tbuckley/cabot-search huggingface dataset:
FRI0011 Type I IFN inhibits arthritis via down-modulation of arthritogenic T-cell proliferation and cytokine production but independently of the enzymatic activity of IDO
Authors: M. Magnusson, J.P. Chalise, S.C. Narendra
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The cytokine interferon-alpha (IFNa) may induce adaptive-immunity independent arthritis if present in the joint (1) but may in contrast prevent antigen-induced arthritis if activated during immunisations (2). Here we investigate if this is due to tolerance development in terms of antigen-specific proliferation and cytokine release and evaluate the role of the tolerance-inducing enzyme indoleamine 2, 3 dioxygenase (IDO). <h3>Objectives</h3> To determine the importance of IDO for the protective effect of IFNa against mBSA-induced arthritis and to determine how presence of IFNa in the sensitization phase of mBSA-induced arthritis affects antigen-specific proliferation and cytokine release. <h3>Methods</h3> Arthritis was induced in pre-sensitized animals (mBSA in Freunds adjuvant with or without addition of IFNa on day 0 and day 7) by intra-articular injection of mBSA in the left knee. PBS was injected in the right knee. IDO was inhibited by inserting a 1-methyl tryptophan releasing pellet under the skin at day 0 or day 21. Placebo-pellet were inserted in the control group. Antigen-specific proliferation was determined by radio immunoassay. Levels of different cytokines were determined by Luminex technology. <h3>Results</h3> Type I IFN-mediated protection was associated with diminished antigen-specific proliferation during the immunisation course and inhibited increased production of IL-17, TNF, IFN-gamma, IL-12, IL-1b but not IL-6 after intra-articular challenge. Thus IFNa induces a state of tolerance towards the antigen, which may explain its protective effect in mBSA-induced arthritis. An important mediator of immunological tolerance is the enzyme indoleamine 2, 3 dioxygenase. To determine the role of IDO in IFNa-mediated protection against antigen-induced arthritis, the IDO activity was inhibited by 1-methyl tryptophan (1-MT), a specific inhibitor of the IDO-mediated transformation of tryptophan to kynurenine. Presence of 1-MT-releasing tablets under the skin of mice from the first immunization and onwards slightly, but not significantly diminished the protective effect of IFNa. Insertion of 1-MT-releasing pellet at the time of intra-articular challenge had no effect on IFNa-mediated protection. No significant effect of 1-MT on antigen-specific proliferation was observed. <h3>Conclusions</h3> Thus mechanisms independent of the enzymatic activity of IDO are responsible for the protective effect of IFNa in mBSA-induced arthritis. <h3>References</h3> Magnusson, Zare &amp; Tarkowski., Arthritis &amp; Rheum. 2006. Jan;54(1):148-57 Ying, Chalise, Narendra &amp; Magnusson, Eur. J. Immunol., 2011. Jun;41(6):1687-95 <h3>Disclosure of Interest</h3> None Declared
Head of WHO's vaccines advisory group defends its policy on competing interests
Authors: J. Zarocostas
Journal: BMJ (2010)

The chief who oversees the World Health Organization’s top advisory group on global vaccines has defended the oversight mechanism that guards against potential conflicts of interest among its members.

Philippe Duclos, executive secretary of the 15 member Strategic Advisory Group of Experts on Immunization (SAGE), said at a press briefing in Geneva that the group strove to ensure “very high standards” to protect against undue influence, whatever the origin.

In recent weeks WHO has been criticised by expert bodies, including the Council of Europe, over allegations that the threat of an H1N1 flu pandemic may have been hyped up as a result of undue influence by the drug industry.

WHO has …
Dynamic Functional Relay between Insulin Receptor Substrate 1 and 2 in Hepatic Insulin Signaling during Fasting and Feeding
Authors: Naoto Kubota, Tetsuya Kubota, Shinsuke Itoh, Hiroki Kumagai, Hideki Kozono, Iseki Takamoto, Tomoka Mineyama, Hitomi Ogata, Kumpei Tokuyama, Mitsuru Ohsugi, Takayoshi Sasako, Masao Moroi, Kaoru Sugi, Shigeru Kakuta, Yoichiro Iwakura, Tetsuo Noda, Shin Ohnishi, Ryozo Nagai, Kazuyuki Tobe, Yasuo Terauchi, Kohjiro Ueki, Takashi Kadowaki
Journal: Cell Metabolism (2008)
Review: Treatment for gestational diabetes reduces risk for shoulder dystocia
Authors: K Horvath
Journal: Annals of Internal Medicine (2010)

