tbuckley/cabot-search huggingface dataset:
2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol
Authors: Bruce M. Psaty, Noel S. Weiss
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Quest for the Grave of Dr Nathaniel Chapman
Authors: Frederick B. Wagner
Journal: JAMA (1985)

AT THE November 1984 meeting of the Francis C. Wood Institute of the History of Medicine in the College of Physicians of Philadelphia, Dr Wood expressed interest in finding the grave of Dr Nathaniel Chapman. The latter had been the first president of the AMA in 1847.<sup>1</sup>As professor of the Practice of Medicine at the University of Pennsylvania, Philadelphia, founder of the Philadelphia Medical Institute, president of the American Philosophical Society, and first editor of what became the<i>American Journal of the Medical Sciences</i>, he exerted a profound influence on the medical education and clinical practice of his era.<sup>2-5</sup>By coincidence, Dr Wood took care of a patient by the name of Ardenia Chapman from 1947 until her death in 1975 (<i>Philadelphia Inquirer</i>, Feb 5, 1975, p 8-B). She was a lineal descendent who remembered that Dr Chapman had been buried in St Stephen's Episcopal Church at
Comparison of Doxorubicin and Cyclophosphamide Versus Single-Agent Paclitaxel As Adjuvant Therapy for Breast Cancer in Women With 0 to 3 Positive Axillary Nodes: CALGB 40101 (Alliance)
Authors: Lawrence N. Shulman, Donald A. Berry, Constance T. Cirrincione, Heather P. Becker, Edith A. Perez, Ruth O'Regan, Silvana Martino, Charles L. Shapiro, Charles J. Schneider, Gretchen Kimmick, Harold J. Burstein, Larry Norton, Hyman Muss, Clifford A. Hudis, Eric P. Winer
Journal: Journal of Clinical Oncology (2014)

Purpose Optimal adjuvant chemotherapy for early-stage breast cancer balances efficacy and toxicity. We sought to determine whether single-agent paclitaxel (T) was inferior to doxorubicin and cyclophosphamide (AC), when each was administered for four or six cycles of therapy, and whether it offered less toxicity. Patients and Methods Patients with operable breast cancer with 0 to 3 positive nodes were enrolled onto the study to address the noninferiority of single-agent T to AC, defined as the one-sided 95% upper-bound CI (UCB) of hazard ratio (HR) of T versus AC less than 1.30 for the primary end point of relapse-free survival (RFS). As a 2 × 2 factorial design, duration of therapy was also addressed and was previously reported. Results With 3,871 patients enrolled onto the trial, a median follow-up period of 6.1 years, and 437 RFS events, we achieved an HR of 1.26 (one sided 95% UCB, 1.48; favoring AC does not allow a conclusion of noninferiority of T with AC; UCB &gt; 1.3). With 266 patient deaths, the HR for overall survival (OS) was 1.27 favoring AC (UCB, 1.56). The estimated absolute advantage of AC at 5 years is 3% for RFS (91 v 88%) and 1% for OS (95 v 94%). All nine treatment-related deaths were patients receiving AC and are included in the analyses of both RFS and OS. Hematologic toxicity was more common in patients treated with AC, and neuropathy was more common in patients treated with T. Conclusion This trial did not show noninferiority of T to AC, a conclusion that is unlikely to change with additional events and follow-up. T was less toxic than AC.
Abstract A45: Signaling Events Associated with Cytoprotective Induction of Nitric Oxide Synthase in a Photodynamic Therapy Model
Authors: Reshma Bhowmick, Albert W. Girotti
Journal: Clinical Cancer Research (2012)

