tbuckley/cabot-search huggingface dataset:
Abstract 349: Leptin-induced epithelial-mesenchymal transition in breast cancer cells requires β-catenin activation via Akt/GSK3-dependent and MTA1/Wnt1-dependent pathways
Authors: Dan Yan, Dimiter B. Avtanski, Neeraj K. Saxena, Dipali Sharma
Journal: Cancer Research (2012)

Abstract Perturbations in the adipocytokines-profile, especially higher levels of leptin, are a major cause of breast tumor progression and metastasis; the underlying mechanisms, however, are not well understood. In particular, it remains elusive whether leptin is involved in epithelial-mesenchymal transition (EMT). Here, we provide first molecular evidence that leptin induces breast cancer cells to undergo a transition from epithelial to spindle-like mesenchymal morphology. Investigating the downstream mediator(s) that may direct leptin-induced EMT, we found functional interactions between leptin, metastasis-associated protein 1 (MTA1) and Wnt1 signaling components. Leptin increases accumulation and nuclear translocation of β-catenin leading to increased promoter recruitment. Silencing of β-catenin or treatment with small molecule inhibitor, ICG-001, inhibits leptin-induced EMT, invasion and tumorsphere formation. Mechanistically, leptin stimulates phosphorylation of glycogen synthase kinase 3β (GSK3β) via Akt activation resulting in a substantial decrease in the formation of GSK3β-LKB1-Axin complex which leads to increased accumulation of β-catenin. Leptin treatment also increases Wnt1 expression that contributes to GSK3β phosphorylation. Inhibition of Wnt1 abrogates leptin-stimulated GSK3β phosphorylation. We also discovered that leptin increases the expression of an important modifier of Wnt1 signaling, MTA1, which is integral to leptin-mediated regulation of Wnt/β-catenin pathway as silencing of MTA1 inhibits leptin-induced Wnt1 expression, GSK3β phosphorylation and β-catenin activation. Furthermore, analysis of leptin-treated breast tumors show increased expression of Wnt1, pGSK3β and Vimentin along with higher nuclear accumulation of β-catenin and reduced E-cadherin expression providing in vivo evidence for a previously unrecognized crosstalk between leptin and MTA1/Wnt signaling in epithelial-mesenchymal transition of breast cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 349. doi:1538-7445.AM2012-349
Skin diseases in children in rural Kenya: long-term results of a dermatology project within the primary health care system
Authors: W. Schmeller, A. Dzikus
Journal: British Journal of Dermatology (2001)

Background Following an epidemiological study on skin diseases in 5780 pupils from 13 schools in rural western Kenya in 1993, a dermatology project within the primary health care system was established in 1994 by the German non-government organization (NGO) 'Doctors in Aid of Children with Skin Diseases in Africa'. Within this project trained community health workers carried out regular visits to schools and nurseries and treated children with hydrocortisone acetate 1% cream for dermatitis, gentian violet 1% solution for bacterial skin infections, Whitfield's ointment for dermatophytoses and benzylbenzoate emulsion 25% for scabies. Objectives To assess the impact of this intervention. Methods In 1999, after a 5-year period, 4961 pupils from the same 13 schools were re-examined and the prevalence rates were compared. Results Non-infective dermatitis had a prevalence of 1·7% in 1993 as well as in 1999; among the communicable diseases bacterial infections declined from 12·7% to 11·3% (not significant), fungal infections rose from 10·1% to 13·9% (P < 0·05) and arthropod infections (mainly scabies) remained at similar levels of 8·3% in 1993 and 8·0% in 1999. A distinctive reduction could only be found for tropical ulcers (0·1% in 1999 compared with 1·2% in 1993). Conclusions The prevalence of dermatoses in children in rural Africa does not only depend on treatment schemes within the primary health care system, but on the socio-economic conditions available.
Innate and Adaptive Interleukin-17–producing Lymphocytes in Chronic Inflammatory Lung Disorders
Authors: Bart M. Vanaudenaerde, Stijn E. Verleden, Robin Vos, Stéphanie I. De Vleeschauwer, Anna Willems-Widyastuti, Rachel Geenens, Dirk E. Van Raemdonck, Lieven J. Dupont, Erik K. Verbeken, Isabelle Meyts
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

