tbuckley/cabot-search huggingface dataset:
Saving myelin from microglia
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2007)

The blood clotting protein fibrinogen can inadvertently promote multiple sclerosis (MS) when it leaks from the blood into the brain. According to Adams et al. (page 571), it does so by activating microglia and sending these cells into phagocytic overdrive. Interrupting this interaction may yield a treatment for MS that doesn't interfere with blood clotting.






Figure 1

Microglial activation (left) is prevented by blocking fibrin (right).




The neurological dysfunction seen in MS is caused by the destruction of myelin sheaths around axons. This destruction is thought to be driven by T helper (Th)-1 cells, and most of the current treatment protocols are focused on inhibiting their activation and entry into the CNS. But responses to anti–T cell therapy are variable, and inflammatory demyelination can sometimes occur in the absence of T cells.

One feature that all MS lesions have in common is a disruption in the blood–brain barrier and the leakage of fibrinogen into the brain through the damaged endothelia. This results in the formation of fibrin deposits, which are detected even before demyelination. These deposits also overlap with regions where resting microglia have differentiated into phagocytic cells that damage myelin, raising the possibility that clotting proteins activate microglia.

Akassoglou and colleagues had previously shown that fibrinogen promotes disease in mouse models of MS. The team now shows that fibrinogen binds to a macrophage-activating receptor called Mac-1 that is expressed by local microglial cells.

Mice expressing a mutant form of fibrinogen that fails to bind Mac-1 had fewer inflammatory lesions and less severe disease. Blocking the fibrinogen–Mac-1 interaction with an antagonist peptide prevented relapses and further myelin damage in diseased mice and allowed these animals to survive with improved motor function.

Fibrinogen is an attractive target for MS therapy as its appearance in the brain is an early sign of neurodegeneration. Current methods to target fibrinogen involve the use of anticoagulants, but their long-term use increases the risk of hemorrhage. The region of fibrinogen that promotes clotting is, however, distinct from its Mac-1–activating site. Specifically targeting the latter interaction might therefore be a safer option in MS therapy, although it is not yet clear whether T cell–dependent pathways would also need to be blocked.
Commentary: Paranoia over Privacy
Authors: Sylvia R. Cruess, Richard L. Cruess
Journal: Annals of Internal Medicine (2006)

Commentary1 August 2006Commentary: Paranoia over PrivacySylvia R. Cruess, MD and Richard L. Cruess, MDSylvia R. Cruess, MDFrom McGill University, Montréal, Québec H3A 1A3, Canada.Search for more papers by this author and Richard L. Cruess, MDFrom McGill University, Montréal, Québec H3A 1A3, Canada.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-145-3-200608010-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Dr. Neubauer's experiences highlight some of the more disturbing aspects of our brave new world in which the Health Information Portability and Accountability Act of 1996 (HIPAA) is an all-too-central part. The insight of a physician as patient is unique and often points out the unexpected consequences of strictly adhering to policies that have irreproachable objectives. Protecting patients' privacy has been fundamental to medicine's professional obligations since the time of Hippocrates. Although the Charter on Medical Professionalism reaffirms the importance of protecting privacy (1), it gives precedence to the principle of “primacy of patient welfare.”The purpose of HIPAA is ...References1. Medical professionalism in the new millennium: a physician charter. Ann Intern Med. 2002;136:243-6. [PMID: 11827500] LinkGoogle Scholar2. Wynia MK, Latham SR, Kao AC, Berg JW, Emanuel LL. Medical professionalism in society. N Engl J Med. 1999;341:1612-6. [PMID: 10577119] CrossrefMedlineGoogle Scholar3. Gruen RL, Pearson SD, Brennan TA. Physician-citizens—public roles and professional obligations. JAMA. 2004;291:94-8. [PMID: 14709581] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From McGill University, Montréal, Québec H3A 1A3, Canada. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoParanoia over Privacy Richard L. Neubauer Metrics 1 August 2006Volume 145, Issue 3Page: 229-230KeywordsDatabasesHealth Insurance Portability and Accountability ActHealth careHealth information technologyLegislationPatients ePublished: 1 August 2006 Issue Published: 1 August 2006 Copyright & PermissionsCopyright © 2006 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Tamiflu: the battle for secret drug data
Authors: D. Payne
Journal: BMJ (2012)

