tbuckley/cabot-search huggingface dataset:
Golgi and sarcolemmal neuronal NOS differentially regulate contraction-induced fatigue and vasoconstriction in exercising mouse skeletal muscle
Authors: Justin M. Percival, Kendra N.E. Anderson, Paul Huang, Marvin E. Adams, Stanley C. Froehner
Journal: Journal of Clinical Investigation (2010)

Signaling via the neuronal NOS (nNOS) splice variant nNOSmu is essential for skeletal muscle health and is commonly reduced in neuromuscular disease. nNOSmu is thought to be the predominant source of NO in skeletal muscle. Here we demonstrate the existence of what we believe to be a novel signaling pathway, mediated by the nNOS splice variant nNOSbeta, localized at the Golgi complex in mouse skeletal muscle cells. In contrast to muscles lacking nNOSmu alone, muscles missing both nNOSmu and nNOSbeta were severely myopathic, exhibiting structural defects in the microtubule cytoskeleton, Golgi complex, and mitochondria. Skeletal muscles lacking both nNOSmu and nNOSbeta were smaller in mass, intrinsically weak, highly susceptible to fatigue, and exhibited marked postexercise weakness. Our data indicate that nNOSbeta is a critical regulator of the structural and functional integrity of skeletal muscle and demonstrate the existence of 2 functionally distinct nNOS microdomains in skeletal muscle, created by the differential targeting of nNOSmu to the sarcolemma and nNOSbeta to the Golgi. We have previously shown that sarcolemmal nNOSmu matches the blood supply to the metabolic demands of active muscle. We now demonstrate that nNOSbeta simultaneously modulates the ability of skeletal muscle to maintain force production during and after exercise. We conclude therefore that nNOS splice variants are critical regulators of skeletal muscle exercise performance.
Our Stubborn Quest for Diagnostic Certainty
Authors: J P Kassirer
Journal: New England Journal of Medicine (1989)

Absolute certainty in diagnosis is unattainable, no matter how much information we gather, how many observations we make, or how many tests we perform. A diagnosis is a hypothesis about the nature of a patient's illness, one that is derived from observations by the use of inference.1 2 3 As the inferential process unfolds, our confidence as physicians in a given diagnosis is enhanced by the gathering of data that either favor it or argue against competing hypotheses. Our task is not to attain certainty, but rather to reduce the level of diagnostic uncertainty enough to make optimal therapeutic decisions.4 5 6 7 Testing is . . .
European Organisation for Research and Treatment of Cancer Recommendations for Planning and Delivery of High-Dose, High-Precision Radiotherapy for Lung Cancer
Authors: Dirk De Ruysscher, Corinne Faivre-Finn, Ursula Nestle, Coen W. Hurkmans, Cécile Le Péchoux, Allan Price, Suresh Senan
Journal: Journal of Clinical Oncology (2010)

To derive recommendations for routine practice and clinical trials for techniques used in high-dose, high-precision thoracic radiotherapy for lung cancer.A literature search was performed to identify published articles considered both clinically relevant and practical to use. Recommendations were categorized under the following headings: patient selection, patient positioning and immobilization, tumor motion, computed tomography and [18F]fluorodeoxyglucose-positron emission technology scanning, generating target volumes, radiotherapy treatment planning, treatment delivery, and scoring of response and toxicity. The American College of Chest Physicians grading of recommendations was used.Recommendations were identified for each of the recommendation categories. Although most of the recommended techniques have not been evaluated in multicenter clinical trials, their use in high-precision thoracic radiotherapy and stereotactic body radiotherapy (SBRT) appears to be justified on the basis of available evidence.Recommendations to facilitate the clinical implementation of high-precision conformal radiotherapy and SBRT for lung tumors were identified from the literature. Some techniques that are considered investigational at present were also highlighted.
635 SIGNIFICANCE OF INTRAHEPATIC TUMOR CONTROL IN THE PROGNOSIS OF PATIENTS WITH HEPATOCELLULAR CARCINOMA AND EXTRAHEPATIC METASTASES
Authors: S.M. Jung, J.W. Jang, C.R. You, S.H. Yoo, J.H. Kwon, K.W. Chung, C.S. Kay, H.S. Jung
Journal: Journal of Hepatology (2011)
Basolateral membrane Na+/H+ antiport, Na+/base cotransport, and Na+-independent Cl-/base exchange in the rabbit S3 proximal tubule.
Authors: I Kurtz
Journal: Journal of Clinical Investigation (1989)

