tbuckley/cabot-search huggingface dataset:
The increased expression of 14q32 small nucleolar RNA transcripts in promyelocytic leukemia cells is not dependent on PML–RARA fusion gene
Authors: Y Cohen, K Hertzog, O Reish, M Mashevich, O Garach-Jehoshua, A Bar-Chaim, L Trakhtenbrot, A Kornberg
Journal: Blood Cancer Journal (2012)

issue of Leukemia, Valleron et al. 1 presented a specific gene-expression signature, characterizing acute promyelocytic leukemia (APL), which was recognizable by ectopic expression of SNORD112-114 small nucleolar RNAs (snoRNAs) located at the DLK1-DIO3 locus.These findings were obtained using microarrays and a high-throughput quantitative PCR strategy.In their in vitro experiments carried out on APL blasts, Valleron et al. noticed that transcription of these snoRNAs was lost under all-trans retinoic acid-mediated differentiation and induced by enforced expression of the PML-RARalpha fusion protein in negative leukemic cell lines.Although PML-RARalpha seemed to be implicated in DLK1-DIO3 snoRNA expression, no direct relationship could be demonstrated, but a binding site for PML-RARalpha was reported close to the DLK1 gene using chip sequencing. 2 Further experiments revealed that the SNORD114-1 (14q(II-1)) variant promoted cell growth through cell-cycle modulation.In addition, transcription of 14q32 snoRNAs was induced by enforced expression of PML-RARalpha fusion protein in negative leukemic cell lines. 1 Recently, we recorded global gene-expression profile (GEP) changes in bone marrow (BM) samples from patients with various hematological malignancies along several time points following BM aspiration. 3By comparing the various GEPs obtained, a clear difference was seen between the three APL cases to all other cases in expression of various transcripts (Figure 1).The maximal differences were seen in SNORD113-3 SNORD113-4, SNORD114-2 and SNORD114-3, for which the expression was many folds higher in the BM samples from the 3 APL cases compared with the samples from 2 cases with other acute myeloid leukemia (AML) subtypes, 10 cases with multiple myeloma (MM), a case with MM in remission and a case with large B-cell lymphoma infiltrating the BM.The APL-related gene signature also involved several other overexpressed genes mainly in 14q32 region, which included MIR154 (14q32.31)and MIR382 (14q32.31)being consistent with Valleron et al results.However, the most important point relating to the findings of Valleron et al. was that in one of our three APL cases (case 15), the translocation was not between PML and RARA but between RARA and yet unknown partner gene in a t(3:17)(q26;q21) translocation (Figure 2).At the presentation, this patient had hyperleukocytosis and the BM karyotype included X0 in addition to the t(3:17) translocation, but the cell morphology and immunophenotype were typical for APL.Our conclusion
IFIT1 is an antiviral protein that recognizes 5′-triphosphate RNA
Authors: Andreas Pichlmair, Caroline Lassnig, Carol-Ann Eberle, Maria W Górna, Christoph L Baumann, Thomas R Burkard, Tilmann Bürckstümmer, Adrijana Stefanovic, Sigurd Krieger, Keiryn L Bennett, Thomas Rülicke, Friedemann Weber, Jacques Colinge, Mathias Müller, Giulio Superti-Furga
Journal: Nature Immunology (2011)
Carnitine deficiency and l-carnitine supplementation in lysinuric protein intolerance
Authors: Laura M. Tanner, Kirsti Näntö-Salonen, Mohamed S. Rashed, Soile Kotilainen, Maija Aalto, Jaana Venetoklis, Harri Niinikoski, Kirsi Huoponen, Olli Simell
Journal: Metabolism (2008)
Ethics and the academic-corporate relationship
Authors: Roy Geronemus
Journal: Journal of the American Academy of Dermatology (1991)

acne has been limited.Standard texts 1 ,2 when I started my residency in 1961 regularly recommended use of L0tio alba (white lotion) for acne at a time when little else was available.The white precipitate of the shake lotion is zinc sulfide, made by correctly adding a sulfurated potash solution into a zinc sulfate solution.The oldest reference 3 I could find dated the formula back to a publication by Raubenheimer.
Indian Supreme Court rules that HIV positive people inform spouses
Authors: G. Mudur
Journal: BMJ (1998)

The Indian Supreme Court has ruled that people who are HIV positive must inform future spouses of their infection. In a judgment made public last week, the court also said that hospitals could not be charged with violating medical ethics when they disclosed the HIV positive status of an infected individual to a person he or she intended to marry.

