tbuckley/cabot-search huggingface dataset:
An Amino Acid-based Amphoteric Liposomal Delivery System for Systemic Administration of siRNA
Authors: Roger C Adami, Shaguna Seth, Pierrot Harvie, Rachel Johns, Renata Fam, Kathy Fosnaugh, Tianying Zhu, Ken Farber, Michael McCutcheon, Thomas T Goodman, Yan Liu, Yan Chen, Erin Kwang, Michael V Templin, Greg Severson, Tod Brown, Narendra Vaish, Feng Chen, Patrick Charmley, Barry Polisky, Michael E Houston
Journal: Molecular Therapy (2011)

We demonstrate a systematic and rational approach to create a library of natural and modified, dialkylated amino acids based upon arginine for development of an efficient small interfering RNA (siRNA) delivery system. These amino acids, designated DiLA₂ compounds, in conjunction with other components, demonstrate unique properties for assembly into monodisperse, 100-nm small liposomal particles containing siRNA. We show that DiLA₂-based liposomes undergo a pH-dependent phase transition to an inverted hexagonal phase facilitating efficient siRNA release from endosomes to the cytosol. Using an arginine-based DiLA₂, cationic liposomes were prepared that provide high in vivo siRNA delivery efficiency and are well-tolerated in both cell and animal models. DiLA₂-based liposomes demonstrate a linear dose-response with an ED₅₀ of 0.1 mg/kg against liver-specific target genes in BALB/c mice.
Hepcidin-Induced Hypoferremia Is a Critical Host Defense Mechanism against the Siderophilic Bacterium Vibrio vulnificus
Authors: João Arezes, Grace Jung, Victoria Gabayan, Erika Valore, Piotr Ruchala, Paul A. Gulig, Tomas Ganz, Elizabeta Nemeth, Yonca Bulut
Journal: Cell Host & Microbe (2015)
The Contract Problem and Its Solution.
Authors: George N. Jack.
Journal: JAMA (1906)

Depew, N. Y., Nov. 19, 1906. <h3>To the Editor:</h3> —The solution of the contract practice problem would result in more real good to the medical profession than that of any other problem that confronts us. As this contract problem concerns all, all should shoulder arms and come to the rescue before it is too late. If all those interested or who have some ideas on this contract question would furnish some practical advice throughThe Journal, it would not only benefit the local medical society referred to, but it might result in a practical solution of the contract problem, thus saving the dignity and honor of our profession. Some ten years ago the physicians of Depew and Lancaster got together and organized themselves into a medical society, known as the Central Medical Association. When this medical society was formed its constitution contained a clause forbidding any member from doing contract
YORK COUNTY HOSPITAL: CASE OF CUTANEOUS OUTGROWTHS FROM THE ANUS IN A MALE: LIGATURE: EXCISION: CURE
Authors: W. D. Husband
Journal: BMJ (1856)

THE patient, who was admitted into the York County Hospital under my care, was a tolerably strong and healthy man, but somewhat pale, of dissolute and irregular habits, and had lately undergone the hard discipline of the House of Correction.He complained of the annoyance of several pendulous tumours hanging down from the margin of the anus, which occasioned him much discomfort, both from their size, especially the largest of the group, and from a most intolerable fetor which they gave off.
Zones of Atrial Vulnerability
Authors: Howard S. Friedman, Bindeshwari Sinha, Aung Tun, Rizwan Pasha, Amir Sharafkhaneh, Anoopendra Bharadwaj
Journal: Circulation (1996)

Background Bradycardia is commonly found in individuals at risk for paroxysmal atrial fibrillation (AF). However, a clear relationship between lengthening of basic cyclic length (BCL) and AF has not been demonstrated. Methods and Results In 20 open-chest dogs, atrial refractoriness, AF vulnerability, and atrial activation times (ACTs) were determined in sinus rhythm and at BCLs of 400, 300, and 200 ms, and the findings at the same coupling intervals and stimulus strengths were compared. As BCL increased, AFV zone lengthened, and its outer limit occurred later in diastole. The outer limit of the AF vulnerability zone for a BCL was its relative refractory period; the inner limit, however, was not its effective refractory period. A border zone, defined by the inner limit of the AF vulnerability zone and the effective refractory period for a BCL, decreased as BCL lengthened, offsetting the increase in the AF vulnerability zone. The border zone was characterized by paradoxical stimulus current strength propagation relations and features suggesting supernormal conduction. ACT also increased with BCL lengthening. When AF induced by rapid atrial burst pacing was contrasted with AF induced by an extrastimulus, it tended to have a more disorganized pattern and lasted longer. Conclusions Lengthening of BCL increases the AF vulnerability zone, extending its outer limit later in diastole and comprising an increasing component of the total duration of the relative refractory period. Very short BCLs create conditions that also favor AF vulnerability.
Elevated Plasma Lipoprotein(a) in Patients with the Nephrotic Syndrome
Authors: Christoph Wanner
Journal: Annals of Internal Medicine (1993)

