tbuckley/cabot-search huggingface dataset:
Cardiac sympathetic neurons provide trophic signal to the heart via β2-adrenoceptor-dependent regulation of proteolysis
Authors: Tania Zaglia, Giulia Milan, Mauro Franzoso, Enrico Bertaggia, Nicola Pianca, Eleonora Piasentini, Vanessa A. Voltarelli, David Chiavegato, Patricia C. Brum, David J. Glass, Stefano Schiaffino, Marco Sandri, Marco Mongillo
Journal: Cardiovascular Research (2012)

Increased cardiac sympathetic neuron (SN) activity has been associated with pathologies such as heart failure and hypertrophy, suggesting that cardiac innervation regulates cardiomyocyte trophism. Whether continuous input from the SNs is required for the maintenance of the cardiomyocyte size has not been determined thus far. To address the role of cardiac innervation in cardiomyocyte size regulation, we monitored the effect of pharmacological sympathetic denervation in mice on cardiac structure, function, and signalling from 24 h to 30 days in the absence of other pathological stimuli. SN ablation caused an immediate reduction in the cardiomyocyte size with minimal consequences on the resting contractile function. Atrophic remodelling was mediated by the ubiquitin–proteasome system through FOXO-dependent early induction of the muscle-specific E3 ubiquitin ligases Atrogin-1/MAFbx and MuRF1, which was followed by activation of the autophagy–lysosome system. MuRF1 was found to be determinant in denervation atrophy as remodelling did not develop in denervated MuRF1 knock-out (KO) hearts. These effects were caused by decreased basal stimulation of cardiomyocyte β2-adrenoceptor (AR), as atrophy was prevented by treatment of denervated mice with the β2-AR agonist clenbuterol. Consistent with these data, we also observed that β2-AR KO mice showed cardiac atrophy at rest. Cardiac SNs are strong regulators of the cardiomyocyte size via β2-AR-dependent repression of proteolysis, demonstrating that the neuro-cardiac axis operates constitutively for the determination of the physiological cardiomyocyte size. These results are of great clinical relevance given the role of β-AR in cardiovascular diseases and their modulation in therapy.
Primitive CML cell expansion relies on abnormal levels of BMPs provided by the niche and on BMPRIb overexpression
Authors: Bastien Laperrousaz, Sandrine Jeanpierre, Karen Sagorny, Thibault Voeltzel, Sophie Ramas, Bastien Kaniewski, Martine Ffrench, Stéphanie Salesse, Franck E. Nicolini, Véronique Maguer-Satta
Journal: Blood (2013)
Changing trends in non‐melanoma skin cancer in South Wales, 1988–98
Authors: S.A. Holme, K. Malinovszky, D.L. Roberts
Journal: British Journal of Dermatology (2000)

In 1988 our department carried out a population-based epidemiological study of non-melanoma skin cancer (NMSC) incidence, over a 6-month period, in West Glamorgan, South Wales. Objectives To reassess the incidence of NMSC in this defined population over a similar 6-month period 10 years after the initial study.All cases of basal cell carcinoma and squamous cell carcinoma diagnosed in West Glamorgan are recorded by the local skin cancer registry. All cases for the relevant 6-month period were analysed.Using these figures, we have identified a significant rise in the crude incidence of NMSC from 173.5 10 years ago to 265.4 per 100,000 population per annum. We also applied the world standard population for age to our crude figures, demonstrating a combined male and female world population-corrected rate of 129.9 per 100,000 population.In our population the crude incidence of NMSC has risen significantly over 10 years. Additionally, the combined male and female world population-corrected rate appears to be the highest published standardized incidence of NMSC to date from any European country.
Effect of Student Loan Indebtedness and Repayment on Resident Physicians' Cash Flow
Authors: John Hernried
Journal: JAMA (1990)

Cumulative figures of "average medical student indebtedness," although meaningful, do not convey the effect of loan repayments on residents' cash flow, effect on a resident's value system and residency performance, and effect on trends in health care manpower allocation. Using a computer-based cash flow model, a "typical" house officer with $20 000 in undergraduate indebtedness who is training in a less expensive city will realize a $2390 deficit during internship and negative cash flow throughout a 5-year residency. House officers with extreme indebtedness (&gt;$80 000) who are training in an expensive metropolitan area would accumulate an overall deficit approaching $75 000 or more,<i>in excess of their undergraduate indebtedness</i>, during a 5-year residency program. Effects of these findings on residency education and health care manpower issues, along with potential solutions for alleviating residents' cash flow problems, are discussed. (<i>JAMA</i>. 1990;263:1102-1105)
Abstract 4772: Novel transforming ErbB2 mutations in leukemia
Authors: Jamie Keck, Brian Druker
Journal: Cancer Research (2014)