<h3>Summary</h3> Efficient nutrient acquisition in the competitive human gut is essential for microbial persistence. While polysaccharides have been well-studied nutrients for the gut microbiome, other resources such as co-factors and nucleic acids have been less examined. We describe a series of ribose utilization systems (RUSs) that are broadly represented in Bacteroidetes and appear to have diversified to allow access to ribose from a variety of substrates. One <i>Bacteroides thetaiotaomicron</i> RUS variant is critical for competitive gut colonization in a diet-specific fashion. Using molecular genetics, we probed the nature of the ribose source underlying this diet-specific phenotype, revealing that hydrolytic functions in RUS (<i>e.g</i>., to cleave ribonucleosides) are present but dispensable. Instead, ribokinases that are activated <i>in vivo</i> and participate in cellular ribose-phosphate metabolism are essential. Our results underscore the extensive mechanisms that gut symbionts have evolved to access nutrients and how metabolic context determines the impact of these functions <i>in vivo</i>.
Acute metabolic effects of exercise in bodybuilders using anabolic steroids.
Authors: G McKillop, F C Ballantyne, W Borland, D Ballantyne
Journal: British Journal of Sports Medicine (1989)

Four male bodybuilders who had started taking anabolic steroids were monitored during exercise. Most metabolic indicators were similar to bodybuilders not taking steroids; i.e. metabolic acidosis with little change in glucose. However, there is a marked elevation of creatine kinase.
A METHOD OF PRESERVING UNBOUND LITERATURE WITH SUGGESTIONS REGARDING A SYSTEM OF CLASSIFICATION.
Authors: D. H. GALLOWAY
Journal: JAMA (1897)

Probably the majority of physicians regard the unbound literature in their libraries as an unmitigated nuisance. They may see much of interest in this literature when received but the liklihood of being able to find it again when wanted is so remote that it is generally consigned to the waste basket. Any plan which will rescue this material from the waste basket and make it useful ought to be received favorably by every one who has realized how difficult the subject is. The problem of preserving unbound literature, so that it is available for convenient reference, is so difficult of solution that few attempt it and those few usually get swamped before the amount of material becomes very great. A system to be valuable, must conform to the following requirements: The scheme must be so simple that it can easily be carried in the mind and it must require the
Reversal of the Pickwickian Syndrome by Long-Term Use of Nocturnal Nasal-Airway Pressure
Authors: David M. Rapoport, Barry Sorkin, Stuart M. Garay, Roberta M. Goldring
Journal: New England Journal of Medicine (1982)

Chronic hypercapnia and daytime hypersomnolence in the obese patient without intrinsic lung disease — the so-called Pickwickian syndrome — has long been associated with periodic breathing.1 The recognition that obstructive sleep apnea with functional upper-airway obstruction is the mechanism of such periodic breathing2 has led to its implication in the development of chronic hypercapnia. The current definitive treatment for severe obstructive sleep apnea is tracheostomy.3 However, medical and psychosocial problems frequently interfere with the acceptance of tracheostomy by both patient and physician, especially when symptoms have been long-standing.3 , 4 Recently, a noninvasive therapeutic method — continuous positive airway pressure applied through . . .
Evaluation of Splenomegaly
Authors: Robert L. Schwarz
Journal: JAMA (1982)

<h3>To the Editor.—</h3> In "Splenomegaly: An Algorhythmic Approach to Diagnosis" (1981;246:2858), Edward R. Eichner, MD, and Charles L. Whitfield, MD, recommend in evaluating the condition of the patient with acute or subacute febrile illness and splenomegaly first to obtain three to six blood cultures to rule out subacute bacterial endocarditis (SBE). If the culture results are negative, then they recommend proceeding with a peripheral smear to rule out infectious mononucleosis. In my opinion, these steps should be reversed. A WBC count with peripheral smear is much less expensive than multiple blood cultures, and infectious mononucleosis is much more common than subacute bacterial endocarditis. If, indeed, the authors have found using blood cultures to rule out SBE more cost-effective than first doing WBC counts and peripheral smears to rule out mononucleosis, they must have quite an interesting patient population. This would definitely not be optimal laboratory use in my practice.
Proton-pump inhibitors were associated with reduced effectiveness of alendronate for preventing hip fractures
Authors: Kouta Ito
Journal: Annals of Internal Medicine (2011)