ACP Journal Club21 September 2010Review: Treatment for gestational diabetes reduces risk for shoulder dystociaDebra A. Guinn, MDDebra A. Guinn, MDNorthwest Perinatal Center, Portland, Oregon, USA (D.A.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-6-201009210-02006 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationHorvath K, Koch K, Jeitler K, et al. Effects of treatment in women with gestational diabetes mellitus: systematic review and meta-analysis. BMJ. 2010;340:c1395. https://pubmed.ncbi.nlm.nih.gov/20360215Clinical Impact RatingsGIM/FP/GP: Endocrinology: References1 Coustan DR, Lowe LP, Metzger BE, Dyer AR. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: paving the way for new diagnostic criteria for gestational diabetes mellitus. Am J Obstet Gynecol. 2010;202:654.e1-6. [PMID: 20510967] Google Scholar2 Crowther CA, Hiller JE, Moss JR, et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med. 2005;352:2477-86. [PMID: 15951574] Google Scholar3 Landon MB, Spong CY, Thom E, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med. 2009;361:1339-48. [PMID: 19797280] Google Scholar Author, Article, and Disclosure InformationAffiliations: Northwest Perinatal Center, Portland, Oregon, USA (D.A.G.)This article was published at Annals.org on 7 September 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 September 2010Volume 153, Issue 6Page: JC3-6KeywordsBirthDietGestational diabetesGlucoseHypoglycemiaMaternal mortalityMortalityNeonatal carePreeclampsiaShoulders ePublished: 21 September 2010 Issue Published: 21 September 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Effects of chronic octreotide treatment on renal function in cirrhotic patients: a randomised, double-blind, controlled trial
Authors: L.H. Ottesen, N.K. Aagaard, M. Kiszka-Kanowitz, M. Rehling, J.H. Henriksen, E.B. Pedersen, A. Flyvbjerg, F. Bendtsen
Journal: Journal of Hepatology (2001)
Due Process in Investigations of Research Misconduct
Authors: Michelle M. Mello, Troyen A. Brennan
Journal: New England Journal of Medicine (2003)

This report reviews federal regulations regarding research misconduct and argues that accused scientists should be guaranteed more procedural safeguards during investigations of alleged misconduct. Currently, the accused researcher's institution performs the investigation, and most institutional policies do not require the presumption of innocence and do not allow scientists to see the evidence against them. Investigations into research misconduct use a low standard of proof — preponderance of evidence — which requires that the evidence point to a finding that is more likely than not.
SOME OBSERVATIONS ON OSTEOID CANCER
Authors: R. Quain
Journal: BMJ (1855)

A ops, tweenty-si hours after death.Abdomen con- sidebly distended; the small intestines and greater part of the colon filled with fiatus.A small part of the ilium, congested, but which has evidently been in process of re- covery, is observed lying free near to the situation of the internal left femoral ring, and is obviously the portion which was released at the operation.On opening it, there is no lesion of the mucous membrane.The transverse colon has a very peculiar position and appearance; it is
Identification of a congenital dysthrombin, thrombin Quick.
Authors: R A Henriksen, W G Owen, M E Nesheim, K G Mann
Journal: Journal of Clinical Investigation (1980)

A dysprothrombin designated prothrombin Quick, is isolated from the plasma of an individual with < 2% of normal functional prothrombin activity and 34% of the normal prothrombin level by immunologic assay. With Factor Xa or taipan snake venom as activators, a fragmentation pattern identical to that of normal prothrombin is observed on gel electrophoresis in dodecylsulfate. This evidence combined with the observed barium citrate adsorption of prothrombin Quick and the low activity suggests that the defect in prothrombin Quick is in the thrombin portion of the molecule. Thrombin Quick is isolated and comigrates with thrombin on dodecyl sulfate gel electrophoresis, either reduced or nonreduced. The activity of thrombin Quick on several biological substrates of thrombin is investigated. Relative to normal thrombin, thrombin Quick is 1/200 as active on fibrinogen and 1/20-1/50 as effective in activating Factors V and VIII and aggregating platelets. A complex with antithrombin III is detected by dodecyl sulfate gel electrophoresis. Further investigation with the active site titrant, dansylanginine-N-(3-ethyl-1,5-pentanediyl)amide showed that the thrombin Quick preparation has the same affinity for the titrant as thrombin, but apparently only 40% active sites per mole protein are titrable.
Doctors and scientists demand reform of England's libel laws
Authors: C. Dyer
Journal: BMJ (2009)

A national petition to reform England’s “unjust” libel laws, backed by MPs, doctors, scientists, writers, and lawyers, was launched on Wednesday 9 December at the House of Commons in London.

