tbuckley/cabot-search huggingface dataset:
Mutational analysis of the structure and functions of hepatitis C virus RNA–dependent RNA polymerase
Authors: Weiping Qin, Tatsuya Yamashita, Yukihiro Shirota, Yong Lin, Wenxiang Wei, Seishi Murakami
Journal: Hepatology (2001)

The hepatitis C virus (HCV) nonstructural protein 5B (NS5B) is an RNA-dependent RNA polymerase (RdRP), a central catalytic enzyme for HCV replication. To further understand the structure and functions of NS5B, we introduced a series of 27 clustered and 19 point substitution mutations within and outside the well-known motifs conserved among RdRP by alanine scanning and investigated effects of these mutants on enzymatic activity of NS5B. Surprisingly, most of the mutations (22 of 27 clustered mutants) do not affect RdRP activity at all, indicating that the side chains of the corresponding amino acid residues are dispensable for the catalytic activity. On the other hand, 4 mutants, cm20t, cm194t, cm2t, and cm3t, are defective in RdRP activity. By further analysis with point mutations within these regions, E18, Y191, C274, Y276, and H502 were determined to be critical for the RdRP activity. Y276 was also shown to be critical for RNA template/primer association, although 3 amino acid sequences were identified to be important for RNA template binding by RNA-filter binding assays. Finally, 4 discontinuous sequences of NS5B (aa139-145, aa149-155, aa 365-371, and aa 382-388) were found to be essential for binding to NS5A as determined by glutathione S-transferase (GST)-pull down assays using GST-NS5A and FLAG-NS5B expressed in cotransfected cells, and GST-pull down assay in vitro. In light of the crystal structure models of NS5B recently reported, our results indicate that the RdRP activity of NS5B requires the longer loop and the helix located at the distal of the thumb, which are unique among RdRPs as well as reverse transcriptases.
Hypocalcaemia after intravenous bisphosphonate
Authors: Rajesh Peter, Vinita Mishra, William D Fraser
Journal: BMJ (2004)

Editor—The word limit for lessons of the week can result in removal of discussion points during editing. We considered several of Breay's and Fergus's comments in early versions of our article. Their points are valid, and doctors prescribing bisphosphonates must read the product information and understand what can happen if the prescribing guidelines are not followed.

Our cases highlighted severe hypocalcaemia after bisphosphonate treatment, and, although mild hypocalcaemia is a well documented side effect, we are sure that Breay would agree that such dangerously low serum calcium values are not seen in 1-10% of patients treated with bisphosphonates. Experienced doctors treating hypercalcaemia of malignancy commonly use doses of 60-90 mg pamidronate for a calcium concentration around 3.0 mmol/l, and the Novartis sponsored study comparing zoledronic acid and pamidronate in patients with values ≥ 3.0 mmol/l used 90 mg pamidronate.1 Although failure to comply with prescribing recommendations may have contributed to the effects seen in our cases, the inability to mount a normal physiological response as described played a large part in the severe hypocalcaemia.

Palmieri et al misquote and wrongly interpret us. At no point did we advocate that “bisphosphonates can be used as prophylaxis against metastatic bone cancer.” We wrote: “Bisphosphonates are increasingly used to treat metabolic bone disease and as prophylaxis against metastatic cancer.”

Reviews and meta-analyses of bisphosphonates in cancer have shown clear advantages in terms of reduced skeletal morbidity.2 Guidelines outline the accepted use of these drugs.3 Recent studies have further defined the value of bisphosphonates such as zoledronic acid in several clinical settings and show treatment advantage in reducing skeletal related events in some cancers.4 The study by Saarto et al seems to contradict these findings, but the methodological problems, including a randomisation schedule that resulted in a significant imbalance of hormone receptor positive breast cancers in the two treatment groups,5 are greatly discussed at international meetings. The adverse effect of clodronate on overall survival lost significance in multivariate analysis. Further trials should clarify the position of adjuvant bisphosphonates in treating and preventing cancer related bone disease.
The Pathology of the Heart
Authors: Massimo Calabresi
Journal: JAMA (1974)

