tbuckley/cabot-search huggingface dataset:
Nrf2-regulated PPARγ Expression Is Critical to Protection against Acute Lung Injury in Mice
Authors: Hye-Youn Cho, Wesley Gladwell, Xuting Wang, Brian Chorley, Douglas Bell, Sekhar P. Reddy, Steven R. Kleeberger
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: The NF-E2 related factor 2 (Nrf2)–antioxidant response element (ARE) pathway is essential for protection against oxidative injury and inflammation including hyperoxia-induced acute lung injury. Microarray expression profiling revealed that lung peroxisome proliferator activated receptor γ (PPARγ) induction is suppressed in hyperoxia-susceptible Nrf2-deficient (Nrf2−/−) mice compared with wild-type (Nrf2+/+) mice. PPARγ has pleiotropic beneficial effects including antiinflammation in multiple tissues.Objectives: We tested the hypothesis that PPARγ is an important determinant of pulmonary responsivity to hyperoxia regulated by Nrf2.Methods: A computational bioinformatic method was applied to screen potential AREs in the Pparg promoter for Nrf2 binding. The functional role of a potential ARE was investigated by in vitro promoter analysis. A role for PPARγ in hyperoxia-induced acute lung injury was determined by temporal silencing of PPARγ via intranasal delivery of PPARγ-specific interference RNA and by administration of a PPARγ ligand 15-deoxy-Δ12,14-prostaglandin J2 in mice.Measurements and Main Results: Deletion or site-directed mutagenesis of a potential ARE spanning -784/-764 sequence significantly attenuated hyperoxia-increased Pparg promoter activity in airway epithelial cells overexpressing Nrf2, indicating that the -784/-764 ARE is critical for Nrf2-regulated PPARγ expression. Mice with decreased lung PPARγ by specific interference RNA treatment had significantly augmented hyperoxia-induced pulmonary inflammation and injury. 15 Deoxy-Δ12,14-prostaglandin J2 administration significantly reduced hyperoxia-induced lung inflammation and edema in Nrf2+/+, but not in Nrf2−/− mice.Conclusions: Results indicate for the first time that Nrf2-driven PPARγ induction has an essential protective role in pulmonary oxidant injury. Our observations provide new insights into the therapeutic potential of PPARγ in airway oxidative inflammatory disorders.
THE MITOTIC POTENTIAL OF FIXED PHAGOCYTES IN THE LIVER AS REVEALED DURING THE DEVELOPMENT OF CELLULAR IMMUNITY
Authors: Robert J. North
Journal: The Journal of Experimental Medicine (1969)

Fixed macrophages in the liver of the mouse undergo mitosis in large numbers during an infection with Listeria monocytogenes. The macrophage mitotic response always precedes the expression of efficient host immunity to infection. It is suggested that macrophage proliferation is an important event in the development of host immunity to L. monocytogenes.
The Psychology of Sleep
Authors: William C. Dement
Journal: JAMA (1967)

The author is writing for the interested layman as well as the specialist, presenting the current status of experimental research on psychological aspects of sleep. Several recently published popular accounts of sleep research have emphasized the physiological work. It is a little disappointing that the first chapter fails to convey the great excitement generated in the whole field of sleep research by the nature of recent findings, and the formulation that there are two entirely different kinds of sleep, so different physiologically that some researchers prefer to think of one of them—REM [rapid eye movement] sleep—as a  state of existence.  The second and third chapters deal with mental activity, during REM sleep, and the fourth and fifth deal with mental activity during NREM sleep. The book definitely picks up in the second chapter, which is a clear and compelling review of research findings regarding the association of dreaming and
The Hand-Foot Syndrome in Sickle Cell β-Thalassemia Disease
Authors: Themistocles Karpathios
Journal: JAMA (1977)

THE HAND-FOOT syndrome is a well-documented manifestation of sickle cell anemia; whether it is equally common in sickle cell β-thalassemia (S/thal) disease seems unlikely, since published reports are scarce.<sup>1,2</sup> We report an infant with S/thal whose first clinical manifestations were pallor, fever, and painful, red swelling of both hands. <h3>Procedures</h3> An 11-month-old boy was admitted to the First Department of Pediatrics of Athens University. He had a high fever and edema of both hands of five days' duration, which did not regress during oral antibiotic therapy. A sister aged 6 years has S/thal disease. The family comes from Trikala of Thessaly, a region of Greece with a high frequency of sickle cell and β-thalassemia traits. Physical examination showed a pale, sick-looking infant. Temperature was 39 °C. Weight was 7,800 g, ie, below the third percentile, and height 77 cm, which corresponds to the 50th percentile. There was a spectacular
THE PROBLEM OF TEACHING GENERAL MEDICINE
Authors: E. P. LYON
Journal: JAMA (1913)

