subunits, explains the angiogenic nature of these tumors, but not tumor initiation. Because the development of renal cysts precedes tumor formation, and because the dysfunction of primary cilium is a common pathogenic mechanism in polycystic kidney diseases, we determined whether kidney-derived VHL− cells required VHL for the generation of cilium. Ectopic expression of VHL in RCC(VHL−) cells induced increased polarization and primary cilium formation. Cilium formation correlated directly with the expression of both wild-type VHL isoforms and a VHL mutant not associated with RCC development, whereas expression of RCC-associated VHL mutants did not support ciliogenesis. Requirement of VHL for ciliogenesis was independent of HIFα abundance. These data indicate separable independent functions for VHL (HIFα degradation and differentiation) and suggest a mechanism whereby disruption of both functions is required for renal carcinogenesis. (Cancer Res 2006; 66(14): 6903-07)
Prospective Study of Sequential Technetium-99m Phosphate and Gallium Imaging in Painful Hip Prostheses (Comparison of Diagnostic Modalities)
Authors: JAMSHID TEHRANZADEH, IRA GUBERNICK, DAVID BLAHA
Journal: Clinical Nuclear Medicine (1988)

Twenty-two painful hip prostheses were studied prospectively with plain radiography, aspiration and arthrography, Tc-99m phosphate bone imaging, and gallium imaging to evaluate loosening, infection, or both and to compare the accuracy of these modalities. Fifteen pros-theses were revised yielding 14 loose femoral and eight loose acetabular components. Five proved to have infected prostheses. Arthrograms, plain radiographs, and bone scans are highly sensitive in detecting loosening of the femoral component. This study confirmed a previous retrospective study in demonstrating that accuracy of diagnosis of an abnormal acetabular component using all tour modalities is less than that for the femoral component. In infected prostheses, phosphate bone imaging showed high sensitivity of a pattern that accurately diagnosed all the infected cases, whereas gallium imaging missed one case.
Hemophilia B (factor IXSeattle 2) due to a single nucleotide deletion in the gene for factor IX.
Authors: B G Schach, S Yoshitake, E W Davie
Journal: Journal of Clinical Investigation (1987)

To understand the molecular basis for hemophilia B in patients with little or no circulating Factor IX antigen, a patient who had less than 0.2% circulating Factor IX antigen (Factor IXSeattle 2) was selected for analysis of his Factor IX gene. Genomic DNA fragments from the abnormal gene were cloned into bacteriophage lambda vectors and recombinant phage were identified using radiolabeled genomic probes obtained from the normal Factor IX gene. The exons and flanking regions of the abnormal gene were sequenced by the dideoxy chain-termination method and this sequence was compared with that of the normal gene. Only one significant difference was observed, the deletion of a single adenine nucleotide in exon V. This resulted in a frameshift that converted an aspartic acid at position 85 in the protein to a valine and the formation of a stop signal at position 86. These data indicate that the gene for Factor IXSeattle 2 codes for an 85 residue polypeptide that terminates after the first epidermal growth factor domain. Thus, the putative Factor IXSeattle 2 polypeptide lacks the second epidermal growth factor domain, the activation peptide, and the catalytic domain present in the normal protein. This provides an explanation for the coagulation disorder in this patient and represents the first report of a single nucleotide deletion and frameshift resulting in hemophilia B.
Acute Coronary Syndromes without ST-Segment Elevation — What Is the Role of Early Intervention?
Authors: William E. Boden
Journal: New England Journal of Medicine (2005)

During the past 15 years, there have been important advances in both percutaneous coronary intervention (PCI) and the pharmacotherapy of acute coronary syndromes without ST-segment elevation. Several carefully designed, randomized clinical trials have evaluated prospectively two contrasting strategies for managing these syndromes (a routine early invasive strategy and a selectively invasive strategy) and their effect on short- and long-term clinical outcomes. With the early invasive strategy, all patients undergo early coronary angiography, followed by PCI if the coronary anatomy permits. With the selectively invasive strategy, angiography and PCI are reserved for those patients who have inducible ischemia on noninvasive testing . . .
Influenza Vaccination and Warfarin Anticoagulation
Authors: BENJAMIN A. LIPSKY
Journal: Annals of Internal Medicine (1984)

