tbuckley/cabot-search huggingface dataset:
Reduced Sodium Pump α <sub>1</sub> , α <sub>3</sub> , and β <sub>1</sub> -Isoform Protein Levels and Na <sup>+</sup> ,K <sup>+</sup> -ATPase Activity but Unchanged Na <sup>+</sup> -Ca <sup>2+</sup> Exchanger Protein Levels in Human Heart Failure
Authors: Robert H. G. Schwinger, Jiangnan Wang, Konrad Frank, Jochen Müller-Ehmsen, Klara Brixius, Alicia A. McDonough, Erland Erdmann
Journal: Circulation (1999)

Background −Cardiac glycosides initiate an increase in force of contraction by inhibiting the sarcolemmal sodium pump (Na + ,K + -ATPase), thereby decreasing Ca 2+ extrusion by the Na + -Ca 2+ exchanger, which increases the cellular content of Ca 2+ . In patients with heart failure the sensitivity toward cardiac glycosides is enhanced. Methods and Results −Because the inotropic effect of cardiac glycosides may be a function of the sodium pump and Na + -Ca 2+ exchanger (NCE) expression levels, the present study aimed to investigate protein expression of both transporters (immunoblot with specific antibodies against the sodium pump catalytic α 1 -, α 2 -, α 3 -, and glycoprotein β 1 -isoforms and against NCE) in left ventricle from failing (heart transplantations, New York Heart Association class IV, n=21) compared with nonfailing (donor hearts, NF, n=22) human myocardium. The density of 3 H-ouabain–binding sites (B max ) and the Na + ,K + -ATPase activity were also measured. In NYHA class IV, protein levels of Na + ,K + -ATPase α 1 - (0.62±0.06 of control), α 3 - (0.70±0.09), and β 1 - (0.61±0.04) but not α 2 -isoforms were significantly reduced ( P &lt;0.01), whereas levels of NCE (0.92±0.13 of control) and calsequestrin (0.98±0.06) remained unchanged. Both Na + ,K + -ATPase activity (NF: 1.9±0.29; NYHA class IV: 1.1±0.17 μmol ATP/min per milligram of protein) and the 3 H-ouabain binding sites (B max NF: 15.9±1.9 pmol/mg protein; NYHA class IV: 9.7±1.5) were reduced in NYHA class IV and correlated significantly to each other ( r 2 =0.73; P &lt;0.0001), as did β 1 -subunit expression. In left ventricular papillary muscle strips from NYHA class IV compared with nonfailing tissue the Na + -channel modulator BDF 9198 exerted an increase in force of contraction with unchanged effectiveness but enhanced potency. Conclusions −The enhanced sensitivity of failing human myocardium toward cardiac glycosides may be, at least in part, attributed to a reduced protein expression and activity of the sarcolemmal Na + ,K + -ATPase without a change in Na + -Ca 2+ exchanger protein expression.
In the Dark — The Case for Electronic Health Records
Authors: Cara B. Litvin
Journal: New England Journal of Medicine (2007)

I sighed as I flipped again through the paperwork sent with my first admission of the night. All I found was a partially legible discharge summary. The patient, a young man who was ventilator dependent and in a vegetative state since receiving a gunshot injury 6 months previously, had been transferred from a nursing home after a workup revealed a new deep venous thrombosis in his leg.From the limited notes provided by the nursing home, I ascertained that the gunshot had initially caused a subarachnoid hemorrhage. It was my job, as a night-float admitting resident, to determine whether it . . .
Skin test reactivity to common aeroallergens and decline of lung function. The Normative Aging Study.
Authors: D J Gottlieb, D Sparrow, G T O'Connor, S T Weiss
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

