tbuckley/cabot-search huggingface dataset:
High Expression of Mammalian Target of Rapamycin Is Associated with Better Outcome for Patients with Early Stage Lung Adenocarcinoma
Authors: Valsamo K. Anagnostou, Gerold Bepler, Konstantinos N. Syrigos, Lynn Tanoue, Scott Gettinger, Robert J. Homer, Daniel Boffa, Frank Detterbeck, David L. Rimm
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Mammalian target of rapamycin (mTOR) is a key kinase downstream of phosphoinositide 3-kinase (PI3K)/AKT predominantly involved in translational control in the presence of nutrients and energy. Despite the well known role of mTOR in carcinogenesis, its prognostic potential in lung cancer has not been investigated. Here, we quantitatively assessed mTOR protein expression in two large data sets to investigate the impact of mTOR expression on patient survival. Experimental Design: Automated quantitative analysis (AQUA), a fluorescent-based method for analysis of in situ protein expression, was used to assess mTOR expression in a training cohort of 167 lung cancer patients. An independent cohort of 235 lung cancer patients (from a second institution) was used for validation. Results: Tumors expressed mTOR in the cytoplasm in 56% and 50% of the cases in training and validation cohorts, respectively; mTOR expression was not associated with standard clinical or pathologic characteristics. Patients with high mTOR expression had a longer median overall survival compared with the low expressers (52.7 versus 38.5 months; log rank P = 0.06), which was more prominent in the adenocarcinoma group (55.7 versus 38.88 months; log rank P = 0.018). Multivariate analysis revealed an independent lower risk of death for adenocarcinoma and adenocarcinoma stage IA patients with mTOR-expressing tumors (hazard ratio, 0.48; 95% confidence interval, 0.24-0.98; P = 0.04, and hazard ratio, 0.12; 95% confidence interval, 0.03-0.72; P = 0.019, respectively). Conclusions: mTOR expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of lung adenocarcinoma patients as well as incorporation of mTOR into clinical decisions.
Use of antibiotics. Cephalosporins.
Authors: R Wise
Journal: BMJ (1978)

The availability of six cephalosporins, all with somewhat similar properties (not to mention names), is confusing to the clinician who is attempting to choose the best antibiotic for his patient, as well as for the bacteriologist who is trying to report the susceptibility of a particular organism to these drugs.The position is likely to become even more confusing as three or four more may be marketed in the near future.I will discuss the general properties of this group of drugs and then comment on the individual preparations.The marketed antibiotics are cephaloridine (Ceporin), cephalothin (Keflin), cephalexin (Ceporex and Keflex), cephradine (Velosef and Eskacef), cephazolin (Kefzol), and cefuroxime (Zinacef).Cefamandole (Kefadol), cefoxitin (Mefoxin), and cefaclor should appear soon. Antibacterial propertiesWith the exception of cefoxitin, the cephalosporins are semi- synthetic derivatives of cephalosporin C, an antibiotic sub- stance obtained from the Cephalosporium mould.Cefoxitin is more correctly a cephamycin rather than a cephalosporin as it is derived from the Streptomyces species.The structural difference between these two groups of compounds is that there is a methoxy group at the 7-position (fig 1) in the cephamycins.
Inducible and Reversible Gene Expression with the rtTA System for the Study of Memory
Authors: Isabelle M Mansuy, Danny G Winder, Theodore M Moallem, Mona Osman, Mark Mayford, Robert D Hawkins, Eric R Kandel
Journal: Neuron (1998)

To obtain rapidly inducible and reversible expression of transgenes in the forebrain of the mouse, we have combined the reverse tetracycline-controlled transactivator (rtTA) system with the CaMKIIalpha promoter. We show that doxycycline induces maximal gene expression in neurons of the forebrain within 6 days and that this expression can be reversed by removal of doxycycline. Using calcineurin as a test transgene, we show that doxycycline-induced expression impairs both an intermediate form of LTP (I-LTP) in the hippocampus and the storage of spatial memory. The reversibility of the rtTA system in turn allowed us to examine the effects of the transgene on memory retrieval after normal storage had occurred. This examination suggests that retrieval requires some of the same molecular components required for storage.
Accident Surgery. Vol 2
Authors: Allan J. Ryan
Journal: JAMA (1964)

