tbuckley/cabot-search huggingface dataset:
β-globin gene transfer to human bone marrow for sickle cell disease
Authors: Zulema Romero, Fabrizia Urbinati, Sabine Geiger, Aaron R. Cooper, Jennifer Wherley, Michael L. Kaufman, Roger P. Hollis, Rafael Ruiz de Assin, Shantha Senadheera, Arineh Sahagian, Xiangyang Jin, Alyse Gellis, Xiaoyan Wang, David Gjertson, Satiro DeOliveira, Pamela Kempert, Sally Shupien, Hisham Abdel-Azim, Mark C. Walters, Herbert J. Meiselman, Rosalinda B. Wenby, Theresa Gruber, Victor Marder, Thomas D. Coates, Donald B. Kohn
Journal: Journal of Clinical Investigation (2013)

Autologous hematopoietic stem cell gene therapy is an approach to treating sickle cell disease (SCD) patients that may result in lower morbidity than allogeneic transplantation. We examined the potential of a lentiviral vector (LV) (CCL-βAS3-FB) encoding a human hemoglobin (HBB) gene engineered to impede sickle hemoglobin polymerization (HBBAS3) to transduce human BM CD34+ cells from SCD donors and prevent sickling of red blood cells produced by in vitro differentiation. The CCL-βAS3-FB LV transduced BM CD34+ cells from either healthy or SCD donors at similar levels, based on quantitative PCR and colony-forming unit progenitor analysis. Consistent expression of HBBAS3 mRNA and HbAS3 protein compromised a fourth of the total β-globin-like transcripts and hemoglobin (Hb) tetramers. Upon deoxygenation, a lower percentage of HBBAS3-transduced red blood cells exhibited sickling compared with mock-transduced cells from sickle donors. Transduced BM CD34+ cells were transplanted into immunodeficient mice, and the human cells recovered after 2-3 months were cultured for erythroid differentiation, which showed levels of HBBAS3 mRNA similar to those seen in the CD34+ cells that were directly differentiated in vitro. These results demonstrate that the CCL-βAS3-FB LV is capable of efficient transfer and consistent expression of an effective anti-sickling β-globin gene in human SCD BM CD34+ progenitor cells, improving physiologic parameters of the resulting red blood cells.
The effect of prolonged exposure to NO2 from birth on airways responsiveness in rabbits sensitized at birth
Authors: G J Douglas, J F Price, C P Page
Journal: European Respiratory Journal (1995)

Our aim was to determine whether daily exposure to 4 ppm nitrogen dioxide (NO2) from birth until 3 months of age influenced the development of airways hyperresponsiveness and atopic sensitivity in immunized rabbits. Littermate New Zealand white (NZW) rabbits were immunized within 24 h of birth by i.p. injection of house dust mite antigen in AI(OH)3 gel, and exposed to either ambient air or 4 ppm NO2 for 2 h.day-1, 5 days.week-1. At 3 months, bronchoalveolar lavage (BAL) and serum samples were obtained. Airways responsiveness was measured as the provocative concentrations (mg.ml-1) of histamine or methacholine required to elicit a 50% increase in airway resistance (RLPC50) and a 35% decrease in dynamic compliance (CdynPC35). There were no differences in total cell or differential cell counts recovered in BAL fluid between control and NO2 exposed animals. Airways responsiveness did not differ between groups of animals (histamine RLPC50 values: air (n = 15) versus NO2 (n = 13), respectively, 9.98 +/- 1.32 versus 16.43 +/- 1.45 mg.ml-1; CdynPC35 values: 16.60 +/- 1.44 versus 14.95 +/- 1.43 mg.ml-1; methacholine RLPC50 values: air (n = 14) versus NO2 (n = 12), respectively, 2.18 +/- 1.51 versus 2.21 +/- 1.32 mg.ml-1; CdynPC35 values: 2.64 +/- 1.41 versus 2.85 +/- 1.31 mg.ml-1). There was no difference in sensitization between groups of animals exposed to air or NO2, evaluated either by cutaneous responsiveness to intradermal antigen, or serum immunoglobulin E (IgE) levels assessed by the passive cutaneous anaphylaxis (PCA) reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanisms Underlying the Lack of Effect of Implantable Cardioverter-Defibrillator Therapy on Mortality in High-Risk Patients With Recent Myocardial Infarction
Authors: Paul Dorian, Stefan H. Hohnloser, Kevin E. Thorpe, Robin S. Roberts, Karl-Heinz Kuck, Michael Gent, Stuart J. Connolly
Journal: Circulation (2010)