The campaign, launched by the charity Sense About Science, with backing from Index on Censorship and the English branch of the international writers’ group PEN, aims to reform laws that are widely criticised for exerting a “chilling” effect on free speech.

England’s libel laws have long been attacked by the media for the high cost of fighting libel cases, for unfairly favouring claimants, and for encouraging “libel tourism” among those overseas who …
Increased insensible water loss in newborn infants nursed under radiant heaters.
Authors: R W Jones, M J Rochefort, J D Baum
Journal: BMJ (1976)

Urine osmolality was studied in 38 babies nursed in conventional incubators or cots and 18 nursed under an overhead radiant heat shield. Among 50 babies receiving a similar fluid intake in the first 48 hours of life mean urinary osmolality was significantly higher in the radiant heater group. In babies weighing less than 1500 g a trend towards higher urinary osmolalities was recorded in those nursed under radiant heaters even though they had received amost double the fluid intake of the incubator group. Severe hypernatraemia occurred in four of the five babies weighing less than 1000 g who were nursed under radiant heaters but in none of the seven babies of similar birth weight nursed in incubators. These findings are consistent with previous observations of an increase in insensible water loss in babies nursed under radiant heaters and emphasise the importance of providing enough extra water for these infants and the need for close monitoring of their fluid balance. The latter may be done at the bedside by measuring urinary specific gravity with a hand refractometer.
Differential Impact of Stent versus PTCA on Restenosis in Large (≥3 mm) and Small &amp;lt;3 mm) Vessels in the STent REStenosis Study
Authors: S. Chiu Wong, John Hirshfeld, Paul Teirstein, Richard Schatz, Alex Shaknovich, Masakiyo Nobuyoshi, Lowell F. Saller, Ya Chien Chuang, Martin B. Leon
Journal: Journal of the American College of Cardiology (1995)
Extended major histocompatibility complex haplotypes in patients with gluten-sensitive enteropathy.
Authors: C A Alper, E Fleischnick, Z Awdeh, A J Katz, E J Yunis
Journal: Journal of Clinical Investigation (1987)

We have studied major histocompatibility complex markers in randomly ascertained Caucasian patients with gluten-sensitive enteropathy and their families. The frequencies of extended haplotypes, defined as haplotypes of specific HLA-B, DR, BF, C2, C4A, and C4B allelic combinations, occurring more frequently than expected, were compared on patient chromosomes, on normal chromosomes from the study families, and on chromosomes from normal families. Over half of patient chromosomes consisted almost entirely of two extended haplotypes [HLA-B8, DR3, SC01] and [HLA-B44, DR7, FC31] which, with nonextended HLA-DR7, accounted for the previously observed HLA markers of this disease: HLA-B8, DR3, and DR7. There was no increase in HLA-DR3 on nonextended haplotypes or in other extended haplotypes with HLA-DR3 or DR7. The distribution of homozygotes and heterozygotes for HLA-DR3 and DR7 was consistent with recessive inheritance of the major histocompatibility complex-linked susceptibility gene for gluten-sensitive enteropathy. On the other hand, by odds ratio analysis and from the sum of DR3 and DR7 homozygotes compared with DR3/DR7 heterozygotes, there was an increase in heterozygotes and a decrease in homozygotes suggesting the presence of modifying phenomena.
Pulmonary Diffusing Capacity
Authors: J. H. BURGESS
Journal: Circulation (1974)

Our own findings indicate an increase in Vc/Dm ratio as the most characteristic abnormality in patients with mitral valve disease.In the accompanying figure Vc has been plotted against Dm in different clinical situations including 19 patients with mitral valve disease.Isopleths of DLco which follow a rectangular hyperbole have been constructed assuming 1/6 = 1.263.Eighteen of the 19 patients with mitral valve disease have a ratio > 3 which is more than the ratio in all the 18 normal subjects.These estimations were performed by a steady state technique, the details of which have been described earlier.6
Muscle Mitochondrial ATP Synthesis and Glucose Transport/Phosphorylation in Type 2 Diabetes
Authors: Julia Szendroedi, Albrecht I Schmid, Marek Chmelik, Christian Toth, Attila Brehm, Martin Krssak, Peter Nowotny, Michael Wolzt, Werner Waldhausl, Michael Roden
Journal: PLoS Medicine (2007)