This volume comprises all of the lectures delivered at the Second Postgraduate Course on Emergency and Accident Trauma, the first having been held in 1961 and already published, the third, held in 1963, yet to be published. The lecturers included 24 physicians, chiefly members of the faculty of McGill University but also W. L. Estes, Jr., H. L. McLaughlin, J. I. Tuell, and P. A. Wade from the United States, and J. C. Scott from England. The subjects covered range from the organization of accident services, use of a resuscitation room and blood bank, through automobile accidents and their prevention, to the specific emergency and definitive management of specific injuries to various organ systems of the body. Emphasis in each of the 31 presentations is on identification and classification of injuries, principles of emergency management, and, in some cases, detailed procedures for definitive management. All are clear and exceedingly practical.
Impact of Xpert MTB/RIF for TB Diagnosis in a Primary Care Clinic with High TB and HIV Prevalence in South Africa: A Pragmatic Randomised Trial
Authors: Helen S. Cox, Slindile Mbhele, Neisha Mohess, Andrew Whitelaw, Odelia Muller, Widaad Zemanay, Francesca Little, Virginia Azevedo, John Simpson, Catharina C. Boehme, Mark P. Nicol
Journal: PLoS Medicine (2014)

Helen Cox and colleagues investigate the impact Xpert MTB/RIF for diagnosing patients with presumptive tuberculosis in a large primary care clinic in Khayelitsha, Cape Town. Please see later in the article for the Editors' Summary
The Kinase PKCα Selectively Upregulates Interleukin-17A during Th17 Cell Immune Responses
Authors: Marlies Meisel, Natascha Hermann-Kleiter, Reinhard Hinterleitner, Thomas Gruber, Katarzyna Wachowicz, Christa Pfeifhofer-Obermair, Friedrich Fresser, Michael Leitges, Cristiana Soldani, Antonella Viola, Sandra Kaminski, Gottfried Baier
Journal: Immunity (2013)

Transforming growth-factor β (TGFβ) has been implicated in T helper 17 (Th17) cell biology and in triggering expression of interleukin-17A (IL-17A), which is a key Th17 cell cytokine. Deregulated TGFβ receptor (TGFβR) signaling has been implicated in Th17-cell-mediated autoimmune pathogenesis. Nevertheless, the full molecular mechanisms involved in the activation of the TGFβR pathway in driving IL-17A expression remain unknown. Here, we identified protein kinase C α (PKCα) as a signaling intermediate specific to the Th17 cell subset in the activation of TGFβRI. We have shown that PKCα physically interacts and functionally cooperates with TGFβRI to promote robust SMAD2-3 activation. Furthermore, PKCα-deficient (Prkca(-/-)) cells demonstrated a defect in SMAD-dependent IL-2 suppression, as well as decreased STAT3 DNA binding within the Il17a promoter. Consistently, Prkca(-/-) cells failed to mount appropriate IL-17A, but not IL-17F, responses in vitro and were resistant to induction of Th17-cell-dependent experimental autoimmune encephalomyelitis in vivo.
Vitality and Aging: Implications of the Rectangular Curve
Authors: ISADORE ROSSMAN
Journal: JAMA (1982)

It is becoming increasingly clear that some of the most important problems that society and the medical profession will face will concern repercussions of aging. Among the alleged consequences are doom and gloom scenarios, in one of which an increasingly old, dependent group will progressively constrict the standard of living of a younger, working population. In another, general hospitals will become geriatric hospitals, referring an increasingly large proportion of patients to satellite nursing homes. Fries and Crapo have considered the various implications and projections of aging in this highly readable monograph. After reviewing various concepts related to prolongation of the human life span, they conclude that it is probably fixed, and as are the life spans of all other species, a biologic given. The best that can be expected (and we are already well embarked on this course) is the attainment by all persons of the maximum life span. It
Edward Nigel Armitage
Authors: C S B Child
Journal: BMJ (2009)

Edward Nigel Armitage was born in Huddersfield in 1935. His education at Oundle was mainly in classics, and he did not start science subjects until he was 15. His career in anaesthesia was perhaps predestined by the motto on the Armitage family crest: “Semper paratus” (always prepared)!

He qualified from University College Hospital, London, in 1960 and undertook his first anaesthetic post there, developing an early interest in regional anaesthesia and analgesia, mentored by the late Massey Dawkins. He then went to Great Ormond Street as a registrar and recognised the need for what was to become perhaps his major interest, regional anaesthesia in children, which was used hardly at all at that time in the United Kingdom.

