tbuckley/cabot-search huggingface dataset:
THE NATURE OF THE SUBSTANCE CAUSING THE COLLOIDAL GOLD REACTION
Authors: PAUL G. WESTON
Journal: American Journal of Psychiatry (1920)

The colloidal gold precipitating substance in the spinal fluid of paretics is a globulin. It is not the Wassermann reacting substance and can be separated from the latter quantitatively. This explains why one may have a paretic curve in the gold test with either a positive or negative Wassermann reaction.
Phase I Pharmacokinetic and Pharmacodynamic Study of the Oral Mammalian Target of Rapamycin Inhibitor Everolimus in Patients With Advanced Solid Tumors
Authors: Anne O'Donnell, Sandrine Faivre, Howard A. Burris, Daniel Rea, Vassiliki Papadimitrakopoulou, Nicholas Shand, Heidi A. Lane, Katharine Hazell, Ulrike Zoellner, John M. Kovarik, Cathryn Brock, Suzanne Jones, Eric Raymond, Ian Judson
Journal: Journal of Clinical Oncology (2008)

To identify the optimal regimen and dosage of the oral mammalian target of rapamycin inhibitor everolimus (RAD001).We performed a dose-escalation study in advanced cancer patients administering oral everolimus 5 to 30 mg/wk, with pharmacokinetic (PK) and pharmacodynamic (PD) studies. PD data prompted investigation of 50 and 70 mg weekly and daily dosing at 5 and 10 mg.Ninety-two patients were treated. Dose-limiting toxicity was seen in one patient each at 50 mg/wk (stomatitis and fatigue) and 10 mg/d (hyperglycemia); hence, the maximum-tolerated dose was not reached. S6 kinase 1 activity in peripheral-blood mononuclear cells was inhibited for at least 7 days at doses >or= 20 mg/wk. Area under the curve increased proportional to dose, but maximum serum concentration increased less than proportionally at doses >or= 20 mg/wk. Terminal half-life was 30 hours (range, 26 to 38 hours). Partial responses were observed in four patients, and 12 patients remained progression free for >or= 6 months, including five of 10 patients with renal cell carcinoma.Everolimus was satisfactorily tolerated at dosages up to 70 mg/wk and 10 mg/d with predictable PK. Antitumor activity and PD in tumors require further clinical investigation. Doses of 20 mg/wk and 5 mg/d are recommended as appropriate starting doses for these studies.
The bovine lactation genome: insights into the evolution of mammalian milk
Authors: Danielle G Lemay, David J Lynn, William F Martin, Margaret C Neville, Theresa M Casey, Gonzalo Rincon, Evgenia V Kriventseva, Wesley C Barris, Angie S Hinrichs, Adrian J Molenaar, Katherine S Pollard, Nauman J Maqbool, Kuljeet Singh, Regan Murney, Evgeny M Zdobnov, Ross L Tellam, Juan F Medrano, J Bruce German, Monique Rijnkels
Journal: Genome biology (2009)