The judgment followed a petition by an HIV positive …
Harrison’s Principles of Internal Medicine
Authors: Preeti N. Malani
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Respiratory Stimulants and Obstructed Airways
Authors: Harry W. Fritts, Dudley F. Rochester
Journal: New England Journal of Medicine (1973)

The past quarter century has seen remarkable advances in the management of acute respiratory failure in patients with chronic obstructive lung disease. Progress began when physiologists demonstrated that the acute episodes were reversible, and it continued as physicians showed that a variety of tools, some old and some new, were helpful in bringing the reversals about: antibiotics dealt successfully with infection; bronchodilators, suction and physiotherapy opened blocked airways; the hazards of sedation were recognized; the importance of controlling the concentration of inhaled oxygen was established; and multiple ventilators became available to support gas exchange while the inciting cause of the . . .
A PLEA FOR THE UNCONCEIVED
Authors: Garold L. Faber
Journal: JAMA (1960)

To the Editor:—  I would like to protest an otherwise fine and pertinent editorial, A Plea for the Unconceived, inThe JournalApril 16, page 1774. I believe I capture the mood of the editorial when the author states Ironically, one group of scientists assures us of mass genetic death by radiation, another group are as insistent that we are so fertile that the planet will have standing room only. But I must part company with him when he goes on to say Obviously, both cannot be correct. I am reminded of the issue of theNew Yorker(Jan. 19, 1946) which was devoted to the Smyth Report. Most of it was pretty grim, but it had theNew Yorkertouch. In a box on the front page of the article appeared the following poem: Man split the atom/ Blew him all to hell/ God rolled over in his sleep/
Book Review Chesley's Hypertensive Disorders in Pregnancy Second edition. Edited by Marshall D. Lindheimer, James M. Roberts, and F. Gary Cunningham. 654 pp., illustrated. Stamford, Conn., Appleton &amp; Lange, 1999. $135. 0-8385-3970-X
Authors: Fiona Broughton Pipkin
Journal: New England Journal of Medicine (1999)
SLEEP THE RESULT OF DIFFERENTIATION.
Authors: GUIDO BELL
Journal: JAMA (1895)

<h3>SYLLABUS.</h3> There are no atypical cells in the organisms; for this reason and others there must be something guiding all biologic processes—species in action is identical with vitality. The fundamental functions are assimilation and proliferation; differentiation is the tendency of bringing assimilation and proliferation in contact with the outer world under most favorable conditions. These influences are either food and air or disengaged (cosmic) energy. Food is preëminently chemic change and is carried on a neutral road through the body; cosmic influences are carried in an electrical form also on neutral roads. Blood and nerves are neutral in consequence of their metaplastic nature as hair and nails are. All biologic phenomena are subject to the law of conservation of energy but controlled by species. Trypsinogen and inogen are transformed by a specific irritation into trypsin, or mechanical force, respectively. Similar to this, we have to assume a product in the
IgM+IgD+CD27+ B cells are markedly reduced in IRAK-4–, MyD88-, and TIRAP- but not UNC-93B–deficient patients
Authors: Sandra Weller, Mélanie Bonnet, Héloïse Delagreverie, Laura Israel, Maya Chrabieh, László Maródi, Carlos Rodriguez-Gallego, Ben-Zion Garty, Chaim Roifman, Andrew C. Issekutz, Simona Eva Zitnik, Cyrille Hoarau, Yildiz Camcioglu, Júlia Vasconcelos, Carlos Rodrigo, Peter D. Arkwright, Andrea Cerutti, Eric Meffre, Shen-Ying Zhang, Alexandre Alcais, Anne Puel, Jean-Laurent Casanova, Capucine Picard, Jean-Claude Weill, Claude-Agnès Reynaud
Journal: Blood (2012)
Leucocyte depletion attenuates the early increase in myocardial capillary permeability to small hydrophilic solutes following ischaemia and reperfusion
Authors: J. H. Svendsen, P. R. Hansen, S. Ali, U. Baandrup, S. Haunso
Journal: Cardiovascular Research (1993)

