tbuckley/cabot-search huggingface dataset:
Stat3 signaling in acute myeloid leukemia: ligand-dependent and -independent activation and induction of apoptosis by a novel small-molecule Stat3 inhibitor
Authors: Michele S. Redell, Marcos J. Ruiz, Todd A. Alonzo, Robert B. Gerbing, David J. Tweardy
Journal: Blood (2011)

Acute myeloid leukemia (AML) is an aggressive malignancy with a relapse rate approaching 50%, despite aggressive chemotherapy. New therapies for AML are targeted at signal transduction pathways known to support blast survival, such as the Stat3 pathway. Aberrant activation of Stat3 has been demonstrated in many different malignancies, including AML, and this finding is frequently associated with more aggressive disease. The objectives of this study were: (1) to characterize Stat3 signaling patterns in AML cells lines and primary pediatric samples; and (2) to test the efficacy and potency of a novel Stat3 inhibitor in inducing apoptosis in AML cells. We found that Stat3 was constitutively activated in 6 of 7 AML cell lines and 6 of 18 primary pediatric AML samples. Moreover, constitutively phosphorylated Stat3 was frequent in samples with normal karyotype but uncommon in samples with t(8;21). Most cell lines and primary samples responded to G-CSF stimulation, although the sensitivity and magnitude of the response varied dramatically. Our novel small-molecule Stat3 inhibitor, C188-9, inhibited G-CSF-induced Stat3 phosphorylation, induced apoptosis in AML cell lines and primary samples, and inhibited AML blast colony formation with potencies in the low micromolar range. Therefore, Stat3 inhibition may be a valuable strategy for targeted therapies for AML.
The Severe Gout of Holy Roman Emperor Charles V
Authors: Jaume Ordi, Pedro L. Alonso, Julian de Zulueta, Jordi Esteban, Martin Velasco, Ernest Mas, Elias Campo, Pedro L. Fernández
Journal: New England Journal of Medicine (2006)

Holy Roman Emperor Charles V was known to have had attacks of gout from early adulthood. This study provides objective confirmation of the clinical diagnosis on the basis of an examination of the mummified terminal phalanx of one of his fingers. The analysis demonstrated typical gouty tophi, eroding bone and extending into the soft tissues.
TCT-777 The Predictive Value of Vascular Complications Following Transcatheter Aortic Valve Implantation Reevaluated by VARC-1 and 2 Definitions
Authors: Arie Steinvil, Eran Leshem-Rubinow, Amir Halkin, Yigal Abramowitz, Eyal Ben-Assa, Avner Bar-Dayan, Gad Keren, Shmuel Banai, Ariel Finkelstein
Journal: Journal of the American College of Cardiology (2014)
The career structure--an indication for major surgery?
Authors: K Andrews
Journal: BMJ (1984)

visiting might underestimate the size of the prob- lem by a similar amount.The data from Hannay and Fraser and Clayton were not "conveniently overlooked" because they were not "truly com- parable."In neither of these studies was the accuracy of apparently updated addresses on general practitioner lists compared before and after home visiting.The former was solely a home visiting programme, whereas the latter did not provide data on postal returns.Professor Fraser has also confused target population with denominator population in evaluating screening.The former is necessary for assessing population coverage, and the observation that as in the present study 25% of the population could not be contacted is of relevance.Conversely the denominator for determining response or accept- ability of screening, or both, should, as Professor Fraser agrees, exclude these missing individuals.The model Professor Fraser describes for screening would not succeed in the area referred to in this study.His estimates of 95% probability of being contactable and 4% per cent for incorrect patient record addresses are large overestimates given the results of this and the other studies.
Dual nature of T cell–epithelium interaction in chronic rhinosinusitis
Authors: Tomasz M. Basinski, David Holzmann, Thomas Eiwegger, Maya Zimmermann, Sven Klunker, Norbert Meyer, Peter Schmid-Grendelmeier, Marek Jutel, Cezmi A. Akdis
Journal: Journal of Allergy and Clinical Immunology (2009)
Legal abortions save women's lives
Authors: W. Savage, J. McGarry, M. Filshie, B. Clayton, P. Diggory, I. McGillivray, K. Frith, M. Macnaughton, P. Huntingford, F. Fisher, D. Paintin
Journal: BMJ (1997)