Abstract Photodynamic therapy (PDT) employs a photosensitizing agent, molecular oxygen, and photosensitizer-exciting light to produce reactive oxygen species that lead to tumor eradication. Nitric oxide (NO) produced by tumor or tumor vasculature cells could be pro-carcinogenic by inhibiting apoptosis and/or promoting angiogenesis and tumor growth. We recently showed that photoactivation of 5-aminolevulinic acid (ALA)-generated protoporphyrin IX in mitochondria of COH-BR1 breast tumor cells strongly upregulated inducible nitric oxide synthase (iNOS) and steady state NO level in these cells. Including the iNOS inhibitor 1400W during photochallenge dramatically enhanced caspase-9 activation and Annexin-assessed apoptotic cell killing while reducing NO production assessed by the intracellular NO probe DAF-2DA. Short hairpin RNA (ShRNA)-based iNOS knockdown (kd) produced similar results, confirming iNOS involvement. An apoptosis-promoting effect of iNOS inhibition was also observed when breast MDA-MB231 and prostate PC-3 cancer cells were subjected to ALA/light stress. We have now examined the signaling events associated with iNOS-mediated hyperresistance of COH-BR1 cells using a combination of immunocytochemistry, western blotting, immunoprecipitaion, and iNOS-kd methods. A soluble guanylyl cyclase inhibitor failed to stimulate ALA/light-provoked apoptosis, ruling out cGMP involvement in stress resistance. ALA/light activated PI3-kinase-dependent signaling via phosphorylation-inactivation of the tumor suppressor PTEN, leading to phosphorylation-activation of pro-survival Akt. Inhibition of PI3K by Wortmannin prevented ALA/light-induced Akt activation as well as iNOS upregulation while enhancing apoptotic photokilling. Moreover, photostress activation of PI3K/Akt was accompanied by a cytosol-to-nucleus translocation of the iNOS transcription factor NF-κB, and an inhibitor of NF-kB activation prevented iNOS induction while stimulating apoptosis. Furthermore, iNOS-kd as well as 1400W treatment resulted in intensified and more prolonged activation of MAP kinases JNK and p38α by ALA/light stress. In addition, photostressed iNOS-kd cells exhibited p53 upregulation and Survivin inactivation/downregulation. The following general mechanism of NO-based cytoprotection is suggested from these and related findings: Photostress activation of PI3K/Akt suppresses pro-apoptotic MAP kinases and p53 while upregulating/activating Survivin via NF-κB-mediated induction of iNOS/NO. This study provides important new insights into photostress-elicited pro-survival signaling that could reduce PDT effectiveness, and suggests iNOS inhibitor-based interventions for counteracting this. (Supported by NIH Grant CA70823 and a grant from the MCW Cancer Center.)
Surrogate endpoints for overall survival in metastatic melanoma: a meta-analysis of randomised controlled trials
Authors: Keith T Flaherty, Michael Hennig, Sandra J Lee, Paolo A Ascierto, Reinhard Dummer, Alexander M M Eggermont, Axel Hauschild, Richard Kefford, John M Kirkwood, Georgina V Long, Paul Lorigan, Andreas Mackensen, Grant McArthur, Steven O'Day, Poulam M Patel, Caroline Robert, Dirk Schadendorf
Journal: The Lancet Oncology (2014)
Surfactant protein-A enhances respiratory syncytial virus clearance in vivo
Authors: Ann Marie LeVine, Jodie Gwozdz, James Stark, Michael Bruno, Jeffrey Whitsett, Thomas Korfhagen
Journal: Journal of Clinical Investigation (1999)

To determine the role of surfactant protein-A(SP-A) in antiviral host defense, mice lacking SP-A (SP-A–/–) were produced by targeted gene inactivation. SP-A–/– and control mice (SP-A+/+) were infected with respiratory syncytial virus (RSV) by intratracheal instillation. Pulmonary infiltration after infection was more severe in SP-A–/– than in SP-A+/+ mice and was associated with increased RSV plaque-forming units in lung homogenates. Pulmonary infiltration with polymorphonuclear leukocytes was greater in the SP-A–/– mice. Levels of proinflammatory cytokines tumor necrosis factor-α and interleukin-6 were enhanced in lungs of SP-A–/– mice. After RSV infection, superoxide and hydrogen peroxide generation was deficient in macrophages from SP-A–/– mice, demonstrating a critical role of SP-A in oxidant production associated with RSV infection. Coadministration of RSV with exogenous SP-A reduced viral titers and inflammatory cells in the lung of SP-A–/– mice. These findings demonstrate that SP-A plays an important host defense role against RSV in vivo.
Pulmonary manifestations of multicentric Castleman's disease in HIV infection: a clinical, biological and radiological study
Authors: A. Guihot, L-J. Couderc, F. Agbalika, L. Galicier, P. Bossi, E. Rivaud, A. Scherrer, D. Zucman, C. Katlama, E. Oksenhendler
Journal: European Respiratory Journal (2005)