It has been hypothesized that allergy is associated with an increased risk of developing chronic irreversible airflow obstruction. We have investigated the relation between immediate cutaneous hypersensitivity to common aeroallergens and the subsequent rate of decline of lung function in 1,025 men participating in the Normative Aging Study; subjects had a mean age of 61 +/- 8 (SD) yr and denied any history of asthma. Subjects performed spirometry and underwent allergen skin testing at a baseline visit and performed repeat spirometry after a median of 3.1 yr. Skin prick tests were performed using four glycerin-preserved allergens (house dust, mixed grasses, mixed trees, and ragweed); wheal size was measured at 20 min. Multiple linear regression analysis was used to examine the annual rate of change of lung function in relation to skin test reactivity, defined as a mean wheal size to the 4 allergens > or = 2 mm, after adjustment for age, height, smoking status, and initial lung function. Skin test reactivity was a significant predictor of the annual rates of decline of FEV1 and FEV1/FVC ratio. The regression model predicted an excess decline of FEV1 of 9.45 ml/yr for subjects with mean wheal diameter > or = 2 mm (p < 0.05); the excess rate of decline of FEV1/FVC ratio was 0.29 percent/yr (p = 0.001). There was no significant relation between mean wheal diameter and rate of decline of FVC. The magnitude of the effects of a mean wheal diameter > or = 2 mm on rates of decline of FEV1 and FEV1/FVC ratio are 34% and 49%, respectively, of the magnitude of the effects of current cigarette smoking in these models. We conclude that cutaneous hypersensitivity to common aeroallergens is a significant independent predictor of subsequent decline of lung function among middle-aged and older men with no history of asthma.
Mumps With Orchitis And Lymphosarcoma
Authors: Mason G. Robertson
Journal: JAMA (1971)

To the Editor.—  Patients with malignant lymphoma exhibit increased susceptibility to herpes zoster and to other kinds of infections. Relationship between infectious mononucleosis, the Epstein Barr virus, and the lymphomas has been much written about in recent years. Cases of well-documented infectious mononucleosis have occurred in patients with leukemia and lymphoma in remission. In light of this, a recent case seen by us seems of more than passing.  Report of a Case.—  A 41-year-old railroad worker suffered from a duodenal ulcer in 1964, treated by gastric freezing, and in 1965, by gastrectomy. The gastrectomy specimen showed lymphosarcoma of a small-cell-type.  Within the year tumors of his parotid gland were biopsied and thought initially to be benign lymphoepithelioma. He went on however to develop pulmonary lesions and an open lung biopsy in March 1969, which showed lymphosarcoma of the lung. Subsequently cobalt 60 therapy to the left lung and later to
Defining and Assessing Alternative Medicine Practices
Authors: Timothy Gorski
Journal: JAMA (1996)

<h3>To the Editor.</h3> —In the Resident Forum calling for resident physicians to look more favorably on "alternative medicine," Dr Dyer<sup>1</sup>equates the term with "treatments and practices that have not gained wide acceptance or have not yet had adequate scientific research to be considered standard medical treatment." However, doing so fails to distinguish what is usually meant by alternative medicine from legitimate emerging medical science, which includes, for example, the use of methotrexate to treat ectopic pregnancy. It would be more accurate to say that alternative medicine refers to treatments and practices that are claimed to be safe and effective but remain unproven (or in many cases disproven) or based on unscientific ideas about health and disease (ie, medical quackery). Thus, while spinal manipulation has been shown to have benefits for acute musculoskeletal-related low back pain in adults,<sup>2,3</sup>it hardly seems appropriate, much less ethical, to spend scarce
Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27–stimulated T cells
Authors: Denise C Fitzgerald, Guang-Xian Zhang, Mohamed El-Behi, Zoë Fonseca-Kelly, Hongmei Li, Shuo Yu, Christiaan J M Saris, Bruno Gran, Bogoljub Ciric, Abdolmohamad Rostami
Journal: Nature Immunology (2007)
THE BIOCHEMICAL INVESTIGATION OF MALIGNANT TUMORS AND ITS DIAGNOSTIC APPLICATIONS
Authors: RICHARD WEIL
Journal: JAMA (1910)

It is not the object of the present paper to review the entire field of the biochemistry of tumors. Large and well tilled as is this field, it would be tempting but impossible to cover the ground in the brief critique assigned me. That aspect of the subject, in this symposium, therefore has been selected, which appears to be of especial interest and importance for the general understanding of cancer as a disease. The present paper will deal with those investigations which have attempted to elucidate the mutual relationship existing between the new growth and its host, the patient—the biochemical evidences regarding the cause of the cachexia and of the anemia induced by neoplasms, and on the other hand the biochemical aspects of the resistance or the relative immunity, which represents the protective mechanism of the host. That such a protective mechanism exists in experimental animals is now no longer
Darier's disease: severe eczematization successfully treated with cyclosporin
Authors: H. SHAHIDULLAH, F. HUMPHREYS, G.W. BEVERIDGE
Journal: British Journal of Dermatology (1994)

