tbuckley/cabot-search huggingface dataset:
Myosin gene expression in the respiratory muscles
Authors: JG Gea
Journal: European Respiratory Journal (1997)

Myosin is one of the basic structural components of skeletal muscles. Its interaction with actin results in muscle contraction. The myosin molecule is composed of two heavy (MyHC) and two light chains (MyLC) that, together with the adenosine triphosphatase (ATPase) activity, determine the functional characteristics of the fibre. Both MyHC and MyLC present different isoforms. The main MyHC isoforms in adult mammals are the slow MyHC (MyHC-I) and fast MyHCs (MyHC-IIa, MyHC-IIb and MyHC-IIx). Muscle fibres can express only one isoform or coexpress different forms. The muscle phenotype is the product of genome plus environmental stimuli. The family of genes that codifies the MyHC isoforms is located in two different clusters, each isoform being encoded by a separate gene. The gene corresponding to slow MyHC is located in chromosome 14, both in humans and in mice. The other genes are positioned in chromosome 17 in humans, and in chromosome 11 in mice. The transcriptional and translational mechanisms that control the expression of MyHC isoforms are not well known, although it is believed that the main regulation is dependent on mechanical signals. These signals are probably mediated by a biochemical messenger. As a general rule, fast MyHC genes seem to be expressed "by default", whereas the slow MyHC gene would be expressed as a response to changes in load. So far, few studies have analysed the in vivo regulation of MyHC gene expression in respiratory muscles. It has recently been reported that breathing against moderate levels of inspiratory resistance quickly induces an increase in the genetic expression of slow MyHC in the diaphragm. This suggests the possibility of eliciting a phenotypic adaptation of respiratory muscles using specific training protocols.
Tolerance to beta-agonists during acute bronchoconstriction
Authors: R.J. Hancox, R.E. Aldridge, J.O. Cowan, E.M. Flannery, G.P. Herbison, C.R. McLachlan, G.I. Town, D.R. Taylor
Journal: European Respiratory Journal (1999)

Previous reports suggest that regular use of beta-agonists does not lead to tolerance to their bronchodilator effects. However, most studies have been conducted in stable asthma. This study investigates whether bronchodilator tolerance can be demonstrated during acute bronchoconstriction. Thirty-four asthmatic subjects were treated with 6 weeks inhaled terbutaline (1 mg q.i.d.), budesonide (400 microg, b.i.d.), both drugs or placebo in a randomized, double-blind, cross-over study. After each treatment methacholine was administered to induce a 20% fall in the forced expiratory volume in one second (FEV1). The response to inhaled salbutamol 100, 100, 200 microg at 5 min intervals) was then measured. Dose-response curves were compared using an analysis of covariance. Pre-methacholine FEV1, the highest pre-methacholine FEV1, the fall in FEV1 induced by methacholine and the logarithm of the provocative dose of methacholine required to induce the 20% fall in FEV1 (PD20) were used as covariates. There was a significantly reduced response to salbutamol after 6 weeks terbutaline treatment: the mean (95% confidence intervals (CI)) area under the dose-response curve was reduced by 36% (24, 47) compared to placebo (p&lt;0.0001). The reduction in bronchodilator response was not affected by concomitant treatment with budesonide. Significant tolerance to the bronchodilator effect of inhaled beta-agonists may be demonstrated when tested during acute bronchoconstriction. Continuous treatment with inhaled beta-agonists may lead to a reduced response to emergency beta-agonist treatment during asthma exacerbations.
THE BACTERICIDAL ACTION OF HUMAN SERUM ON HEMOLYTIC STREPTOCOCCI
Authors: William S. Tillett
Journal: The Journal of Experimental Medicine (1937)

Sera obtained from patients at the time of acute active infections were found, in every instance, to be bactericidal for hemolytic streptococci. The observations were made with sera from twenty-five patients. The group consisted of cases of pneumococcus, hemolytic streptococcus, staphylococcus, meningococcus, tubercle bacillus, and malarial infections; the etiology of the diseases in other patients was either uncertain or may have been a mixed infection. In sera taken from the same group of patients, soon after recovery or marked improvement had taken place, the streptococcidal property was absent or greatly diminished in potency. By comparative tests made with sera from twenty healthy adults, the streptococcidal action was not demonstrable. Three different strains of Streptococcus hemolyticus of the beta type were employed in the experiments. Differences in susceptibility of the strains to the killing power of the serum were noted.
Averting a change to the date of the royal succession
Authors: Margaret Hope Robinson
Journal: BMJ (2004)