Background— Although implantable cardioverter-defibrillators (ICDs) lower mortality in stable patients with low ejection fraction late after myocardial infarction, randomized trials of ICD versus control subjects implanted early after myocardial infarction do not show mortality benefit. Our objective was to investigate possible mechanisms underlying the lack of mortality benefit in the Defibrillation in Acute Myocardial Infarction Trial (DINAMIT). Methods and Results— This is a secondary analysis of the prospective randomized clinical trial. Outpatients with recent (6 to 40 days) acute myocardial infarction, left ventricular dysfunction (ejection fraction &lt;35%), and low heart rate variability were randomized to ICD (n=311) or to standard medical therapy (n=342). In a competing-risks analysis, those factors that increased the risk of arrhythmic death also increased the risk of nonarrhythmic deaths. After adjustment for these factors, receiving an ICD was associated with a decreased risk of arrhythmic death (hazard ratio, 0.33; 95% confidence interval, 0.15 to 0.71) but an increase in nonarrhythmic death (hazard ratio, 1.70; 95% confidence interval, 1.00 to 2.80). In an adjusted time-dependent analysis, patients receiving an ICD and having appropriate ICD therapy had a 15.1% yearly hazard of mortality compared with 5.2% in ICD patients with no appropriate therapy ( P &lt;0.001). The reduction in sudden death in ICD patients was completely offset by increased nonarrhythmic deaths, which were greatest in patients receiving ICD shock therapy (hazard ratio, 6.0; 95% confidence interval, 2.8 to 12.7). Conclusions— In patients receiving ICDs early after myocardial infarction, those factors that are associated with arrhythmia requiring ICD therapy are also associated with a high risk of nonsudden death, negating the benefit of ICDs in this setting.
Juxtaglomerular cells grown as monolayer cell culture contain renin, angiotensin I-converting enzyme, and angiotensin I and II/III.
Authors: W A Rightsel, T Okamura, T Inagami, J A Pitcock, Y Takii, B Brooks, P Brown, E E Muirhead
Journal: Circulation Research (1982)

A monolayer cell culture of juxtaglomerular cells (JGC) was derived from the renal cortex of neonatal rats. The JGC had the characteristics of those within the kidney, including peripheral dense bodies and myofibrils indicating a smooth muscle origin; rough ER containing fluffy material consistent with protein synthesis; a prominent Golgi apparatus for packaging granules, and granules having the characteristics of secretory granules and lysosomes. Transplants of the cultured cells into syngeneic recipients survived for 2 weeks or longer and retained the features of JGC. The JGC granules fluoresced when treated with a rabbit antibody against pure rat renin, followed by fluorescein isothyocyanate conjugated F(ab')2 fragment of goat antirabbit IgG (Fc fragment) heavy chain specific. The latter indicated the presence of renin. The JGC were lysed in the presence of DFP, captopril, leupeptin, and EDTA, and were extracted in the presence of pepstatin. The lysate contained renin activity that was inhibited by a specific renin antibody. Nonspecific proteases were excluded by the antibody and its pH optimum. Angiotensin I-converting enzyme was detected in the lysate prepared without the use of EDTA and captopril. Angiotensins I and II/III were derived from the extract by additional extractions, TLC, and RIA, using highly specific antibodies. The angiotensins were confirmed by chromatography monitored by authentic angiotensins. We concluded that the cultured JGC contained renin, angiotensin I-converting enzyme, and angiotensin I and II/III.
Extrahepatic Biliary Obstruction Caused by Small-Cell Lung Cancer
Authors: DAVID H. JOHNSON
Journal: Annals of Internal Medicine (1985)

Twelve patients with small-cell lung cancer seen during a 30-month period had jaundice at diagnosis. Five patients had a pancreatic metastasis resulting in extrahepatic biliary obstruction, and seven had diffuse hepatic metastases without extrahepatic obstruction. All patients with pancreatic masses had complete (or nearly complete) resolution of jaundice and abdominal pain within 3 weeks of starting chemotherapy. Patients with extensive liver metastases usually remained icteric in spite of intensive treatment. Three patients with pancreatic metastases survived more than 12 months after the institution of therapy. No patient presenting with jaundice caused solely by hepatic metastases survived beyond 8 months. Small-cell lung cancer can present with jaundice due to diffuse hepatic parenchymal involvement, which is associated with a poor prognosis, or as a result of extrahepatic biliary obstruction, which has potential for rapid palliation and prolonged survival.
Pharmacy Practice and Antibiotic-Resistant Tuberculosis Along the US-Mexico Border
Authors: Noelle G. Pyle
Journal: JAMA (1994)