Because influenza vaccine can markedly depress hepatic cytochrome P450 activity and may have caused an extreme prolongation of the prothrombin time in one patient receiving warfarin, we studied the effect of influenza vaccine on anticoagulation in 21 male outpatients receiving chronic warfarin therapy. Prothrombin times measured three to five times in the month after vaccination were in the therapeutic range as often as those measured before vaccination. Mean changes in prothrombin times measured after vaccination were not significantly different from those on the day of vaccination or in the 3 months before vaccination. The size of this study assured an 80% chance that any deviation from the observed mean prothrombin times would not exceed 2.1 s. No patient had any bleeding or thromboembolic problems. Thus, influenza vaccination of patients anticoagulated with warfarin appears to be safe.
Genetic Susceptibility, Dietary Antioxidants, and Long-Term Incidence of Age-Related Macular Degeneration in Two Populations
Authors: Jie Jin Wang, Gabriëlle H.S. Buitendijk, Elena Rochtchina, Kristine E. Lee, Barbara E.K. Klein, Cornelia M. van Duijn, Victoria M. Flood, Stacy M. Meuer, John Attia, Chelsea Myers, Elizabeth G. Holliday, Ava G. Tan, Wayne T. Smith, Sudha K. Iyengar, Paulus T.V.M. de Jong, Albert Hofman, Johannes R. Vingerling, Paul Mitchell, Ronald Klein, Caroline C.W. Klaver
Journal: Ophthalmology (2013)
Number needed to treat
Authors: S. K Talluri
Journal: BMJ (2009)

In a trial comparing a drug with a placebo for the prevention of myocardial infarction, the incidence of myocardial infarction was 5% in the group receiving drug A (treatment group) and 10% in the group receiving placebo (control group); P=0.01.

How many patients need to be treated with drug A to prevent …
Smooth muscle tumors associated with X-linked Alport syndrome: Carrier detection in females
Authors: Karin Dahan, Laurence Heidet, Jing Zhou, G. Mettler, Kathleen A. Leppig, Willem Proesmans, Albert David, Bernard Roussel, J.G. Mongeau, J.M.D. Gould, Jean-Pierre Grünfeld, Marie-Claire Gubler, Corinne Antignac
Journal: Kidney International (1995)
Clinical Features of Epidemic St. Louis Encephalitis.
Authors: Paul M. Southern
Journal: Annals of Internal Medicine (1967)

s1 May 1967Clinical Features of Epidemic St. Louis Encephalitis.Paul M. Southern Jr., M.D., James W. Smith, M.D., Jack A. Barnett, M.D., James P. Luby, M.D., Jay P. Sanford, M.D., F.A.C.P.Paul M. Southern Jr., M.D.Search for more papers by this author, James W. Smith, M.D.Search for more papers by this author, Jack A. Barnett, M.D.Search for more papers by this author, James P. Luby, M.D.Search for more papers by this author, Jay P. Sanford, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-5-1049_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptEpidemic St. Louis Encephalitis (SLE), which occurred in Dallas in late summer 1966, afforded the opportunity for sequential prospective clinical studies. Concurrently, patients having central nervous disease with cerebrospinal fluid (CSF) pleocytosis not due to SLE were evaluated in an effort to elicit contrasting clinical features.Ninety-one patients with laboratory-confirmed SLE form the basis of this report. The mortality rate was 15%. The median age was 53 years, with a range of 16 months to 87 years. There was no sex or race predominance. One third had a significant underlying disease. Clinical features included fever (99%), an altered sensorium, and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Paul M. SouthernJr., M.D.; James W. Smith, M.D.; Jack A. Barnett, M.D.; James P. Luby, M.D.; Jay P. Sanford, M.D., F.A.C.P.Affiliations: Dallas, Texas PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1967Volume 66, Issue 5Page: 1049-1049KeywordsCerebrospinal fluidColony stimulating factorDeath ratesEncephalitisFeversLeukocytosisProspective studiesRacial and ethnic issues ePublished: 1 December 2008 Issue Published: 1 May 1967 PDF downloadLoading ...
John Hugh Auchinleck Jewell
Authors: T. Jewell
Journal: BMJ (2011)

John Hugh Auchinleck Jewell was a medical scholar at Trinity College Dublin, winning the Cunningham anatomy medal on successive years and the Haughton medal for clinical medicine, as well as obtaining part 1 of the FRCS while a student. He was also a successful sportsman (knight of the campanile), …
A Comparison of Central Venous and Arterial Blood Gas Values in the Critically Ill
Authors: BARRIE PHILLIPS
Journal: Annals of Internal Medicine (1969)

Forty-one patients in an intensive care unit were studied with simultaneous central venous and femoral-arterial blood gas studies. The data obtained indicate that central venous blood samples are a reliable practical substitute for arterial sampling in assessing metabolic abnormalities in the acid-base status of the patient. However, central venous blood is at best a rough screening procedure in the assessment of respiratory acid-base abnormalities. In these 41 cases it was found that if the central venous blood gases were normal, then the arterial blood gases were invariably within the normal range, making arterial puncture unnecessary. In smaller hospitals, where physicians are not constantly in attendance, it would appear from these data that central venous blood gas analysis may substitute for arterial puncture in assessing the metabolic acid-base status of the patient, and, if the venous results are normal, it can be assumed that the arterial pressures will be within normal limits.
More dorsal cortex, yes, but what flavor?
Authors: Alessandro Treves
Journal: Behavioral and Brain Sciences (2003)