I will be 90 years old in 2005 and have a very clear memory of an episode which took place at my home in Mansfield in 1926 when I was 11. My father, H L Flint, was a general practitioner but was much involved with cardiology. We understood (rightly or wrongly) that he was the first person in the Midlands able to take electrocardiographs. One fair-sized room in our house was his surgery. (Panel patients had a scruffy place in the town.) The electrocardiograph took up nearly the whole length of one wall. The patient sat with both feet and arms in saline baths and …
Microsatellite Variability Differs Between Dinucleotide Repeat Motifs—Evidence from Drosophila melanogaster
Authors: Doris Bachtrog, Martin Agis, Marianne Imhof, Christian Schlötterer
Journal: Molecular Biology and Evolution (2000)

Recently, the use of microsatellites as genetic markers has become very popular. While their evolutionary dynamics are not yet fully understood, the emerging picture is that several factors are influencing microsatellite mutation rates. Recent experiments demonstrated a significant effect of repeat motif length on microsatellite mutation rates. Here, we studied the influence of the base composition of the microsatellite. Forty-two microsatellite loci on the second chromosome with the three most abundant dinucleotide repeat motifs (TC/AG, AT/TA, GT/CA) were characterized for six different Drosophila melanogaster populations. Applying ANOVA to the variance in repeat number, we found a significant influence of repeat motif on microsatellite variability. Calculating relative mutation rates, GT/CA appears to have the highest mutation rate, and AT/TA appears to have the lowest. Similar differences in mutation rates were obtained by an alternative method which estimates microsatellite mutation rates from their genomic length distribution.
External validation of the Simplified Acute Physiology Score (SAPS) 3 in a cohort of 28,357 patients from 147 Italian intensive care units
Authors: Daniele Poole, Carlotta Rossi, Abramo Anghileri, Michele Giardino, Nicola Latronico, Danilo Radrizzani, Martin Langer, Guido Bertolini
Journal: Intensive Care Medicine (2009)
High-Density Lipoproteins Inhibit Vascular Endothelial Inflammation by Increasing 3β-Hydroxysteroid-Δ24 Reductase Expression and Inducing Heme Oxygenase-1
Authors: Ben J. Wu, Kang Chen, Sudichhya Shrestha, Kwok L. Ong, Philip J. Barter, Kerry-Anne Rye
Journal: Circulation Research (2012)

Lipid-free apolipoprotein (apo) A-I and discoidal reconstituted high-density lipoproteins (rHDL) containing apoA-I, (A-I)rHDL, inhibit vascular inflammation by increasing 3β-hydroxysteroid-Δ24 reductase (DHCR24) expression.To determine whether the lipid-free apoA-I-mediated and (A-I)rHDL-mediated increase in DHCR24 expression induces the cytoprotective and potentially cardioprotective enzyme, heme oxygenase-1 (HO-1).In vivo: A single intravenous infusion of lipid-free apoA-I (8 mg/kg) administered 24 hours before inserting a nonocclusive periarterial carotid collar into New Zealand White rabbits decreased collar-induced endothelial vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression, reduced intima/media neutrophil infiltration, and increased DHCR24 and HO-1 mRNA levels. Knockdown of vascular DHCR24 and HO-1 and systemic administration of tin-protoporphyrin-IX, an HO inhibitor, abolished these anti-inflammatory effects. In vitro: Preincubation of human coronary artery endothelial cells with (A-I)rHDL before activation with tumor necrosis factor-α increased DHCR24 and HO-1 mRNA levels and inhibited cytokine-induced vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression. Transfection of the cells with DHCR24 and HO-1 small interfering RNA and tin-protoporphyrin-IX treatment abolished these effects. The (A-I)rHDL-mediated induction of HO-1 was reduced in human coronary artery endothelial cells transfected with DHCR24 small interfering RNA. Transfection of human coronary artery endothelial cells with HO-1 small interfering RNA and tin-protoporphyrin-IX treatment did not inhibit the (A-I)rHDL-mediated increase in DHCR24 expression. Inhibition of phosphatidylinositol 3-kinase/Akt reduced the (A-I)rHDL-mediated increase in HO-1, but not DHCR24 expression. The activation of phosphatidylinositol 3-kinase/Akt by (A-I)rHDL was decreased in human coronary artery endothelial cells that were transfected with DHCR24 small interfering RNA.Lipid-free apoA-I and (A-I)rHDL inhibit inflammation by increasing DHCR24 expression, which, in turn, activates phosphatidylinositol 3-kinase/Akt and induces HO-1.
Stent Graft versus Balloon Angioplasty for Failing Dialysis-Access Grafts
Authors: Ziv J. Haskal, Scott Trerotola, Bart Dolmatch, Earl Schuman, Sanford Altman, Samuel Mietling, Scott Berman, Gordon McLennan, Clayton K Trimmer, John Ross, Thomas Vesely
Journal: New England Journal of Medicine (2010)