The Committee on Pedagogy was authorized by the Cleveland meeting of our association in 1908. The first report was made by Dr. H. B. Ward in 1909. This was an excellent discussion of the qualification of teachers and methods of instruction. The report was properly embalmed and laid away in that mausoleum entitled Proceedings of the New York Meeting. Most of you were present at the obsequies. The reports of 1911 and 1912 were made by Dr. G. H. Hoxie. He considered the crowded schedule and the desirability of leaving the students a little time to think. He made some practical suggestions along these lines. These were respectfully listened to by the same men present to-day, but few or none of his ideas have been carried into effect. The reports were injected with formaldehyd and laid away in the archives. Recently the state of Pennsylvania has decreed that any medical
Balloon dilatation of heart valves.
Authors: R. Hall, R. Kirk
Journal: BMJ (1992)

Much remains to be learnt about the effect of treatment on the persistent vegetative state.One problem is the possibility of selffulfilling prophecy-the prognosis is poor, therefore no treatment is given, therefore the prognosis is poor.Doctors increasingly believe that these patients should be offered the opportunity of admission to a rehabilitation programme.Because of the small number of patients this is unlikely to be available locally and may require regional or supraregional services.As patients in a persistent vegetative state may live for many years attention to basic care is likely to have an appreciable effect on their quality of life.Specialist treatment, especially if provided early, probably offers the greatest opportunities for optimal recovery and improvement in quality of life for both patient and family.
Thromboxane and prostacyclin release in adult respiratory distress syndrome
Authors: G. Deby-Dupont, M. Braun, M. Lamy, C. Deby, J. Pincemail, M.E. Faymonville, P. Damas, L. Bodson, M.P. Lecart, R. Goutier
Journal: Intensive Care Medicine (1987)
A few reasons why we don't share Tomasello et al.'s intuitions about sharing
Authors: György Gergely, Gergely Csibra
Journal: Behavioral and Brain Sciences (2005)

Tomasello et al.'s two prerequisites, we argue, are not sufficient to explain the emergence of Joint Collaboration. An adequate account must include the human-specific capacity to communicate relevant information (that may have initially evolved to ensure efficient cultural learning). This, together with understanding intentional actions, does provide sufficient preconditions for Joint Collaboration without the need to postulate a primary human motive to share others' psychological states.
Scrotal Scintigraphy in an Infant With Yolk Sac Tumor Imitating Acute Epididymo-Orchitis
Authors: RUTH HARDOFF, YOEL MECZ, AHARON LURIE, MENASHE BARZILAI
Journal: Clinical Nuclear Medicine (1994)

Testicular tumors in infants are uncommon; yolk sac tumor is the most prevalent germ cell malignancy. When the patient is diagnosed with this tumor before two years of age and the alpha-fetoprotein level returns to normal following the surgical removal of the tumor, the prognosis is improved. Scintigraphy is performed to show increased flow and heterogeneous tracer distribution. The authors present a case of an infant who underwent testicular scintigraphy for suspected acute scrotum. The study was performed to differentiate between torsion and epididymo-orchitis. Testicular scintigraphy was consistent with an inflammatory process; however, the patient did not develop the clinical signs of epididymoorchitis. On histology, a yolk sac tumor was identified. Thus, when the clinical presentation of a swollen scrotum is uncharacteristic of infection, scintigraphy can be misleading and testicular tumor should be considered.
ENDOTHELIN-1 IS A KEY CANDIDATE TO EXERT PATHOPHYSIOLOGICAL EFFECTS ON CARDIOMYOCYTES DERIVED FROM HYPERTROPHIC CARDIOMYOPATHY-INDUCED PLURIPOTENT STEM CELL
Authors: Atsushi Tanaka, Shinsuke Yuasa, Koichi Node, Keiichi Fukuda
Journal: Journal of the American College of Cardiology (2013)
Reconstitution of Excitable Cell Membrane Structure in Vitro
Authors: PAUL MUELLER, DONALD O. RUDIN, H. TI TIEN, WILLIAM C. WESCOTT
Journal: Circulation (1962)

Single stable bimolecular lipid and proteolipid membranes having the inert physical properties of cell membrane can be reconstituted in saline solution. After adsorption of appropriate molecules, these membranes become electrically excitable.
The EphB6 Receptor Cooperates with c-Cbl to Regulate the Behavior of Breast Cancer Cells
Authors: Luke Truitt, Tanya Freywald, John DeCoteau, Nigel Sharfe, Andrew Freywald
Journal: Cancer Research (2010)