Journal Article Darier's disease: severe eczematization successfully treated with cyclosporin Get access H. SHAHIDULLAH, H. SHAHIDULLAH University Department of Dermatology, Level 4, Lauriston Building, The Royal Infirmary, Edinburgh EH3 9YW, U.K. Search for other works by this author on: Oxford Academic Google Scholar F. HUMPHREYS, F. HUMPHREYS University Department of Dermatology, Level 4, Lauriston Building, The Royal Infirmary, Edinburgh EH3 9YW, U.K. Search for other works by this author on: Oxford Academic Google Scholar G.W. BEVERIDGE G.W. BEVERIDGE University Department of Dermatology, Level 4, Lauriston Building, The Royal Infirmary, Edinburgh EH3 9YW, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 131, Issue 5, 1 November 1994, Pages 713–716, https://doi.org/10.1111/j.1365-2133.1994.tb04990.x Published: 01 November 1994 Article history Accepted: 09 March 1994 Published: 01 November 1994
Immunohistological identification of interleukin-1 activated chondrocytes.
Authors: J T Dingle, M E Davies, B Y Mativi, H F Middleton
Journal: Annals of the Rheumatic Diseases (1990)

Interleukin-1 activated chondrocytes have been identified in pig articular cartilage by immunolocalisation using a polyclonal antiserum recognising cytokine induced surface epitopes. Although chondrocytes with membrane staining were noted in all zones of the cartilage, only a proportion of the cells were positive within the range of antiserum dilution used (1:100-1:2000). Maximum staining was found after four days' treatment of cultured cartilage with pig IL-1 alpha, though weak staining was just detectable after treatment for one day at high antiserum concentration. Immunoreactivity was also shown in cartilage which had been cultured with human recombinant IL-1 alpha.
Hypophysentumoren, Hypophysektomie: Klinik, Therapie, Ergebnisse
Authors: Oscar Sugar
Journal: JAMA (1967)

Disorders and tumors of the pituitary gland influence so much of the body that this little organ is well worth the detailed study by two eminent neurosurgeons from Freiburg. The introductory discussion of anatomy and physiology is followed by a special section by P. M. Reisert on endocrine investigations. Clinical symptomatology, roentgenologic investigations, operative and roentgenotherapeutic techniques precede the detailed exposition of results of these treatments, culled from the authors' extensive experiences and from the worldwide literature. Particular emphasis, of encyclopedic proportion, is given to the authors' specialties —stereotaxy and radioactive isotopes. Techniques, indications for hypophysectomy in metastatic tumors, and the results, diabetes mellitus, arterial hypertension, and malignant exophthalmos constitute the last 50 pages of this wellprinted, profusely illustrated, expensive (10c per page) German monograph. It should be made available to all physicians who have more than a casual interest in the hypophysis—that singular connecting link between nervous and endocrine
Obtaining a History From Hard-of-Hearing Patients
Authors: Albert B. Lowenfels
Journal: JAMA (1975)

To the Editor.—  Dr. Schotz (232:73, 1975) asks how other physicians handle the problem of history-taking in the hard-of-hearing patient. I have had good luck with a readily available medical amplifying system: the reversed stethoscope. Have the patient listen through the ear pieces while you talk normally into the bell. In many patients, the method is surprisingly effective.
A Reformation for our times
Authors: J. Shaw
Journal: BMJ (2009)

