tbuckley/cabot-search huggingface dataset:
Improved Myocardial β-Adrenergic Responsiveness and Signaling With Exercise Training in Hypertension
Authors: Scott M. MacDonnell, Hajime Kubo, Deborah L. Crabbe, Brian F. Renna, Patricia O. Reger, Jun Mohara, L. Ashley Smithwick, Walter J. Koch, Steven R. Houser, Joseph R. Libonati
Journal: Circulation (2005)

Cardiac responses to beta-adrenergic receptor stimulation are depressed with pressure overload-induced cardiac hypertrophy. We investigated whether exercise training could modify beta-adrenergic receptor responsiveness in a model of spontaneous hypertension by modifying the beta-adrenergic receptor desensitizing kinase GRK2 and the abundance and phosphorylation of some key Ca2+ cycling proteins.Female spontaneously hypertensive rats (SHR; age, 4 months) were placed into a treadmill running (SHR-TRD; 20 m/min, 1 h/d, 5 d/wk, 12 weeks) or sedentary group (SHR-SED). Age-matched Wistar Kyoto (WKY) rats were controls. Mean blood pressure was higher in SHR versus WKY (P<0.01) and unaltered with exercise. Left ventricular (LV) diastolic anterior and posterior wall thicknesses were greater in SHR than WKY (P<0.001) and augmented with training (P<0.01). Langendorff LV performance was examined during isoproterenol (ISO) infusions (1x10(-10) to 1x10(-7) mol/L) and pacing stress (8.5 Hz). The peak LV developed pressure/ISO dose response was shifted rightward 100-fold in SHR relative to WKY. The peak ISO LV developed pressure response was similar between WKY and SHR-SED and increased in SHR-TRD (P<0.05). SHR-TRD showed the greatest lusitropic response to ISO (P<0.05) and offset the pacing-induced increase in LV end-diastolic pressure and the time constant of isovolumic relaxation (tau) observed in WKY and SHR-SED. Improved cardiac responses to ISO in SHR-TRD were associated with normalized myocardial levels of GRK2 (P<0.05). SHR displayed increased L-type Ca2+ channel and sodium calcium exchanger abundance compared with WKY (P<0.001). Training increased ryanodine receptor phosphorylation and phospholamban phosphorylation at both the Ser16 and Thr17 residues (P<0.05).Exercise training in hypertension improves the inotropic and lusitropic responsiveness to beta-adrenergic receptor stimulation despite augmenting LV wall thickness. A lower GRK2 abundance and an increased phosphorylation of key Ca2+ cycling proteins may be responsible for the above putative effects.
miR-34a Induces the Downregulation of Both<i>E2F1</i>and<i>B-Myb</i>Oncogenes in Leukemic Cells
Authors: Giorgio Zauli, Rebecca Voltan, Maria Grazia di Iasio, Raffaella Bosco, Elisabetta Melloni, Maria Elena Sana, Paola Secchiero
Journal: Clinical Cancer Research (2011)

To elucidate new molecular mechanisms able to downregulate the mRNA levels of key oncogenes, such as B-Myb and E2F1, in a therapeutic perspective.B-Myb and E2F1 mRNA levels were evaluated in primary B chronic lymphocytic leukemia (B-CLL, n = 10) and acute myeloid leukemia (AML, n = 5) patient cells, in a variety of p53(wild-type) and p53(mutated/deleted) leukemic cell lines, as well as in primary endothelial cells and fibroblasts. Knockdown experiments with siRNA for p53 and E2F1 and overexpression experiments with miR34a were conducted to elucidate the role of these pathways in promoting B-Myb downregulation.In vitro exposure to Nutlin-3, a nongenotoxic activator of p53, variably downregulated the expression of B-Myb in primary leukemic cells and in p53(wild-type) myeloid (OCI, MOLM) and lymphoblastoid (SKW6.4, EHEB) but not in p53(mutated) (NB4, BJAB, MAVER) or p53(deleted) (HL-60) leukemic cell lines. The transcriptional repression of B-Myb was also observed in primary normal endothelial cells and fibroblasts. B-Myb downregulation played a critical role in the cell-cycle block in G(1) phase induced by Nutlin-3, as shown by transfection experiments with specific siRNA. Moreover, we have provided experimental evidence suggesting that miR-34a is a central mediator in the repression of B-Myb both directly and through E2F1.Owing to the role of B-Myb and E2F1 transcription factors in controlling cell-cycle progression of leukemic cells, the downregulation of these oncogenes by miR-34a suggests the usefulness of therapeutic approaches aimed to modulate the levels of miR-34a.
The case for low dose diuretics in hypertension: comparison of low and conventional doses of cyclopenthiazide.
Authors: G. McVeigh, D. Galloway, D. Johnston
Journal: BMJ (1988)