Objective: To examine the influence of the nephrotic syndrome on lipoprotein(a) (Lp[a]), a plasma lipoprotein associated with atherosclerotic cardiovascular disease independently of low-density lipoproteins. Factors that modulate plasma Lp(a) concentrations are poorly understood. Patients: A total of 62 patients: 47 with primary kidney disease and 15 with diabetic nephropathy. Measurements: Lipoprotein(a) levels were determined by enzyme-linked immunosorbent assay. Because apo(a) phenotype has a significant effect on Lp(a) levels, apo(a) isoforms were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and immunoblotting; the data were compared with a healthy control group. Results: Nephrotic patients had significantly higher Lp(a) levels (mean, SE, 69 10 mg/dL; median, 46 mg/dL, <0.01) compared with 91 healthy controls (mean, 18 2 mg/dL; median 9 mg/dL). Sixty percent of the patients and 18% of the controls had values greater than 30 mg/dL. Lipoprotein(a) levels correlated significantly with apolipoprotein B, serum cholesterol, and low-density lipoprotein cholesterol but showed no correlation with creatinine, albumin, or proteinuria. Within all apo(a) isoform classes, higher concentrations of Lp(a) were seen in the nephrotic patients compared with controls (P < 0.05). Finally, in nine patients with primary kidney disease and elevated Lp(a) levels, remission of the nephrotic syndrome was induced using immunosuppressive drugs and Lp(a) values decreased dramatically (pretreatment mean, 90 15 mg/dL versus remission mean, 31 8 mg/dL). A decrease in Lp(a) levels was also observed when patients with diabetic nephropathy progressed to end-stage renal disease (nephropathy mean, 56 11 mg/dL versus dialysis mean, 34 10 mg/dL; n = 7). Conclusions: Most patients with the nephrotic syndrome have Lp(a) concentrations that are substantially elevated compared with controls of the same apo(a) isoform. Because Lp(a) concentrations are substantially reduced when remission of the nephrotic syndrome is induced, it is likely that the nephrotic syndrome results directly in elevation of Lp(a) by an as yet unknown mechanism. The high levels of Lp(a) in the nephrotic syndrome could cause glomerular injury as well as increase the risk for atherosclerosis and thrombotic events associated with this disorder.
Sued's corner
Authors: Imre Loefler
Journal: BMJ (2004)

Serving hot coffee without warning of the risks attracts litigation. It follows that the bestdefence against liability is to assume that everyone is a moron.

Aircraft makers and airlines are also liable if their products fall down. They may be able toprotect themselves by displaying audiovisual messages, indicating that aeroplanes are known to crash and that air travel is dangerous.

The makers of all products and the providers of …
Private member's bill proposes plain packaging of tobacco products in India
Authors: S. Bhaumik
Journal: BMJ (2013)

Health advocates, experts in public health, and cancer activists in India are rallying around a draft private member’s bill that seeks to introduce plain packaging of tobacco products across the nation.

Plain packaging of tobacco products, which has been described “as a weapons-grade public health policy that is causing apoplexy in the international industry,”1 was first rolled out in Australia in December last year.2

Exposure to advertising and promotion of tobacco products have been consistently linked to tobacco use, so plain packaging “would definitely contribute to addressing the tobacco epidemic in the Indian context,” Monika Arora, head of health promotion and tobacco control at the Public …
A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans
Authors: Kunihiro Yoshida, Kenichi Furihata, Shin'ichi Takeda, Akinori Nakamura, Kanji Yamamoto, Hiroshi Morita, Shuichi Hiyamuta, Shu-ichi Ikeda, Norikazu Shimizu, Nobuo Yanagisawa
Journal: Nature Genetics (1995)
Nobel Prize to Stanley Prusiner for Prion Discovery
Authors: Joan Stephenson
Journal: JAMA (1997)