The basolateral membrane Na+ and Cl(-)-dependent acid-base transport processes were studied in the isolated perfused rabbit S3 proximal straight tubule. Intracellular pH (pHi) was measured with 2'7'-biscarboxyethyl-5,6-carboxyfluorescein (BCECF) and a microfluorometer coupled to the tubule perfusion apparatus. Reduction of basolateral HCO3- from 25 to 5 mM caused pHi to decrease at a rate of 0.81 pH/min. Approximately 50% of this rate was Na+-dependent, 30% Cl(-)-dependent and 20% Na+ and Cl(-)-independent. Two basolateral Na+-dependent acid base transport pathways were detected: (a) an amiloride-sensitive Na+/H+ antiporter and (b) a stilbene-sensitive Na+/base cotransporter. No evidence was found for a Na+-dependent Cl-/base exchanger. The Cl(-)-dependent component of basolateral base efflux was mediated by a stilbene-sensitive Na+-independent Cl-/base exchange pathway. The results suggest that the acid base transport pathways of the basolateral membrane of the S3 proximal tubule differ from more proximal nephron segments.
The new CONSORT statement
Authors: G. Antes
Journal: BMJ (2010)

The guidance is clear, but awareness and endorsement are lagging behind

Full and transparent reporting of results of clinical trials is essential for assessing the quality of healthcare interventions. Inadequate reporting of trials is common, and it impedes the use of trial results in healthcare research and practice.1 Consequently, during the past 15 years, a series of reporting guidelines have been developed and recently collected by the Equator Initiative (www.equator-network.org).2 The pioneering first step of this framework was the CONSORT statement in 1996,3 which provided recommendations for the publication of randomised controlled clinical trials, the gold standard to assess healthcare interventions. The 2010 update of the statement (doi:10.1136/bmj.c332)4 is accompanied by a comparative study by Hopewell and colleagues (doi:10.1136/bmj.c723),5 which assesses whether the quality of reporting of randomised trials has improved since publication of the CONSORT statement in 2001. 

Concerns have been raised that such publication guidelines may be too prescriptive, impede the creativity of research, and lack authorisation of the …
Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis
Authors: B L Scott, B M Sandmaier, B Storer, M B Maris, M L Sorror, D G Maloney, T R Chauncey, R Storb, H J Deeg
Journal: Leukemia (2005)
Open lung biopsy in nonresolving ARDS frequently identifies diffuse alveolar damage regardless of the severity stage and may have implications for patient management
Authors: Claude Guerin, Frédérique Bayle, Véronique Leray, Sophie Debord, Alina Stoian, Hodane Yonis, Jean-Baptiste Roudaut, Gael Bourdin, Mojgan Devouassoux-Shisheboran, Elodie Bucher, Louis Ayzac, Sylvie Lantuejoul, Carole Philipponnet, Jean Louis Kemeny, Bertrand Souweine, Jean-Christophe Richard
Journal: Intensive Care Medicine (2014)
The HLA-DRB1*15
Authors: Joshua D. Ooi, Janet Chang, Kim M. O’Sullivan, Vadim Pedchenko, Billy G. Hudson, Arthur A. Vandenbark, Lars Fugger, Stephen R. Holdsworth, A. Richard Kitching
Journal: Journal of the American Society of Nephrology (2013)