Abstract Cancer invasiveness plays a major role in the mortality of patients with solid tumors, and deregulated cell adhesion and migration are suspected to drive invasive behavior. Since Eph receptor tyrosine kinases control both cell attachment and migration, they may act to define the level of cancer invasiveness. EphB6 is an unusual Eph receptor, lacking catalytic capacity due to alterations in its kinase domain. Interestingly, increased metastatic activity is associated with reduced EphB6 receptor expression in several tumor types, including breast cancer. This emphasizes the potential of EphB6 to act as a suppressor of cancer aggressiveness; however, the mechanism of its action is not well understood. We show that restoration of EphB6 expression in invasive breast cancer cells supports actin-dependent spreading and attachment and blocks invasiveness. EphB6 stimulation induces its tyrosine phosphorylation, which is crucial for its function and is mediated by the EphB4 receptor. This is accompanied by EphB6–c-Cbl interaction and phosphorylation of c-Cbl partner, the Abl kinase. Cbl silencing suppresses Abl phosphorylation, cell adhesion, and morphologic changes and blocks the ability of EphB6 to inhibit invasiveness, confirming its importance for EphB6 activity. Despite its crucial role in EphB6 responses, EphB4 also acts in an EphB6-independent manner to enhance invasive activity, suggesting that cancer invasiveness may be defined by the balance in the EphB6-EphB4 system. Overall, our observations suggest a new role for EphB6 in suppressing cancer invasiveness through c-Cbl–dependent signaling, morphologic changes, and cell attachment and indicate that EphB6 may represent a useful prognostic marker and a promising target for therapeutic approaches. Cancer Res; 70(3); 1141–53
Regulation of the Brain’s Vascular Responses to Oxygen
Authors: Ivan T. Demchenko, Tim D. Oury, James D. Crapo, Claude A. Piantadosi
Journal: Circulation Research (2002)

The mechanism of oxygen-induced cerebral vasoconstriction has been sought for more than a century. Using genetically altered mice to enhance or disrupt extracellular superoxide dismutase (EC-SOD, SOD3), we tested the hypothesis that this enzyme plays a critical role in the physiological response to oxygen in the brain by regulating nitric oxide (NO*) availability. Cerebral blood flow responses in these genetically altered mice to changes in PO2 demonstrate that SOD3 regulates equilibrium between superoxide (*O2-) and NO*, thereby controlling vascular tone and reactivity in the brain. That SOD3 opposes inactivation of NO* is shown by absence of vasoconstriction in response to PO2 in the hyperbaric range in SOD3+/+ mice, whereas NO-dependent relaxation is attenuated in SOD3-/- mutants. Thus, EC-SOD promotes NO* vasodilation by scavenging *O2- while hyperoxia opposes NO* and promotes constriction by enhancing endogenous *O2- generation and decreasing basal vasodilator effects of NO*.
Metabolic Modification of Some Neurologic Disorders
Authors: George C. Cotzias
Journal: JAMA (1969)

Some of the most spectacular drugs in the history of medicine (digitalis, quinine, penicillin) were discovered when at least two events collided randomly: a biological accident and an observer who happened to be in a perceptive state. Since such discoveries depend on an improbable happenstance, society has not yet proved capable of promoting them willfully to an appreciable degree. By sharp contrast, insulin and cortisone were developed after a slow accumulation of data, that were subjected later to novel interpretation. This approach is not a spectacular one. It is, however, readily amenable to promotion by the sequential testing of hypotheses in the laboratory and on the wards. This latter consideration may justify the personal character of the present account. <h3>Background</h3> My colleagues and I have long been interested in the metabolism of biogenic amines<sup>1,2</sup>and in that of essential trace metals like manganese.<sup>3,4</sup>Both classes of substances are
Coordinating Care across Diseases, Settings, and Clinicians: A Key Role for the Generalist in Practice
Authors: Christopher J. Stille, Anthony Jerant, Douglas Bell, David Meltzer, Joann G. Elmore
Journal: Annals of Internal Medicine (2005)