Abstract The ErbB2/Her2 type 1 transmembrane receptor tyrosine kinase heterodimerizes with ligand-bound EGFR, ErbB3, or ErbB4 to activate multiple signaling pathways. ErbB2 is commonly amplified in breast, stomach, cervical, and bladder tumors and point mutations are found in many cancers. However, little is known about aberrant ErbB2 in hematologic malignancies. Deep sequencing was performed on primary leukemia patient samples and point mutations were identified within the extracellular receptor binding domains and the intracellular C-terminal region of ErbB2. Expression of these mutations in NIH 3T3 fibroblasts exhibited a transformed morphological phenotype and in Ba/F3 pro-B cells led to IL-3-independent growth and differential signaling within the MAPK and PI3K pathways. Further characterization of the mutations will assess migration properties, differential sensitivity to ErbB-family drug inhibitors, and heterodimer formation using bimolecular fluorescence complementation microscopy. Overall, this work identifies novel transforming ErbB2 mutations and may provide insight into effective therapy for leukemia patients harboring ErbB2 mutations. Citation Format: Jamie Keck, Brian Druker. Novel transforming ErbB2 mutations in leukemia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4772. doi:10.1158/1538-7445.AM2014-4772
973 SEVERE HEPATOTOXICITY AFTER INGESTION OF HERBALIFE NUTRITIONAL SUPPLEMENTS CONTAMINATED WITH BACILLUS SUBTILIS
Authors: F. Stickel, S. Droz, E. Patsenker, K. Boegli-Stuber, B. Aebi, L. Wilkens, S.L. Leib
Journal: Journal of Hepatology (2008)
A distinct subtype of idiopathic myelofibrosis with bone marrow features mimicking hairy cell leukemia: Evidence of an autoimmune pathogenesis
Authors: Hans Hasselbalch, Henning Jans, Preben Løvgreen Nielsen
Journal: American Journal of Hematology (1987)

Abstract A young female patient presented with severe anemia and myelofibrosis. The spleen was not enlarged on clinical examination and no leukoerythroblastosis or tear‐drop poikilocytosis was found. A bone marrow biopsy disclosed severe myelofibrosis and many megakaryocytes, which appeared morphologically normal. A striking feature was a heavy spongy infiltration by large lymphocytic cells, which were tartrateresistant acid phosphatase negative and without hairy projections. This bone marrow appearance highly resembled the clear cell appearance of the hairy cell infiltrate in hairy cell leukemia. A diagnosis of acute autoimmune myelofibrosis was made. During high‐dose glucocorticoid therapy the bone marrow fibrosis completely resolved and there was an improvement of peripheral blood values. The disorder is supposed to feature a distinct clinicopathological entity within the syndrome of idiopathic myelofibrosis. The disease should be considered in the differential diagnosis of patients with myelofibrosing disorders, including acute myelofibrosis and hairy cell leukemia.
Mechanism for enhanced glucose transport response to insulin in adipose cells from chronically hyperinsulinemic rats. Increased translocation of glucose transporters from an enlarged intracellular pool.
Authors: B B Kahn, E S Horton, S W Cushman
Journal: Journal of Clinical Investigation (1987)

The mechanism for the increased glucose transport response to insulin in adipose cells from chronically hyperinsulinemic rats was examined. Rats were infused with insulin s.c. for 2 wk. Isolated adipose cells were incubated with and without insulin, 3-O-methylglucose transport was measured, and glucose transporters in subcellular membrane fractions were assessed by cytochalasin B binding. Adipose cells from insulin-treated rats showed no change in basal but a 55% increase in insulin-stimulated glucose transport activity compared with those from control rats (7.1 +/- 0.8 vs. 4.6 +/- 0.5 fmol/cell per min, mean +/- SEM) and a corresponding increase in the concentration of glucose transporters in the plasma membranes (44 +/- 5 vs. 32 +/- 6 pmol/mg of membrane protein). In the low-density microsomes, glucose transporter concentrations in both basal and insulin-stimulated states were the same, but the total numbers were greater in cells from the insulin-treated rats because of a 39% increase in low-density microsomal protein. Therefore, chronic experimental hyperinsulinemia in the rat enhances the stimulatory action of insulin on glucose transport in the adipose cell by increasing the concentration of glucose transporters in the plasma membranes. This results from an enlarged intracellular pool due to increased intracellular protein and enhanced glucose transporter translocation in response to insulin.
Magnetic Resonance Imaging of the Central Nervous System-Reply
Authors: William R. Hendee
Journal: JAMA (1988)