Next, he went to work with the late John Bonica in Seattle. There, almost every patient received a regional block, and this experience cemented his combined interest in regional and paediatric anaesthesia. On returning to the UK he went to Brighton, initially as a senior registrar, and was appointed consultant paediatric anaesthetist in 1973. Using conscientious clinical observation he developed his now well known formula for the volume of local anaesthetic required for …
The Technique of Adeno-Tonsillectomy
Authors: J. C. G. MacNab
Journal: BMJ (1926)

IN thio surlgery of the digestive tract post-operative treat- nlenit is of great impolrtanice throughout the first week.A patienit who has suffered for months from malnutrition due to ulceration or gall stones comes to operation in a cachlectic and emiiaciated condition, the operation perhaps made urgenliy niecessary by perforation or pain.Suclh a patienit, lackillg reserves, is unable to stand the semi- star'vationl whichll follows, anid may die withiin three or' four days fromll thirst or stairvation.Tule stomach will not retain enoughl fluid.The rectum returnis it.Blood tranis- fusioni and initravenious infusions of various kinds are useful for the monieiit, but their effect is transitory.Jejunostomy jeopardizes a most vulnerable and impor- tant l)art of the gut,-alnd appendicostomy has hithelto entailed a gridiron or other secondary incision.I wish now to describe a method by which appendicostomny may be performed in a few seconds at the close of aniy or-dinlairy abdominal operation by mealns of a stab incision.Afcthod.
Inotropic and toxic effects of a polar cardiac glycoside derivative in the dog.
Authors: G H Mudge, B L Lloyd, D J Greenblatt, T W Smith
Journal: Circulation Research (1978)

It has been suggested that central nervous system (CNS) neuroexcitation plays an important role in digitalis-induced cardiac arrhythmias. To elucidate further the role of the CNS in digitalis-induced arrhythmias, the inotropic and toxic effects of a highly polar semisynthetic cardiac glycoside, 3beta-O-(4 amino-4,6 dideoxy-beta-D-galactopyranosyl)-digitoxigenin (ASI-222) were compared to those of digoxin and correlated with plasma and cerebrospinal fluid (CSF) concentrations of each drug. Thirteen dogs anesthetized with sodium pentobarbital were given repeated intravenous doses of digoxin or ASI-222. Ventricular tachycardia was elicited at a mean dose of digoxin of 0.12 mg/kg, compared with 0.09 mg/kg for ASI-222 (not significant). Terminal ventricular fibrillation occurred after 0.18 mg/kg of digoxin, a value significantly larger than the ASI-222 dose (0.14 mg/kg, P less than 0.05) required to produce lethal arrhythmias. Digoxin produced a 21% increase in LV dP/dt at a plasma digoxin concentration of 20.0 +/- 2 ng/ml (mean +/- SEM) 30 minutes after 0.05 mg/kg; the CSF digoxin concentration at this time averaged 0.7 +/- 0.1 ng/ml. At death, the plasma digoxin concentration was 88 +/- 16 ng/ml and CSF digoxin concentration was 5.7 +/- 1.6 ng/ml. ASI-222 produced a similar 25% increase in LV dP/dt 30 minutes after administration of 0.05 mg/kg, with a plasma concentration of 18 +/- 2 ng/ml as determined by a newly developed radioimmunoassay. The plasma ASI-222 concentration at death, 95 +/- 18 ng/ml, was similar to that of digoxin. However, CSF samples at 30 minutes and at death showed no detectable levels of ASI-222. Thus, despite similar inotropic and toxic responses and similar plasma drug concentrations compared to digoxin, ASI-222 was demonstrated to have limited if any access to the CNS as judged by CSF concentrations. These findings suggest that direct CNS stimulation does not play a primary part in the genesis of digitalis-induced cardiac arrhythmias in this experimental model, or that CNS effects are mediated by an area or areas lacking an effective blood-brain barrier.
Mouse H-2k-restricted cytotoxic T cells recognize antigenic determinants in both the HA1 and HA2 subunits of the influenza A/PR/8/34 hemagglutinin.
Authors: K G Gould, H Scotney, A R Townsend, J Bastin, G G Brownlee
Journal: The Journal of Experimental Medicine (1987)

We have constructed two chimeric influenza hemagglutinin (HA) genes in which the HA1 and HA2 subunits of the HA molecule have been interchanged between influenza A/PR/8/34 (H1 subtype) and A/NT/60/68 (H3 subtype). These genes were used to construct recombinant vaccinia viruses that expressed intact chimeric HA. These recombinant viruses were used to test whether murine CTL recognize antigenic determinants in either the HA1, HA2, or both subunits. We found that both subunits of the HA molecule contain determinants for CTL. This implies that CTL have, at least in part, separate antigenic determinants from B lymphocytes, which recognize mainly epitopes within the HA1 subunit.
The Financially Distressed Hospital
Authors: Jack Hadley, Ross Mullner, Judith Feder
Journal: New England Journal of Medicine (1982)