Human anti-glomerular basement membrane (GBM) disease strongly associates with HLA-DRB1*15:01. The target autoantigen in this disease is the noncollagenous domain of the α3 chain of type IV collagen, α3(IV)NC1, but critical early T cell epitopes presented by this human MHC class II molecule are unknown. Here, by immunizing HLA-DRB1*15:01 transgenic mice with whole recombinant α3(IV)NC1 and with overlapping α3(IV)NC1 peptides, we defined a HLA-DRB1*15:01-restricted α3(IV)NC1 T cell epitope (α3136-146) with four critical residues. This peptide was not immunogenic in HLA-DRB1*01:01 transgenic or C57BL/6 mice. The T cell epitope is naturally processed from α3(IV)NC1. CD4(+) T cell clones, generated from HLA-DRB1*15:01 transgenic mice and specific for α3136-146, transferred disease into naive HLA-DRB1*15:01 transgenic mice, evidenced by the development of necrotizing crescentic GN, albuminuria, renal impairment, and accumulation of CD4(+) T cells and macrophages in glomeruli. Because Fcγ receptors are implicated in disease susceptibility, we crossed HLA transgenic mice onto an FcγRIIb-deficient background. Immunization with either α3136-146 or α3(IV)NC1 induced GN in HLA-DRB1*15:01 transgenic FcγRIIb-deficient mice, but HLA-DRB1*01:01 transgenic FcγRIIb-deficient mice were unaffected. Taken together, these results demonstrate that the HLA-DRB1*15:01-restricted T cell epitope α3136-146 can induce T cell responses and injury in anti-GBM GN.
Effect of 5-Azacytidine on the Protein Expression of Porcine Bone Marrow Mesenchymal Stem Cells <i>in Vitro</i>
Authors: Neng-Sheng Ye, Rong-Li Zhang, Yan-Feng Zhao, Xue Feng, Yi-Ming Wang, Guo-An Luo
Journal: Genomics Proteomics & Bioinformatics (2006)

Abstract Bone marrow-derived mesenchymal stem cells (MSCs) are pluripotent stem cells that show a vital potential in the clinical application for cell transplantation. In the present paper, proteomic techniques were used to approach the protein profiles associated with porcine bone marrow MSCs and investigate the regulation of MSC proteins on the effect of 5-azacytidine (5-aza). Over 1,700 protein species were separated from MSCs according to gel analysis. Compared with the expression profiling of control MSCs, there were 11 protein spots up-regulated and 26 down-regulated in the protein pattern of 5-aza-treated cells. A total of 21 proteins were successfully identified by MALDI-TOF-MS analysis, among which some interesting proteins, such as alpha B-crystallin, annexin A2, and stathmin 1, had been reported to involve in cell proliferation and differentiation through different signaling pathways. Our data should be useful for the future study of MSC differentiation and apoptosis.
Ability of Circular Extrachromosomal DNA Molecules to Carry Amplified MYCN Protooncogenes in Human Neuroblastomas In Vivo
Authors: D. R. VanDevanter, V. D. Piaskowski, J. T. Casper, E. C. Douglass, D. D. Von Hoff
Journal: JNCI Journal of the National Cancer Institute (1990)

Amplification of the proto-oncogene MYCN (also known as N-myc) in neuroblastomas has been shown to correlate with both disease stage and prognosis, yet little is known about the DNA structures that carry amplified MYCN genes in neuroblastomas in vivo. We have used DNA irradiation and pulsed-field gel electrophoresis to analyze MYCN amplification structures in eight neuroblastomas from separate patients (four primary tumors and four metastatic lesions exhibiting MYCN amplification). Six of the eight neuroblastomas (three primary tumors and three metastatic lesions) exhibited MYCN DNA irradiation profiles consistent with the presence of circular extrachromosomal DNA amplification structures. Five neuroblastomas possessed amplification structures within the size range of double minute chromosomes, and one contained smaller DNA circles. Two neuroblastomas exhibited MYCN DNA irradiation patterns consistent with larger (presumably chromosomal) amplification structures. Multiple sizes of DNA circles were observed in the neuroblastomas of four different patients, implying in vivo multimerization of amplification structures. The presence of circular MYCN amplification structures in six of eight neuroblastomas examined suggests that circular DNA molecules are important structures in in vivo gene amplification. [J Natl Cancer Inst 82:1815–1821, 1990]
Some Questions on Cancer of the Lung, Larynx, and Urinary Tract
Authors: E. Kennaway
Journal: BMJ (1957)

The study of cancer as it occurs in man must be carried on empirically while others attack the fundamental question, " How, and why, does a cell divide ?" The distribution of cancer in man, and all factors which might affect this distribution, must be examined systematically.Some Characters of Cancer in Man These characters are: (1) sex lence-increasing, decreasing, or gradient -rise or fall, or neither, in relation to the Registrar-General's Social Classes I to V; (4) urbanrural rates-urban incidence; (2) preva- stationary; (3) social +, rural +, or .
Plasma theophylline concentrations, six minute walking distances, and breathlessness in patients with chronic airflow obstruction
Authors: D W Brown
Journal: BMJ (1985)