<h3>To the Editor.</h3> —Multiply-resistant tuberculosis is increasing in the United States and is emerging as a significant public health problem.<sup>1</sup>Contributing to this is opportunistic infection of those immunocompromised with human immunodeficiency virus<sup>2,3</sup>and possible indiscriminate or inappropriate use of therapeutic agents.<sup>4</sup> Inappropriate use may be promoted by the discrepant regulation of drugs along the US-Mexico border. Health professionals are aware that Mexican and American consumers are frequenting pharmacies on the Mexican side of the border to obtain drugs that commonly can be purchased without a prescription and often at lower cost than in the United States. The density of pharmacies in many Mexican border towns exceeds possible demand for pharmacy services from the local population and appears to serve transient consumers crossing the border. In May 1993, a nurse practicing in the US city of Nogales, Ariz, encountered a mother who was treating her child for
Controlled Human Infection and Rechallenge with <i>Streptococcus pneumoniae</i> Reveals the Protective Efficacy of Carriage in Healthy Adults
Authors: Daniela M. Ferreira, Daniel R. Neill, Mathieu Bangert, Jenna F. Gritzfeld, Nicola Green, Adam K. A. Wright, Shaun H. Pennington, Laura Bricio Moreno, Adriana T. Moreno, Eliane N. Miyaji, Angela D. Wright, Andrea M. Collins, David Goldblatt, Aras Kadioglu, Stephen B. Gordon
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

The immunological and protective role of pneumococcal carriage in healthy adults is not known, but high rates of disease and death in the elderly are associated with low carriage prevalence.We employed an experimental human pneumococcal carriage model to investigate the immunizing effect of a single carriage episode.Seventy healthy adults were challenged, and of those with carriage, 10 were rechallenged intranasally with live 6B Streptococcus pneumoniae up to 11 months after clearance of the first carriage episode. Serum and nasal wash antibody responses were measured before and after each challenge.A total of 29 subjects were experimentally colonized. No subjects were colonized by experimental rechallenge, demonstrating the protective effect of initial carriage against subsequent infection. Carriage increased both mucosal and serum IgG levels to pneumococcal proteins and polysaccharide, resulting in a fourfold increase in opsonophagocytic activity. Importantly, passive transfer of postcarriage sera from colonized subjects conferred 70% protection against lethal challenge by a heterologous strain in a murine model of invasive pneumococcal pneumonia. These levels were significantly higher than the protection conferred by either precarriage sera (30%) or saline (10%).Experimental human carriage resulted in mucosal and systemic immunological responses that conferred protection against recolonization and invasive pneumococcal disease. These data suggest that mucosal pneumococcal vaccination strategies may be important for vulnerable patient groups, particularly the elderly, who do not sustain carriage.
Sphingosine Facilitates SNARE Complex Assembly and Activates Synaptic Vesicle Exocytosis
Authors: Frédéric Darios, Catherine Wasser, Anastasia Shakirzyanova, Artur Giniatullin, Kerry Goodman, Jose L. Munoz-Bravo, Jesica Raingo, Jernej Jorgačevski, Marko Kreft, Robert Zorec, Juliana M. Rosa, Luis Gandia, Luis M. Gutiérrez, Thomas Binz, Rashid Giniatullin, Ege T. Kavalali, Bazbek Davletov
Journal: Neuron (2009)
News Reports of Medical Meetings: How Reliable Are Abstracts?
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1980)

ON May 9th last, so said the press release, a "special briefing on the newest health research" was held in the Rayburn House Office Building in Washington, D.C. It was the day before the annual meetings of the three major clinical research societies (the American Federation for Clinical Research, the American Society for Clinical Investigation, and the Association of American Physicians), and their officers were trying a new scheme to enhance public appreciation of clinical investigation.A dozen carefully chosen investigators, whose latest unpublished work was scheduled for presentation during the scientific sessions of the next three days, were on . . .
Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenström macroglobulinemia
Authors: Irene M. Ghobrial, Federico Campigotto, Timothy J. Murphy, Erica N. Boswell, Ranjit Banwait, Feda Azab, Stacey Chuma, Janet Kunsman, Amanda Donovan, Farzana Masood, Diane Warren, Scott Rodig, Kenneth C. Anderson, Paul G. Richardson, Edie Weller, Jeffrey Matous
Journal: Blood (2013)
Geographic Variation in Physicians' Fees
Authors: Ira L. Burney
Journal: JAMA (1978)