<h3>In Reply.—</h3> The American Medical Association's Council on Scientific Affairs has no argument with Dr Kaminski's statements, as we believe they are in agreement with the Council's article on MRI of the central nervous system. The Council states that MRI is the imaging technology of choice in multiple sclerosis, but does not imply that it should be the sole determinant in the diagnosis of this condition. For patients of any age, criteria for ordering an MRI examination should certainly extend beyond dizziness and a single past episode of blurred vision. Patients may not qualify for a clinically indicated MRI examination for several reasons, including an inability to remain still during the examination, uncontrolled claustrophobic reaction, and the presence of life-support apparatus or a cardiac pacemaker. For these patients, alternate imaging technologies obviously are required. The Council did not consider it necessary to elaborate on this issue for each clinical application
Regressing cutaneous lymphomas of T-cell and B-cell lineage
Authors: J.E. HOLDER, P.S. COLLOBY, A. FLETCHER, P.E. HUTCHINSON
Journal: British Journal of Dermatology (2006)

We report two cases of regressing cutaneous lymphoma. The first case is a CD30‐positive T‐cell lymphoma with immunogenetic evidence of clonality. The second case is a diffuse large‐cell non‐Hodgkin's lymphoma of B‐cell lineage in which clonality was established by immunogenetic analysis and in situ hybridization for light‐chain mRNA.
Optimal risk factor management in the patient after coronary revascularization. A statement for healthcare professionals from an American Heart Association Writing Group.
Authors: T Pearson, E Rapaport, M Criqui, C Furberg, V Fuster, L Hiratzka, W Little, I Ockene, G Williams
Journal: Circulation (1994)

MembersR evascularization with coronary artery bypass graft surgery (CABG) and percutaneous transluminal coronary angioplasty (PTCA) is well accepted as a method of relieving anginal pain and thus improving quality of life.In addition, CABG has been shown to improve survival in certain subgroups of patients with coronary disease, which has led to the widespread use of this procedure in revascularization.In 1991 407 000 bypasses and 303 000 PTCA procedures were performed.'Currently, coronary atherectomy, var- ious laser techniques, and coronary stents are being evaluated as additional approaches to revascularization.While often effective, there is the risk of complica- tions with CABG and PTCA.These procedures are also costly because they require skilled personnel, sophisti- cated equipment, and hospitalization.Thus, the proba- bility of long-term success should be optimized for maximum patient benefit and the best use of healthcare resources.Shortand long-term failure rates for these procedures have been defined.Approximately 10% to 20% of CABG procedures in the United States are performed in patients who had previously undergone this procedure, in large part because of the closure of bypass grafts from thrombosis and accelerated athero- sclerosis.Restenosis rates for PTCA and atherectomy at 6 months are about 40%.2,3The patient who undergoes revascularization probably has atherosclerotic disease in other coronary arteries and other vascular beds (eg, cerebrovascular and peripheral arteries).The renewed interest in preventive interventions in patients undergoing revascularization is derived from a variety of sources, including improved understanding of the role of risk factors in atherosclerotic and thrombotic diseases, results of clinical observations documenting the role of these risk factors in revascularization failure, the results of clinical trials that specifically tested the ability to prevent disease progression and recurrence, and evidence that such interventions are cost-effective "Optimal Risk Factor Management in the Patient After Coro- nary Revascularization" was approved by the SAC/Steering Com- mittee of the American Heart Association on June 16, 1994.
Rooting a Phylogeny with Homologous Genes on Opposite Sex Chromosomes (Gametologs): A Case Study Using Avian CHD
Authors: Jaime García-Moreno, David P. Mindell
Journal: Molecular Biology and Evolution (2000)