ACP Journal Club18 October 2011Proton-pump inhibitors were associated with reduced effectiveness of alendronate for preventing hip fracturesKouta Ito, MD, MSKouta Ito, MD, MSBrigham and Women's Hospital, Boston, Massachusetts, USA (K.I.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-8-201110180-02013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationAbrahamsen B, Eiken P, Eastell R. Proton pump inhibitor use and the antifracture efficacy of alendronate. Arch Intern Med. 2011;171:998-1004. https://pubmed.ncbi.nlm.nih.gov/21321287Clinical Impact RatingsGIM/FP/GP: Gastroenterology: Geriatrics: Rheumatology: References1 Yu EW, Bauer SR, Bain PA, Bauer DC. Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies. Am J Med. 2011;124:519-26. [PMID: 21605729] Google Scholar2 de Vries F, Cooper AL, Cockle SM, van Staa TP, Cooper C. Fracture risk in patients receiving acid-suppressant medication alone and in combination with bisphosphonates. Osteoporos Int. 2009;20:1989-98. [PMID: 19333676] Google Scholar3 Jacobson BC, Ferris TG, Shea TL, et al. Who is using chronic acid suppression therapy and why? Am J Gastroenterol. 2003;98:51-8. [PMID: 12526936] Google Scholar Author, Article, and Disclosure InformationAuthors: Kouta Ito, MD, MSAffiliations: Brigham and Women's Hospital, Boston, Massachusetts, USA (K.I.)This article was published at Annals.org on 4 October 2011. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 October 2011Volume 155, Issue 8Page: JC4-13KeywordsCalciumDatabasesDrugsHazard ratioHip fracturesHumerusObservational studiesProton pump inhibitorsSpineVitamin D ePublished: 18 October 2011 Issue Published: 18 October 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Objective evaluation of regional left ventricular wall motion during dobutamine stress echocardiographic studies using segmental analysis of color kinesis images
Authors: Rick Koch, Roberto M Lang, Maria-Jurema Garcia, Lynn Weinert, James Bednarz, Claudia Korcarz, Brendan Coughlan, Alan Spiegel, Eugene Kaji, Kirk T Spencer, Victor Mor-Avi
Journal: Journal of the American College of Cardiology (1999)
Decrease in microviscosity and cholesterol content of rat liver plasma membranes after chronic ethanol feeding.
Authors: S Yamada, C S Lieber
Journal: Journal of Clinical Investigation (1984)

This investigation was performed to determine whether chronic ethanol feeding alters the lipid composition or the fluidity of liver plasma membranes. Male Sprague-Dawley rats were pair-fed nutritionally adequate liquid diets containing ethanol as 36% of energy or an isocaloric amount of carbohydrate for 4-5 wk. Contrasting with other membranes, chronic ethanol feeding resulted in an increase in hepatic plasma membrane fluidity as assessed by fluorescence anisotropy. This alteration was associated with a decrease in plasma membrane cholesterol content.
Systemic Embolism in Mitral Stenosis
Authors: N. Coulshed, E. J. Epstein, E. Walker, R. W. Galloway
Journal: BMJ (1964)

Buccal Oxytocin SIR,-Oxytocin can have a powerful effect upon the pregnant uterus, however it reaches the blood-stream.The intravenous " pitocin drip" was at first regarded by some as a dangerous technique-; and so it was until experience had made plain the pitfalls and careful investigation had shown how these could be avoided.To-day it can only be
Age‐ and infection‐related maturation of the nasal immune response in 0–2‐year‐old children
Authors: I. J. van Benten, C. M. van Drunen, L. P. Koopman, B. C. van Middelkoop, W. C. J. Hop, A. D. M. E. Osterhaus, H. J. Neijens, W. J. Fokkens
Journal: Allergy (2005)