This treatise, concise and didactic yet pleasantly readable, presents the pathological anatomy of the heart and attempts to correlate morphologic and clinical manifestations of cardiac diseases. The first part describes the technique recommended for microscopic examination; the histology, cytology, and general pathology of the myocardium, including chapters on hypertrophy, endocardial changes secondary to abnormal flow and to carcinoid. Part 2 deals with acquired diseases; myocardial infarction and rheumatic carditis are extensively presented. Due to space limitation, the description of other diseases tends to be little more than a catalog. The congenital malformations are presented in the third part, which is conveniently divided into chapters according to practical criteria. Part 4 discusses cardiomyopathies, primary or associated to systemic disease; pulmonary hypertension; cardiac tumors; and rejection of cardiac transplants. The author states his aim: to provide the practicing cardiologist with the essential information on anatomic pathology of the heart. The need for
The Immunology of Transplantation.
Authors: Rupert E. Billingham
Journal: Annals of Internal Medicine (1964)

s1 April 1964The Immunology of Transplantation.Rupert E. Billingham, Ph.D.Rupert E. Billingham, Ph.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-4-733_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAn introductory account of the basic principles of transplantation immunology will be briefly presented. This will include a survey of the various manifestations of homograft-type reactivities, and of the genetic determination and chemical nature of the isoantigenic determinant groups responsible for eliciting the homograft reaction.The widely held thesis, that the reaction evoked by solid tissue homografts that establish vascular connections with their hosts is put into effect by blood-borne, immunologically activated cells of the lymphocytic series, will be critically discussed in the light of recent work. Pertinent evidence derives from studies: (1) on the adoptive transfer of sensitivity to... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Rupert E. Billingham, Ph.D.Affiliations: Philadelphia, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1964Volume 60, Issue 4Page: 733-733KeywordsCellsGenetic determinismHomograftsImmunologyTransplantationTransplantation immunology ePublished: 1 December 2008 Issue Published: 1 April 1964 PDF downloadLoading ...
Increased serum and blister fluid levels of creatine kinase in patients with toxic epidermal necroiysis
Authors: F. CAUX, O. CHOSIDOW, C. PHTLIPPON, J.C. ROUJEAU, J. REVUZ
Journal: British Journal of Dermatology (1994)

Keratinocytes have recently been reported to contain creatine kinase (CK) of brain-type isoenzyme. The aim of this study was to investigate whether necrosis of keratinocytes induced raised CK levels in toxic epidermal necrolysis (TEN). The serum and blister fluid levels of creatine kinase and its isoenzymes [muscular-type (MM), brain-type (BB), myocardial-type (MB)] were measured in 40 patients with TEN, 10 patients with other bullous dermatoses, and in suction blisters in five controls. The mean serum CK was significantly higher in TEN patients than in patients with other bullous dermatoses (mean +/- SD: 480 +/- 535 U/l vs. 107 +/- 44 U/l, P < 0.05). The MM-isoenzyme was predominant (94%). A positive correlation was found between the level of the serum CK and the percentage of body surface area (BSA) involved (r = 0.49, P < 0.001). The mean blister CK was significantly higher in TEN patients than in patients with other bullous dermatoses or controls (mean +/- SD: 728 +/- 437 U/l vs. 310 +/- 244 U/l and 268 +/- 194 U/l, respectively, P < 0.02). The isoenzyme distribution of blister CK in TEN patients was: 76.8% MM, 18.1% MB and 5% BB. Although a significant part of blister CK comigrating with CK-MB, after preincubation with protein A-Sepharose, appeared to be CK-BB/IgG complex, the CK-BB fraction constituted less than 25% of blister CK. Therefore, the CK present in increased amounts in serum and blister fluid in TEN was not directly produced by keratinocytes.
Mutation-Specific RAS Oncogenicity Explains NRAS Codon 61 Selection in Melanoma
Authors: Christin E. Burd, Wenjin Liu, Minh V. Huynh, Meriam A. Waqas, James E. Gillahan, Kelly S. Clark, Kailing Fu, Brit L. Martin, William R. Jeck, George P. Souroullas, David B. Darr, Daniel C. Zedek, Michael J. Miley, Bruce C. Baguley, Sharon L. Campbell, Norman E. Sharpless
Journal: Cancer Discovery (2014)