The newly assembled Bos taurus genome sequence enables the linkage of bovine milk and lactation data with other mammalian genomes.Using publicly available milk proteome data and mammary expressed sequence tags, 197 milk protein genes and over 6,000 mammary genes were identified in the bovine genome. Intersection of these genes with 238 milk production quantitative trait loci curated from the literature decreased the search space for milk trait effectors by more than an order of magnitude. Genome location analysis revealed a tendency for milk protein genes to be clustered with other mammary genes. Using the genomes of a monotreme (platypus), a marsupial (opossum), and five placental mammals (bovine, human, dog, mice, rat), gene loss and duplication, phylogeny, sequence conservation, and evolution were examined. Compared with other genes in the bovine genome, milk and mammary genes are: more likely to be present in all mammals; more likely to be duplicated in therians; more highly conserved across Mammalia; and evolving more slowly along the bovine lineage. The most divergent proteins in milk were associated with nutritional and immunological components of milk, whereas highly conserved proteins were associated with secretory processes.Although both copy number and sequence variation contribute to the diversity of milk protein composition across species, our results suggest that this diversity is primarily due to other mechanisms. Our findings support the essentiality of milk to the survival of mammalian neonates and the establishment of milk secretory mechanisms more than 160 million years ago.
Serotonin Antagonists: A New Class of Antiemetic Agents
Authors: P. J. Hesketh, D. R. Gandara
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Serotonin Antagonists: A New Class of Antiemetic Agents Get access Paul J. Hesketh, Paul J. Hesketh * Section of Medical Oncology, Evans Memorial Department of Clinical Research, and Department of Medicine, Boston University Medical CenterBoston, Mass *Correspondenee to: Paul J. Hesketh, MD, Section of Medical Oncology, The University Hospital, 88 E Newton St, Boston, MA 02118 Search for other works by this author on: Oxford Academic PubMed Google Scholar David R. Gandara David R. Gandara Division of Hematology/Oncology, University of California, Davis, and Veterans Administration Medical CenterMartinez, Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 9, 1 May 1991, Pages 613–620, https://doi.org/10.1093/jnci/83.9.613 Published: 01 May 1991 Article history Received: 09 August 1990 Revision received: 06 February 1991 Accepted: 21 February 1991 Published: 01 May 1991
Jaundice and rectal bleeding in a young man
Authors: J. He, L. Yu, S. Zhang
Journal: Gut (2010)

A 21-year-old man was referred with haematochezia for 1 month and scleral icterus for 4 days. His history was unremarkable except chronic anaemia. Physical examination showed scleral icterus, pale conjunctivas, and melanosis on his lips, buccal mucosa and fingers (figure 1). Blood test revealed decreased haemoglobin 7.7 g/dl (normal, 12–16) and elevated white cell count 14.1×103/μl (4–10×103). Liver function …
Adrenal Hyperplasia and Adenomas Are Associated with Inhibition of Phosphodiesterase 11A in Carriers of <i>PDE11A</i> Sequence Variants That Are Frequent in the Population
Authors: Anelia Horvath, Christoforos Giatzakis, Audrey Robinson-White, Sosipatros Boikos, Elizabeth Levine, Kurt Griffin, Erica Stein, Virginia Kamvissi, Payal Soni, Ioannis Bossis, Wouter de Herder, J. Aidan Carney, Jérôme Bertherat, Peter K. Gregersen, Elaine F. Remmers, Constantine A. Stratakis
Journal: Cancer Research (2006)

Abstract Several types of adrenocortical tumors that lead to Cushing syndrome may be caused by aberrant cyclic AMP (cAMP) signaling. We recently identified patients with micronodular adrenocortical hyperplasia who were carriers of inactivating mutations in the 2q-located phosphodiesterase 11A (PDE11A) gene. We now studied the frequency of two missense substitutions, R804H and R867G, in conserved regions of the enzyme in several sets of normal controls, including 745 individuals enrolled in a longitudinal cohort study, the New York Cancer Project. In the latter, we also screened for the presence of the previously identified PDE11A nonsense mutations. R804H and R867G were frequent among patients with adrenocortical tumors; although statistical significance was not reached, these variants affected significantly enzymatic function in vitro with variable increases in cAMP and/or cyclic guanosine 3′,5′-monophosphate levels in HeLa and HEK293 cells. Adrenocortical tissues carrying the R804H mutation showed 2q allelic losses and higher cyclic nucleotide levels and cAMP-responsive element binding protein phosphorylation. We conclude that missense mutations of the PDE11A gene that affect enzymatic activity in vitro are present in the general population; protein-truncating PDE11A mutations may also contribute to a predisposition to other tumors, in addition to their association with adrenocortical hyperplasia. We speculate that PDE11A genetic defects may be associated with adrenal pathology in a wider than previously suspected clinical spectrum that includes asymptomatic individuals. (Cancer Res 2006; 66(24): 11571-5)
Impact of Community-Wide Police Car Deployment of Automated External Defibrillators on Survival From Out-of-Hospital Cardiac Arrest
Authors: Robert J. Myerburg, Jeffrey Fenster, Mauricio Velez, Donald Rosenberg, Shenghan Lai, Paul Kurlansky, Starbuck Newton, Melenda Knox, Agustin Castellanos
Journal: Circulation (2002)