The hygiene hypothesis suggests that exposure to micro-organisms influences development of the immune system in children.In this study, we examined nasal immune responses in the first 2 years of life in relation to age of children and the number of viral infections they have experienced. Nasal brushes were taken during rhinovirus- (n = 20) or respiratory syncytial virus (RSV)-induced (n = 7) upper respiratory tract infections (URTI), and of controls (n = 40).The number of macrophages were higher during URTI and increased with age. The number of T lymphocytes increased with age in controls and were higher during URTI at all ages. We found an age-related decrease in the number of interleukin (IL)-4- and IL-10-positive cells in controls, while the number of IL-12-positive cells remained unchanged. Changes in T lymphocyte and IL-4 cell number were stronger related to the age of the child than to the number of respiratory infections, while the opposite was true for macrophages.In infants, we found an infection- and age-related increase respectively for nasal macrophages and T lymphocytes during URTI. Furthermore, the number of IL-4- and IL-10-positive cells decreased with age. Whether this maturation reflects a natural age-related maturation, the degree of exposure to respiratory infections, or possibly both, could not be resolved and needs further study.
The role of myocardial revascularization surgery and percutaneous coronary intervention in the long-term follow-up of elderly patients with myocardial infarction
Authors: JoséC. Nicolau, Renata T. Ladeira, Luciano M. Baracioli, Marcelo Franken, Luis F. Seguro, José Brum, Michael Sprafka, JoséA. Ramires
Journal: Journal of the American College of Cardiology (2003)
Lactic Acidosis Secondary to Pernicious Anemia
Authors: Andrew Coronato, Allan B. Cohen
Journal: Annals of Internal Medicine (1969)

The first reported case of lactic acidosis secondary to severe anemia with complete and immediate reversal of the acidosis after transfusion with packed red blood cells is described in a patient with pernicious anemia. Experimental evidence that severe anemia can cause widespread tissue hypoxia is cited. The pathophysiology, causal classification, and diagnosis of lactic acidosis are reviewed.
Pharmacological Emptying of the Stomach with Metoclopramide
Authors: T. H. Howells, T. Khanam, L. Kreel, C. Seymour, B. Oliver, J. A. H. Davies
Journal: BMJ (1971)

This paper evaluates the use of metoclopramide (Maxolon) in emptying human stomach contents into the duodenum and beyond. A method of quantitative assessment of content by barium swallow radiography is used in the study, and the method is recommended as a diagnostic manoeuvre in patients presenting for emergency surgery in whom the stomach content is in doubt. Oral metoclopramide was found effective in emptying stomachs challenged by water load, and the intravenous route has been found effective in emptying semisolid contents in emergency clinical situations. A radiographic scan of the resting stomach was made on patients waiting for routine surgery who had received a variety of common premedication; it was shown that significant residues occur. We believe that metoclopramide deserves further investigation in order to exploit its potential in reducing the hazard of regurgitation and vomiting in patients requiring emergency anaesthesia and surgery.
Melamine, Powdered Milk, and Nephrolithiasis in Chinese Infants
Authors: Craig B. Langman
Journal: New England Journal of Medicine (2009)

Melamine, a synthetic nitrogenous product found in many industrial goods and even in fertilizer destined for use in growing crops for human consumption, was recently found to have been added to foods in China — including many different powdered infant formulas1 — to increase their measured, but not biologically available, protein content. Melamine is largely not degraded in humans, although several other compounds (ammeline, ammelide, and cyanuric acid) may become cocontaminants during the manufacturing process, and the main route of excretion after absorption from the gastrointestinal tract appears to be through the urine.2 The findings of acute kidney failure and . . .
Unstable angina pectoris: an examination of modes and costs of therapy.
Authors: J J Kronenfeld, E D Charles, J B Wayne, A Oberman, N T Kouchoukos, W J Rogers, J A Mantle, C E Rackley, R O Russell
Journal: Circulation (1979)