During T-cell receptor activation in a particular cytokine environment, naive CD4+ T cells may differentiate into lineages defined by their pattern of cytokine production and transcription factors: T helper type 1 (Th1), Th2, Th17, and Th22 cells; follicular helper T cells; and inducible regulatory T cells. Th17 cells have been recognized as a distinct lineage of Th cells, and associations between IL-17 and human disease have been known somewhat longer. It would be an oversimplification to restrict IL-17 to Th17 cells. Indeed, IL-17 is also expressed by other cells including IL-17-producing γδ T (γδ T-17) cells, natural killer T-17 cells, and IL-17-producing lymphoid tissue-induced cells. IL-17 was cloned in 1995 as a cytokine expressed by T cells, exerting inflammatory effects on epithelial, endothelial, and fibroblast cells. IL-17 is a solid link between innate and adaptive immunity and can exert both beneficial and deleterious effects. The discovery of IL-17 T cells has provided exciting new insights into host defense, immunoregulation, and autoimmunity. Unquestionably, data from mouse models have contributed enormously to our insight into immunological mechanisms. However, because of numerous differences between murine and human immunology, data obtained in mice are not simply interchangeable. We review IL-17 T cells exclusively in the human situation and more specifically their potential role in respiratory diseases. The advances in our understanding of IL-17 regulation offer opportunities to dissect the human IL-17 system and to reflect on the clinical presentation of lung diseases. More importantly, the IL-17 system allows us to speculate on new therapeutic opportunities. Some results have been previously reported in an abstract.
A-V Conduction in Auricular Flutter
Authors: M. BESOAIN-SANTANDER, A. PICK, R. LANGENDORF
Journal: Circulation (1950)

Flutter of the auricles may be associated with either a regular or an irregular ventricular rate. The former occurs as a rule in the untreated patient, the latter as a result of digitalis therapy. An attempt was made to explain the irregular ventricular response in auricular flutter as a result of a conduction disturbance similar to that seen in sinus rhythm with second degree A-V block characterized by progressive lengthening of the A-V conduction time preceding the dropped beat (Wenckebach phenomenon). Such an approach was suggested by the peculiar arrangement of the ventricular beats in some cases of auricular flutter. Similarly, in order to account for certain features of the arrhythmia it was assumed that some of the non-conducted flutter impulses penetrate into the A-V junction and thus influence the conduction of the subsequent flutter impulses.
Case 4-2002: Cancer-Associated Obstruction and Glomerular Damage
Authors: Alfredo Blas, Rita McGill, Stephen Sandroni
Journal: New England Journal of Medicine (2002)

To the Editor: Case 4-2002 (Jan. 31 issue) described a 75-year-old man with acute renal failure five months after cystoprostatectomy and urethrectomy for carcinoma.1 Recently, we cared for a 52-yea...
UK major trauma outcome study
Authors: C Davis
Journal: BMJ (1992)

incidents jointly with the British Association for Accident and Emergency Medicine.The association organises courses on major incidents, and the five day course on immediate care includes formal training on the same subject.The diploma in immediate medical care of the Royal College of Surgeons of Edinburgh examines candidates on skills gained in these courses.The courses and the diploma are much more relevant to on site medical services at major incidents than the much promoted advanced trauma life support courses, which relate to the care of a single patient by a single doctor in hospital.4We believe that the key issues are, firstly, that the person serving as medical incident officer must be properly trained in managing major incidents and must participate regularly in exercises with colleagues from other services; and, secondly, that members of site medical teams must regularly work outside hospital on the many cases of trauma seen in day to day practice.
897 LOW HEPATIC IRON BURDEN IN MORBIDLY OBESE WOMEN: A LINK WITH CHRONIC INFLAMMATION
Authors: R. Anty, M. Dahman, S. Bekri, A. Iannelli, P. Gual, A. Staccini-Myx, M.C. Saint-Paul, P.M. Huet, S.K.S. Srai, R. Unwin, Y. Le Marchand-Brustel, J. Gugenheim, A. Tran
Journal: Journal of Hepatology (2008)
Expression of functional leukotriene B4 receptors on human airway smooth muscle cells
Authors: Satoko Watanabe, Akira Yamasaki, Kiyoshi Hashimoto, Yasushi Shigeoka, Hiroki Chikumi, Yasuyuki Hasegawa, Takashi Sumikawa, Miyako Takata, Ryota Okazaki, Masanari Watanabe, Tsuyoshi Yokogawa, Miki Yamamura, Tatsuya Hayabuchi, William T. Gerthoffer, Andrew J. Halayko, Eiji Shimizu
Journal: Journal of Allergy and Clinical Immunology (2009)
On the Indications for Manual Interference and Other Agencies in the Treatment of Abortions, with Cases in Illustration
Authors: H. Sandwith
Journal: BMJ (1867)