NRAS mutation at codons 12, 13, or 61 is associated with transformation; yet, in melanoma, such alterations are nearly exclusive to codon 61. Here, we compared the melanoma susceptibility of an NrasQ61R knock-in allele to similarly designed KrasG12D and NrasG12D alleles. With concomitant p16INK4a inactivation, KrasG12D or NrasQ61R expression efficiently promoted melanoma in vivo, whereas NrasG12D did not. In addition, NrasQ61R mutation potently cooperated with Lkb1/Stk11 loss to induce highly metastatic disease. Functional comparisons of NrasQ61R and NrasG12D revealed little difference in the ability of these proteins to engage PI3K or RAF. Instead, NrasQ61R showed enhanced nucleotide binding, decreased intrinsic GTPase activity, and increased stability when compared with NrasG12D. This work identifies a faithful model of human NRAS-mutant melanoma, and suggests that the increased melanomagenecity of NrasQ61R over NrasG12D is due to heightened abundance of the active, GTP-bound form rather than differences in the engagement of downstream effector pathways.This work explains the curious predominance in human melanoma of mutations of codon 61 of NRAS over other oncogenic NRAS mutations. Using conditional "knock-in" mouse models, we show that physiologic expression of NRASQ61R, but not NRASG12D, drives melanoma formation.
Constraint and Consent — On Being a Patient and a Subject
Authors: Howard M. Spiro
Journal: New England Journal of Medicine (1975)

I FIND it hard to believe that "informed consent," of which we physicians are now so proud, is very often valid. Many others have commented on this problem.1 , 2 It is hard, for example, to believe that the patient in the coronary-care unit, where his physicians and their machines battle for him against death, can deny any procedure or process to those wrestling for his life. Indeed, I doubt if any physician caring for any patient can ever get really informed consent from that patient; the patient-physician relation is, or should be, so strong as to make the likely-hood of free . . .
Pulmonary surfactant protein D in sera and bronchoalveolar lavage fluids.
Authors: Y Honda, Y Kuroki, E Matsuura, H Nagae, H Takahashi, T Akino, S Abe
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Pulmonary surfactant protein D (SP-D) is a hydrophilic glycoprotein with a reduced molecular mass of 43 kDa and a member of the C-type lectin superfamily, along with mannose-binding proteins and surfactant protein A (SP-A). We have recently prepared monoclonal antibodies against human SP-D and developed an enzyme-linked immunosorbent assay (ELISA). In this study, the levels of SP-D in sera and bronchoalveolar lavage (BAL) fluids of patients with lung diseases were determined by ELISA, using human recombinant SP-D as a standard. We demonstrated that the concentrations of SP-D in sera are prominently increased in patients with idiopathic pulmonary fibrosis (IPF), interstitial pneumonia with collagen disease (IPCD), and pulmonary alveolar proteinosis (PAP). Patients with IPF, IPCD, and PAP exhibited levels of serum SP-D 5.1-fold, 7.2-fold, and 7.0-fold, respectively, of those in healthy volunteers; 91.5% of the patients with IPF, 81.3% with IPCD, and 100% with PAP exhibited serum SP-D levels that exceeded the cut-off value (mean + 2 SD of control value). Serum SP-D levels appeared to reflect the disease activity of IPF and IPCD and the disease severity of PAP. High levels of SP-D in BAL fluids were shown in patients with PAP, but not with IPF and IPCD. We conclude that measurement of SP-D in sera can provide an easily identifiable and useful clinical marker for the diagnosis of IPF, IPCD, and PAP, and can predict the disease activity of IPF and IPCD and the disease severity of PAP.
Brachytherapy for prostate cancer
Authors: A. T. Porter, J. C. Blasko, P. D. Grimm, S. M. Reddy, H. Ragde
Journal: CA A Cancer Journal for Clinicians (1995)

Brachytherapy is one of the oldest techniques of radiation therapy for prostate cancer. However, its use has been controversial due to mixed results with older implant techniques and the availability of different treatment methods. New methods of brachytherapy based on improved technology and increased understanding of radiobiology hold promise for consistently improved results. This article describe the various methods of prostate brachytherapy and reviews the clinical results for these methods.
Critical Access Hospitals and the Challenges to Quality Care
Authors: Martin S. Lipsky, Michael Glasser
Journal: JAMA (2011)