<h3>Abstract</h3> Intracellular inclusions containing an enrichment of alpha-synuclein protein are characteristic for several neuropathological diseases including Parkinson’s disease (PD). Recent studies using cryo-electron microscopy and helical reconstruction approaches had determined the structure of fibrillar recombinant human alpha-synuclein (polymorphs 1a and 1b). Here, we describe two new polymorphic atomic structures of alpha-synuclein fibrils (polymorph 2a at 3.1 Å resolution and polymorph 2b at 3.5 Å), which show a radically different arrangement in the protofilament compared to the previously investigated polymorphs. All structures are fibrils of 10 nm diameter that are composed of two protofilaments. The strong steric-zipper geometry at the protofilament interface in previously described polymorphs is absent in the polymorphs described here. Instead, they interact via intermolecular salt-bridges between amino acids K45, E57 (polymorph 2a) or E46 (polymorph 2b). The non-amyloid component (NAC) region of alpha-synuclein is fully buried by previously non-described interactions with the N-terminus. A hydrophobic cleft, the location of familial PD mutation sites, and the nature of the protofilament interface now invite to formulate hypotheses about fibril formation, growth and stability. If such structures can be identified in human brain they open new avenues for the design of tools such as small molecules or antibodies targeting the various amyloid forms of alpha-synuclein for better diagnosis and assessment of potential therapies targeting alpha-synuclein deposits. <h3>Impact statement</h3> Two new polymorphic structures of recombinant human alpha-synuclein fibrils are reported here. Besides striking differences with previous structures, familial PD mutation sites remain crucial for protofilament interaction and fibril stability.
Abstract 215: Aminoflavone exhibits <i>in vivo</i> efficacy on cancer stem cells in a spontaneous estrogen-dependent breast cancer murine model
Authors: Mariana Callero, Damian Berardi, Laura Todaro, Marina Simian, Eileen J. Brantley, Ubaldo Soto, Andrea Loaiza-Perez
Journal: Cancer Research (2014)

Abstract Stem-cell populations have been identified in a range of solid tumors and possess the capacity to self renew. It is thought that these cancer stem cells (CSCs) play an important role in cancer establishment, progression, and resistance to current treatments. CSCs have been identified in primary breast cancer tissues and cell lines derived from metastatic tumors. Traditional cancer therapies are effective at debulking some tumors but often fail to produce long-term clinical remissions, presumably due to their inability to eradicate the cancer stem cell population. Therefore, novel treatments aimed at targeting this population can potentially enhance treatment of both primary and metastatic tumors. Aminoflavone (AF; NSC 686288) is a novel anticancer agent. Previous work from our research group demonstrated that AF is a ligand of the aryl hydrocarbon receptor (AhR) and displays cytotoxicity in the MCF-7 breast cancer cell line. A prodrug formulation of AF (AFP464, NSC710464), recently entered phase II clinical trials. Moreover, we previously found that AF disrupts MCF-7 mammosphere formation via AhR signaling activation to inhibit alpha 6-integrin expression. To investigate the efficacy of AF in vivo, we used an estrogen dependent, Tamoxifen-sensitive spontaneous M05 model system involving 1-year-old virgin female BALB/c mice developed in our animal facility. The M05 tumor is a semi-differentiated adenocarcinoma that expresses estrogen and progesterone receptors. After AF treatment (12 mg/kg, i.p., QD × 5 days) tumor size and growth rate decreased substantially compared to control animals. Cytometric analyses of cells obtained from AF-treated and control animals revealed that Lin (-)/ CD29 (Hi)/CD24 (+) cancer stem cells were lower in animals treated with AF than in the vehicle control group. We also observed a diminished capacity for mammosphere formation in cells obtained from tumors treated with AF. These data suggest AF diminishes the quantity of breast cancer stem cells as well as their integrity and capacity to form mammospheres in vitro and in vivo. These findings shed additional insight into the molecular mechanism of anticancer action for this novel anticancer agent to strengthen the rationale for its inclusion in breast cancer treatment regimens. Citation Format: Mariana Callero, Damian Berardi, Laura Todaro, Marina Simian, Eileen J. Brantley, Ubaldo Soto, Andrea Loaiza-Perez. Aminoflavone exhibits in vivo efficacy on cancer stem cells in a spontaneous estrogen-dependent breast cancer murine model. [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 215. doi:10.1158/1538-7445.AM2014-215
Treatments for Esophageal Cancer
Authors: Daniel G. Haller
Journal: New England Journal of Medicine (1992)

FOR oncologists, who deal with disabling and life-threatening diseases on a daily basis, esophageal cancers represent an unusually difficult problem. Although these cancers are not especially common, they produce enormous suffering and a high death rate, challenging clinical investigators to develop better treatments. Large retrospective reviews suggest that neither radiation therapy nor surgery reliably provides long-term control for unselected patients with apparently localized disease.1 In patients who undergo surgery, recurrence and death are most often attributed to untreated and unsuspected early metastatic disease, the presence of which has been documented in autopsies performed relatively soon after surgery.2 In patients treated . . .
Somatostatin or its analogs and terlipressin: Different evidence levels, Same recommendations?
Authors: Yu Bai, Jun Gao, Duo‐Wu Zou, Zhao‐Shen Li
Journal: Hepatology (2008)