THE BRITISH MEDICAL 7OURNAL EJUIY 3,.a well-defined character-the absence of the second event, or true dicrotism, which means that the diastolic collapse occurs immediately after the primary expansion (the vertical ascent of the tracing ending at once in a nearly vertical ascent), and that the contraction of the heart, however violent it may be, produces little effect in increasing the arte- rial tension. (Figs. 5 and 6.)]
Color Atlas of Oral Diseases. 3rd edition
Authors: Jeffrey D Bernhard
Journal: Journal of the American Academy of Dermatology (2004)

This is a lovely atlas with 777 very nicely done, high-quality color illustrations, and is a very worthwhile addition to the compleat dermatologist's atlas collection. Oral diseases do not receive the attention they deserve in dermatology residency training programs, and books like this can help remedy deficiencies in our diagnostic powers. The problem with most atlases, including this one, is that they tend to go from diagnosis to physical finding, which is opposite to the direction ordinarily required when trying to go from finding to differential diagnosis in the clinic. Nonetheless, the chapter groupings and pictures in this book are sufficiently clear and well-organized to enable someone who doesn't already know a torus from a schwannoma to get off to a good start.
Weight gain in smokers after quitting cigarettes: meta-analysis
Authors: H.-J. Aubin, A. Farley, D. Lycett, P. Lahmek, P. Aveyard
Journal: BMJ (2012)

<b>Objective</b> To describe weight gain and its variation in smokers who achieve prolonged abstinence for up to 12 months and who quit without treatment or use drugs to assist cessation. <b>Design</b> Meta-analysis. <b>Data sources</b> We searched the Central Register of Controlled Trials (CENTRAL) and trials listed in Cochrane reviews of smoking cessation interventions (nicotine replacement therapy, nicotinic partial agonists, antidepressants, and exercise) for randomised trials of first line treatments (nicotine replacement therapy, bupropion, and varenicline) and exercise that reported weight change. We also searched CENTRAL for trials of interventions for weight gain after cessation. <b>Review methods</b> Trials were included if they recorded weight change from baseline to follow-up in abstinent smokers. We used a random effects inverse variance model to calculate the mean and 95% confidence intervals and the mean of the standard deviation for weight change from baseline to one, two, three, six, and 12 months after quitting. We explored subgroup differences using random effects meta-regression. <b>Results</b> 62 studies were included. In untreated quitters, mean weight gain was 1.12 kg (95% confidence interval 0.76 to 1.47), 2.26 kg (1.98 to 2.54), 2.85 kg (2.42 to 3.28), 4.23 kg (3.69 to 4.77), and 4.67 kg (3.96 to 5.38) at one, two, three, six, and 12 months after quitting, respectively. Using the means and weighted standard deviations, we calculated that at 12 months after cessation, 16%, 37%, 34%, and 13% of untreated quitters lost weight, and gained less than 5 kg, gained 5-10 kg, and gained more than 10 kg, respectively. Estimates of weight gain were similar for people using different pharmacotherapies to support cessation. Estimates were also similar between people especially concerned about weight gain and those not concerned. <b>Conclusion</b> Smoking cessation is associated with a mean increase of 4-5 kg in body weight after 12 months of abstinence, and most weight gain occurs within three months of quitting. Variation in weight change is large, with about 16% of quitters losing weight and 13% gaining more than 10 kg.
Abstract 2357: Gene expression profiling robustly predicts the outcome of patients diagnosed with early stage lung adenocarcinoma
Authors: Yann Gaston-Mathé, CHARLES FERTE, benoit gauthier, mathilde bateson, david planchard, benjamin besse, Jean-Pierre Armand, jean-charles soria
Journal: Cancer Research (2014)