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
Aneuploidy in Bowen's disease
Authors: JULIA A. NEWTON, R.S. CAMPLEJOHN, D.H. MCGIBBON
Journal: British Journal of Dermatology (1986)

Distinct aneuploid clones of keratinocytes were detected in six cases of cutaneous Bowen's disease. As Bowen's disease is an accepted precursor of malignancy, aneuploidy may prove to be a useful indicator of the risk of invasive change in dermatoses questionably pre-malignant.
Three-Dimensional Mapping of Optimal Left Ventricular Pacing Site for Cardiac Resynchronization
Authors: Robert H. Helm, Melissa Byrne, Patrick A. Helm, Samantapudi K. Daya, Nael F. Osman, Richard Tunin, Henry R. Halperin, Ronald D. Berger, David A. Kass, Albert C. Lardo
Journal: Circulation (2007)

The efficacy of cardiac resynchronization therapy (CRT) depends on placement of the left ventricular lead within the late-activated territory. The geographic extent and 3-dimensional distribution of left ventricular (LV) locations yielding optimal CRT remain unknown.Normal or tachypacing-induced failing canine hearts made dyssynchronous by right ventricular free wall pacing or chronic left bundle-branch ablation were acutely instrumented with a nonconstraining epicardial elastic sock containing 128 electrodes interfaced with a computer-controlled stimulation/recording system. Biventricular CRT was performed using a fixed right ventricular site and randomly selected LV sites covering the entire free wall. For each LV site, global cardiac function (conductance catheter) and mechanical synchrony (magnetic resonance imaging tagging) were determined to yield 3-dimensional maps reflecting CRT impact. Optimal CRT was achieved from LV lateral wall sites, slightly more anterior than posterior and more apical than basal. LV sites yielding > or = 70% of the maximal dP/dtmax increase covered approximately 43% of the LV free wall. This distribution and size were similar in both normal and failing hearts. The region was similar for various systolic and diastolic parameters and correlated with 3-dimensional maps based on mechanical synchrony from magnetic resonance imaging strain analysis.In hearts with delayed lateral contraction, optimized CRT is achieved over a fairly broad area of LV lateral wall in both nonfailing and failing hearts, with modest anterior or posterior deviation still capable of providing effective CRT. Sites selected to achieve the most mechanical synchrony are generally similar to those that most improve global function, confirming a key assumption underlying the use of wall motion analysis to optimize CRT.
Notch1 Expression in Early Lymphopoiesis Influences B versus T Lineage Determination
Authors: John C Pui, David Allman, Lanwei Xu, Susan DeRocco, Fredrick G Karnell, Sonia Bakkour, Julia Y Lee, Tom Kadesch, Richard R Hardy, Jon C Aster, Warren S Pear
Journal: Immunity (1999)

Notch receptors regulate fate decisions in many cells. One outcome of Notch signaling is differentiation of bipotential precursors into one cell type versus another. To investigate consequences of Notch1 expression in hematolymphoid progenitors, mice were reconstituted with bone marrow (BM) transduced with retroviruses encoding a constitutively active form of Notch1. Although neither granulocyte or monocyte differentiation were appreciably affected, lymphopoiesis was dramatically altered. As early as 3 weeks following transplantation, mice receiving activated Notch1-transduced BM contained immature CD4+ CD8+ T cells in the BM and exhibited a simultaneous block in early B cell lymphopoiesis. These results suggest that Notch1 provides a key regulatory signal in determining T lymphoid versus B lymphoid lineage decisions, possibly by influencing lineage commitment from a common lymphoid progenitor cell.
Walter Stanborough Sutton
Authors: Victor A. McKusick
Journal: JAMA (1961)