We describe a previously unrecognized form of gene homology using the term "gametology," which we define as homology arising through lack of recombination and subsequent differentiation of sex chromosomes. We demonstrate use of gametologous genes to root each other in phylogenetic analyses of sex-specific avian Chromo-helicase-DNA binding gene (CHD) sequences. Phylogenetic analyses of a set of neognath bird sequences yield monophyletic groups for CHD-W and CHD-Z gametologs, as well as congruent relationships between these two clades and between them and current views of avian taxonomy. Phylogenetic analyses including paleognath bird CHD sequences and rooting with crocodilian CHD sequences, suggest an early divergence for paleognath CHD within the avian CHD clade. Based on our CHD analyses calibrated with avian fossil dates, we estimate the divergence between CHD-W and CHD-Z at 123 MYA, suggesting an early differentiation of sex chromosomes that predates most extant avian orders. In agreement with the notion of male-driven evolution, we find a faster rate of change in male-linked CHD-Z sequences.
The Year of the Death
Authors: George L. Fite
Journal: JAMA (1965)

During the 14th century the popes reigned at Avignon, but, for a year or two in the middle of the century, neither popes nor princes held sway. It was plague that ruled in the valley of the Rhone. Walled cities kept wolves out, but rats in. The year 1348 saw terror of disease, accusations of heresy, and the autoda-fé rampant in southern France. In Marseilles three fourths of the people died. In this milieu Dr. Merliss has woven a picaresque novel of the wanderings of a young physician who sought the cause or cure of the plague. There is enough letting of blood to gratify the most sanguine reader. Purulent miseries compete with thieveries and assaults to stifle dullness. Romance is replaced by somewhat more elemental biological necessities. Although it was not until 1897 that Ogata proved the relevance of the rat to plague, the beast had been suspected several
South Carolina Practice of Medicine Act.
Authors: C. F. McGahan
Journal: JAMA (1894)

AikenS. C., June 9, 1894. <h3>To the Editor:</h3> In the issue of your paper March 10, 1894, page 355 in the article, "Legal Requirements for the Practice of Medicine in the United States," you have the law for South Carolina wrong; please correct it as it is apt to mislead doctors wishing to come in the State to practice. The Legislature of 1893 passed a law which went into effect Jan. 4, 1894. The law provided for the appointment of a State Board of Medical Examiners to be composed of seven members, whose duty it is to examine all candidates who wish to practice medicine in the State and who were not registered Jan. 4, 1894. The candidate must first show his diploma and he is then given a written examination of two hours on each of the seven principal branches. The next meeting of the Board is
Abstract 4331: Advantages of polyacetal polymer-based antibody drug conjugates employing cysteine bioconjugation.
Authors: Alex Yurkovetskiy, Natalya Bodyak, Mao Yin, Joshua Thomas, Patrick Conlon, Cheri Stevenson, Alex Uttard, Liu Qin, Dmitry Gumerov, Elena Ter-Ovaneysan, Michael DeVit, Timothy B. Lowinger
Journal: Cancer Research (2013)

Abstract The application of polymers to antibody drug conjugate (ADC) design and preparation can provide numerous advantages, including 1) significantly higher capacity for drug payload; 2) utilization of alternative payloads not suitable for direct conjugation approaches; 3) improvement of physicochemical properties of resulting ADCs; 4) utilization of protein recognition scaffolds beyond the commonly used IgGs; and 5) improvements in PK and biodistribution. Herein we present results of a novel, biodegradable polyacetal polymer-based conjugation system to create next-generation ADCs. The basis of this new conjugation system is a hydrophilic, fully biodegradable polyacetal carrier (PHF or poly(1-hydroxymethylethylene hydroxymethylformal) modified with chemically orthogonal linkers. One linker is used to covalently attach a targeting moiety (mAb or alternative) via cysteine conjugation, while a second, chemically distinct linker is used to attach a drug payload and to control the mechanism and rate of drug release. Previously we have reported highly efficacious polyacetal ADCs prepared by utilizing random lysine modification. In this report we present an alternative cysteine-based bioconjugation strategy. Conventional, direct drug-cysteine linked ADCs are destabilized due to loss of inter-chain disulfide bridges. In contrast, the polyacetal polymer conjugated via cysteines in the antibody hinge region stabilizes the resulting ADCs through the formation of inter-chain bridge structures. To demonstrate the benefits of this approach, we prepared Her-2 targeted ADCs with protein recognition scaffolds ranging in size from 15 kDa to 150 kDa, all targeting the Her-2 antigen, and bearing an anti-tubulin agent as the drug payload. ADCs were highly active and selective in vitro in Her-2 expressing cell lines. These polyacetal cysteine-based ADCs exhibited prolonged plasma and tumor exposure in the Her-2 expressing BT474 mouse xenograft model and tumor-specific accumulation. The ADCs were well-tolerated, and resulted in 100% tumor-free survivors. Citation Format: Alex Yurkovetskiy, Natalya Bodyak, Mao Yin, Joshua Thomas, Patrick Conlon, Cheri Stevenson, Alex Uttard, Liu Qin, Dmitry Gumerov, Elena Ter-Ovaneysan, Michael DeVit, Timothy B. Lowinger. Advantages of polyacetal polymer-based antibody drug conjugates employing cysteine bioconjugation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4331. doi:10.1158/1538-7445.AM2013-4331
Multiphasic screening. Case-finding tool in a Teaching Hospital Medical Clinic
Authors: S. W. Fletcher
Journal: JAMA (1977)