Editor—As doctors who saw the serious and sometimes fatal consequences of illegal abortion before 1967, we believe strongly that equating legal abortion with the inhumanity practised by doctors in Nazi Germany is wrong.1 In all societies throughout history women faced with an unwanted pregnancy have resorted to abortion, and millions …
912 Involvement of P21WAF1/CIP1, P27KIP1, CDK2, CDK4, CDC2, cyclin A and cyclin B1 and map kinase signal pathway in growth inhibition and cell cycle arrest by a selective cyclooxygenase 2 inhibitor, etodolac, in human hepatocellular carcinoma cell lines
Authors: J CHENG, H IMANISHI, W LIU, A IWASAKI, H NAKAMURA, J YAMANAKA, J FUJIMOTO, T HADA
Journal: Hepatology (2003)

In this study, we investigated the effect of the 3-hydroxy-3-methylgutaryl-CoA reductase inhibitor lovastatin, as a sensitizer of lung cancer cells to ionizing radiation (IR).A549 lung adenocarcinoma cells were treated with 0 to 50 μM lovastatin alone or in combination with 0 to 8 Gy IR and subjected to clonogenic survival and proliferation assays. To assess the mechanism of drug action, we examined the effects of lovastatin and IR on the epidermal growth factor (EGF) receptor and AMP-activated kinase (AMPK) pathways and on apoptotic markers and the cell cycle.Lovastatin inhibited basal clonogenic survival and proliferation of A549 cells and sensitized them to IR. This was reversed by mevalonate, the product of 3-hydroxy-3-methylgutaryl-CoA reductase. Lovastatin attenuated selectively EGF-induced phosphorylation of EGF receptor and Akt, and IR-induced Akt phosphorylation, in a mevalonate-sensitive fashion, without inhibition on extracellular signal-regulated kinase 1/2 phosphorylation by either stimulus. IR phosphorylated and activated the metabolic sensor and tumor suppressor AMPK, but lovastatin enhanced basal and IR-induced AMPK phosphorylation. The drug inhibited IR-induced expression of p53 and the cyclin-dependent kinase inhibitors p21cip1 and p27kip1, but caused a redistribution of cells from G1-S phase (control and radiated cells) and G2-M phase (radiated cells) of cell cycle into apoptosis. The latter was also evident by induction of nuclear fragmentation and cleavage of caspase 3 by lovastatin in both control and radiated cells.We suggest that lovastatin inhibits survival and induces radiosensitization of lung cancer cells through induction of apoptosis, which may be mediated by a simultaneous inhibition of the Akt and activation of the AMPK signaling pathways.
Growth factor-induced acceleration of tissue repair through direct and inductive activities in a rabbit dermal ulcer model.
Authors: T A Mustoe, G F Pierce, C Morishima, T F Deuel
Journal: Journal of Clinical Investigation (1991)

The roles of polypeptide growth factors in promoting wound healing and in directing the specificity and sequence of responses of different tissues in wounds are little understood. We investigated the influence of four growth factors on the rates of healing of a novel full thickness dermal ulcer placed on an avascular base in the rabbit ear. The wound model precludes significant wound contraction and requires new granulation tissue and epithelial cells for healing to originate centripetally. 5 micrograms (7-31 pmol/mm2) of platelet-derived growth factor-B chain (PDGF-BB), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) applied locally at the time of wounding resulted in a twofold increase in complete reepithelialization of treated wounds (PDGF-BB, P = 0.02 chi square analysis; bFGF, P = 0.04; EGF, P = 0.05); transforming growth factor (TGF)-beta 1 significantly inhibited reepithelialization (P = 0.05). Both PDGF-BB and TGF-beta 1 uniquely increased the depth and area of new granulation tissue (P less than 0.005), the influx of fibroblasts, and the deposition of new matrix into wounds. Explants from 7-d old PDGF-BB-treated wounds remained metabolically far more active than controls, incorporating 473% more [3H]thymidine into DNA (P = 0.05) and significantly more [3H]leucine and [3H]proline into collagenase-sensitive protein (P = 0.04). The results establish that polypeptide growth factors have significant and selective positive influences on healing of full thickness ulcers in the rabbit.
A Vaccine for Viral Hepatitis Type B Appears on the Horizon
Authors: Joseph L. Melnick
Journal: New England Journal of Medicine (1973)