<h3>To the Editor:—</h3> In the editorial entitled Triple X-Sex inThe Journal, Sept. 10, page 176, you correctly credit Sutton (1903) with first developing, and assembling evidence in support of, the chromosomal theory of Mendelian inheritance. You failed to mention (it is not generally known) that Sutton was studying medicine at the time he did this important work and that he was subsequently a prominent surgeon. Walter Stanborough Sutton (1877-1916) began his cytologic work on the mechanics of spermatogenesis in the lubber grasshopper at Kansas University while he was a "premed" student. He continued the studies under Professor E. B. Wilson when he transferred to Columbia. He completed the equivalent of the first two years of medical school in 1903, the year his monumental paper<i>The Chromosomes in Heredity</i>was published. Sutton spent the period 1903 to 1905 as a foreman in the oil fields of Chautauqua County, Kansas, to
Is It Time for Physicians to Focus on the Public Health Threat of Gun Violence?
Authors: Melvin E. Belding
Journal: Annals of Internal Medicine (2013)

Letters4 June 2013Is It Time for Physicians to Focus on the Public Health Threat of Gun Violence?Melvin E. Belding, MDMelvin E. Belding, MDFrom Seattle, Washington.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-158-11-201306040-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The editorial by Dr. Laine and the editors (1) calling for an active response from American College of Physicians (ACP) members and fellows certainly is appropriate. Fear of the National Rifle Association and gun lobby by academic and public health physicians driven by concern over research support is sad but understandable. Perhaps those of us who are now retired or in positions shielded from threats of sanctions should lead the charge. What better way to finish a career in medicine than to spearhead a well-thought-out, self-funded campaign that could possibly push politicians to enact some sensible gun ...Reference1. Laine C, Taichman DB, Mulrow C, Berkwits M, Cotton D, Williams SV. A resolution for physicians: time to focus on the public health threat of gun violence. Ann Intern Med. 2013;158:493-4. [PMID: 23277894] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Seattle, Washington.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoA Resolution for Physicians: Time to Focus on the Public Health Threat of Gun Violence Christine Laine , Darren B. Taichman , Cynthia Mulrow , Michael Berkwits , Deborah Cotton , and Sankey V. Williams Is It Time for Physicians to Focus on the Public Health Threat of Gun Violence? James F. Bush Is It Time for Physicians to Focus on the Public Health Threat of Gun Violence? Jeffrey Johnson Is It Time for Physicians to Focus on the Public Health Threat of Gun Violence? E. Michael Lewiecki Is It Time for Physicians to Focus on the Public Health Threat of Gun Violence? E. Lee Murray Metrics 4 June 2013Volume 158, Issue 11Page: 850KeywordsConflicts of interestFearFirearm injuriesIntellectual disabilityPrevention, policy, and public healthViolent crime ePublished: 4 June 2013 Issue Published: 4 June 2013 Copyright & PermissionsCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Tangier Disease in Severely Progressive Coronary and Peripheral Artery Disease
Authors: Tiziana Sampietro, Mariarita Puntoni, Federico Bigazzi, Benedetto Pennato, Francesco Sbrana, Beatrice Dal Pino, Antonio Azzarà, Enrico Magagnini, Paolo Perossini, Giovanni Cei, Giovanni Bacci
Journal: Circulation (2009)
Effect of eplerenone in percutaneous coronary intervention‐treated post‐myocardial infarction patients with left ventricular systolic dysfunction: a subanalysis of the<scp>EPHESUS</scp>trial
Authors: Javaid Iqbal, Renaud Fay, David Adlam, Iain Squire, Yasir Parviz, Julian Gunn, Bertram Pitt, Faiez Zannad
Journal: European Journal of Heart Failure (2014)
Workplace healthcare initiatives reduce cardiovascular risks, Indian study concludes
Authors: G. Mudur
Journal: BMJ (2009)

Advocating healthy lifestyles in the workplace can reduce the risk of cardiovascular disease in staff and in their families, a new study from India indicates. Such interventions cost only about $7.30 (£4.60; €5.30) per person per year, it says.

The ripple effect seen in a large intervention study on cardiovascular disease refutes concerns in medical circles that workplace initiatives relating to health are ineffective or too expensive to pursue, the investigators say.

The researchers, from the Public Health Foundation of India, the Centre for Chronic Disease Control in New Delhi, and other institutions selected five workplaces representing various industry sectors and one agricultural workplace for the intervention. Each workplace provided educational material on healthy …