The aim of the present study was to report clinical, radiological and bronchoalveolar lavage (BAL) findings in patients with pulmonary manifestations of HIV-associated multicentric Castleman's disease (MCD). This was a retrospective study of 12 patients with histologically proven MCD. Clinical manifestations were as follows: dyspnoea (nine out of 12 cases), cough (n = 10), bilateral crackles (n = 10), together with high fever, malaise, peripheral lymphadenopathy (n = 12), and hepatosplenomegaly (n = 10). Two patients developed acute respiratory distress syndrome. Chest radiographs and computed tomography scans showed reticular (n = 7) and/or nodular (n = 7) interstitial patterns, with mediastinal lymphadenopathy (n = 9), and bilateral pleural effusion (n = 3). Fibreoptic endoscopy was normal in all cases. BAL analysis showed hypercellularity (n = 6) and/or lymphocytosis (n = 6), and human herpesvirus-8 DNA was detected in two out of two cases. Specific stains and cultures for pathogens were negative. All patients received etoposide and/or vinblastine, and improved after 2–4 days. Relapses were frequent (50 attacks in 12 patients). Six patients developed a non-Hodgkin's lymphoma, and five died. In conclusion, the pulmonary manifestation of HIV-related multicentric Castleman's disease is an acute reticulo-nodular interstitial pneumonitis, associated with severe systemic symptoms and peripheral lymphadenopathy. In bronchoalveolar lavage fluid, cellularity is not specific and human herpesvirus-8 DNA is detected. The clinical course is specific due to a rapid onset and regression, frequent relapses and a high occurrence of non-Hodgkin's lymphoma.
Elastic Deformation in Orthotropic Vessels
Authors: JULIUS MELBIN, ABRAHAM NOORDERGRAAF
Journal: Circulation Research (1971)

Excursions of the semiaxes were used to define the distortion and shape of the vessel cross section considered for conic and almost conic models. Some describing functions and mensuration expressions closely approximate, yet greatly simplify, calculations of perimeter and cross sections. Theory and experiments with models were in good agreement, but preliminary experiments showed the real case to be more complicated. Physical properties of the pulmonary trunk varied along its axis, growing stiffer toward the periphery. Furthermore, the dimension variations with transmural loading alter concepts of properties derived from measurements of a single diameter. The influence of the pericardium on the deformation of the main pulmonary artery under transmural stress was also explored. It was seen that the pericardium exerts significant restraint on the distortion and volume variations of this vessel. Over normal pressure ranges, removal of the pericardium can result in trunk volumes up to 100% greater than realized with the pericardium intact.
Evolutionary dynamics of a mitochondrial rearrangement "hot spot" in the Hymenoptera
Authors: M. Dowton, A. D. Austin
Journal: Molecular Biology and Evolution (1999)

The arrangement of tRNA genes at the junction of the cytochrome oxidase II and ATPase 8 genes was examined across a broad range of Hymenoptera. Seven distinct arrangements of tRNA genes were identified among a group of wasps that have diverged over the last 180 Myr (suborder Apocrita); many of the rearrangements represent evolutionarily independent events. Approximately equal proportions of local rearrangements, inversions, and translocations were observed, in contrast to vertebrate mitochondria, in which local rearrangements predominate. Surprisingly, homoplasy was evident among certain types of rearrangement; a reversal of the plesiomorphic gene order has arisen on three separate occasions in the Insecta, while the tRNA(H) gene has been translocated to this locus on two separate occasions. Phylogenetic analysis indicates that this gene translocation is real and is not an artifactual translocation resulting from the duplication of a resident tRNA gene followed by mutation of the anticodon. The nature of the intergenic sequences surrounding this region does not indicate that it should be especially prone to rearrangement; it does not generally have the tandem or inverted repeats that might facilitate this plasticity. Intriguingly, these findings are consistent with the view that during the evolution of the Hymenoptera, rearrangements increased at the same time that the rate of point mutations and compositional bias also increased. This association may direct investigations into mitochondrial genome plasticity in other invertebrate lineages.
Recombinant alpha 1-antitrypsin Pittsburgh (Met 358----Arg) is a potent inhibitor of plasma kallikrein and activated factor XII fragment.
Authors: M Schapira, M A Ramus, S Jallat, D Carvallo, M Courtney
Journal: Journal of Clinical Investigation (1986)