The leading cause of failure of a prosthetic arteriovenous hemodialysis-access graft is venous anastomotic stenosis. Balloon angioplasty, the first-line therapy, has a tendency to lead to subsequent recoil and restenosis; however, no other therapies have yet proved to be more effective. This study was designed to compare conventional balloon angioplasty with an expanded polytetrafluoroethylene endovascular stent graft for revision of venous anastomotic stenosis in failing hemodialysis grafts.We conducted a prospective, multicenter trial, randomly assigning 190 patients who were undergoing hemodialysis and who had a venous anastomotic stenosis to undergo either balloon angioplasty alone or balloon angioplasty plus placement of the stent graft. Primary end points included patency of the treatment area and patency of the entire vascular access circuit.At 6 months, the incidence of patency of the treatment area was significantly greater in the stent-graft group than in the balloon-angioplasty group (51% vs. 23%, P<0.001), as was the incidence of patency of the access circuit (38% vs. 20%, P=0.008). In addition, the incidence of freedom from subsequent interventions at 6 months was significantly greater in the stent-graft group than in the balloon-angioplasty group (32% vs. 16%, P=0.03 by the log-rank test and P=0.04 by the Wilcoxon rank-sum test). The incidence of binary restenosis at 6 months was greater in the balloon-angioplasty group than in the stent-graft group (78% vs. 28%, P<0.001). The incidences of adverse events at 6 months were equivalent in the two treatment groups, with the exception of restenosis, which occurred more frequently in the balloon-angioplasty group (P<0.001).In this study, percutaneous revision of venous anastomotic stenosis in patients with a prosthetic hemodialysis graft was improved with the use of a stent graft, which appears to provide longer-term and superior patency and freedom from repeat interventions than standard balloon angioplasty. (ClinicalTrials.gov number, NCT00678249.)
Use of Genotypic Resistance Testing To Guide HIV Therapy: Clinical Impact and Cost-Effectiveness
Authors: Milton C. Weinstein, Sue J. Goldie, Elena Losina, Calvin J. Cohen, John D. Baxter, Hong Zhang, April D. Kimmel, Kenneth A. Freedberg
Journal: Annals of Internal Medicine (2001)

Background: Genotypic sequencing for drug-resistant strains of HIV can guide the choice of antiretroviral therapy. Objective: To assess the cost-effectiveness of genotypic resistance testing for patients acquiring drug resistance through failed treatment (secondary resistance) and those infected with resistant virus (primary resistance). Design: Cost-effectiveness analysis with an HIV simulation model incorporating CD4 cell count and HIV RNA level as predictors of disease progression. Data Sources: Published randomized trials and data from the Multicenter AIDS Cohort Study, the national AIDS Cost and Services Utilization Survey, the Red Book, and an institutional cost-accounting system. Target Population: HIV-infected patients in the United States with baseline CD4 counts of 0.250 × 109 cells/L. Time Horizon: Lifetime. Perspective: Societal. Interventions: Genotypic resistance testing and clinical judgment, compared with clinical judgment alone, in two contexts: after initial treatment failure (secondary resistance testing) and before initiation of antiretroviral therapy (primary resistance testing). Outcome Measures: Life expectancy, quality-adjusted life expectancy, and cost-effectiveness in dollars per quality-adjusted life-year (QALY) gained. Results of Base-Case Analysis: Secondary resistance testing increased life expectancy by 3 months, at a cost of $17 900 per QALY gained. The cost-effectiveness of primary resistance testing was $22 300 per QALY gained with a 20% prevalence of primary resistance but increased to $69 000 per QALY gained with 4% prevalence. Results of Sensitivity Analysis: The cost-effectiveness ratio for secondary resistance testing remained under $25 000 per QALY gained, even when effectiveness and cost of testing and antiretroviral therapy, quality-of-life weights, and discount rate were varied. Conclusions: Genotypic antiretroviral resistance testing following antiretroviral failure is cost-effective. Primary resistance testing also seems to be reasonably cost-effective and will become more so as the prevalence of primary resistance increases.
THE PASSAGE OF RABBIT VIRULENT TYPE III PNEUMOCOCCI FROM THE RESPIRATORY TRACT OF RABBITS INTO THE LYMPHATICS AND BLOOD
Authors: Reuben Z. Schulz, Madeleine F. Warren, Cecil K. Drinker
Journal: The Journal of Experimental Medicine (1938)