Where the isocortex comes from is an important question, but even more important is understanding what it leads to – that is, what advantage is afforded by its peculiar organization in layers of distinct neuronal types. A computational hypothesis accounts for granulation and for the differentiation between supra- and infragranular pyramidal layers, as quantitatively advantageous to support fine topography in sensory maps.
Response to Letter Regarding Article, “Oxidant Stress Impairs In Vivo Reendothelialization Capacity of Endothelial Progenitor Cells From Patients With Type 2 Diabetes Mellitus: Restoration by the Peroxisome Proliferator- Activated Receptor-γ Agonist Rosiglitazone”
Authors: Sajoscha A. Sorrentino, Christian Besler, Maja Müller, Svenja Schulz, Nina Kirchhoff, Carola Doerries, Tibor Horváth, Anne Limbourg, Florian Limbourg, Helmut Drexler, Ulf Landmesser, Ferdinand H. Bahlmann, Danilo Fliser, Hermann Haller
Journal: Circulation (2008)
Incidence of Neonatal Herpes Simplex Infections
Authors: William Nersesian
Journal: JAMA (1985)

<h3>To the Editor.—</h3> Sullivan-Bolyai et al<sup>1</sup>make a good case for an increasing incidence of neonatal herpes simplex infections in King County, Washington. Although I, too, feel that this neonatal infection is on the rise, I do not believe the increase is as dramatic as portrayed in this particular article, although a number of biases may make it appear so. The case definition used in the article required a positive viral culture. Although it is mentioned that laboratory procedures did not vary throughout the study period (1966 through 1982), it is difficult to believe that proficiency in isolating the virus did not improve during that span. There may very well have been refinements in obtaining cultures, transport media, and improved transport time that enhanced viral isolation and that were not under the control of the virus laboratory (user-dependent variables). Improved isolation capability would increase case counts over time.
Coping with loss: The dying child
Authors: D. Black
Journal: BMJ (1998)

This is the eighth in a series of 10 articles dealing with the different types of loss that doctors will meet in their practice Series editors: Colin Murray Parkes and Andrew Markus The terminal phase of a life threatening illness may be defined as one where curative treatments are not applicable but palliation is given. There is evidence that children, even young ones, are usually aware that they are dying. They may pick up these cues from parents and hospital staff, who in one study gave significantly less time and attention to children who were terminally ill than to others.1 They may not let anyone know that they know. Child and parents may maintain a "mutual pretence,"2 and yet families who have an open communication fare better psychologically. The refusal of parents and medical carers to talk about issues of death and dying with children who have life threatening diseases impedes coping for the whole family.3 Parents appreciate staff openness and many years later remember vividly the method of imparting the bad news. Accurate information, delivered with skill and sympathy and updated regularly, lessens the parents' sense of helplessness and isolation and sets up a therapeutic alliance.4 #### Summary points
Effect of an End-of-Life Planning Intervention on the Completion of Advance Directives in Homeless Persons
Authors: John Song, Edward R. Ratner, Melanie M. Wall, Dianne M. Bartels, Nancy Ulvestad, Dawn Petroskas, Melissa West, Anne Marie Weber-Main, Leah Grengs, Lillian Gelberg
Journal: Annals of Internal Medicine (2010)

Few interventions have focused on improving end-of-life care for underserved populations, such as homeless persons.To determine whether homeless persons will complete a counseling session on advance care planning and fill out a legal advance directive designed to assess care preferences and preserve the dignity of marginalized persons.Prospective, single-blind, randomized trial comparing self-guided completion of an advance directive with professionally assisted advance care planning. (ClinicalTrials.gov registration number: NCT00546884)8 sites serving homeless persons in Minneapolis, Minnesota.262 homeless persons recruited between November 2007 and August 2008.Minimal, self-guided intervention consisting of advance directive forms and written educational information versus a one-on-one advance planning intervention consisting of counseling and completing an advance directive with a social worker.Rate of advance directive completion, assessed by inspection of completed documents.The overall completion rate for advance directives was 26.7% (95% CI, 21.5% to 32.5%), with a higher rate in the counselor-guided group (37.9%) than in the self-guided group (12.8%) (CI of adjusted difference, 15.3 to 34.3 percentage points). This difference persisted across all sites and most subgroups. The advance directive's 4 clinical scenarios found a preference for surrogate decision making in 29% to 34% of written responses.Sampling was limited to a more stable subset of the homeless population in Minneapolis and may have been subject to selection bias. Modest compensation to complete the preintervention survey could have influenced participants to complete advance directives.Both a simple and complex intervention successfully engaged a diverse sample of homeless persons in advance care planning. One-on-one assistance significantly increased the completion rate. Homeless persons can respond to an intervention to plan for end-of-life care and can express specific preferences for care or a surrogate decision maker, but additional studies are needed to assess the effect of these directives on subsequent care.National Institute for Nursing Research and National Center on Minority Health and Health Disparities.
On Rules and Regulations
Authors: G. D. LeMaitre
Journal: JAMA (1979)