In a double blind placebo controlled randomised parallel study the antihypertensive activity and adverse biochemical effects of three doses of cyclopenthiazide were evaluated in patients with mild essential hypertension that had been recently diagnosed or was being treated with a single drug. After a four week placebo washout period 53 patients with diastolic blood pressures between 90-110 mm Hg were randomly assigned to 50, 125, or 500 micrograms cyclopenthiazide or matching placebo for an eight week period of treatment. Blood pressure was measured in the patients9 homes by the same observer every two weeks. Serum urea, electrolytes, urate, and creatinine concentrations and 24 hour urinary sodium excretion were monitored every four weeks and serum magnesium concentration and plasma renin activity at the end of the washout and treatment periods. After eight weeks of treatment systolic and diastolic blood pressures were significantly reduced in patients taking 125 and 500 micrograms cyclopenthiazide when compared with those taking placebo. The decrement in serum potassium concentration (0.6 mmol/l) and increase in serum urate concentration 0.06 mmol/l) were greatest with the 500 micrograms dose, the increase in serum urate concentration alone being significant. No change in serum magnesium concentration or 24 hour urinary sodium excretion was noted with any dose of cyclopenthiazide. Only the 500 micrograms dose of cyclopenthiazide significantly increased the mean plasma renin activity (1.8 (95% confidence interval 0.2 to 3.4)-5.4 (3.9 to 6.8) nmol angiotensin I/l/h); the other doses like the placebo had no effect. Cyclopenthiazide 125 micrograms, a dose lower than is currently marketed, produced a similar hypotensive response to 500 micrograms of the drug without upsetting the biochemical profile.
DEATH FROM RESPIRATORY PARALYSIS FOLLOWING HYOSCIN-MORPHIN-CACTIN ANESTHESIA.
Authors: B. F. VAN METER
Journal: JAMA (1907)

<h3>Patient.</h3> —J. H. E., male, white, aged 51, was seen by me in consultation with Dr. G. M. Centers, Hazelgreen, and Dr. J. A. Stucky, Lexington. <h3>Family History.</h3> —Mother and father living and in good health. Two sisters and one brother living and in good health. One sister dead; cause of death unknown. No history of malignant growth in family. <h3>Personal History.</h3> —Patient was a bookkeeper and clerk. Married. Up to one year previously had always enjoyed good health. Drank whisky to excess. Present illness began one year before I saw him with an attack of tonsillitis. After the attack he noticed an enlargement at the angle of the left jaw. This increased slowly in size until two months previously, when it grew rapidly and caused a great deal of pain, for which morphin was given; at the time I saw him he was taking one grain of morphin daily.
CAN ANTITOXIN STATISTICS BE RELIED UPON?
Authors: GUSTAVUS BLECH
Journal: JAMA (1896)

The many fiascoes in modern medicine have taught me a lesson, viz: Never to be the first and never to be the last one, to adopt a new remedy. Liberality is one of the first conditions for progress and success in medicine; conservatism, the preventative for poetic illusions and errors, undiscovered on account of the blinding effect of enthusiasm. I have quietly watched the reports of cures of diphtheria with antitoxin, and have wondered how easy it is to catch the masses, even if one knows next to nothing about the<i>modus operandi</i>of a remedy. Beside, its origin and composition is mystery as yet, its preparation being controlled entirely by a few enterprising chemists. But neither this nor the fact that its introduction into the human system is apt cause a good many dangers like leucocythemia, shall be brought as an argument against its value; even the fact, that
P777Arterial stiffness as a biomarker of arterial wall involvement in patients with non-specific congenital connective tissue disorders
Authors: O Chindareva, A Semenkin, G Nechaeva, O Drokina, L Zhivilova
Journal: Cardiovascular Research (2014)

Purpose: Systemic manifestations of connective tissue disorders (CTD) as for example in Marfan, Ehler-Danlos, and other genetic syndromes may include changes of vascular wall structure and function. Our aim was to evaluate the arterial stiffness in patients with clinical signs of possible congenital CTD.
Complete Excision of Primary Breast Tumor Improves Survival of Patients With Metastatic Breast Cancer at Diagnosis
Authors: Elisabetta Rapiti, Helena M. Verkooijen, Georges Vlastos, Gerald Fioretta, Isabelle Neyroud-Caspar, André Pascal Sappino, Pierre O. Chappuis, Christine Bouchardy
Journal: Journal of Clinical Oncology (2006)