IN<i>CAT'S CRADLE</i>, novelist Kurt Vonnegut conjured a bizarre ice crystal called ice-nine that brings about disaster by converting the earth's oceans into ice. Last month, the 1997 Nobel Prize for Medicine or Physiology honored Stanley B. Prusiner, MD, of the University of California, San Francisco (UCSF), for controversial research showing that a novel class of infectious "rogue proteins" called prions similarly appears to wreak a type of transformational havoc on the brain of humans and other mammals. Prusiner's pioneering work, said the Nobel committee of the Karolinska Institute, Stockholm, Sweden, in its announcement of the award, uncovered "an entirely new genre of disease-causing agents" that many scientists believe are responsible for a variety of deadly neurodegenerative diseases. The list includes kuru, Creutzfeldt-Jakob disease (CJD),Gertsmann-Sträussler-Scheinker (GSS) disease, and fatal familial insomnia in humans, as well as transmissible spongiform encephalopathies such as scrapie and mad cow disease (bovine spongiform encephalopathy [BSE])
MotifCluster: an interactive online tool for clustering and visualizing sequences using shared motifs
Authors: Micah Hamady, Jeremy Widmann, Shelley D Copley, Rob Knight
Journal: Genome biology (2008)

MotifCluster finds related motifs in a set of sequences, and clusters the sequences into families using the motifs they contain. MotifCluster, at http://bmf.colorado.edu/motifcluster , lets users test whether proteins are related, cluster sequences by shared conserved motifs, and visualize motifs mapped onto trees, sequences and three-dimensional structures. We demonstrate MotifCluster's accuracy using gold-standard protein superfamilies; using recommended settings, families were assigned to the correct superfamilies with 0.17% false positive and no false negative assignments.
WHO inquiry into SARS leaves questions unanswered
Authors: F. Fleck
Journal: BMJ (2003)

Experts on the severe acute respiratory syndrome (SARS) virus converged at the headquarters of the World Health Organization in Geneva on Monday to update recommendations on the syndrome, at the same time as WHO released a report of the latest findings on the disease.

The report collates recently published and as yet unpublished studies into the disease, as well as the views of experts in public health, epidemiology, and clinical virology who have experience of major outbreaks of SARS in China, Hong Kong, Singapore, and Canada.

The meeting …
Book Review Anesthesia Third edition. Edited by Ronald D. Miller, with Roy F. Cucchiara, Edward D. Miller, Jr., J.G. Reves, Michael F. Roizen, and John J. Savarese. 2420 pp. in two volumes, illustrated. New York, Churchill Livingstone, 1990. $175.
Authors: Kenneth L. Blazier, Bucknam McPeek
Journal: New England Journal of Medicine (1991)
THE TREATMENT OF PUERPERAL SEPSIS.
Authors: E. E. MONTGOMERY
Journal: JAMA (1897)

Before the Obstetric Section at Atlanta, last year, I read a paper on the "Administration of Antistreptococcic Serum," based on my experience in one patient treated the February preceding. But little had been done at that time in the treatment and study of this practice. During the year very much has been added to the literature, although its value still remains<i>subjudice</i>. The importance of the subject can not be overestimated when we appreciate not only the serious mortality, but the influence upon the subsequent health of the individual, which must result from an attack of sepsis. I do not feel that the subject of the value of the serum therapy has as yet been sufficiently demonstrated to justify the physician in trusting to it alone; in other words, every means should be exercised which will increase the vitality of the patient, and thus enable us to secure immunity against
Rat liver stem cells: Prospects for the future
Authors: D SHAFRITZ
Journal: Hepatology (2000)

Hepatic stem cells have been identified in adult liver. Recently, the origin of hepatic progenitors and hepatocytes from bone marrow was demonstrated. Hematopoietic and hepatic stem cells share the markers CD 34, c-kit, and Thy1. Little is known about liver stem cells during liver development. In this study, we investigated the potential stem cell marker Thy1 and hepatocytic marker CK-18 during liver development to identify putative fetal liver stem cell candidates. Livers were harvested from embryonic and fetal day (ED) 16, ED 18, ED 20, and neonatal ED 22 stage rat fetuses from Sprague-Dawley rats. Fetal livers were digested by collagenase-DNAse solution and purified by percoll centrifugation. Magnetic cell sorting (MACS) depletion of fetal liver cells was performed using OX43 and OX44 antibodies. Cells were characterized by immunocytochemistry for Thy1, CK-18, and proliferating cell antigen Ki-67 and double labeling for Thy1 and CK-18. Thy1 expression was found at all stages of liver development before and after MACS in immunocytochemistry. Thy1 positive cells were enriched after MACS only in early developmental stages. An enrichment of CK-18 positive cells was found after MACS at all developmental stages. Cells coexpressing Thy1 and CK-18 were identified by double labeling of fetal liver cell isolates. In conclusion, hepatic progenitor cells (CK-18 positive) in fetal rat liver express Thy1. Other progenitors express only CK-18. This indicates the coexistence of different hepatic cell compartments. Isolation and further characterization of such cells is needed to demonstrate their biologic properties. (HEPATOLOGY 2003;37:148-154.)
Previous Preterm and Small-for-Gestational-Age Births and the Subsequent Risk of Stillbirth
Authors: Pamela J. Surkan, Olof Stephansson, Paul W. Dickman, Sven Cnattingius
Journal: New England Journal of Medicine (2004)