Multiphasic screening as a case-finding tool was evaluated in a randomized, controlled study. For each of 112 physicians, a patient was assigned to one of three groups: multiphasic screening group (SG), chart abstract group (AG), or chart review group (RG). Medical problem lists constructed before and after receiving additional information were compared. Physicians for 36 SG patients identified considerably more new medical problems, both total (77) and ones they considered important (25), than 40 AG physicians (14 and 8) and 36 RG physicians (4 and 0). One year later, 38 of the 95 newly identified problems had been acted on, 31 in the SG. Medical care was affected in nine patients: six in SG, two in AG, and one in RG. Multiphasic screening may help physicians identify new medical problems in clinic patients. (<i>JAMA</i>237:887-891, 1977)
The Confession of an Erstwhile Bureaucrat
Authors: John Archer
Journal: JAMA (1978)

<h3>To the Editor.—</h3> The consequences of a seemingly minor decision may be difficult to foresee. In mid-1962, after noting with dissatisfaction the manner in which the clinical investigation of thalidomide had been conducted in the United States, the then Secretary of Health, Education, and Welfare ordered the Food and Drug Administration to develop regulations for investigational drugs. An official in the agency's Bureau of Medicine had, in fact, written a draft of such regulations about two years before, and with moderate revision, these were published as a proposal in the<i>Federal Register</i>. During the process of revision, I was in his office and he asked my opinion about a passage. This involved the obligations of the pharmaceutical industry in investigating a new drug for the purpose of submitting an application to market it. The passage was written in terms of what a manufacturer must do. I noted a potential problem
Foot Disorders: Medical and Surgical Management
Authors: Reginald R. Cooper
Journal: JAMA (1973)

Although allegedly the author wrote this book simply because he "enjoyed doing so," its quality reveals much more than a volume merely produced as a pastime. For the most part, the contents reflects the devoted attention of several writers obviously expert in their subject. This comprehensive treatise represents a welcome addition to our understanding of the human foot, an appendage deserving much more attention than it has received formerly. Anyone who reads this will certainly agree with the admonition of the author: "Be good to your feet. They outnumber people two to one." Initial sections on embryology, anatomy, development, and function provide the essential background for a thorough grasp of subsequent chapters describing numerous afflictions. The monograph on the pronated foot in childhood and the bibliography reflect the tragic lack of hard data to substantiate endless claims about methods of treatment for this common variation of children's feet. A well-designed
Safety of Oral Contraceptives
Authors: D. A. Cahal
Journal: BMJ (1966)

skilled psychotherapists.A patient of my own who has been referred for L.S.D. treat- ment with great success may have therapy terminated soon.It is difficult to understand how a reput- able drug company such as Sandoz can act in this way without consultation with the profession, who have enjoyed free access up until now to the use of any drug which benefited their patients.There has been little evidence of misuse of this drug in Great Britain in comparison, for example, with Drinamyl and dexamphetamine, both of which are still freely available to doctors.I believe and hope that this petulant and ill-considered decision may be revoked, failing which action there can be little doubt that much more damage will be done to the public image of Sandoz than could ever have resulted from misuse of a drug which in any case is now in the U.S.A. freely available from illicit sources.-Iam, etc., Hornchurch, Essex.