In normal plasma, the serine protease inhibitor alpha 1-antitrypsin (alpha 1-AT) plays little or no role in the control of plasma kallikrein or activated Factor XII fragment (Factor XIIf), this function being performed by Cl-inhibitor. Recently, an alpha 1-AT variant was described with a Met----Arg mutation at the reactive center P1 residue (position 358) which altered the specificity of inhibition from the Met- or Val-specific protease neutrophil elastase to thrombin, an Arg-specific protease. We have now examined the inhibition of plasma kallikrein and Factor XIIf, both Arg-specific enzymes, with recombinant alpha 1-AT(Met358----Arg) produced by an Escherichia coli strain carrying a mutated human alpha 1-AT gene. The engineered protein was a very efficient inhibitor of both enzymes. It was more effective than Cl-inhibitor by a factor of 4.1 for kallikrein and 11.5 for Factor XIIf. These results suggest that recombinant alpha 1-AT(Met358----Arg) has therapeutic potential for disease states where activation of the plasma kinin-forming system is observed, for example in hereditary angioedema or septic shock.
Regulation of Cardiac cAMP Synthesis and Contractility by Nucleoside Diphosphate Kinase B/G Protein βγ Dimer Complexes
Authors: Hans-Joerg Hippe, Mark Luedde, Susanne Lutz, Henrike Koehler, Thomas Eschenhagen, Norbert Frey, Hugo A. Katus, Thomas Wieland, Feraydoon Niroomand
Journal: Circulation Research (2007)

Heterotrimeric G proteins are pivotal regulators of myocardial contractility. In addition to the receptor-induced GDP/GTP exchange, G protein alpha subunits can be activated by a phosphate transfer via a plasma membrane-associated complex of nucleoside diphosphate kinase B (NDPK B) and G protein betagamma-dimers (Gbetagamma). To investigate the physiological role of this phosphate transfer in cardiomyocytes, we generated a Gbeta1gamma2-dimer carrying a single amino acid exchange at the intermediately phosphorylated His-266 in the beta1 subunit (Gbeta1H266Lgamma2). Recombinantly expressed Gbeta1H266Lgamma2 were integrated into heterotrimeric G proteins in rat cardiomyocytes but were deficient in intermediate Gbeta phosphorylation. Compared with wild-type Gbeta1gamma2 (Gbeta1WTgamma2), overexpression of Gbeta1H266Lgamma2 suppressed basal cAMP formation up to 55%. A similar decrease in basal cAMP production occurred when the formation of NDPK B/Gbetagamma complexes was attenuated by siRNA-mediated NDPK B knockdown. In adult rat cardiomyocytes expressing Gbeta1H266Lgamma2, the basal contractility was suppressed by approximately 50% which correlated to similarly reduced basal cAMP levels and reduced Ser16-phosphorylation of phospholamban. In the presence of the beta-adrenoceptor agonist isoproterenol, the total cAMP formation and contractility were significantly lower in Gbeta1H266Lgamma2 than in Gbeta1WTgamma2 expressing cardiomyocytes. However, the relative isoproterenol-induced increased was not affected by Gbeta1H266Lgamma2. We conclude that the receptor-independent activation of G proteins via NDPK B/Gbetagamma complexes requires the intermediate phosphorylation of G protein beta subunits at His-266. Our results highlight the histidine kinase activity of NDPK B for Gbeta and demonstrate its contribution to the receptor-independent regulation of cAMP synthesis and contractility in intact cardiomyocytes.
Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases
Authors: G R Burmester, P Mease, B A C Dijkmans, K Gordon, D Lovell, R Panaccione, J Perez, A L Pangan
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objectives:</h3> Clinical trials of tumour necrosis factor antagonists have raised questions about the potential risk of certain serious adverse events (SAE). To assess the safety of adalimumab in rheumatoid arthritis (RA) over time and across five other immune-mediated inflammatory diseases and to compare adalimumab malignancy and mortality rates with data on the general population. <h3>Methods:</h3> This analysis included 19 041 patients exposed to adalimumab in 36 global clinical trials in RA, psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease (CD), psoriasis and juvenile idiopathic arthritis (JIA) to 15 April 2007. Events per 100 patient-years were calculated using SAE reported after the first dose to 70 days after the last dose. Standardised incidence rates were calculated for malignancies using national and state-specific databases. Standardised mortality rates (SMR) were calculated for each disease using data from the World Health Organization. <h3>Results:</h3> Cumulative rates of SAE of interest in RA have remained stable over time. Rates of SAE of interest for PsA, AS, CD, psoriasis and JIA were similar to or lower than rates for RA. Overall malignancy rates for adalimumab-treated patients were as expected for the general population. SMR across all six diseases indicated that no more deaths occurred with adalimumab than expected in the general population. <h3>Conclusions:</h3> Based on 10 years of clinical trial experience across six diseases, this safety report and the established efficacy of adalimumab in these diseases provide the foundation for a better understanding of its benefit–risk profile.
Variable Thyrotropin Response to Thyrotropin-releasing Hormone after Small Decreases in Plasma Free Thyroid Hormone Concentrations in Patients with Nonthyroidal Diseases
Authors: Susan J. Maturlo, Robert L. Rosenbaum, Chao Pan, Martin I. Surks
Journal: Journal of Clinical Investigation (1980)