Surgery of the primary tumor usually is not advised for patients with metastatic breast cancer at diagnosis because the disease is considered incurable. In this population-based study, we evaluate the impact of local surgery on survival of patients with metastatic breast cancer at diagnosis.We included all 300 metastatic breast cancer patients recorded at the Geneva Cancer Registry between 1977 and 1996. We compared mortality risks from breast cancer between patients who had surgery of the primary breast tumor to those who had not and adjusted these risks for other prognostic factors.Women who had complete excision of the primary breast tumor with negative surgical margins had a 40% reduced risk of death as a result of breast cancer (multiadjusted hazard ratio [HR], 0.6; 95% CI, 0.4 to 1.0) compared with women who did not have surgery (P = .049). This mortality reduction was not significantly different among patients with different sites of metastasis, but in the stratified analysis the effect was particularly evident for women with bone metastasis only (HR, 0.2; 95% CI, 0.1 to 0.4; P = .001). Survival of women who had surgery with positive surgical margins was not different from that of women who did not have surgery.Complete surgical excision of the primary tumor improves survival of patients with metastatic breast cancer at diagnosis, particularly among women with only bone metastases.
ABC of Rheumatology: POLYMYALGIA RHEUMATICA AND GIANT CELL ARTERITIS
Authors: G. Pountain, B. Hazleman
Journal: BMJ (1995)

In recent years giant cell arteritis and polymyalgia rheumatica have increasingly been considered as closely related conditions. The two syndromes form a spectrum of disease and affect the same types of patient. The conditions may occur independently or may occur in the same patient, either together or separated in time. Polymyalgia rheumatica is a clinical syndrome of middle aged and elderly patients and is characterised by: Swollen temporal artery of patient with giant cell arteritis. #### Aetiology of polymyalgia rheumatica and giant cell arteritis Polymyalgia rheumatica—At present it is impossible to define the underlying pathological abnormality in polymyalgia rheumatica, and several different mechanisms may be responsible for a largely similar pattern of pain. Giant cell arteritis is limited to vessels with an internal elastic component. Both humoral and cellular immunological mechanisms have been implicated in its development, and the latter seem to be more important. Giant cell arteritis affects white people almost exclusively, but it has been reported in black Americans. In all studies both conditions are very rare under the age of 50 years. Reports from Olmsted County, Minnesota, and Gothenburg, Sweden, have shown that the incidence is increasing in women but not in men. About half of patients with giant cell arteritis have symptoms of polymyalgia rheumatica, whereas 15-50% of patients with polymyalgia rheumatica have giant cell arteritis. Problems with case definition and ascertainment complicate epidemiological observations. #### Epidemiology of giant cell arteritis
The effects of premature stimulation of the His bundle on epicardial activation and body surface late potentials in dogs susceptible to sustained ventricular tachyarrhythmias.
Authors: J F Spear, D A Richards, G J Blake, M B Simson, E N Moore
Journal: Circulation (1985)

Experiments were performed on 20 anesthetized dogs to determine the effects of premature stimulation of the His bundle on epicardial conduction and late potentials recorded on the body surface. Fifteen dogs underwent occlusion of the left anterior descending coronary for 2 hr followed by reperfusion, and five that did not undergo operation served as controls. Animals were studied 2 to 52 weeks after the induction of infarction, and four animals with infarction and four control animals exhibited no sustained arrhythmias in response to programmed ventricular extrastimulation. Five dogs with infarction and one control dog had ventricular fibrillation while the six remaining dogs had inducible sustained ventricular tachycardia. All animals with ventricular tachycardia had late potentials in the terminal portion of the signal-averaged body surface QRS complexes during sinus rhythm and QRS durations in the animals were 64 msec or greater. The voltage in the last 20 msec of the QRS complex was 13.5 microV or less and the duration of late activity below 30 microV was 18.2 msec or more. These values did not overlap values in animals with no inducible arrhythmias. Ventricular fibrillation was a nonspecific end point in these experiments and values overlapped those in animals with no arrhythmias and those with ventricular tachycardia. All animals with infarction and late potentials associated with their QRS complexes also had delayed and prolonged epicardial electrograms that extended into the time of the late potentials recorded from 45 standard sites in the infarcted regions. A single premature beat evoked by His bundle pacing (coupling interval of 192 to 270 msec) had no significant effect on late potentials or their relationship to epicardial activation in the area of infarct. However, changes in the durations of electrograms in response to premature beats were different in animals with infarction and ventricular tachycardia than in those with ventricular fibrillation. In animals with ventricular tachycardia, electrograms at 15 of 210 sites increased in duration by more than 10 msec while those at 61 of 210 sites decreased in duration. In animals with ventricular fibrillation, electrograms at 40 of 207 sites were of increased duration while those at 26 of 207 decreased. The decreases in duration were usually due to components of fractionated electrograms "dropping out" and likely represent local conduction block near the recording electrode.(ABSTRACT TRUNCATED AT 400 WORDS)
A Brief Review of Software Tools for Pangenomics
Authors: Jingfa Xiao, Zhewen Zhang, Jiayan Wu, Jun Yu
Journal: Genomics Proteomics & Bioinformatics (2015)