The continued support for over 30 years of research in viral hepatitis by the United States Army Medical Research and Development Command seems about to pay off. This is becoming apparent to other agencies that are now jumping on the band wagon and supporting research in this area. Perhaps those in control of federal budgets might learn from this example of the necessity of sustained support; if the present abrupt curtailment of training and research funds for the biomedical sciences is not reversed, the consequences will be unconscionable delays in solving problems affecting human health. If the momentum of the . . .
The rs12255372(G/T) and rs7903146(C/T) polymorphisms of the TCF7L2 gene are associated with type 2 diabetes mellitus in Asian Indians
Authors: Dhanasekaran Bodhini, Venkatesan Radha, Monalisa Dhar, Nagarajan Narayani, Viswanathan Mohan
Journal: Metabolism (2007)
Frequent p16&amp;sol;MTS1 Inactivation in Early Stages of Urothelial Carcinoma of the Bladder Is Not Associated with Tumor Recurrence
Authors: Martin G. Friedrich, Constanze Blind, Karin Milde-Langosch, Andreas Erbersdobler, Stefan Conrad, Thomas L&ouml;ning, Peter Hammerer, Hartwig Huland
Journal: European Urology (2001)
Laceration of the Distal Esophagus Due to Vomiting (the Mallory-Weiss Syndrome)
Authors: Andrew B. Small, Paul R. Ellis
Journal: New England Journal of Medicine (1958)

IN 1929 Mallory and Weiss1 reported on a series of 15 patients who experienced nausea, retching, vomiting and massive gastric hemorrhage after drinking. The source of the bleeding was not determined. Cirrhosis of the liver was suspected, but there was no evidence of it.Post-mortem examination of 4 of these patients showed 2 to 4 definite fissurelike lesions of the esophagogastric junction. These lesions were described as being 3 to 20 mm. in length and 2 or 3 mm. in width, with edges raised and slightly thickened but not indurated. In 3 cases, the lesions were limited to the stomach, . . .
Arylsulfatase B-deficient mucopolysaccharidosis in rats.
Authors: M Yoshida, J Noguchi, H Ikadai, M Takahashi, S Nagase
Journal: Journal of Clinical Investigation (1993)

A rat colony with mucopolysaccharidosis VI was established and the clinical, pathological, and biochemical features were characterized. Affected rats had facial dysmorphia, dysostosis multiplex, and increased urinary excretion of glucosaminoglycans (GAGs). Ultrastructural studies revealed storage of GAGs throughout the reticuloendothelial cells, cartilage, and other connective tissues, but no deposition was observed in the nervous system. Biochemical analyses demonstrated that the excreted GAG was dermatan sulfate and the activity of hepatic arylsulfatase B was < 5% of the normal mean value. Pedigree analysis showed that the phenotype was inherited as an autosomal recessive single trait. The availability of a rat model of human mucopolysaccharidosis VI should permit the development and evaluation of various strategies to treat the human disease.
Antibiotic resistance in Streptococcus pneumoniae and Haemophilus influenzae.
Authors: M Rahman
Journal: BMJ (1978)

sort of figure that surgical results must be balanced.While late surgery in a younger person must take account of the risks of rebleeding in the very long term,3 this is obviously not so in the elderly, whose mean expectation of life is in any case limited.It is not valid to compare the treatment of an aneurysmal subarachnoid haemorrhage with that of a fractured hip, an intestinal obstruction, or a dissecting aneurysm in an old person.Patients with the latter conditions will die if left untreated.Most patients with a ruptured aneurysm who survive the first haemorrhage and the next few weeks will recover to resume a normal life without any surgical treatment.
Other Healers: Unorthodox Medicine in America
Authors: Florence A. Ruderman
Journal: JAMA (1990)