Although a normal serum thyrotropin (TSH) concentration is generally considered to be the most important finding to support the clinical impression of euthyroidism in patients with nonthyroidal diseases and decreased serum triiodothyronine (T3), the regulation of TSH secretion in sick patients has not been studied previously. Accordingly, we studied the regulation of TSH secretion in 23 patients with nonthyroidal diseases; 15 of the patients had decreased serum T3. TSH regulation was studied by measuring the TSH response to injected thyrotropin-releasing hormone (TRH) before and after effecting a small decrease in serum thyroxine (T4) and/or T3 concentrations by iodide treatment, 262 mg daily for 10 d. Iodide treatment significantly decreased (> 10%) the free T4 index (FT4-I) and/or free T3 index (FT3-I) in all patients. FT4-I values were correlated (0.611, P < 0.001), with free T4 concentration determined by equilibrium dialysis. Despite decreased FT4-I and/or FT3-I after iodide treatment in all patients, the TSH response to TRH after iodide treatment was augmented in only 8 of 15 patients who had decreased serum T3 (group 1) and in only 5 of 8 patients who had a normal serum T3. Mean base-line TSH concentration was increased significantly (P < 0.05) from 0.9±0.1 to 1.5±0.3 μU/ml in group 1 only. Comparison of the mean TSH response to TRH showed that there was no significant difference between groups 1 and 2. Moreover, no significant difference in thyroidal parameters was observed between patients who had augmented TSH response to TRH after iodides and those who had either similar or decreased TSH response irrespective of the initial serum T3. These studies show that an augmented TSH response to TRH in response to a small reduction in serum T4 and T3 concentration occurred in only 57% of the entire group of patients with nonthyroidal diseases and that the presence or absence of a normal TSH response to this stimulus did not seem to be related to the base-line serum T3 concentration. Because an increase in serum TSH in response to decreased serum T4 and T3 did not occur in about one-half of patients with nonthyroidal diseases, normal serum TSH may not be a reliable index of the euthyroid state in these patients.
Acute Effects of Orally Administered Levamisole on Random Monocyte Motility and Chemotaxis in Man&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S. David Nathanson, Peter L. Zamfirescu, Joseph K. Portaro, Jean B. deKernion, John L. Fahey
Journal: JNCI Journal of the National Cancer Institute (1978)

Cellular immune functions were studied in patients with early bladder cancer 2 hours after ingestion of either levamisole or a placebo. Random monocyte motility was significantly increased (P less than 0.025) in 13 of 17 patients receiving levamisole. Monocyte chemotaxis was significantly increased (P less than 0.025) in 16 of the 17 patients. Random monocyte motility and monocyte chemotaxis did not change in either 8 patients on the placebo or in 15 normal controls. Monocytes from normal donors showed increased random motility and chemotaxis after incubation with levamisole in vitro. These results indicated that increases in peripheral blood monocyte motility followed oral administration of levamisole. Kinetic studies indicated that these effects were rapid in onset and short lived.
Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial
Authors: Hector H Garcia, Isidro Gonzales, Andres G Lescano, Javier A Bustos, Mirko Zimic, Diego Escalante, Herbert Saavedra, Martin Gavidia, Lourdes Rodriguez, Enrique Najar, Hugo Umeres, E Javier Pretell
Journal: The Lancet Infectious Diseases (2014)