For at least a decade policy makers have been trying to contain health-care costs while maintaining access to care. The "financially distressed" hospital epitomizes the conflict between costs and access that makes this task so difficult. Financial distress or deficits can result from inefficiency and underuse — the very targets of regulatory or competitive strategies to contain costs. Hospitals' deficits in these circumstances need not be a cause for public distress. On the contrary, they may be evidence of the success of policy or the working of the market.On the other hand, deficits can result from the hospital's serving . . .
Increased prostaglandin E<sub>2</sub> levels in the airway of patients with eosinophilic bronchitis
Authors: B. Sastre, M. Fernández‐Nieto, R. Mollá, E. López, C. Lahoz, J. Sastre, V. Del Pozo, S. Quirce
Journal: Allergy (2007)

Eosinophilic bronchitis is a common cause of chronic cough, which like asthma is characterized by sputum eosinophilia, but unlike asthma there is no variable airflow obstruction or airway hyperresponsiveness. We tested the hypothesis that the different airway function in patients with eosinophilic bronchitis and asthma could be caused by an imbalance in the production of bronchoconstrictor (LTC(4)) and bronchoprotective (prostaglandin E(2); PGE(2)) lipid mediators.We measured cytokines levels, proinflammatory mediators and eicosanoids concentration in sputum from 13 subjects with nonasthmatic eosinophilic bronchitis, 13 subjects with asthma, and 11 healthy control subjects. Cytokines mRNA levels were measured by real time PCR, proinflammatory mediators, PGE(2), and LTC(4) were measured by enzyme immunoassays.The median sputum eosinophil count was not statistically different in patients with asthma (7.95%) and eosinophilic bronchitis (15.29%). The levels of mRNA specific to interleukin-5 (IL-5), IL-4, IL-10, IL-13, interferon gamma (IFN-gamma), IL-2, vascular endothelial growth factor and transforming growth factor beta were similar in both conditions. In addition, no differences were found between asthma and eosinophilic bronchitis in proinflammatory cytokines, such as IL-8, IFN-gamma and tumor necrosis factor alpha (TNF-alpha) levels. Sputum cysteinyl-leukotrienes concentration was raised both in eosinophilic bronchitis and asthma patients. We found that induced sputum PGE(2) concentrations were significantly increased in subjects with eosinophilic bronchitis (838.3 +/- 612 pg/ml) when compared with asthmatic (7.54 +/- 2.14 pg/ml) and healthy subjects (4 +/- 1.3 pg/ml).This data suggest that the difference in airway function observed in subjects with eosinophilic bronchitis and asthma could be due to differences in PGE(2) production in the airways.
Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: Validating the European Liver Fibrosis Panel and exploring simple markers
Authors: Indra Neil Guha, Julie Parkes, Paul Roderick, Dipanker Chattopadhyay, Richard Cross, Scott Harris, Philip Kaye, Alastair D. Burt, Steve D. Ryder, Guruprasad P. Aithal, Christopher P. Day, William M. Rosenberg
Journal: Hepatology (2007)

The detection of fibrosis within nonalcoholic fatty liver disease (NAFLD) is important for ascertaining prognosis and the stratification of patients for emerging therapeutic intervention. We validated the Original European Liver Fibrosis panel (OELF) and a simplified algorithm not containing age, the Enhanced Liver fibrosis panel (ELF), in an independent cohort of patients with NAFLD. Furthermore, we explored whether the addition of simple markers to the existing panel test could improve diagnostic performance. One hundred ninety-six consecutively recruited patients from 2 centers were included in the validation study. The diagnostic accuracy of the discriminant scores of the ELF panel, simple markers, and a combined panel were compared using receiver operator curves, predictive values, and a clinical utility model. The ELF panel had an area under the curve (AUC) of 0.90 for distinguishing severe fibrosis, 0.82 for moderate fibrosis, and 0.76 for no fibrosis. Simplification of the algorithm by removing age did not alter diagnostic performance. Addition of simple markers to the panel improved diagnostic performance with AUCs of 0.98, 0.93, and 0.84 for the detection of severe fibrosis, moderate fibrosis, and no fibrosis, respectively. The clinical utility model showed that 82% and 88% of liver biopsies could be potentially avoided for the diagnosis of severe fibrosis using ELF and the combined panel, respectively. The ELF panel has good diagnostic accuracy in an independent validation cohort of patients with NAFLD. The addition of established simple markers augments the diagnostic performance across different stages of fibrosis, which will potentially allow superior stratification of patients with NAFLD for emerging therapeutic strategies. (HEPATOLOGY 2007.)
Association between the<i>PNPLA3</i>(rs738409 C&gt;G) variant and hepatocellular carcinoma: Evidence from a meta-analysis of individual participant data
Authors: Eric Trépo, Pierre Nahon, Gianluca Bontempi, Luca Valenti, Edmondo Falleti, Hans-Dieter Nischalke, Samia Hamza, Stefano Ginanni Corradini, Maria Antonella Burza, Erwan Guyot, Benedetta Donati, Ulrich Spengler, Patrick Hillon, Pierluigi Toniutto, Jean Henrion, Denis Franchimont, Jacques Devière, Philippe Mathurin, Christophe Moreno, Stefano Romeo, Pierre Deltenre
Journal: Hepatology (2013)