Abstract Background: Although the management of metastatic lung adenocarcinoma has been profoundly modified by the identification of actionnable molecular traits, decision making for early-stage lung adenocarcinoma still relies on the tumor stage (TNM) only. Most of these patients recur within 5 years after tumor resection and are given platinum based adjuvant chemotherapy. The recent availability of multiple gene expression data and the concomitant developments of novel algorithms - such as the Hypercube algorithm - could dramatically improve such predictive challenges. Methods: Datasets were selected from public repositories (Director's challenge (DC) n=274, Rousseaux n=86, Hou n=35, JBR.21 n=31) upon the following criteria: lung adenocarcinoma, stage IA-3A, no adjuvant therapy, R0 tumor resection. To generate robust predictors of 3-year overall survival, an iterative feature selection framework (Hypercube algorithm) was applied successively on DC and Hou. Only highly predictive rules in both datasets (AUC &amp;gt;.7) were then included in a subsequent logistic regression model and finally assessed for external validation. The predictive performance of the models was evaluated by ROC-AUC and by Kaplan Meier curves. Results: Our best model combining gene expression (10 genes) and clinical data (TNM) was robust across three lung adenocarcinoma datasets (AUC= .85, .80 and .59). Particularly, it was able to better predict the 3 year of survival compared to the TNM-based clinical model only (100% vs. 77%). Kaplan Meier estimates of overall survival in the validation datasets were dramatically discriminated according to the high- and low-risk groups predicted by our model (all P values =.01). Interestingly, this predictive classifier was specific to lung adenocarcinoma and has no predictive value in lung squamous datasets. Conclusion: We developed a robust and highly performing gene expression predictive signature of 3-year overall survival, specific to the lung adenocarcinoma setting. These promising results have the potential to change the decision making at bedside for early stage lung adenocarcinoma patients. Citation Format: Yann Gaston-Mathé, CHARLES FERTE, benoit gauthier, mathilde bateson, david planchard, benjamin besse, Jean-Pierre Armand, jean-charles soria. Gene expression profiling robustly predicts the outcome of patients diagnosed with early stage lung adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2357. doi:10.1158/1538-7445.AM2014-2357
FDG PET/CT Imaging of Oropharyngeal Squamous Cell Carcinoma
Authors: Abdel K. Tahari, Krishna C. Alluri, Harry Quon, Wayne Koch, Richard L. Wahl, Rathan M. Subramaniam
Journal: Clinical Nuclear Medicine (2013)

Objective The objective of this study was to assess differences in morphological and glycolytic characteristics of primary tumors and locoregional nodal disease between human papillomavirus (HPV)–positive and HPV-negative oropharyngeal head and neck squamous cell carcinoma. Methods This was a retrospective analysis of 123 baseline FDG PET/CT scans from patients (aged 57.0 ± 10.6 years) with newly diagnosed oropharyngeal SCC between January 2003 and June 2012. There were 98 HPV-positive and 25 HPV-negative patients. SUVmax, SUVpeak, and SUVmean based on lean body mass, as well as RECIST (Response Evaluation Criteria In Solid Tumors) dimensions, metabolic tumor volume (gradient and threshold-segmentation methods) and total lesion glycolysis, were determined for primary and locoregional nodal disease. Results Human papillomavirus–negative primary tumors were significantly larger as measured by RECIST longest diameter (P = 0.002) and slightly more heterogeneous as measured by the heterogeneity index (P = 0.07), higher SUVmax (P < 0.01), SUVpeak (P = 0.01), SUVmean (P = 0.01), metabolic tumor volume (P = 0.002), and total lesion glycolysis (P = 0.001), for both segmentation methods. Index parameters of HPV-positive nodal disease tend to be larger, but some with no statistical significance (P > 0.05). There was no significant difference in the metabolic parameters of primary tumor or nodal metastases for HPV-positive patients with and without smoking history. Conclusions Index morphologic and glycolytic parameters as measured in FDG PET/CT are significantly larger in HPV-negative as compared with HPV-positive primary oropharyngeal carcinoma. In contrast, the same parameters trended to be larger in HPV-positive regional nodal disease.
Comparative nasal effects of bradykinin and histamine: influence on nasal airways resistance and plasma protein exudation.
Authors: K Rajakulasingam, R Polosa, L C Lau, M K Church, S T Holgate, P H Howarth
Journal: Thorax (1993)