Objective: The aim was to assess the significance of polymorphonuclear leucocytes on the myocardial capillary permeability to a small hydrophilic indicator, on the vascular tone of the resistance vessels, and on contractile function following ischaemia and reperfusion. Methods: Open chest, anaesthetised dogs were randomised to treatment with polyclonal antibody against polymorphonuclear leucocytes (anti-PMN group) or non-specific antibody (control group), and subjected to 40 min of coronary occlusion followed by 3 h of reperfusion. The capillary extraction fraction and the myocardial plasma flow rate were quantitated in vivo by intracoronary indicator bolus injection and external registration of the washout, and the capillary permeability-surface area product was calculated. Postischaemic vasodilator tone in the myocardial resistance vessels was measured by the local 133xenon washout method. Results: 20 dogs were included (10 in each group), and 13 dogs completed the ischaemia-reperfusion protocol (anti-PMN group, n=7; control group, n=6). In the anti-PMN group, blood polymorphonuclear leucocyte counts were reduced to a minimum of 15% of pretreatment values. After ischaemia and 5 min reperfusion, the capillary extraction increased by 17% in the control group but decreased by 22% in the anti-PMN group (p<0.05). The corresponding capillary permeability-surface area product increased by 22% in the control group, but decreased by 16% in the anti-PMN group (p<0.05). Neither maximum myocardial plasma flow during reactive hyperaemia nor contractile function were influenced by anti-PMN treatment. Conclusions: Polymorphonuclear leucocytes appear to participate in the increase in myocardial capillary permeability observed early after reperfusion following a 40 min period of ischaemia, but do not influence postischaemic vascular tone or postischaemic contractile function. During normal physiological conditions reduction of the circulating polymorphonuclear leucocyte counts did not induce significant changes in myocardial capillary permeability. Cardiovascular Research 1993;27:1288-1294
Use-dependent block of the pacemaker current I(f) in rabbit sinoatrial node cells by zatebradine (UL-FS 49). On the mode of action of sinus node inhibitors.
Authors: M Goethals, A Raes, P P van Bogaert
Journal: Circulation (1993)

BACKGROUND Zatebradine (UL-FS 49) is a drug with a specific bradycardiac electrophysiological profile. It reduces heart rate by lengthening the duration of diastolic depolarization in the sinoatrial (SA) node. The ionic basis of this action, however, is not clarified. METHODS AND RESULTS We used the whole-cell patch-clamp technique to study the effects of zatebradine on ionic currents underlying diastolic depolarization of isolated rabbit SA node cells. Low concentrations of zatebradine simultaneously reduced diastolic depolarization rate and the pacemaker current I(f). The drug blocked the pacemaker current, I(f), in a use-dependent manner without causing a shift of its activation curve. At hyperpolarized potentials, unblock of I(f) occurred. Clinically relevant concentrations of the drug have little effect on the L-type calcium current or delayed rectifier potassium current. CONCLUSIONS This use-dependent block of the If channel can account for most of the pharmacological characteristics of zatebradine and is probably the mechanism of heart rate reduction caused by this agent. Thus, the sinus node inhibitor zatebradine belongs to a new class of "I(f) blockers" with possible advantages over currently available drugs for the treatment of ischemic heart disease.
Should forced expiratory volume in six seconds replace forced vital capacity to detect airway obstruction?
Authors: J. E. Hansen, X-G. Sun, K. Wasserman
Journal: European Respiratory Journal (2006)