Abstract Since the proposal for pangenomic study, there have been a dozen software tools actively in use for pangenomic analysis. By the end of 2014, Panseq and the pan-genomes analysis pipeline (PGAP) ranked as the top two most popular packages according to cumulative citations of peer-reviewed scientific publications. The functions of the software packages and tools, albeit variable among them, include categorizing orthologous genes, calculating pangenomic profiles, integrating gene annotations, and constructing phylogenies. As epigenomic elements are being gradually revealed in prokaryotes, it is expected that pangenomic databases and toolkits have to be extended to handle information of detailed functional annotations for genes and non-protein-coding sequences including non-coding RNAs, insertion elements, and conserved structural elements. To develop better bioinformatic tools, user feedback and integration of novel features are both of essence.
Return of the <i>memento mori</i>: Imaging death in public health
Authors: Estelle Noonan, Miles Little, Ian Kerridge
Journal: Journal of the Royal Society of Medicine (2013)

Death has always held a morbid fascination for humans. Indeed, awareness of one’s own mortality may well be one of the defining features of the ‘human condition’ – symbols of death appearing in most civilizations since artefacts have been made. The Latin phrase memento mori, meaning literally ‘remember to die’, encapsulates a rich and varied artistic tradition, dating back to the Middle Ages, of figuring death by symbolizing its literal processes and remainders. From the decomposed effigies of 15th-century ‘cadaver tombs’, to the humorous medieval iconography of the skeletal danse macabre, the works of this genre draw on the destructive physical changes that are a part of our understanding of death. Prolific within its morbid imagery are the use of skull, skeleton and verminous or rotting flesh as ‘trope’ or symbol of the processes that eventually take away the person who lived, and who was once like us.
Effect of natural seasonal pollen exposure and repeated nasal allergen provocations on elevation of exhaled nitric oxide
Authors: K. Bergmann‐Hug, R. Wirth, M. Henseler, A. Helbling, W. J. Pichler, B. Schnyder
Journal: Allergy (2009)

Exhaled nitric oxide (FENO) is a marker for allergic airway inflammation. We wondered whether in patients with intermittent allergic rhinitis only (i) natural pollen exposure and (ii) artificial pollen exposure by repeated nasal allergen provocations may lead to an elevation of FENO.In two prospective studies, we compared the FENO of nonatopic controls with the FENO of nonasthmatic individuals with mild intermittent rhinitis to tree and/or grass pollen. Study I: 13 atopic individuals and seven controls had measurements of FENO, blood eosinophils and eosinophilic cationic protein (ECP) before, during and after pollen season. Study II: 16 atopic individuals and 12 controls had nasal allergen provocations on four following days out of pollen season, with daily measurements of FENO before, 2 and 6 h after provocation, and determination of blood eosinophils, ECP and FEV1 at baseline, on days 5 and 10-12.Natural pollen exposure (study I) caused a significant elevation of FENO in allergic individuals. Nasal allergen provocations (study II) did not elicit a statistically significant rise neither of FENO nor of blood eosinophils between baseline and day 5. However, a subgroup of four individuals with a rise of blood eosinophils during nasal allergen provocations showed also a rise of FENO.We suppose that in allergic rhinitis a concomitant reaction of the bronchial system is dependent on a strong local inflammation leading to a generalized immune stimulation.
Transcriptome analysis of controlled and therapy-resistant childhood asthma reveals distinct gene expression profiles
Authors: Helena Persson, Andrew T. Kwon, Jordan A. Ramilowski, Gilad Silberberg, Cilla Söderhäll, Christina Orsmark-Pietras, Björn Nordlund, Jon R. Konradsen, Michiel J.L. de Hoon, Erik Melén, Yoshihide Hayashizaki, Gunilla Hedlin, Juha Kere, Carsten O. Daub
Journal: Journal of Allergy and Clinical Immunology (2015)