The incidence of hepatocellular carcinoma (HCC) is increasing in Western countries. Although several clinical factors have been identified, many individuals never develop HCC, suggesting a genetic susceptibility. However, to date, only a few single-nucleotide polymorphisms have been reproducibly shown to be linked to HCC onset. A variant (rs738409 C>G, encoding for p.I148M) in the PNPLA3 gene is associated with liver damage in chronic liver diseases. Interestingly, several studies have reported that the minor rs738409[G] allele is more represented in HCC cases in chronic hepatitis C (CHC) and alcoholic liver disease (ALD). However, a significant association with HCC related to CHC has not been consistently observed, and the strength of the association between rs738409 and HCC remains unclear. We performed a meta-analysis of individual participant data including 2,503 European patients with cirrhosis to assess the association between rs738409 and HCC, particularly in ALD and CHC. We found that rs738409 was strongly associated with overall HCC (odds ratio [OR] per G allele, additive model=1.77; 95% confidence interval [CI]: 1.42-2.19; P=2.78 × 10(-7) ). This association was more pronounced in ALD (OR=2.20; 95% CI: 1.80-2.67; P=4.71 × 10(-15) ) than in CHC patients (OR=1.55; 95% CI: 1.03-2.34; P=3.52 × 10(-2) ). After adjustment for age, sex, and body mass index, the variant remained strongly associated with HCC. Overall, these results suggest that rs738409 exerts a marked influence on hepatocarcinogenesis in patients with cirrhosis of European descent and provide a strong argument for performing further mechanistic studies to better understand the role of PNPLA3 in HCC development.
A subset of t(11;14) lymphoma with mantle cell features displays mutated IgVH genes and includes patients with good prognosis, nonnodal disease
Authors: Jenny Orchard, Richard Garand, Zadie Davis, Gavin Babbage, Surinder Sahota, Estella Matutes, Daniel Catovsky, Peter W. Thomas, Hervé Avet-Loiseau, David Oscier
Journal: Blood (2003)
Bronchiectasis following colectomy for Crohn's disease
Authors: T E Eaton, N Lambie, A U Wells
Journal: Thorax (1998)

Bronchiectasis developing following colectomy for ulcerative colitis has been reported in a few cases. This may be the first report of bronchiectasis developing after colectomy for Crohn’s disease. The close temporal relationship to colectomy, lack of bacterial pathogens in the sputum, and an impressive response to oral steroids suggest a difference in pathogenesis from idiopathic bronchiectasis.
De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot
Authors: Steven C Greenway, Alexandre C Pereira, Jennifer C Lin, Steven R DePalma, Samuel J Israel, Sonia M Mesquita, Emel Ergul, Jessie H Conta, Joshua M Korn, Steven A McCarroll, Joshua M Gorham, Stacey Gabriel, David M Altshuler, Maria de Lourdes Quintanilla-Dieck, Maria Alexandra Artunduaga, Roland D Eavey, Robert M Plenge, Nancy A Shadick, Michael E Weinblatt, Philip L De Jager, David A Hafler, Roger E Breitbart, Jonathan G Seidman, Christine E Seidman
Journal: Nature Genetics (2009)
Reply to ‘Aberrant cytoplasmic expression of C-terminal truncated NPM leukaemic mutant is dictated by tryptophans loss and a new NES motif’ by Falini et al.
Authors: A S Pitiot, I Santamaría, O García-Suárez, I Centeno, A Astudillo, C Rayón, M Balbín
Journal: Leukemia (2007)