BACKGROUND--Bradykinin may contribute to the pathogenesis of allergic rhinitis. Like histamine, nasal challenge with bradykinin induces rhinorrhoea, nasal blockage, and plasma protein leakage. Their comparative nasal potencies have not, however, been fully elucidated. METHODS--Three double blind, randomised, placebo controlled and cross-over studies were undertaken to compare objectively the nasal effects of bradykinin, histamine, and vehicle. RESULTS--Both bradykinin and histamine produced dose dependent increases in nasal airways resistance (NAR). There was no significant difference in the effects of bradykinin and histamine on NAR at any dose level. On a molar basis, however, bradykinin was 6.98 times more potent than histamine in inducing a 50% increase in NAR. Nasal challenge with bradykinin and histamine also induced significant rhinorrhoea compared with vehicle. The amount of rhinorrhoea induced by histamine was significantly greater than that induced by bradykinin at any dose level. Bradykinin and histamine induced dose dependent nasal pain and nasal itch respectively. When administered as single doses both bradykinin (1.9 mumol) and histamine (1.9 mumol) induced significant rhinorrhoea compared with the vehicle. The volume of rhinorrhoea secretions induced by histamine was 29% greater than that induced by bradykinin. In contrast, although NAR was increased significantly more by histamine than by the vehicle, the effect of bradykinin on NAR was significantly greater than histamine and vehicle in both magnitude and duration of effect. The incremental effect of bradykinin on lavage albumin levels was also significantly greater than both histamine and vehicle. CONCLUSIONS--This study shows that the nasal vascular effects of histamine are less prominent than its actions on rhinorrhoea, and that the greater obstructive effect of bradykinin than histamine on NAR may contribute to the relative lack of efficacy of H1 antihistamines on nasal blockage in clinical disease.
GLOMERULAR FILTRATION RATE DETERMINED IN CONJUNCTION WITH ROUTINE RENAL SCAN
Authors: John H. Jackson, Peter W. Blue, Nasser Ghaed
Journal: Clinical Nuclear Medicine (1984)

A method has been developed to estimate glomerular filtration rate (GFR) by means of computer evaluation of information obtained during routine renal scanning with intravenous Tc-99m DTPA. Thirty minutes of data were accumulated as a 30 sec/frame dynamic study following injection, with kidneys and a portion of the heart included in the imaging field. From the computer acquired study, a plasma activity disappearance curve was generated using: (1) a region of interest outlining the imaged portion of the heart, and (2) a single blood sample obtained near the end of the study. Average plasma activity concentration during the study (PAVG) was then determined. Total urinary activity (TUA) generated from onset to conclusion of the study at time T, was determined using subsequent pre- and post-void bladder images, and measured volume and activity of the voided urine. Clearance was calculated using the formula: C1 (ml/min) = TUA DTPA (PAVG)(T) The urinary radionuclide clearance correlated highly with standard 24-hour creatinine clearance over a wide range of clearance values in thirteen patients. The method described to estimate GFR can be performed using less than 40 minutes of imaging time, requires only a single blood sample, does not require measurement of administered dose, is accurate even when the dose is partially or largely infiltrated, and unlike many popular indirect methods for estimating GFR adequately accounts for variations in volume of distribution.
The Src-family kinase, Fyn, regulates the activation of phosphatidylinositol 3-kinase in an interleukin 2-responsive T cell line.
Authors: L M Karnitz, S L Sutor, R T Abraham
Journal: The Journal of Experimental Medicine (1994)

The proliferation of antigen-activated T cells is mediated by the T cell-derived growth factor, interleukin 2 (IL-2). The biochemical signaling cascades initiating IL-2-induced growth are dependent upon protein tyrosine kinase (PTK) activity. One IL-2-regulated PTK implicated in this cascade is the Src-family kinase, Fyn. Previous studies have described a physical association between Fyn and a potential downstream substrate, phosphatidylinositol 3-kinase (PI3-kinase) as well as the IL-2-dependent activation of PI3-kinase in T cells; however, the role of Fyn in IL-2-induced PI3-kinase activation remains unclear. In this report, we demonstrate that IL-2 stimulation triggers tyrosine phosphorylation of the p85 subunit of PI3-kinase in the murine T cell line, CTLL-2. Lysates prepared from growth factor-deprived and IL-2-stimulated T cells reconstituted both the binding of CTLL-2 cell-derived Fyn to and the IL-2-inducible tyrosine phosphorylation of exogenously added recombinant p85. Furthermore, overexpression of wild-type Fyn in these cells enhanced both the basal and IL-2-mediated activation of PI3-kinase. Additional studies of the Fyn-PI3-kinase interaction demonstrated that the Src homology 3 (SH3) domain of Fyn constitutes a direct binding site for the p85 subunit of PI3-kinase. These results support the notion that Fyn may be directly involved in the activation of the downstream signaling enzyme, PI3-kinase, in IL-2-stimulated T cells.
Propylhexedrine chewing and psychosis.
Authors: J. Johnson, D. A. Johnson, A. J. Robins
Journal: BMJ (1972)

in-fertility, so it would be expected that a group of pregnant patients would have a lower incidence of positive tuberculin tests than non-pregnant controls.Even if the con- trols were accurately matched for age and parity it would be desirable to do tests in the same individuals in the pregnant and non-pregnant state.Montgomery and colleagues3 did this and found no influence of pregnancy.-Iam, etc.,