We read with great interest the recent guideline1 titled "Prevention and Management of Gastroesophageal Varices and Variceal Hemorrhage in Cirrhosis".This guideline provided a comprehensive in-depth review on the issues of prophylaxis and treatment of variceal bleeding in patients with cirrhosis. However, there are some comments we would like to raise. In the section of "Specific measures to control acute hemorrhage and prevent early recurrence", the authors clearly stated that results of meta-analyses of trials of octreotide are controversial and a more recent meta-analysis of trials of somatostatin analogs showed a negligible beneficial effect. However, Recommendation 14 classified the evidence of pharmacological therapy (somatostatin or its analogs octreotide and vapreotide; terlipressin) as Class I, Level A. This may cause some confusion, because table 1 ("Grading System for Recommendations") in the article states that Class I means conditions for which there is evidence and/or general agreement that a treatment is beneficial, useful, and effective. In the case of somatostatin and its analogs, it can only be stated this pharmacological therapy is safe, but not definitely beneficial, useful, and effective. In view of this, the recommendation of somatostatin and its analogs shall be categorized as Class IIa, Level A. On the contrary, terlipressin is the only vasoactive agent that has been shown to reduce mortality in single studies and meta-analyses,2 and the recommendation on the use of terlipressin shall be categorized as Class I, Level A. However, this recent excellent Cochrane systematic review was not included in the references list. Thus, we suggest that distinguishing the recommendations between somatostatin and/or its analogs and terlipressin would be more appropriate. Yu Bai M.D.*, Jun Gao M.D., Ph.D.*, Duo-Wu Zou M.D.*, Zhao-Shen Li M.D.*, * Evidence-Based Medicine Group, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
Response to Etanercept in Juvenile Idiopathic Arthritis
Authors: Hao Pang, Xue-Hui Wu, Jian-Zhong Xu
Journal: JAMA (2012)

in Juvenile Idiopathic Arthritis To the Editor: The study presented by Dr Otten and colleagues assessed factors associated with treatment response to etanercept in patients with juvenile idiopathic arthritis (JIA). They found that approximately one-third of the patients with JIA achieved an excellent response, which was associated with low baseline disability scores, low numbers of disease-modifying antirheumatic drugs used before initiating etanercept, and younger age at onset of JIA. Onethird achieved a poor response, which was associated with systemic JIA and female sex. However, we think that their conclusions are problematic because differences between systemic JIA and other types exist in terms of intrinsic etiology and pathogenesis. Information about the immune pathogenesis of JIA discovered in the past 5 years has confirmed that systemic JIA is a different disease from other types of JIA and should be treated as an acquired autoinflammatory disease. Juvenile idiopathic arthritis is not only a heterogeneous group of diseases characterized by arthritis of unknown origin with onset before the age of 16 years but also a diagnosis of exclusion, which is made only when other causes such as congenital joint deformity, neurovascular disorder, trauma, and infection have been ruled out. The discrepancies in treatment response in Otten et al’s study also suggest that the diagnosis of JIA encompasses different categories with different etiologies and pathogenesis, so the major factor associated with treatment response to etanercept in JIA may be the type rather than sex or age. Thus, the comparison of treatment response between systemic JIA and other categories may not be helpful; the comparison with greater significance for clinical practice would be a comparison within types—systemic or nonsystemic.
Coronary Revascularization in Context
Authors: Richard A. Lange, L. David Hillis
Journal: New England Journal of Medicine (2009)

Coronary-artery bypass grafting (CABG), introduced in 1968, was the only method of coronary revascularization until 1977, when percutaneous balloon angioplasty was first performed. The complications of balloon angioplasty (acute vessel closure in 3 to 5% of patients and restenosis in almost half) prevented its use in patients with severe coronary artery disease. In the 1990s, the introduction of bare-metal stents led to reduced rates of these complications. The improved short-term and long-term procedural success with percutaneous coronary intervention (PCI) allowed for its safe and effective performance in patients with severe coronary artery disease. By the year 2000, more PCI procedures . . .