Background— Disappointing survival rates from out-of-hospital cardiac arrests encourage strategies for faster defibrillation, such as use of automated external defibrillators (AEDs) by nonconventional responders. Methods and Results— AEDs were provided to all Miami-Dade County, Florida, police. AED-equipped police (P-AED) and conventional emergency medical rescue (EMS) responders are simultaneously deployed to possible cardiac arrests. Times from 9-1-1 contact to the scene were compared for P-AED and concurrently deployed EMS, and both were compared with historical EMS experience. Survival with P-AED was compared with outcomes when EMS was the sole responder. Among 420 paired dispatches of P-AED and EMS, the mean±SD P-AED time from 9-1-1 call to arrival at the scene was 6.16±4.27 minutes, compared with 7.56±3.60 minutes for EMS ( P &lt;0.001). Police arrived first to 56% of the calls. The time to first responder arrival among P-AED and EMS was 4.88±2.88 minutes ( P &lt;0.001), compared with a historical response time of 7.64±3.66 minutes when EMS was the sole responder. A 17.2% survival rate was observed for victims with ventricular fibrillation or pulseless ventricular tachycardia (VT/VF), compared with 9.0% for standard EMS before P-AED implementation ( P =0.047). However, VT/VF benefit was diluted by the observation that 61% of the initial rhythms were nonshockable, reducing the absolute survival benefit among the total study population to 1.6% (P-AED, 7.6%; EMS, 6.0%). Conclusions— P-AED establishes a layer of responders that generate improved response times and survival from VT/VF. There was no benefit for victims with nonshockable rhythms.
A 2-Hour Diagnostic Protocol for Possible Cardiac Chest Pain in the Emergency Department
Authors: Martin Than, Sally Aldous, Sarah Jane Lord, Stephen Goodacre, Christopher M. A. Frampton, Richard Troughton, Peter George, Christopher Michael Florkowski, Michael Ardagh, David Smyth, David Lewis Jardine, William Frank Peacock, Joanna Young, Gregory Hamilton, Joanne M. Deely, Louise Cullen, A. Mark Richards
Journal: JAMA Internal Medicine (2013)