It has been suggested that forced expiratory volume in six seconds (FEV 6 ) should be substituted for forced vital capacity (FVC) to measure fractions of timed expired volume for airflow obstruction detection. The present authors hypothesised that this recommendation might be questionable because flow after 6 s of forced expiration from more diseased lung units with the longest time constants was most meaningful and should not be ignored. Furthermore, previous studies comparing FEV 6 and FVC included few subjects with mild or no disease. The present study used spirometric data from the USA Third National Health and Nutrition Evaluation Survey with prior published ethnicity- and sex-specific equations for FEV 1 /FEV 6 , FEV 1 /FVC and FEV 3 /FVC, and new equations for FEV 3 /FEV 6 , all derived from ∼4,000 adult never-smokers aged 20–80 yrs. At 95% confidence intervals, 21.3% of 3,515 smokers and 41.3% of smokers aged &gt;51 yrs had airway obstruction; when comparing FEV 1 /FEV 6 with FEV 1 /FVC, 13.5% were concurrently abnormal, 1.5% were false positives and 4.1% were false negatives; and when comparing FEV 3 /FEV 6 with FEV 3 /FVC, 11.6% were concurrently abnormal, 3.3% were false positives and 5.7% were false negatives. Substituting forced expiratory volume in six seconds for forced vital capacity to determine the fractional rates of exhaled volumes reduces the sensitivity of spirometry to detect airflow obstruction, especially in older individuals and those with lesser obstruction.
Reflux "increases risk of adenocarcinoma of oesophagus"
Authors: S. Gottlieb
Journal: BMJ (1999)

Chronic heartburn can greatly increase a person's risk of developing adenocarcinoma of the oesophagus, according to a new study that adds strong epidemiological support to a widely held assumption.

The study, published in the New England Journal of Medicine (1999;340:825-31), found that the risk of oesophageal adenocarcinoma was almost eight times higher among people in whom heartburn, regurgitation, or both occurred at least once a week than among people without these …
LOCALIZATION OF THE VIRUS AND PATHOGENESIS OF EPIDEMIC POLIOMYELITIS
Authors: Simon Flexner, Harold L. Amoss
Journal: The Journal of Experimental Medicine (1914)

The virus of poliomyelitis is capable of penetrating the retina without producing apparent injury, to reach the central nervous organs. The virus injected into the blood is deposited promptly in the spleen and bone marrow, but not in the kidneys, spinal cord, or brain. Notwithstanding the affinity which the nervous tissues possess for the virus, it is not removed from the blood by the spinal cord and brain until the choroid plexus and blood vessels have suffered injury. The intervertebral ganglia remove the virus from the blood earlier than do the spinal cord and brain. An aseptic inflammation produced by an intraspinous injection of horse serum facilitates and insures the passage of the virus to the central nervous organs, and the production of paralysis. The unaided virus, even when present in large amounts, passes inconstantly from the blood to the substance of the spinal cord and brain. When the virus within the blood fails to gain access to the central nervous organs, and to set up paralysis, it is destroyed by the body, in course of which destruction it undergoes, as a result of the action of the spleen and, perhaps, other organs, diminution of virulence. The histological lesions that follow the intravenous injections of the virus in some but not in all cases differ from those which result from intraneural modes of infection. In escaping from the blood into the spinal cord and brain, the virus causes a lymphatic invasion of the choroid plexus and widespread perivascular infiltration, and from the latter cellular invasions enter the nervous tissues. A similar lymphoid infiltration of the choroid plexus may arise also from an intracerebral injection of the virus. The histological lesions present in the central nervous organs in human cases of poliomyelitis correspond to those that arise from the intraneural method of infection in the monkey. The virus in transit from the blood through the cerebrospinal fluid to the substance of the spinal cord and brain is capable of being neutralized by intraspinous injection of immune serum, whereby the production of paralysis is averted. Carmin in a sterile and finely divided state introduced into the meninges and ventricles sets up an aseptic inflammation, but is quickly taken up by cells, including ependymal cells. When an aseptic inflammation has been previously established by means of horse serum, or when the nervous tissues are already injured by the poliomyelitic virus, the pigment appears to enter the ependymal cells more freely. The experiments described support the view that infection in epidemic poliomyelitis in man is local and neural, and by way of the lymphatics, and not general and by way of the blood. Hence they uphold the belief that the infection atrium is the upper respiratory mucous membrane.
Cows' milk protein intolerance: a possible association with gastroenteritis, lactose intolerance, and IgA deficiency.
Authors: M Harrison, A Kilby, J A Walker-Smith, N E France, C B Wood
Journal: BMJ (1976)