To study geographic differences in physician fees recognized by the Medicare and Medicaid programs, we analyzed physician reimbursement rates at the national, regional, state, and county levels. The results indicate that nationally, Medicaid specialist fees are 77% of Medicare specialist fees. Meidcare specialist fees in metropolitan areas are 23% higher than those in nonmetropolitan areas, but there are no differences under Medicaid. State Medicare specialist fees varied from 73% to 132% of the national Medicare average, while Medicaid specialist fees ranged from 49% to 179% of the national Medicaid average. State Medicaid fees for specialists ranged from 39% to 100% of Medicare specialist fees. These results indicate that under national health insurance, fees set at national or statewide levels could have notable effects on physician remuneration in some localities.
Soluble Receptor Activator of Nuclear Factor-κB Ligand and Risk for Cardiovascular Disease
Authors: Stefan Kiechl, Georg Schett, Judith Schwaiger, Klaus Seppi, Paula Eder, Georg Egger, Peter Santer, Agnes Mayr, Qingbo Xu, Johann Willeit
Journal: Circulation (2007)

Overexpression of receptor activator of nuclear factor-kappaB ligand (RANKL) is a prominent feature of vulnerable atherosclerotic lesions prone to rupture and was thought to contribute to the transition from a stable to an unstable plaque phenotype in both human and murine atherosclerosis because of its ability to promote matrix degradation, monocyte/macrophage chemotaxis, and vascular calcification.The Bruneck Study is a prospective, population-based survey of men and women 40 to 79 years of age at the 1990 baseline examination. Levels of soluble RANKL and other variables were assessed in 909 subjects (1990). All cases of cardiovascular disease were carefully recorded between 1990 and 2005. During follow-up, cardiovascular disease (defined as ischemic stroke and transient ischemic attack, myocardial infarction, and vascular death) manifested in 124 of the 909 subjects. Baseline serum level of RANKL emerged as a highly significant predictor of vascular risk (adjusted hazard ratio per 1-unit increase in soluble RANKL, 1.27; 95% confidence interval, 1.16 to 1.40; P<0.001). Predictive significance was independent of that afforded by the classic vascular risk factors, C-reactive protein, osteoprotegerin concentration, and severity of carotid atherosclerosis. Findings were internally consistent and robust in a variety of sensitivity analyses. Notably, soluble RANKL was not associated with carotid or femoral artery atherosclerosis.Our study lends large-scale epidemiological support to a role for RANKL in cardiovascular disease. In the absence of a significant association between RANKL and atherosclerosis, the idea that RANKL promotes plaque destabilization and rupture is a highly appealing concept.
Analysis of trends in deaths from accidental drug poisoning in teenagers, 1985-95
Authors: I. Roberts, M. Barker, L. Li
Journal: BMJ (1997)

Surveys in secondary schools over the past 25 years have shown large increases in the number of teenagers exposed to drugs.A study in Wolverhampton found that the proportion of secondary school pupils who had been offered drugs more than doubled between 1989 and 1994. 1 The proportion of pupils who had been offered the psychostimulant drug Ecstasy (3,4-methylenedioxymethamphetamine) increased from 5% to 43% between 1989 and 1994. 1 Accidental overdose and acute severe complications are important causes of death among drug misusers. 2 We examined trends in death rates from accidental poisoning in teenagers aged 15-19 years from 1985 to 1995.
Germinal Center Founder Cells Display Propensity for Apoptosis before Onset of Somatic Mutation
Authors: Serge Lebecque, Odette de Bouteiller, Christophe Arpin, Jacques Banchereau, Yong-Jun Liu
Journal: The Journal of Experimental Medicine (1997)

B lymphocytes undergo affinity maturation of their antigen receptors within germinal centers. These anatomical structures develop in secondary lymphoid organs from the clonal expansion of a few antigen-specific founder B cells, whose isolation and characterization are reported here. Human germinal center founder cells express the naive B cell markers surface IgM and IgD as well as the germinal center B cell markers CD10 and CD38. They express low levels of Bcl-2, high levels of Fas, and undergo rapid apoptosis in culture. The smaller nonproliferating sIgM+IgD+CD38+ B cells displayed a lower level of somatic mutation in their immunoglobulin variable region genes compared with the large proliferating ones. Unmutated sIgM+IgD+CD38+ tonsillar B cells may thus represent germinal center founder cells in which the program for apoptotic cell death is triggered before the onset of somatic mutation, allowing the selection of the germline antibody repertoire at an early stage.
Transient Systolic Dysfunction after Relief of Cardiac Tamponade
Authors: Mark W. Wolfe
Journal: Annals of Internal Medicine (1993)