Debate exists over the most appropriate form of treatment for patients with unstable angina pectoris. This study examined 106 patients randomized at the University of Alabama in Birmingham as part of the National Cooperative Study Group and focuses on the phenomenon of patients who fail medical therapy and thus require late surgery, and the costs of therapy. Discriminant function analysis revealed that the significant predictors (p less than 0.01) of patients who would later require surgery were: total number of vessels diseased, angina severly, presence of congestive heart failure, hypertension, and number of years that the patient had had angina. By means of this analysis, 85% of the late surgery patients were correctly predicted. Late surgery patients averaged 2.4 diseased vessels vs 1.5 for persistent medical patients (p less than 0.01). Mean charges for the first 2 years in the study were $6,226 (SD $2,967) for persistent medical patients, $10,416 (SD $2,146) for surgery patients, and $20,059 (SD $10,748) for late surgery patients (p less than 0.001). These data indicate that surgery is clearly an expensive procedure; but that it is more expensive for late surgery patients, who have total costs that are twice as high as surgical costs and 3.5 times as high as persistent medical costs.
General practice records.
Authors: D Wilkins
Journal: BMJ (1972)

motor end plates of the lower portion of the face where the injury was situated the concentration of the toxin could have been high enough to produce palsy.The other possibility would be for the toxin to ascend up the nerve fibres in high enough concen- tration to paralyse the motor end plates while some toxin could be absorbed via the blood stream to reach the C.N.S., and give rise to genealized excitatory features.Whatever the explanation, facial palsy as a complication of tetanus is a rare occurrence.An intriguing aspect of the case was that the forehead had escaped while the lower portion of the face (including the orbicularis oculi) was affected.-Weare, etc.,
EXERCISE-INDUCED INCREASE IN EFFECTIVE MITRAL VALVE AREA AFTER RESTRICTIVE MITRAL VALVE ANNULOPLASTY
Authors: Philippe B. Bertrand, David Verhaert, Christophe J. Smeets, Frederik H. Verbrugge, Lars Grieten, Wilfried Mullens, Herbert Gutermann, Robert A. Dion, Robert Levine, Pieter M. Vandervoort
Journal: Journal of the American College of Cardiology (2014)
The Doctor's Role in Wartime
Authors: Charles G. Green
Journal: Annals of Internal Medicine (1991)

Letters15 August 1991The Doctor's Role in WartimeCharles G. Green Jr., MDCharles G. Green Jr., MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-115-4-331_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:I take issue with the editorial by Dr. Porter (1) in which he states that a physician in essence becomes unethical when he becomes a combatant. Unfortunately, despite the Geneva Convention, the modern-day battlefield does not necessarily offer a distinction between combatant and non-combatant. Although we, as physicians, attest to this distinction in theory, those who have served in a combat zone understand the situation differently. Having recently returned from the Gulf War, I am convinced that my fellow physicians, who were indeed armed, would not have hesitated to use their weapons either in a defensive or...Reference1. Porter W. The doctor's role in wartime. Ann Intern Med. 1991;114:997-8. LinkGoogle Scholar1. Porter W. The doctor's role in wartime. Ann Intern Med. 1991;114:987-8. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Charles G. GreenJr., MDAffiliations: Augusta Diagnostic Associates Augusta, GA 30910 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 August 1991Volume 115, Issue 4Page: 331-331 ePublished: 1 December 2008 Issue Published: 15 August 1991 PDF downloadLoading ...
Fusobacterium nucleatum Promotes Colorectal Carcinogenesis by Modulating E-Cadherin/β-Catenin Signaling via its FadA Adhesin
Authors: Mara Roxana Rubinstein, Xiaowei Wang, Wendy Liu, Yujun Hao, Guifang Cai, Yiping W. Han
Journal: Cell Host & Microbe (2013)

Fusobacterium nucleatum (Fn) has been associated with colorectal cancer (CRC), but causality and underlying mechanisms remain to be established. We demonstrate that Fn adheres to, invades, and induces oncogenic and inflammatory responses to stimulate growth of CRC cells through its unique FadA adhesin. FadA binds to E-cadherin, activates β-catenin signaling, and differentially regulates the inflammatory and oncogenic responses. The FadA-binding site on E-cadherin is mapped to an 11-amino-acid region. A synthetic peptide derived from this region of E-cadherin abolishes FadA-induced CRC cell growth and oncogenic and inflammatory responses. The fadA gene levels in the colon tissue from patients with adenomas and adenocarcinomas are >10–100 times higher compared to normal individuals. The increased FadA expression in CRC correlates with increased expression of oncogenic and inflammatory genes. This study unveils a mechanism by which Fn can drive CRC and identifies FadA as a potential diagnostic and therapeutic target for CRC.