Coordinated care is a defining principle of primary care, but it is becoming increasingly difficult to provide as the health care delivery system in the United States becomes more complex. To guide recommendations for research and practice, the evidence about implementation of coordinated care and its benefits must be considered. On the basis of review of the published literature this article makes recommendations concerning needs for a better-developed evidence base to substantiate the value of care coordination, generalist practices to be the hub of care coordination for most patients, improved communication among clinicians, a team approach to achieve coordination, integration of patients and families as partners, and incorporation of medical informatics. Although coordination of care is central to generalist practice, it requires far more effort than physicians alone can deliver. To make policy recommendations, further work is needed to identify essential elements of care coordination and prove its effectiveness at improving health outcomes.
CASE OF BROWN-SEQUARD'S PARALYSIS, FROM STAB IN THE CERVICAL REGION, WITH COMPLETE HEMIPLEGIA, CROSSED MONOPLEGIA AND CROSSED TOTAL HEMIANESTHESIA.
Authors: ARTHUR R. EDWARDS
Journal: JAMA (1902)

I am indebted for the full, accurate and careful history to Dr. Tiecken, lately senior of the Cook County Hospital resident staff. The patient was admitted July 10, 1900, after having been stabbed twice in the neck by an Italian compatriot during an argument. He fell, lost consciousness and remembered nothing till his arrival at the hospital in an ambulance. Previous history: No previous injury nor illness. Family history is negative. Personal history: Patient admitted a venereal sore, not followed, however, by secondaries, but denied gonorrhea, although some slight urethral discharge was noted. Smoked and drank moderately. <h3>Examination.</h3> —Middle-aged, male, of short stature, well nourished, florid complexion and anxious expression; mind was usually clear but at times slightly delirious. Head and scalp were negative. There was no evidence of violence, no edema. Skull was negative; no evidence of fracture; no tenderness. Neck: One inch to the right of the median
Autoimmunity: Genetic, Immunologic, Virologic, and Clinical Aspects
Authors: Paul P. VanArsdel
Journal: JAMA (1978)

This book, the product of 40 different contributors from eight countries, is divided into four major parts. The first is devoted to genetic aspects: the major histocompatibility complex and disease, the genetics of autoimmune disease in animals, and the genetic regulation in autoimmune thyroiditis. Part 2 discusses concepts of pathogenesis, self-recognition and tolerance, suppressor T-cell dysfunction, lymphoid malignant neoplasms, thymic hormones, and the biology of immune complexes. Part 3 studies the influence of viral infection on the immune response. The last part consists of nine clinically related chapters that deal with immunodeficiency, aging, and receptor autoimmunity, with three whole chapters given to systemic lupus erythematosus, rheumatoid arthritis, and neurologic disease. The book concludes on a positive theme with a chapter on the possible beneficial role of certain autoimmune phenomenons. Each chapter is an extensively referenced review that could stand on its own in a medical journal, and each can serve
Introduction of laparoscopic bariatric surgery in England: observational population cohort study
Authors: E. M. Burns, H. Naseem, A. Bottle, A. I. Lazzarino, P. Aylin, A. Darzi, K. Moorthy, O. Faiz
Journal: BMJ (2010)

<b>Objectives</b> To describe national trends in bariatric surgery and examine the factors influencing outcome in bariatric surgery in England. <b>Design</b> Observational population cohort study. <b>Setting</b> Hospital Episode Statistics database. <b>Participants</b> All patients who had primary gastric bypass, gastric banding, or sleeve gastrectomy procedures between April 2000 and March 2008. <b>Main outcome measures</b> 30 day mortality, mortality at one year after surgery, unplanned readmission to hospitalwithin 28 days, and duration of stay in hospital. <b>Results</b> 6953 primary bariatric procedures were carried out during the study period, of which 3649 were gastric band procedures, 3191 were gastric bypass procedures, and 113 were sleeve gastrectomy procedures. A marked increase occurred in the numbers of bariatric procedures done, from 238 in 2000 to 2543 in 2007, with an increase in the percentage of laparoscopic procedures over the study period (28% (66/238) laparoscopic procedures in 2000 compared with 74.5% (1894/2543) in 2007). Overall, 0.3% (19/6953) patients died within 30 days of surgery. The median length of stay in hospital was 3 (interquartile range 2-6) days. An unplanned readmission to hospital within 28 days of surgery occurred in 8% (556/6953) of procedures. No significant increase in mortality or unplanned readmission was seen over the study period, despite the exponential increase in minimal access surgery and consequently bariatric surgery. <b>Conclusions</b> Bariatric surgery has increased exponentially in England. Although postoperative weight loss and reoperation rates were not evaluated in this observational population cohort study, patients selected for gastric banding had lower postoperative mortality and readmission rates and a shorter length of stay than did those selected for gastric bypass.
SIMULTANEOUS PRODUCTION OF TWO CAPSULAR POLYSACCHARIDES BY PNEUMOCOCCUS
Authors: Robert Austrian, Harriet P. Bernheimer
Journal: The Journal of Experimental Medicine (1959)