Cardiac tamponade is known to directly affect the diastolic function of the myocardium, but no cases have been reported in which systolic function was affected. We describe two patients with malignant pericardial effusions and previously normal left ventricular function in whom marked reductions in left ventricular systolic function developed after the relief of tamponade by pericardiocentesis. The patients received serial follow-up with transthoracic echocardiography, which documented a progressive return to normal systolic function in the absence of further intervening therapy. These two cases suggest that cardiac tamponade may transiently affect systolic function. Potential pathophysiologic mechanisms include changes in coronary blood flow and sympathetic tone induced by tamponade.
The plasma estradiol as an index of fetoplacental function
Authors: Dan Tulchinsky, Stanley G. Korenman
Journal: Journal of Clinical Investigation (1971)

A radioligand assay has been developed for the measurement of unconjugated 17beta-estradiol in as little as 0.01 ml of pregnancy plasma employing rabbit uterine cytosol as specific binder and activated charcoal as nonspecific absorbant. Large numbers of samples could be processed simultaneously at relatively little expense and results were obtainable within 3 hr. The procedure was sensitive to 1 ng/ml. No diurnal or positional variations were found. Values from 250 unselected normal patients showed a constantly rising mean plasma E(2) from 18 to 35 wk gestation from 4.5 to 14 ng/ml. From 35 to 40 wk, mean E(2) rose only to 15 ng/ml and the range of values increased substantially. When 22 normal pregnant subjects were followed serially, rising levels of plasma E(2) were found with no significant fall ever seen. By contrast, patients exhibiting fetal distress generally had falling or reduced E(2) levels. However, 3 cases of Rh isoimmunization had elevated or normal E(2) concentrations even after clearcut evidence of fetal demise. A decrease of 45% in E(2) concentration was associated with intraamniotic instillation of hypertonic saline prior to delivery supporting the view that placental conversion of maternal adrenal precursors is responsible for about half of the E(2) production in pregnancy. The postpartum clearance of endogenous E(2) was measured and found to fit a two compartment model with mean half-time of 22 min and 7 hr. Follicular phase levels of E(2) were attained by 35 hr postpartum. The concentration of unconjugated E(2) in pregnancy plasma correlated as well with the state of the placenta as other placental hormone measurements and holds promise of being a rapid, inexpensive, and reliable method of following patients with high-risk pregnancies in a variety of clinical settings.
SHORT AND LONG TERM MORTALITY IN NEW ONSET ATRIAL FIBRILLATION AFTER CORONARY ARTERY BYPASS GRAFT: A SYTEMATIC REVIEW AND META-ANALYSIS
Authors: Roop K. Kaw, Adrian V. Hernandez, Iqbal Masood, Walid Saliba, A. Marc Gillinov, Eugene H. Blackstone
Journal: Journal of the American College of Cardiology (2010)
Peritoneal dialysis per se is a risk factor for sclerostin-associated adynamic bone disease
Authors: Rodrigo A. de Oliveira, Fellype C. Barreto, Monique Mendes, Luciene M. dos Reis, João Henrique Castro, Zita Maria L. Britto, Igor D.B. Marques, Aluizio B. Carvalho, Rosa M. Moysés, Vanda Jorgetti
Journal: Kidney International (2014)
Retained Surgical Instrument
Authors: Anne Dembitzer, Edwin J Lai
Journal: New England Journal of Medicine (2003)

A 59-year-old man with a history of diverticulosis came to the clinic with abdominal pain in the right upper quadrant of two weeks' duration. His surgical history included a subtotal colectomy for pancolitis and subsequent laparoscopic removal of an intraabdominal surgical clamp (in 2000). His most recent surgery, performed in October 2001, was a ventral hernia repair. Postoperatively, he had intermittent loose stools but felt well and gained weight. In June 2002, the patient presented to our center with abdominal pain, anorexia, and nausea, which had developed two weeks earlier. Abdominal computed tomographic scans showed a 16-cm Mayo clamp (Panels . . .