Patients with chest pain represent a high health care burden, but it may be possible to identify a patient group with a low short-term risk of adverse cardiac events who are suitable for early discharge.To compare the effectiveness of a rapid diagnostic pathway with a standard-care diagnostic pathway for the assessment of patients with possible cardiac chest pain in a usual clinical practice setting.A single-center, randomized parallel-group trial with blinded outcome assessments was conducted in an academic general and tertiary hospital. Participants included adults with acute chest pain consistent with acute coronary syndrome for whom the attending physician planned further observation and troponin testing. Patient recruitment occurred from October 11, 2010, to July 4, 2012, with a 30-day follow-up.An experimental pathway using an accelerated diagnostic protocol (Thrombolysis in Myocardial Infarction score, 0; electrocardiography; and 0- and 2-hour troponin tests) or a standard-care pathway (troponin test on arrival at hospital, prolonged observation, and a second troponin test 6-12 hours after onset of pain) serving as the control.Discharge from the hospital within 6 hours without a major adverse cardiac event occurring within 30 days.Fifty-two of 270 patients in the experimental group were successfully discharged within 6 hours compared with 30 of 272 patients in the control group (19.3% vs 11.0%; odds ratio, 1.92; 95% CI, 1.18-3.13; P = .008). It required 20 hours to discharge the same proportion of patients from the control group as achieved in the experimental group within 6 hours. In the experimental group, 35 additional patients (12.9%) were classified as low risk but admitted to an inpatient ward for cardiac investigation. None of the 35 patients received a diagnosis of acute coronary syndrome after inpatient evaluation.Using the accelerated diagnostic protocol in the experimental pathway almost doubled the proportion of patients with chest pain discharged early. Clinicians could discharge approximately 1 of 5 patients with chest pain to outpatient follow-up monitoring in less than 6 hours. This diagnostic strategy could be easily replicated in other centers because no extra resources are required.anzctr.org.au Identifier: ACTRN12610000766011.
Peritonitis Causes Diaphragm Weakness in Rats
Authors: KEVIN M. KRAUSE, MELANIE R. MOODY, FRANCISCO H. ANDRADE, ADDISON A. TAYLOR, CHARLES C. MILLER, LESTER KOBZIK, MICHAEL B. REID
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Section:ChooseTop of pageAbstract <<METHODSRESULTSDISCUSSIONCONCLUSIONReferencesCITING ARTICLES
Detection of Tumor DNA at the Margins of Colorectal Cancer Liver Metastasis
Authors: Matthias Holdhoff, Kerstin Schmidt, Frank Diehl, Nishant Aggrawal, Philipp Angenendt, Katharine Romans, Daniel L. Edelstein, Michael Torbenson, Kenneth W. Kinzler, Bert Vogelstein, Michael A. Choti, Luis A. Diaz
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Defining an adequate resection margin of colorectal cancer liver metastases is essential for optimizing surgical technique. We have attempted to evaluate the resection margin through a combination of histopathologic and genetic analyses. Experimental Design: We evaluated 88 samples of tumor margins from 12 patients with metastatic colon cancer who each underwent partial hepatectomy of one to six liver metastases. Punch biopsies of surrounding liver tissue were obtained at 4, 8, 12, and 16 mm from the tumor border. DNA from these biopsies was analyzed by a sensitive PCR-based technique, called BEAMing, for mutations of KRAS, PIK3CA, APC, or TP53 identified in the corresponding tumor. Results: Mutations were identified in each patient's resected tumor and used to analyze the 88 samples circumscribing the tumor-normal border. Tumor-specific mutant DNA was detectable in surrounding liver tissue in 5 of these 88 samples, all within 4 mm of the tumor border. Biopsies that were 8, 12, and 16 mm from the macroscopic visible margin were devoid of detectable mutant tumor DNA and of microscopically visible cancer cells. Tumors with a significant radiologic response to chemotherapy were not associated with any increase in mutant tumor DNA in beyond 4 mm of the main tumor. Conclusions: Mutant tumor-specific DNA can be detected beyond the visible tumor margin, but never beyond 4 mm, even in patients whose tumors were larger prior to chemotherapy. These data provide a rational basis for determining the extent of surgical excision required in patients undergoing resection of liver metastases. Clin Cancer Res; 17(11); 3551–7. ©2011 AACR.
Targeting neuropilin-1 in human leukemia and lymphoma
Authors: Katja Karjalainen, Diana E. Jaalouk, Carlos E. Bueso-Ramos, Amado J. Zurita, Akihiko Kuniyasu, Bedrich L. Eckhardt, Frank C. Marini, Benjamin Lichtiger, Susan O'Brien, Hagop M. Kantarjian, Jorge E. Cortes, Erkki Koivunen, Wadih Arap, Renata Pasqualini
Journal: Blood (2010)
Would they dope? Revisiting the Goldman dilemma
Authors: James Connor, Jules Woolf, Jason Mazanov
Journal: British Journal of Sports Medicine (2013)