1. Rabbit virulent Type III pneumococci when instilled into the nose or trachea were recovered from the lymphatics draining the area involved in the lymph collected during a subsequent 4 hour period. Their detection rarely failed, and not infrequently was possible at the end of the 1st hour. 2. The organisms practically invariably appeared first in the lymphatics and subsequently in a few cases were recovered from the blood during the 4 hour test period. 3. The intravenous administration of antiserum 2½ to 3 hours before the instillation of organisms decreased the number of animals whose lymph or blood became positive and the total length of time in which organisms were recovered in lymph from the efferent lymphatics during the test period.
Initiation codon mutation in an Asian Indian family
Authors: Anju Gupta, Yukio Hattori, Sarita Agarwal
Journal: American Journal of Hematology (2002)

Abstract The β‐thalassemias are a heterogeneous group of hereditary anemias. A multitude of mutations have been reported, resulting in varied phenotypes. In each ethnic group there is always a subset of common, less common, and rare mutations, which makes population screening, prenatal diagnosis, and genetic counseling easier. In this paper we report a rare β‐thalassemia mutation found in an Indian subject by SSCP and sequencing analysis. The mutation, initiation ATG → ACG, was found in heterozygous condition in a patient belonging to Brahmin family of Uttar Pradesh origin. Haplotype analysis was performed to identify the chromosomal background associated with the mutation and to tracing the origin and spread of the mutation. This study, as previous studies, suggests that rare β‐thalassemia mutations, such as the initiation codon mutations, have no set geographical distribution and are relatively recent. Am. J. Hematol. 71:134–136, 2002. © 2002 Wiley‐Liss, Inc.
Oxidation-Mediated DNA Crosslinking Contributes to Toxicity of 6-Thioguanine in Human Cells — Letter
Authors: Nanne K.H. de Boer, Dirk P. van Asseldonk, Margien L. Seinen, Adriaan A. van Bodegraven
Journal: Cancer Research (2013)

With great interest, we read the paper written by Brem and Karran concerning the unravelling of a novel pathway of toxicity during 6-thioguanine (6-TG) administration. The thiopurine 6-TG itself acts as a source of reactive oxygen species (ROS), which in combination with incorporated 6-TG
Retraction Note: Genomic signatures to guide the use of chemotherapeutics
Authors: Anil Potti, Holly K Dressman, Andrea Bild, Richard F Riedel, Gina Chan, Robyn Sayer, Janiel Cragun, Hope Cottrill, Michael J Kelley, Rebecca Petersen, David Harpole, Jeffrey Marks, Andrew Berchuck, Geoffrey S Ginsburg, Phillip Febbo, Johnathan Lancaster, Joseph R Nevins
Journal: Nature Medicine (2011)
Distinguishing Depression From Functional Impairment in the Medical Outcomes Study
Authors: Stephen F. Jencks
Journal: JAMA (1990)

<h3>To the Editor.—</h3> Wells et al<sup>1</sup>report that certain depressed patients show more functional impairment than certain patients with eight major chronic medical conditions. Their findings emphasize for clinicians the importance of depression as a cause of functional impairment in patients. On the other hand, the findings may not represent the relative functional impairment burdens of the diseases that the authors examined. Wells et al define depression, whether the symptom complex or the full disease, in terms of symptoms that are related closely to functional impairment. Although the symptoms used to define depression are not identical with the measures of functional impairment, there is an evident similarity. By contrast, chronic medical conditions were defined either on the basis of what the patient had been told by a physician or on the basis of the patient's report of "having" the condition; there is no requirement that the condition ever
LOBOTOMY FOR INTRACTABLE PAIN
Authors: JOHN B. DYNES
Journal: JAMA (1949)