Muscular insulin resistance is frequently characterized by blunted increases in glucose-6-phosphate (G-6-P) reflecting impaired glucose transport/phosphorylation. These abnormalities likely relate to excessive intramyocellular lipids and mitochondrial dysfunction. We hypothesized that alterations in insulin action and mitochondrial function should be present even in nonobese patients with well-controlled type 2 diabetes mellitus (T2DM).We measured G-6-P, ATP synthetic flux (i.e., synthesis) and lipid contents of skeletal muscle with (31)P/(1)H magnetic resonance spectroscopy in ten patients with T2DM and in two control groups: ten sex-, age-, and body mass-matched elderly people; and 11 younger healthy individuals. Although insulin sensitivity was lower in patients with T2DM, muscle lipid contents were comparable and hyperinsulinemia increased G-6-P by 50% (95% confidence interval [CI] 39%-99%) in all groups. Patients with diabetes had 27% lower fasting ATP synthetic flux compared to younger controls (p = 0.031). Insulin stimulation increased ATP synthetic flux only in controls (younger: 26%, 95% CI 13%-42%; older: 11%, 95% CI 2%-25%), but failed to increase even during hyperglycemic hyperinsulinemia in patients with T2DM. Fasting free fatty acids and waist-to-hip ratios explained 44% of basal ATP synthetic flux. Insulin sensitivity explained 30% of insulin-stimulated ATP synthetic flux.Patients with well-controlled T2DM feature slightly lower flux through muscle ATP synthesis, which occurs independently of glucose transport /phosphorylation and lipid deposition but is determined by lipid availability and insulin sensitivity. Furthermore, the reduction in insulin-stimulated glucose disposal despite normal glucose transport/phosphorylation suggests further abnormalities mainly in glycogen synthesis in these patients.
ALCOHOL INJECTION OF BRAIN CORTEX IN JACKSONIAN EPILEPSY
Authors: CHARLES E. DOWMAN
Journal: JAMA (1924)

Practically every case of jacksonian epilepsy should be subjected to an exploratory craniotomy in the hope of finding and removing a lesion causing the attacks. Unfortunately, those performing such exploratory operations are not infrequently disappointed in not finding such removable lesions. The problem under such circumstances is one of grave importance to the patient, and one that causes the neurologic surgeon considerable worry. Many years ago Sir Victor Horsley recommended excision of the so-called  zone, a procedure, however, of very doubtful value in that the defect is replaced by scar tissue, which, in turn, may give rise to irritative phenomena. In the two cases reported here, the so-called epileptic zone was first mapped out by faradic stimulation and then injected with 95 per cent, alcohol. I have been unable to find in the literature any reference to the clinical use of this method. Koljubakin and Uroda 1 proved that
Radiation Effects on Pulmonary Ventilation and Perfusion
Authors: JAMES D. SLAVIN, NICHOLAS C. FRIEDMAN, RICHARD P. SPENCER
Journal: Clinical Nuclear Medicine (1993)

A woman with breast cancer was noted as having lung ventilation/perfusion mismatch, consistent with a pulmonary embolus. The patient had prior thoracic radiation, corresponding to the site of the perfusion defect. Thus, this was a false-positive result. A second case is presented with markedly decreased lung perfusion after radiation. Effects of therapeutic radiation must be considered when localized decreased pulmonary perfusion is noted.
Adrenergic Receptor Gene Variation and Selective Norepinephrine Reuptake Inhibitors
Authors: Ayana A. Gibbs, Sirpreet K. Somal, Ki Fung D. Chan, Carla E. Bautista, Florence D. Mowlem, Kris H. Naudts, Kees van Heeringen, Theodora Duka
Journal: American Journal of Psychiatry (2013)
Blood Muramidase Activity in Colorectal Cancer
Authors: E. H. Cooper, R. Turner, L. Steele, J. C. Goligher
Journal: BMJ (1974)

The serum muramidase levels were measured in 128 patients with primary or metastatic colorectal cancer, 166 tumour-free patients after resection of a colorectal cancer, and 172 controls. Muramidase levels over 10 mug/ml were detected in 30%-39% of the tumour-bearing patients, in 8.2% of the tumour free, and in only 1.7% of the controls (normal level 6.68 +/- 1.42 mug/ml). Long-term follow up indicated that raised levels may occur as a transient phenomenon in recurrent or metastatic disease. The likely relation of abnormal serum muramidase activity and stimulation of the reticuloendothelial system is discussed.
Psychology and groups at the junction of genes and culture
Authors: Linnda R. Caporael
Journal: Behavioral and Brain Sciences (2005)

Replacements for the self-interest axiom may posit weak to strong theories of sociality. Strong sociality may be useful for positing social cognitive mechanisms and their evolution, but weak sociality may work better for identifying interesting group-level outcomes by focusing on deviations from self-interested psychological assumptions. Such theoretical differences are likely to be based on disciplinary expertise, and the challenge for Darwinian integration is to keep the conversation flowing.
CCGs must commission for England's whole population, not just for "those with sharp elbows," conference hears
Authors: M. Limb
Journal: BMJ (2013)

Patients are being photographed in hospitals by their families because of “unprecedented” levels of anxiety about their care, a conference has heard.