This book is a useful addition to the growing literature on unorthodox medical care in the United States. Of its ten chapters, eight deal with specific "alternatives." These are various botanical practices; health reform movements, such as vegetarianism and Grahamism, that stressed diet, exercise, and "clean living"; hydrotherapy; homeopathic medicine; osteopathic medicine; chiropractic; Christian Science; and divine or faith healing, usually associated with revivalist sects but sometimes with more traditional churches or denominations. The remaining two chapters—the first and last—are different and more problematic. In the first, the editor considers possible approaches to the study of unorthodox healing. And in the last, there is a rather vague discussion of contemporary "folk medicine"; the only specific alternative discussed is the Pennsylvania "powwow," a faith-healing ritual of German folk origin. Each of the eight substantive chapters gives us a quite detailed and sound account of its topic. Each covers a particular movement's
Cervical pregnancy managed by local excision.
Authors: M J Whittle
Journal: BMJ (1976)

In Crohn's disease the mean plasma propranolol levels were significantly raised at all sampling times apart from the first.The area under the curve was also significantly greater than that of the controls (P=0 01-0 001).The values in Crohn's disease showed a much greater spread than those of the controls or the patients with coeliac disease.They fell into two groups: high values and those nearer control values.The high values seemed to relate to a rise in the erythrocyte sedimentation rate.Except in one patient who had a slightly lowered plasma albumin concentration, no abnormalities in liver function were found.The relevance of these findings to multiple dosing as used clinically is to be investigated.
Interleukin-21 Augments the Efficacy of T-Cell Therapy by Eliciting Concurrent Cellular and Humoral Responses
Authors: Takekazu Iuchi, Seagal Teitz-Tennenbaum, Jianhua Huang, Bruce G. Redman, Steven D. Hughes, Mu Li, Guihua Jiang, Alfred E. Chang, Qiao Li
Journal: Cancer Research (2008)

Abstract Interleukin (IL)-21 modulates T-cell–associated, B-cell–associated, and natural killer cell–associated immunity. However, the potential of IL-21 to simultaneously stimulate cellular and humoral antitumor responses and the mechanisms involved have not yet been adequately explored. In this report, we examined the immune-modulating effect of IL-21 when used in vitro and its adjuvant effects when administrated concomitantly with T-cell transfer for cancer therapy. Use of IL-21 in concert with IL-2 in culture up-regulated both type 1 and type 2 cytokine production of activated tumor-draining lymph node cells and enhanced their therapeutic efficacy. Administration of IL-21 and IL-2 as an adjuvant to T-cell transfer resulted in simultaneously elicited cellular and humoral responses. This concurrent response has led to effective regression of established pulmonary metastatic tumors and s.c. tumors. T-cell transfer plus IL-21/IL-2 administration conferred systemic immunity to the treated hosts. This was evident by the induction of protective immunity against tumor rechallenge, expansion of memory T cells, and significantly elevated serum levels of IFNγ and IL-10. Furthermore, we observed significantly enhanced tumor-associated antibody response after T-cell + IL-2 + IL-21 therapy. Cytotoxic antibody subclass IgG2b increased strikingly in the sera of treated animals; they bound specifically to MCA205 tumor cells, and such immune sera mediated tumor cell lysis in the presence of complement. Use of B-cell–deficient mice provided direct evidence that humoral responses contribute to T-cell + IL-2 + IL-21–elicited antitumor immunity. Collectively, these findings provide a rationale to evaluate the use of IL-21 in T-cell therapy of human cancers. [Cancer Res 2008;68(11):4431–41]
Effect of BN 50739, a new platelet activating factor antagonist, on ischaemia induced ventricular arrhythmias in isolated working rat hearts
Authors: M. Koltai, A. Tosaki, D. Hosford, A. Esanu, P. Braquet
Journal: Cardiovascular Research (1991)