Background/aim Discussions of doping often report Goldman's sensational results that half of the elite athletes asked would take a drug that guaranteed sporting success which would also result in their death in 5 years’ time. There has never been any effort to assess the properties of the ‘Goldman dilemma’ or replicate the results in the post World Anti-Doping Agency context. This research evaluated the dilemma with contemporary elite athletes. Methods Participants at an elite-level track and field meet in North America were segregated into an interview or online response. After basic demographics, participants were presented with three variant ‘Goldman’ dilemmas counter-balanced for presentation order. Results Only 2 out of 212 samples (119 men, 93 women, mean age 20.89) reported that they would take the Faustian bargain offered by the original Goldman dilemma. However, if there were no consequences to the (illegal) drug use, then 25/212 indicated that they would take the substance (no death condition). Legality also changes the acceptance rate to 13/212 even with death as a consequence. Regression modelling showed that no other variable was significant (gender, competitive level, type of sport) and there was no statistical difference between the interview and online collection method. Conclusions Goldman's results do not match our sample. A subset of athletes is willing to dope and another subset is willing to sacrifice their life to achieve success, although to a much lesser degree than that observed by Goldman. A larger scale online survey is now viable to answer important questions such as variation across sports.
Distinctive selection mechanisms govern the T cell receptor repertoire of peripheral CD4-CD8- alpha/beta T cells.
Authors: L Huang, I N Crispe
Journal: The Journal of Experimental Medicine (1992)

The T cell receptor (TCR) repertoire of CD4+ and CD8+ alpha/beta T cells is heavily influenced by positive and negative selection events that occur during T cell development in the thymus. The coreceptors CD4 and CD8 appear to be essential for this selection to occur. To gain insight into whether T cells that express TCR alpha/beta but lack either coreceptor (CD4- CD8- TCR alpha/beta or alpha/beta double-negative [DN] cells) are also subject to positive and negative selection, and whether selection can occur in the absence of coreceptors, we have performed an extensive immunogenetic analysis of the TCR V beta repertoire of alpha/beta DN cells in lymph nodes of normal mice. Our results show that alpha/beta DN cells appear to be unaffected by clonal deletion of V beta 5 and V beta 11 in I-E-expressing mice, and do not undergo deletion of V beta 6- and V beta 8.1-expressing T cells in Mls-1a-positive mice. They are also unaffected by positive selection of V beta 17a+ T cells in the context of I-Aq. The results suggest that most selection events require the participation of CD4 and CD8, while alpha/beta DN cells are unselected. This argues that most alpha/beta DN cells probably have never expressed CD4 or CD8. However, a unique form of repertoire selection occurs: enrichment of V beta 17a+ alpha/beta DN cells in I-E+ mice. This could be an instance of coreceptor-independent selection.
Impaired response to <i>Listeria</i> in H2-M3–deficient mice reveals a nonredundant role of MHC class Ib–specific T cells in host defense
Authors: Honglin Xu, Taehoon Chun, Hak-Jong Choi, Bin Wang, Chyung-Ru Wang
Journal: The Journal of Experimental Medicine (2006)

The major histocompatibility complex (MHC) class Ib molecule H2-M3 primes the rapid expansion of CD8+ T cells by presenting N-formylated bacterial peptides. However, the significance of H2-M3–restricted T cells in host defense against bacteria is unclear. We generated H2-M3–deficient mice to investigate the role of H2-M3 in immunity against Listeria monocytogenes (LM), a model intracellular bacterial pathogen. H2-M3–deficient mice are impaired in early bacterial clearance during primary infection, with diminished LM-specific CD8+ T cell responses and compromised innate immune functions. Although H2-M3–restricted CD8+ T cells constitute a significant proportion of the anti-listerial CD8+ T cell repertoire, the kinetics and magnitude of MHC class Ia–restricted T cell responses are not altered in H2-M3–deficient mice. The fact that MHC class Ia–restricted responses cannot compensate for the H2-M3–mediated immunity suggests a nonredundant role of H2-M3 in the protective immunity against LM. Thus, the early H2-M3–restricted response temporally bridges the gap between innate and adaptive immune responses, subsequently affecting the function of both branches of the immune system.
The effect of hypertonic saline dextran solutions on hypoxic pulmonary vasoconstriction in anaesthetised piglets
Authors: M. Bellezza, F. Kerbaul, L. Roussel, M. Imbert, C. Guidon
Journal: European Respiratory Journal (2002)