Pain is a frequent symptom of disease or injury and in most instances may be relieved by the removal of the underlying cause or by the use of anesthetic agents or analgesic drugs, or it may be tolerated with fortitude and varying degrees of resignation by those who possess such qualities of temperament. Every physician has patients in his practice who experience pain which is unrelieved by the usual measures and in whom great physical and mental suffering result. Not infrequently such patients are totally incapacitated, a burden to their families, addicted to drugs, at times mentally unbalanced, unpredictable and always self concerned. In the majority of instances, if not in all, there is originally a discernible anatomic or physiologic reason for the pain experienced. In certain instances, however, a fixed pain pattern is set up prior to the removal of the existing cause. This pain pattern may be interrupted
Evidence based medicine needs to be more pragmatic
Authors: D. Oliver
Journal: BMJ (2014)

I agree with Greenhalgh and colleagues that evidence based medicine works best for single diseases and not for patients with complex comorbidity, frailty, and dementia.1 But such patients are now the “core business” of health services. Their exclusion from clinical trials, with research funding mainly allocated to younger people with single diseases, means that much of the …
The Osteopathic Dilemma: Separate or Same?
Authors: Michael J. Dainer
Journal: JAMA (1987)

<h3>To the Editor.—</h3> Dr Gevitz<sup>1</sup>has explored, concisely, the history of homeopathy and osteopathy in the United States. His article described osteopathy's heritage and original tenets. The subsequent development and incorporation of a medical curriculum in osteopathic institutions has permitted contemporary osteopathic physicians to enjoy previously unknown prestige and uncompromised opportunity. Many of us have proudly accepted opportunities to pursue specialty training programs leading to board certification. Our success has permitted us, individually and collectively, to become recognized as fully qualified physicians of equal stature. During this period of transition, osteopathic physicians have had an increasingly difficult time maintaining their separate professions. Can we honestly maintain that the tenets of osteopathy responsible for the development of a separate philosophy, theory, and practice of medicine are germane today? Osteopathic medical practice at the turn of the century bore no resemblance to standard allopathic practice. Osteopathy cast aside an entire body of
LIMITATIONS OF NON-SURGICAL TREATMENT IN ACUTE INTESTINAL OBSTRUCTION.
Authors: JOSEPH RILUS EASTMAN
Journal: JAMA (1903)

The term "acute obstruction of the bowel," broadly used, embraces all of those conditions, however varying in their etiology and pathology, which suddenly obstruct the lumen of the intestine to the extent of interfering with the passage of its contents. It is well known that the intestine may be obstructed by omental bands, fibrousbands, the result of peritoneal adhesions, as in appendicitis or peritonitis (<i>ante et post operationem</i>), by Meckel's and other diverticula, or at the neck of an internal or external hernia; that it may become kinked or twisted as in volvulus; that one segment of the intestine may become telescoped into a neighboring segment, as in intussusception; that the lumen of the intestinemay be obstructed by gallstones, enteroliths, foreign bodies or its own normal contents; that it may be narrowed by pressure of tumors from without; that its lumen may be narrowed by benign or malignant strictures, or
Diagnoses of melanoma need further investigation
Authors: S. Shuster
Journal: BMJ (1996)

their condition, to rate how badly they are affected, and, finally, to weight the relative importance of potential improvements in these areas.Although the MYMOP is promoted as a patient centred measure, it imposes three professionally derived dimensions on the patient and fails to take account of the relative importance that he or she attaches to these disparate domains.It is unclear if the patient centredness of the original measure has been compromised.An instrument that is valid must be reliable, but validity is a relative concept.The methods used by researchers in assessing validity are crude, particularly when applied to quality of life measures.The fact that the MYMOP seems to be "fairly" valid does not mean that it is precise enough to detect real differences in an individual over repeated administrations.It may well satisfy the reliability requirements for assessments of individual patients, but this needs to be shown.In summary, we would recommend the following methods to anyone wishing to develop the MYMOP approach: in depth interviews with patients who have completed the instrument to assess qualitatively its face and content validity; a content analysis of the symptoms and activities that patients include in their MYMOP; reliability testing; and correlation of scores obtained with the MYMOP with those obtained with a quality of life measure such as the patient generated index.