<h3>To the Editor.—</h3> Aring's well-written COMMENTARY, "On Rules and Regulations" (240:2543, 1978), deserves further attention. Aring has read Nisbet but does not quite comprehend the all-or-none nature of the individualist's soul. Aring still likes rules but wants to sugarcoat them. He prefers to call them "preferred direction." Come now, Doctor, the bureaucratic-mind set does not intend to issue suggestions with a smile. It is seeking homogeniety and nothing less, for it cannot tolerate the imperfections that an individualist-oriented society considers its very strength. In his quest for perfection, the bureaucrat intentionally destroys all attempts at creativity, self-development, and so forth. If anyone doubts this, visit our nursing homes. See and talk with nurses by the thousands who perform like turned-off zombies, no longer able or willing to risk upsetting the countless number of regulators and inspectors who come to sell their rules like snake oil. Speak to middle-aged physicians who
Bifurcational coronary artery lesion treatment with rapamicine-eluting stents: Results from a single center experience
Authors: Flavio Airoldi, Vassilis Spanos, Goran Stankovic, Carlo Di Mario, Alaide Chieffo, Carlo Briguori, Francesco Liistro, Mauro Carlino, Matteo Montorfano, Massimo Ferraro, Antonio Colombo
Journal: Journal of the American College of Cardiology (2003)
Chromosomes in rheumatoid arthritis.
Authors: K Goh, R F Jacox
Journal: Annals of the Rheumatic Diseases (1982)

This procedure for measuring aggregate represents a modi- fication of methods as described."To my knowledge there is no method one can use to obtain pure aggregate.The classical method for obtaining aggregate employing cen- trifugation in caesium chloride density gradients does not yield 100% aggregate.There are nonaggregatable proteo- glycans present in this fraction as well.
Mercury as a Potential Hazard in Medical Laboratories
Authors: Frances E. Noe
Journal: New England Journal of Medicine (1959)

CONTROL of mercury vapor as a possible source of toxic reactions has been well established in industry, but little information about this potential poison has been brought to the attention of those responsible for physiologic and medical laboratories. The current interest in pulmonary-function centers and establishment of new laboratories in this field exposes an increased number of persons to metallic mercury, many of whom may be unaware of its danger.The insidious nature of poisoning due to this metal is such that the patient may be relatively symptom free for years and then acquire serious chronic illness. Though conditions in . . .
The Moonlighting Dilemma
Authors: Shepard N. Cohen
Journal: JAMA (1989)

Moonlighting by medical residents is a highly controversial topic that has recently received new interest and concern as states are implementing legislative and regulatory efforts to limit residents' work hours and as teaching hospitals are increasingly concerned about liability exposure. Despite the potential problems, moonlighting, or outside employment, represents additional income to residents that enables repayment of massive student loans and/or improves their standard of living. It means additional clinical experience and responsibility, which many feel enhances their educational experience, and it permits essential night and weekend coverage for community hospital emergency departments and walk-in centers. Because of these important considerations for residents, community hospitals, and risk management, the University of Massachusetts Medical Center has developed a unique approach to the problems of moonlighting that addresses the concerns of all involved parties. The development of extended employment guidelines has also enabled the medical center to maintain a detailed database on the volume of such activity. (<i>JAMA</i>. 1989;262:529-531)
A 50-Year-Old Woman With Disabling Spinal Stenosis
Authors: Steven R. Garfin
Journal: JAMA (1995)

<h3>Dr Delbanco:</h3> Miss W is a 50-year-old woman who has a long history of low back pain. Divorced, she lives in an apartment by herself and works as a medical technician in a community-based doctor's office. She is insured through a large not-for-profit managed care organization. At 4 years of age, Miss W fell off a horse, but she did not have subsequent problems until 18 years of age when she experienced low back pain. Since then, she has had intermittent pain and multiple therapeutic recommendations from chiropractors, orthopedists, and a neurosurgeon in addition to her primary care doctor. At times, she has been on prolonged periods of bed rest and has had to miss work. Approximately 8 years ago, Miss W developed symptoms of fibromyalgia with generalized pain focused on her knees, bunions, elbows, wrists, shoulders, and pelvic region. She has been treated with multiple nonsteroidal anti-inflammatory agents (NSAIDs),