Hypoxic pulmonary vasoconstriction (HPV) is a regulatory mechanism by which blood is diverted from poorly ventilated to better ventilated areas of the lung. The aim of the present study was to assess the extent to which hypertonic saline dextran and dextran solutions modify the magnitude of HPV during isovolumic haemodilution in intact acutely instrumented piglets. Eighteen large white piglets were anesthetised and assigned to two groups. Mean pulmonary arterial pressure (PAP) and cardiac output (Q), systemic arterial pressure and left arterial pressure (LAP) were measured. A decrease in Q was obtained by reducing venous return. This enabled measurement of transpulmonary pressures (mean PAP minus LAP) at four levels of Q in hyperoxia (inspiratory oxygen fraction (<i>F</i><sub>i,O<sub>2</sub></sub>)=0.4), then in hypoxia (<i>F</i><sub>i,O<sub>2</sub></sub>=0.1) in the two groups before blood soustraction (10 mL·kg<sup>−1</sup>) and after loading with sodium chloride (NaCl) 7.5% and dextran 6% or with dextran 6% alone. Dextran alone led to a decrease in mean PAP–LAP/Q values, and NaCl with dextran was associated with a significant shift of mean PAP–LAP/Q plots to higher pressures in hypoxia. Hypertonic saline dextran solution, as replacement fluid in isovolaemic haemodilution increased the magnitude of hypoxic pulmonary vasoconstriction, whereas dextran solution reduced it.
Effects of 2,4-dinitrophenol or low [ATP]i on cell excitability and action potential propagation in guinea pig ventricular myocytes.
Authors: G E Morley, J M Anumonwo, M Delmar
Journal: Circulation Research (1992)

Inhibition of aerobic metabolism leads to a major disruption of cardiac cell homeostasis. The purpose of the present study was twofold: 1) We determined the relative importance of junctional and nonjunctional membrane resistance (Rj and Rm, respectively) in the development of propagation failure during inhibition of aerobic metabolism in guinea pig ventricular cell pairs. 2) We used the patch-action potential clamp technique in single ventricular myocytes to study some of the properties of the membrane channels that are responsible for shortening of action potential duration and eventual failure of cell excitation after metabolic blockade. In most experiments, whole-cell patch pipettes were filled with a solution containing 1 mM EGTA, 5 mM HEPES, and 5 mM ATP. Our results in cell pairs showed that pharmacological inhibition of aerobic metabolism with the mitochondrial uncoupler 2,4-dinitrophenol (DNP) led to a drop in Rm followed by an increase in Rj. The increase in Rj was not sufficient to cause a measurable delay in cell-to-cell propagation, whereas the drop in Rm consistently led to failure of cell excitation. Similar results were obtained in additional experiments in which the EGTA concentration in the pipette was reduced to 50 microM. Similar results were also obtained by loading the recording patch pipettes with a solution containing only 0.1 mM ATP. Our patch-action potential clamp experiments, on the other hand, revealed that DNP induced the opening of time- and voltage-independent membrane channels, with a unitary conductance of 23 pS. The channels allowed for the passage of outward current in the voltage range of the action potential, and the increase in membrane patch conductance correlated with the observed shortening of action potential duration during DNP superfusion. Our experiments provide the first simultaneous recordings of action potentials and DNP-induced channel currents in guinea pig ventricular myocytes. Overall, the data provide new evidence for the understanding of the cellular and subcellular mechanisms involved in the development of slow conduction velocity and propagation block after metabolic blockade.