Pneumococci manifesting binary capsulation have been produced through the agency of transformation reactions. Such cells produce two capsular polysaccharides which are closely similar if not identical with those produced by corresponding singly capsulated strains. Binary capsulation in pneumococcus provides a new basis for serologic cross-reactivity in this species.
Sublingual immunotherapy in children modulates allergen‐induced <i>in vitro</i> expression of cytokine mRNA in PBMC
Authors: J. Savolainen, L. Jacobsen, E. Valovirta
Journal: Allergy (2006)

Background: During subcutaneous immunotherapy (SCIT), there is a local mucosal shift from Th2 to Th1 type cytokine predominance and downregulation of interleukin (IL)‐5 and eosinophilia. According to recent studies IL‐10‐ and transforming growth factor (TGF)‐ β ‐induced tolerance is another key phenomenon in SCIT. Few data to date is available on mechanisms and roles of these cytokines in sublingual immunotherapy (SLIT). Scope: This study was undertaken to analyse the allergen‐induced in vitro mRNA expression of IL‐4, IL‐5, IL‐10, TGF‐ β and interferon (IFN)‐ γ during SLIT in peripheral blood mononuclear cells (PBMC) of children with allergic rhinitis (AR). Methods: Ten patients with AR undergoing pollen SLIT with a weekly dose of 200 000 SQ‐U, 10 with a weekly dose of 24 000 SQ‐U of glycerinated mixture of Betula verrucosa , Corylus avellana and Alnus glutinosa and 10 with placebo were included in the study. Peripheral blood mononuclear cell samples were collected and stimulated with pollen allergen extract prior to the treatment, after 1 and 2 years of the treatment. The cytokine mRNA expression was assessed using kinetic real time reverse transcription polymerase chain reaction (RT‐PCR; TaqMan ® ). Results: The in vitro allergen‐induced mRNA expression of IL‐5 by PBMC in the placebo group at 1 ( P = 0.0065) and 2 ( P = 0.013) years of therapy were increased in comparison with the highest dose. The expression of IL‐10 mRNA was increased in the highest dose group ( P = 0.0016) and the lower dose group ( P = 0.034) at 2 years of therapy when compared with placebo. The change in the expression of allergen‐induced TGF‐ β had an inversed correlation with the change of IL‐5 ( r = −0.38, P = 0.036) and positive correlation with the change of IL‐10 ( r = 0.58, P = 0.0019). Conclusions: Sublingual immunotherapy induced a dose‐dependent systemic allergen‐specific immunological response in children with AR. During high‐dose SLIT, there was activation of regulatory cytokine IL‐10 and an inhibitory effect on IL‐5 expression increase that was associated with TGF‐ β .
Plasma nicotine levels after cigarette smoking and chewing nicotine gum.
Authors: M A Russell, C Feyerabend, P V Cole
Journal: BMJ (1976)

Plasma nicotine levels were measured over seven hours of smoking cigarettes (1-2 mg nicotine) in a single subject under standardised conditions, and were compared with the levels obtained from chewing-gum containing either 2 mg or 4 mg nicotine. Levels comparable to those resulting from smoking were not obtained with the 2-mg gum, but peak levels on the 4-mg gum averaged 40-1 ng/ml from the third gum onwards compared with 49-2ng/ml after cigarettes. Nicotine was absorbed much more slowly from the gum than from cigarettes. It took 15-30 minutes for the 4-mg gum to raise the plasma nicotine by an average of 11-9 ng/ml compared with an average increase of 27-8 ng/ml within two minutes of completing each cigarette. In a sample of 15 smokers attending a withdrawal clinic the average plasma nicotine concentration while taking 2-mg nicotine chewing-gum was only 10-8 ng/ml compared with 30-4 ng/ml two minutes after smoking a cigarette. Although plasma nicotine levels equivalent to those following cigarette smoking may be obtained by chewing at least 10 pieces of 4-mg nicotine gum daily, the slower rate of absorption may limit its therapeutic value as a substitute for cigarette smoking.
Structure-based targeting of bioactive proteins into cypovirus polyhedra and application to immobilized cytokines for mammalian cell culture
Authors: Hiroshi Ijiri, Fasséli Coulibaly, Gento Nishimura, Daisuke Nakai, Elaine Chiu, Chiemi Takenaka, Keiko Ikeda, Hiroshi Nakazawa, Norio Hamada, Eiji Kotani, Peter Metcalf, Shin Kawamata, Hajime Mori
Journal: Biomaterials (2009)