<b><i>Background:</i></b> Downbeat nystagmus (DBN), a frequent ocular motor sign often caused by cerebellar lesions, is a fixational nystagmus with fast phases directed downward. Its precise etiology is not known. One hypothesis is that it is caused by a central imbalance of pathways of the vertical vestibulo-ocular reflex (VOR). Such an imbalance would cause not only ocular drift but also deficient and asymmetric vertical VOR responses. <b><i>Objective:</i></b> To test this hypothesis, the authors analyzed the functionally relevant VOR responses to head impulses in the roll, pitch, and yaw planes. <b><i>Methods:</i></b> Head and eye movements were measured with the search-coil method in 10 patients with DBN and 10 age-matched control subjects. <b><i>Results:</i></b> Analysis revealed no gain difference in patients with DBN compared with control subjects. Specifically, upward and downward VOR responses in patients with DBN in the pitch plane were symmetric. <b><i>Conclusions:</i></b> These findings do not support the hypothesis of a vertical VOR imbalance and put into question the view that DBN is a central vestibular syndrome in the sense of vestibular dysfunction. Although DBN possibly involves vestibulocerebellar pathways, in the patients that we studied, DBN did not affect the immediate VOR responses in the high-frequency range that corresponds to natural head movements.
Rel/NF-κB and IκB proteins: an overview
Authors: Michael J. May, Sankar Ghosh
Journal: Seminars in Cancer Biology (1997)

Rel/NF-κB proteins constitute a family of structurally-related transcription factors that are regulated by interaction with a family of regulatory proteins, the IκB proteins. In this review, we will familiarize the reader with the known Rel/NF-κB and IκB molecules, and will discuss the types of interactions that occur between these proteins to regulate their function. In addition, we will describe what is known about the structure of Rel/NF-κB transcription complexes on DNA. Lastly, we will discuss the wide variety of biological stimuli and conditions which activate NF-κB and the genes whose expression are regulated by this family of transcription factors.
Molecular and immunologic characterization of new isoforms of the Hevea brasiliensis latex allergen Hev b 7: Evidence of no cross-reactivity between Hev b 7 isoforms and potato patatin and proteins from avocado and banana☆☆☆★
Authors: Slawomir Sowka, Christine Hafner, Christian Radauer, Margit Focke, Randolf Brehler, James D. Astwood, Siti A.M. Arif, Amin Kanani, Gordon L. Sussman, Otto Scheiner
Journal: Journal of Allergy and Clinical Immunology (1999)
CORRESPONDENCE OF THE A.P.A. FOUNDERS
Authors: ROBERT E. JONES
Journal: American Journal of Psychiatry (1963)

One hundred and ten letters from the founders of the American Psychiatric Association to its first secretary, and forty letters from Dr. Thomas S. Kirkbride to the founders, have been reviewed. The letters, dated from 1843 to 1865, cover the founding and early years of the Association and reveal the character of the "Original Thirteen" as well as their concerns and struggles. Probably the only founder who would have supposed that this correspondence would be preserved was Pliny Earle, who with his usual wit, wrote to Dr. Kirkbride:
Cerebral Venous Air Embolism: What Is It and Do We Know How to Deal With It Properly?
Authors: Christoph J. Schlimp, Pieter A. Bothma, Andreas E. Brodbeck
Journal: JAMA Neurology (2014)

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Prescriptions for the Elderly
Authors: J. A. Frais
Journal: BMJ (1971)

<h3>Abstract</h3> Recent successes in genome-wide association studies (GWASs) make it possible to address important questions about the genetic architecture of complex traits, such as allele frequency and effect size. One lesser-known aspect of complex traits is the extent of allelic heterogeneity (AH) arising from multiple causal variants at a locus. We developed a computational method to infer the probability of AH and applied it to three GWAS and four expression quantitative trait loci (eQTL) datasets. We identified a total of 4152 loci with strong evidence of AH. The proportion of all loci with identified AH is 4-23% in eQTLs, 35% in GWAS of High-Density Lipoprotein (HDL), and 23% in schizophrenia. For eQTLs, we observed a strong correlation between sample size and the proportion of loci with AH (<i>R</i><sup>2</sup>=0.85, P = 2.2e-16), indicating that statistical power prevents identification of AH in other loci. Understanding the extent of AH may guide the development of new methods for fine mapping and association mapping of complex traits.
Childhood Lead Poisoning in 1994-Reply
Authors: Lynn R. Goldman
Journal: JAMA (1995)