Some causes of stillbirth may also lead to fetuses that are small for gestational age (have a low birth weight with respect to their gestational age) or are delivered preterm (before 37 weeks of gestation). It is not known whether the birth of a previous small-for-gestational-age or preterm infant increases the subsequent risk of stillbirth.
Granulomatous Hepatitis Associated With Jejunoileal Bypass Surgery
Authors: Edward D. Kalat
Journal: JAMA (1981)

GRANULOMATOUS hepatitis is an uncommon form of liver pathology. It has been described as occurring after jejunoileal bypass surgery. Some of these patients had tuberculosis. In other bypass patients with hepatic granulomas, neither a diagnosis of tuberculosis nor of sarcoidosis was proved, and the cause of the granulomas was obscure.<sup>1,2</sup> We report the case of an intestinal bypass patient in whom granulomata developed and who then underwent reanastomosis of her intestinal tract with resolution of the granulomas without antituberculous therapy. <h3>Report of a Case</h3> A 28-year-old woman weighing 127.2 kg underwent jejunoileal bypass surgery. She was hospitalized six months later with nausea, vomiting, weakness, dizziness, and depression. Liver enzyme level abnormalities were present, and a liver biopsy specimen showed extensive fatty metamorphosis. Eighteen months later she weighed 55.4 kg and complained of undesired weight loss, night sweats, shaking chills, easy fatigue, and diarrhea. Physical examination uncovered hepatosplenomegaly but no
Acid-sensing ion channel 3 expressed in type B synoviocytes and chondrocytes modulates hyaluronan expression and release
Authors: S. J. Kolker, R. Y. Walder, Y. Usachev, J. Hillman, D. L. Boyle, G. S. Firestein, K. A. Sluka
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Background</h3> Rheumatoid arthritis is an inflammatory disease marked by intra-articular decreases in pH, aberrant hyaluronan regulation and destruction of bone and cartilage. Acid-sensing ion channels (ASICs) are the primary acid sensors in the nervous system, particularly in sensory neurons and are important in nociception. ASIC3 was recently discovered in synoviocytes, non-neuronal joint cells critical to the inflammatory process. <h3>Objectives</h3> To investigate the role of ASIC3 in joint tissue, specifically the relationship between ASIC3 and hyaluronan and the response to decreased pH. <h3>Methods</h3> Histochemical methods were used to compare morphology, hyaluronan expression and ASIC3 expression in <i>ASIC3+/+</i> and <i>ASIC3−/−</i> mouse knee joints. Isolated fibroblast-like synoviocytes (FLS) were used to examine hyaluronan release and intracellular calcium in response to decreases in pH. <h3>Results</h3> In tissue sections from <i>ASIC3+/+</i> mice, ASIC3 localised to articular cartilage, growth plate, meniscus and type B synoviocytes. In cultured FLS, <i>ASIC3</i> mRNA and protein was also expressed. In FLS cultures, pH 5.5 increased hyaluronan release in <i>ASIC3+/+</i> FLS, but not <i>ASIC3−/−</i> FLS. In FLS from <i>ASIC3+/+</i> mice, approximately 50% of cells (25/53) increased intracellular calcium while only 24% (14/59) showed an increase in <i>ASIC3−/−</i> FLS. Of the cells that responded to pH 5.5, there was significantly less intracellular calcium increases in <i>ASIC3−/−</i> FLS compared to <i>ASIC3+/+</i> FLS. <h3>Conclusion</h3> ASIC3 may serve as a pH sensor in synoviocytes and be important for modulation of expression of hyaluronan within joint tissue.
Vasomotor Responses in the Extremities of Subjects with Various Neurologic Lesions
Authors: WALTER REDISCH, FRANCISCO T. TANGCO, LOTHAR WERTHEIMER, ARTHUR J. LEWIS, J. MURRAY STEELE, Dorothy Andrews
Journal: Circulation (1957)