Edna Robinson, managing director of NHS Clinical Commissioning Community, said this “spectacular loss of confidence” in the wake of the Francis inquiry would pose a huge challenge to new commissioning bodies.

She said that England’s primary care trusts (PCTs), which are being disbanded from 1 April, had plainly failed to connect with the public and assure the quality of care despite doing good work in other areas. The new Clinical Commissioning Groups (CCGs) now being set up would have to have the confidence to “walk the …
Cyclic GMP Cascade of Vision
Authors: L Stryer
Journal: Annual Review of Neuroscience (1986)

Cyclic GMP is central to visual excitation in vertebrate retinal rod cells. Sodium channels in the plasma membrane of the outer segment are kept open in the dark by a high level of cGMP. Light closes these channels by activating an enzymatic cascade that leads to the rapid hydrolysis of cGMP. Photoexcited rhodopsin triggers transducin by catalyzing the exchange of GTP for bound GDP. The activated GTP-form of transducin then switches on the phosphodiesterase by overcoming an inhibitory constraint. The overall gain of this cascade is about 10(5). The cascade is turned off by the GTPase activity of transducin and by the action of rhodopsin kinase and arrestin. One of the challenges now is to delineate the interplay of cGMP, calcium ion, and phosphoinositides in excitation and adaptation. Transducin belongs to a family of signal-coupling proteins that includes the G proteins of the hormone-regulated adenylate cyclase cascade. The initial events in visual excitation in molluscs and arthropods are probably similar to those of vertebrates. The triggering of transducin by photoexcited rhodopsin is a recurring motif in visual transduction. The coming together of electrophysiology, biochemistry, and molecular genetics affords new opportunities in unraveling the molecular mechanism of visual transduction.
Tips for Giving a Memorable Presentation, Part I
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2012)

Giving an excellent presentation is critical for the success of many people, including leaders, managers, team members, business people, those in nonprofit societies, coaches, and educators. The audience may vary from a few people to thousands of people, but many of the principles are the same. This is the first in a multipart article giving some advice on the writing, rehearsal, and delivery of a fine presentation.
Management of Childhood Asthma
Authors: Salmon R. Halpern
Journal: JAMA (1974)

In a society that demands a drug for the cure of every illness, Reay's remarks (p 830) contribute to overkill. His premise is that childhood asthma can be managed by drugs. Brief remarks are made about dust control and animal exposure while the subject of desensitization is dismissed with the statement some older children whose clinical history points clearly to one specific allergen and in whom skin tests are confirmatory are helped by desensitization. Such a regimen may do the child and his family a disservice.  Reay prescribes three drugs; (1) an aerosol adrenergic agent such as albuterol (salbutamol), (2) cromolyn sodium, and (3) an aerosol topical steroid. Aminophylline is reserved for intravenous use in hospitalized patients, along with oxygen, steroids, and antibiotics.  Such management of childhood asthma is not representative of the prevailing attitude of pediatric allergists in the United States, who believe that any child who requires this
Mixed lymphocyte culture determinants and C2 deficiency: LD-7a associated with C2 deficiency in four families.
Authors: S M Fu, R Stern, H G Kunkel, B Dupont, J A Hansen, N K Day, R A Good, C Jersild, M Fotino
Journal: The Journal of Experimental Medicine (1975)

Four families with C2 deficiency were studied. Among eight HL-A haplotypes involved with C2 deficiency, five were HL-A 10,W18. Three homozygotes for C2 deficiency from different families were mutually nonreactive in mixed lymphocyte cultures (MLC) and the heterozygotes from the fourth family failed to react to the homozygous cells. It appeared that identical MLC determinants were associated with all the genes from the different families that related to C2 deficiency. Further experiments identified the MLC determinant, LD-7a, as being involved. These results suggest marked linkage disequilibrium between the genes for C2 deficiency and the major histocompatibility complex (MHC). Studies of possible recombinants have offered tentative evidence for the positioning of the locus for C2 deficiency with respect to other segments of the MHC.