BackgroundChildren with problematic severe asthma have poor disease control despite high doses of inhaled corticosteroids and additional therapy, leading to personal suffering, early deterioration of lung function, and significant consumption of health care resources. If no exacerbating factors, such as smoking or allergies, are found after extensive investigation, these children are given a diagnosis of therapy-resistant (or therapy-refractory) asthma (SA).ObjectiveWe sought to deepen our understanding of childhood SA by analyzing gene expression and modeling the underlying regulatory transcription factor networks in peripheral blood leukocytes.MethodsGene expression was analyzed by using Cap Analysis of Gene Expression in children with SA (n = 13), children with controlled persistent asthma (n = 15), and age-matched healthy control subjects (n = 9). Cap Analysis of Gene Expression sequencing detects the transcription start sites of known and novel mRNAs and noncoding RNAs.ResultsSample groups could be separated by hierarchical clustering on 1305 differentially expressed transcription start sites, including 816 known genes and several novel transcripts. Ten of 13 tested novel transcripts were validated by means of RT-PCR and Sanger sequencing. Expression of RAR-related orphan receptor A (RORA), which has been linked to asthma in genome-wide association studies, was significantly upregulated in patients with SA. Gene network modeling revealed decreased glucocorticoid receptor signaling and increased activity of the mitogen-activated protein kinase and Jun kinase cascades in patients with SA.ConclusionCirculating leukocytes from children with controlled asthma and those with SA have distinct gene expression profiles, demonstrating the possible development of specific molecular biomarkers and supporting the need for novel therapeutic approaches.
GENERAL PRINCIPLES OF BLOOD TRANSFUSION
Authors: T. J. Greenwalt
Journal: JAMA (1965)

Those of us who have had our 25th class reunions will recall that there was a time when a blood transfusion was a formidable procedure to be avoided whenever possible. The technical developments in blood-banking procedures during the last two decades have made blood transfusion appear superficially as simple as ordering an infusion of glucose. Many fail to recognize that it is rather remarkable that blood, the fluid portion of the hematopoietic organ, can be taken from one person and given to another with beneficial effects. With most other tissues, elaborate preparations are necessary before transplantation is attempted, unless donor and recipient are identical twins. It is therefore not surprising that blood transfusions may be complicated by deleterious reactions and should be undertaken only after judicious weighing of expected benefits against potential dangers.  The literature describing new developments in transfusion practice has become prohibitively voluminous. In order to help the
Important New Findings in Sepsis
Authors: Roger C. Bone
Journal: JAMA (1997)

In this issue ofThe Journal, Sands et al<sup>1</sup>present important results in an epidemiologic study of sepsis in 8 academic medical centers. The most interesting conclusion is that sepsis occurred in as many as 2 cases per 100 admissions in academic tertiary care centers. This rate is much higher than that found in previous investigations<sup>2</sup>and probably results from more complicated cases, a higher incidence of nosocomial infection, and inclusion of non-intensive care unit (ICU) patients. For example, Brun-Buisson et al<sup>3</sup>looked at the incidence of sepsis in ICUs in France and found an attack rate of 9% overall and 10.3% in very large institutions. In the study by Sands et al, ICU patients accounted for only 59% of the cases; of the 41% remaining non-ICU patients, 11% had positive blood cultures and 30% had negative blood cultures. See also p 234. This analysis also supports
CT scanning in lung cancer
Authors: H K BUNGAY
Journal: Thorax (2001)

Myositis associated with graft-versus-hostdisease (GVHD) typically presents with proximal muscle weakness, myalgias, and a raised creatinine phosphokinase (CPK) level.We report a case of a 51 year old man who developed respiratory muscle weakness five years after an allogeneic bone marrow transplant for multiple myeloma.His symptoms included tachypnoea, abdominal paradox, and orthopnoea.Pulmonary function tests revealed diminished vital capacity and maximal inspiratory and expiratory pressures.Serum CPK levels were raised and a peripheral muscle biopsy specimen was consistent with GVHD.He improved with immunosuppressive therapy.