Vascular responses to warming were studied in hemiplegic patients and after sympathectomy, using venous occlusion plethysmography of foot and leg. Comparisons were made with corresponding age groups. The pattern of response was essentially unchanged in hemiplegic patients, but was altered substantially where sympathetic pathways had been interrupted.
Heparin and acute renal failure.
Authors: E N Wardle
Journal: BMJ (1975)

At start of On recovery At start of At end of Gentamicin from illness Gentamicin Gentamicin Effect of gentamicin on renal function (creatinine clearance) in six oliguric patients (left-hand column) and 23 patients with stable renal function (right-hand column).associated with transplant rejection.The authors give no indication as to the renal pathology in four patients whose function deteriorated to such an extent that they re- quired graft nephrectomy or dialysis but im- plied that gentamicin was the causative agent.We suggest that there is a wide gap
Metabolism of arachidonic acid in ionophore-stimulated neutrophils. Esterification of a hydroxylated metabolite into phospholipids.
Authors: W F Stenson, C W Parker
Journal: Journal of Clinical Investigation (1979)

[14C]Arachidonic acid incubated with human neutrophils was esterified into phospholipids and triglycerides. Stimulation of these labeled neutrophils with ionophore A23187 (2 microM) results in release of [14C]arachidonate from phospholipid and its metabolism to prostaglandin E2 and 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), a lipoxygenase product. The released arachidonate is also metabolized to a polar lipid of unknown composition here disignated compound A. 5-HETE was found to be released into the medium and then taken up again by the cells. To determine its metabolic fate, [14C]5-HETE was prepared biosynthetically, purified, and incubated with stimulated, unlabeled neutrophils. Most of the radioactivity entered the cells and was esterified into phospholipids and triglycerides. The radiolabeled complex lipids were saponified, and the released fatty acids cochromatographed with authentic 5-HETE. The esterification of 5-HETE, a hydroxylated fatty acid, into membrane phospholipids may be an example of a more generalized mechanism for altering membrane characteristics.
Left ventricular discoordination index measured by speckle tracking strain rate imaging predicts reverse remodelling and survival after cardiac resynchronization therapy
Authors: Chun‐Li Wang, Brian D. Powell, Margaret M. Redfield, Chinami Miyazaki, Nowell M. Fine, Lyle J. Olson, Yong‐Mei Cha, Raul E. Espinosa, David L. Hayes, David O. Hodge, Grace Lin, Paul A. Friedman, Jae K. Oh
Journal: European Journal of Heart Failure (2012)
Gibbon's Surgery of the Chest
Authors: Earle W. Wilkins
Journal: JAMA (1984)

How often, in an era of expanding surgical knowledge and extending operative techniques, does a major textbook require revision? Sabiston and Spencer believe in a cycle of sevens. This fourth edition of<i>Gibbon's Surgery of the Chest</i>continues the seven-year pattern: 1962, 1969, 1976, and now 1983. A number of new subjects appear, each covered in considerable detail, including thoracic outlet syndrome, bronchoplastic surgical techniques, surgery in myasthenia gravis, management of cardiac dysrhythmias, and even the artificial heart. The fourth edition is a two-volume set of 54 chapters, by 106 authors representing 42 medical schools (including six outside the United States), with 1,776 pages. The 1,636 pages of actual text includes 1,453 illustrations, a rate of 0.89 illustrations per page, a commendably high ratio, unusual in texts other than atlases. The new edition is printed on 8X11-in pages and is separated into two volumes, which increases the ease of handling
Reaching for the wrong whistle
Authors: G. DeLacey
Journal: BMJ (1992)

x Values when ratings ofprofessional groups are compared with ratings of consensus panel regarding likelihood of sexual abuse Professional group x Clinical importance Specialist psychiatrists 0-780 Excellent General psychiatrists 0 567 Fair Experimental psychologists 0 705 Good Trainee social workers 0-683 Good Trainee clinical psychologists 0 661 Good Lawyers 0-717 Good Police 0 821 Excellent All groups 0 706 Good to 0 567 for general psychiatrists.The table shows the clinical importance of each of the x values according to the criteria of Cicchetti and Sparrow.IAs Harrington highlights, the levels of agreement between each group of raters and consensus are not perfect (as is true for all clinical assessments); the specialist psychiatrists and police, however, have x values that would be considered excellent levels of agreement, and only the general psychiatrists have levels of agreement below those considered to be good.We therefore stand by our original conclusions that the levels of agreement between the professional groups and the consensus panel are generally good to excellent.We also recognise, as does Harrington, that continued efforts to standardise the interview are necessary to improve the clinical assessment of children suspected of being sexually abused.We believe that our report is an important first step in that process.