The aim was to investigate the role of platelet activating factor (PAF) in myocardial ischaemia by using BN 50739, a new specific PAF receptor antagonist with a hetrazepine framework.Isolated working rat hearts were subjected to regional ischaemia, induced by ligation of the left main coronary artery for 30 min, followed by reperfusion. BN 50739 was applied at concentrations of 10(-7), 10(-6), 10(-5) and 5 X 10(-5) M, and its effects on the incidence of ischaemia induced and reperfusion induced ventricular tachycardia and ventricular fibrillation and heart functions, such as heart rate, coronary flow, aortic flow, left ventricular developed pressure (LVDP), its first derivative (LVdP/dtmax), and left ventricular end diastolic pressure (LVEDP), were determined.Studies were performed on isolated working hearts of male Sprague-Dawley rats weighing 300-360 g. Hearts were perfused with BN 50739 dissolved in dimethylsulphoxide. Control hearts were perfused with the vehicle.Regional ischaemia triggered ventricular arrhythmias showing high incidence between 12 and 20 min with peak appearance at 16 min. BN 50739 induced dose dependent protection against ventricular tachycardia and fibrillation: incidences declined from their respective control values of 91% and 75% to 33% (p less than 0.05) and 8% (p less than 0.05) after exposure to 10(-5) M, and to 25% (p less than 0.05) and 8% (p less than 0.05) after exposure to 5 X 10(-5) M concentrations. Reperfusion of the ischaemic myocardium resulted in an immediate appearance of ventricular tachycardia and fibrillation, but these were not suppressed by the PAF antagonist. Regional ischaemia slightly reduced heart rate, markedly decreased coronary flow, aortic flow, LVDP and LVdP/dtmax, and increased LVEDP. With the exception of LVEDP, these variables were not influenced by the drug. BN 50739, applied at a concentration of 5 X 10(-5) M, reduced LVEDP significantly during the whole ischaemic period.Under in vitro conditions PAF is likely to be involved in the genesis of ischaemia induced ventricular arrhythmias since BN 50739, a specific PAF receptor antagonist, exerts a protective effect against these rhythm disturbances. This suggests that PAF antagonists may have benefit in the clinical management of acute myocardial ischaemia.
Stress Hyperglycaemia in Hospitalised Patients and Their 3-Year Risk of Diabetes: A Scottish Retrospective Cohort Study
Authors: David A. McAllister, Katherine A. Hughes, Nazir Lone, Nicholas L. Mills, Naveed Sattar, John McKnight, Sarah H. Wild
Journal: PLoS Medicine (2014)

In a retrospective analysis of a national database of hospital admissions, David McAllister and colleagues identify the 3-year risk of diabetes of hospitalized patients with hyperglycemia in Scotland. Please see later in the article for the Editors' Summary
Characterization of SR 121463A, a highly potent and selective, orally active vasopressin V2 receptor antagonist.
Authors: C Serradeil-Le Gal, C Lacour, G Valette, G Garcia, L Foulon, G Galindo, L Bankir, B Pouzet, G Guillon, C Barberis, D Chicot, S Jard, P Vilain, C Garcia, E Marty, D Raufaste, G Brossard, D Nisato, J P Maffrand, G Le Fur
Journal: Journal of Clinical Investigation (1996)

SR 121463A, a potent and selective, orally active, nonpeptide vasopressin V2 receptor antagonist, has been characterized in several in vitro and in vivo models. This compound displayed highly competitive and selective affinity for V2 receptors in rat, bovine and human kidney (0.6 < or = Ki [nM] < or = 4.1). In this latter preparation, SR 121463A potently antagonized arginine vasopressin (AVP)-stimulated adenylyl cyclase activity (Ki = 0.26+/-0.04 nM) without any intrinsic agonistic effect. In autoradiographic experiments performed in rat kidney sections, SR 121463A displaced [3H]AVP labeling especially in the medullo-papillary region and confirmed that it is a suitable tool for mapping V2 receptors. In comparison, the nonpeptide V2 antagonist, OPC-31260, showed much lower affinity for animal and human renal V2 receptors and lower efficacy to inhibit vasopressin-stimulated adenylyl cyclase (Ki in the 10 nanomolar range). Moreover, OPC-31260 exhibited a poor V2 selectivity profile and can be considered as a V2/V1a ligand. In normally hydrated conscious rats, SR 121463A induced powerful aquaresis after intravenous (0.003-0.3 mg/kg) or oral (0.03-10 mg/kg) administration. The effect was dose-dependent and lasted about 6 hours at the dose of 3 mg/kg p.o. OPC-31260 had a similar aquaretic profile but with markedly lower oral efficacy. The action of SR 121463A was purely aquaretic with no changes in urine Na+ and K+ excretions unlike that of known diuretic agents such as furosemide or hydrochlorothiazide. In addition, no antidiuretic properties have been detected with SR 121463A in vasopressin-deficient Brattleboro rats. Thus, SR 121463A is the most potent and selective, orally active V2 antagonist yet described and could be a powerful tool for exploring V2 receptors and the therapeutical usefulness of V2 blocker aquaretic agents in water-retaining diseases.