Twenty-five children with cows' milk protein intolerance were studied. Twenty had presented with an illness clinically indistinguishable from infantile gastroenteritis; an enteropathogenic Escherichia coli was isolated from the stools in two children, and in six another member of the family simultaneously developed acute diarrhoea and vomiting. Twenty-three children had lactose intolerance secondary to cows' milk protein intolerance. Eight out of 20 children were found to be partially IgA deficient. An acute attack of gastroenteritis, in damaging the small mucosa, may act as a triggering mechanism in cows' milk protein intolerance, and a deficiency in IgA may be a predisposing factor in so far as it allows the patient to become sensitised to foreign protein.
Absorption, Distribution, Metabolism, and Excretion of a Respirable Antisense Oligonucleotide for Asthma
Authors: SHAHID ALI, SHERRY A. LEONARD, CINDY A. KUKOLY, W. JAMES METZGER, WALLACE R. WOOLES, JACQUELINE F. McGINTY, MAKOTO TANAKA, ANTHONY SANDRASAGRA, JONATHAN W. NYCE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

EPI-2010 is a respirable antisense oligonucleotide (RASON), which selectively attenuates discordantly overexpressed adenosine A1 receptors in allergic lung (Nature 1997;385:721). In the present study, aerosolized [35S]-labeled EPI-2010 (5 mg exposure; specific activity 0.055 Ci/mmol) was administered to normal rabbits by endotracheal tube to assess biodistribution, route of elimination, and potential cardiovascular toxicity. The animals were killed at 0, 6, 24, 48, and 72 h after inhalation of EPI-2010. Duplicate aliquots from different tissues and samples were solubilized and assessed for radioactivity. Approximately 1.4% of the total aerosolized EPI-2010 was deposited into the lung. The concentration of the drug in the lung at 0, 6, 24, 48, and 72 h was 64.0 ± 1.5, 67.0 ± 4.4, 32.0 ± 3.7, 23.4 ± 1.4, and 2.1 ± 0.5 μ g equivalents, respectively. Only a small amount of the radioactivity was detected in extrapulmonary tissues. By 72 h, 67.5% of the administered dose was excreted in the urine, which represented the major pathway of elimination. In postlabeling studies, intact full-length EPI-2010 could only be detected in the lung. Autoradiographic analysis after inhalation of [35S]-labeled EPI-2010 showed a relatively uniform deposition of drug throughout the lung. The aerosolized EPI-2010 did not have any significant systemic effects on the cardiovascular system as determined by Cardiomax-II analysis. This pattern of distribution and the lack of effect on cardiovascular function support the concept that RASONs offer the potential to safely address respiratory targets for which systemic distribution and systemic bioavailability may be contraindicated.
Clinical Assistantships and General Practitioners
Authors: J. D. Baston, D. M. Baston
Journal: BMJ (1964)

MEDICA JUURNAL 1443retained only in the genuinely specialist unit and teaching hospitals.Duties of the general hospital doctor would be far more varied than at present allowed by the subspecialties under which junior hospital staff are often forced to work and would consequently be more interesting.I feel it is important to establish the prin- ciple that hospital work at junior level does not necessarily require employment of embryo
Response to Krogsboll and colleagues: NHS health checks or government by randomised controlled trial?
Authors: M. Soljak, A. Majeed, C. Millett
Journal: BMJ (2013)

Krogsboll and colleagues have followed up their Cochrane systematic review of health checks with a call to abandon the NHS Health Check programme.1 We challenge their view that a randomised controlled trial (RCT) of the current programme should be the sole arbiter of national health policy decisions. The dearth of RCTs of screening for risk of cardiovascular disease since 1999 is unfortunate, but there were many RCTs of individual screening components over this period.

RCTs are expensive and time consuming, …