<h3>In Reply.</h3> —Dr Cunningham agrees that there is a need for a more targeted approach to lead screening. Certainly a tenet of public health is that our preventive efforts are most effective when we focus on those who are most at risk. However, how can we target in the absence of supportive data? In 1991, the CDC concluded that it would not be possible to predict which communities are at low enough risk of childhood lead exposure that screening would not be required.<sup>1</sup>The NHANES III data<sup>2</sup>would indicate that surveillance of lead exposure and reassessment of the CDC guidelines may well result in screening being more targeted in the future. In the meanwhile, unless there are data and methods available to determine which areas are of low risk, it is sound public policy for legislatures to follow the CDC guidelines. Dr Schoen is certainly entitled to his
Patricia Anne Doran
Authors: Judi Rogers
Journal: BMJ (2005)

Former general practitioner Stamford, Lincolnshire (b Stoke-on-Trent 1933; q Manchester 1957; DCH), died from colon cancer on 29 November 2004.​2004.




Figure 1




On qualifying Anne worked at Manchester Royal Infirmary and the Royal Manchester Children's Hospital. After starting her family she continued to practise in the community health service in Lancashire and then in the Lincolnshire area. When family commitments allowed, she took up partnership in general practice in Stamford. After retirement Anne enrolled on a foundation course at the Slade School of Fine Art, later progressing to a diploma in fine art. She was awarded (joint) prize for best painting at the Royal Society of Medicine Medical Art Society's summer exhibition at the Mall Galleries in 2004. She leaves her second husband, Robert Chappell; four children; a stepdaughter; and five grandchildren.
Immune deficiency as a risk factor in Epstein-Barr virus-induced malignant diseases.
Authors: D T Purtilo, M Okano, H L Grierson
Journal: Environmental Health Perspectives (1990)

Epstein-Barr virus (EBV) is a ubiquitous DNA virus that normally infects silently, establishing lifelong latency. Substantial empirical observations support the view that immunodeficiency is permissive in EBV-induced lymphoproliferative diseases (LPD). Primary immune deficient patients such as those with X-linked lymphoproliferative disease and individuals with acquired immune deficiency secondary to immunosuppressive drugs for organ transplantation or individuals infected with human immunodeficiency virus are also at very high risk for lethal LPD. The importance of immunodeficiency and EBV in the development of head and neck carcinomas and uterine cervical carcinoma is less clear. Methods are available for detecting immunodeficiency and EBV genome and thus preventive strategies are being developed to preclude LPD from occurring.
Risk factors for Mycobacterium chelonae-abscessus pulmonary disease persistence and deterioration
Authors: Meng-Rui Lee, Li-Ta Keng, Chin-Chung Shu, Shih-Wei Lee, Chih-Hsin Lee, Jann-Yuan Wang, Li-Na Lee, Chong-Jen Yu, Pan-Chyr Yang
Journal: Journal of Infection (2011)
Mechanisms of atrial natriuretic peptide secretion from the atrium
Authors: J DIETZ
Journal: Cardiovascular Research (2005)

Since the discovery of atrial natriuretic peptide (ANP) more than 20 years ago, numerous studies have focused on the mechanisms regulating ANP secretion. From a physiological standpoint, the most important factor governing ANP secretion is mechanical stretching of the atria, which normally occurs when extracellular fluid volume or blood volume is elevated. In addition, the ability of several vasoconstrictors to increase ANP secretion can be traced to their indirect effects on atrial stretch via increases in cardiac preload or afterload. Whether vasoconstrictors such as angiotensin II and vasopressin have a direct positive or negative effect on ANP secretion has not been determined with certainty. Two paracrine factors derived from endothelial cells play important roles in modulating ANP secretion. Endothelin, a potent vasoconstrictor, stimulates ANP secretion and augments stretch induced ANP secretion. The dramatic increase in ANP release produced by cardiac ischemia appears to be mediated in part by endothelin. Nitric oxide (NO), an important vasodilator, is also produced by endothelial cells and inhibits ANP secretion acting through cyclic GMP as an intracellular messenger. Several recent studies have helped to define the cellular mechanism contributing to regulation of ANP secretion including stretch-activated ion channels, prostaglandins, cytochrome P450, G proteins and cell calcium. A number of steps in the cellular transduction of the ANP signal remain to be resolved. The release of ANP in disease states such as myocardial infarction and heart failure appears to be related to both mechanical and cellular events.