tbuckley/cabot-search huggingface dataset:
Relative ion permeability of normal and cystic fibrosis nasal epithelium.
Authors: M Knowles, J Gatzy, R Boucher
Journal: Journal of Clinical Investigation (1983)

The raised transepithelial electric potential difference (PD) across respiratory epithelia in cystic fibrosis (CF) has suggested an abnormality in ion permeation. We characterized this abnormality further by measuring in the nasal epithelia of CF and normal subjects the concentration-PD relationship for amiloride, an inhibitor of cell Na+ permeability, and PD responses to superfusion with solutions of different composition. Amiloride was more efficacious in the CF subjects but the ED50 was not different from that of normals (approximately 2 X 10(-6) M). Na+ replacement by choline induced effects similar to those of amiloride, i.e. a greater depolarization in CF subjects. A 10-fold increase in the K+ concentration of the perfusate induced a small (less than 10 mV) depolarization in both subject populations. When Cl- in the perfusate was replaced by gluconate or SO2-(4) the nasal PD of normal subjects hyperpolarized (lumen became more negative) by approximately 35 mV. A significantly smaller response (less than 17 mV) was induced in CF homozygotes but not in heterozygotes (38 mV). The smaller response of CF subjects appears to reflect an absolute decrease in luminal surface Cl- permeability because pretreatment with amiloride did not increase the response to Cl- free solution (7 mV). Accordingly, three abnormalities (decreased Cl- permeability, raised PD, greater amiloride efficacy) have been identified in CF respiratory epithelia. Whereas "excessive" active Na+ transport can account for these abnormalities and the dessication of airway surface liquid, it is possible that a lower lumenal cell membrane Cl- permeability and inhibition of a potential path of Cl- secretion can also explain the observations.
Cotreatment with 17-Allylamino-Demethoxygeldanamycin and FLT-3 Kinase Inhibitor PKC412 Is Highly Effective against Human Acute Myelogenous Leukemia Cells with Mutant FLT-3
Authors: Prince George, Purva Bali, Pamela Cohen, Jianguo Tao, Fei Guo, Celia Sigua, Anasuya Vishvanath, Warren Fiskus, Anna Scuto, Srinivas Annavarapu, Lynn Moscinski, Kapil Bhalla
Journal: Cancer Research (2004)

Presence of the activating length mutation (LM) in the juxtamembrane domain or point mutation in the kinase domain of FMS-like tyrosine kinase-3 (FLT-3) mediates ligand-independent progrowth and prosurvival signaling in approximately one-third of acute myelogenous leukemia (AML). PKC412, an inhibitor of FLT-3 kinase activity, is being clinically evaluated in AML. Present studies demonstrate that treatment of human acute leukemia MV4-11 cells (containing a FLT-3 LM) with the heat shock protein 90 inhibitor 17-allylamino-demethoxy geldanamycin (17-AAG) attenuated the levels of FLT-3 by inhibiting its chaperone association with heat shock protein 90, which induced the poly-ubiquitylation and proteasomal degradation of FLT-3. Treatment with 17-AAG induced cell cycle G(1) phase accumulation and apoptosis of MV4-11 cells. 17-AAG-mediated attenuation of FLT-3 and p-FLT-3 in MV4-11 cells was associated with decrease in the levels of p-AKT, p-ERK1/2, and p-STAT5, as well as attenuation of the DNA binding activity of STAT-5. Treatment with 17-AAG, downstream of STAT5, reduced the levels of c-Myc and oncostatin M, which are transactivated by STAT5. Cotreatment with 17-AAG and PKC412 markedly down-regulated the levels of FLT-3, p-FLT-3, p-AKT, p-ERK1/2, and p-STAT5, as well as induced more apoptosis of MV4-11 cells than either agent alone. Furthermore, the combination of 17-AAG and PKC412 exerted synergistic cytotoxic effects against MV4-11 cells. Importantly, 17-AAG and PKC412 induced more loss of cell viability of primary AML blasts containing FLT-3 LM, as compared with those that contained wild-type FLT-3. Collectively, these in vitro findings indicate that the combination of 17-AAG and PKC412 has high level of activity against AML cells with FLT-3 mutations.
The Hedgehog Transcription Factor Gli3 Modulates Angiogenesis
Authors: Marie-Ange Renault, Jérôme Roncalli, Jörn Tongers, Sol Misener, Tina Thorne, Kentaro Jujo, Aiko Ito, Trevor Clarke, Chris Fung, Meredith Millay, Christine Kamide, Andrew Scarpelli, Ekaterina Klyachko, Douglas W. Losordo
Journal: Circulation Research (2009)

The Gli transcription factors are mediators of Hedgehog (Hh) signaling and have been shown to play critical roles during embryogenesis. Previously, we have demonstrated that the Hh pathway is reactivated by ischemia in adult mammals, and that this pathway can be stimulated for therapeutic benefit; however, the specific roles of the Gli transcription factors during ischemia-induced Hh signaling have not been elucidated.To investigate the role of Gli3 in ischemic tissue repair.Gli3-haploinsufficient (Gli3(+/-)) mice and their wild-type littermates were physiologically similar in the absence of ischemia; however, histological assessments of capillary density and echocardiographic measurements of left ventricular ejection fractions were reduced in Gli3(+/-) mice compared to wild-type mice after surgically induced myocardial infarction, and fibrosis was increased. Gli3-deficient mice also displayed reduced capillary density after induction of hindlimb ischemia and an impaired angiogenic response to vascular endothelial growth factor in the corneal angiogenesis model. In endothelial cells, adenovirus-mediated overexpression of Gli3 promoted migration (modified Boyden chamber), small interfering RNA-mediated downregulation of Gli3 delayed tube formation (Matrigel), and Western analyses identified increases in Akt phosphorylation, extracellular signal-regulated kinase (ERK)1/2 activation, and c-Fos expression; however, promoter-reporter assays indicated that Gli3 overexpression does not modulate Gli-dependent transcription. Furthermore, the induction of endothelial cell migration by Gli3 was dependent on Akt and ERK1/2 activation.Collectively, these observations indicate that Gli3 contributes to vessel growth under both ischemic and nonischemic conditions and provide the first evidence that Gli3 regulates angiogenesis and endothelial cell activity in adult mammals.
Novel Polymeric Nanoparticles for Intracellular Delivery of Peptide Cargos: Antitumor Efficacy of the BCL-2 Conversion Peptide NuBCP-9
Authors: Manoj Kumar, Dikshi Gupta, Gurpal Singh, Sapna Sharma, Madhusudan Bhat, C.K. Prashant, A.K. Dinda, Surender Kharbanda, Donald Kufe, Harpal Singh
Journal: Cancer Research (2014)

Abstract The preclinical development of peptidyl drugs for cancer treatment is hampered by their poor pharmacologic properties and cell penetrative capabilities in vivo. In this study, we report a nanoparticle-based formulation that overcomes these limitations, illustrating their utility in studies of the anticancer peptide NuBCP-9, which converts BCL-2 from a cell protector to a cell killer. NuBCP-9 was encapsulated in polymeric nanoparticles composed of a polyethylene glycol (PEG)–modified polylactic acid (PLA) diblock copolymer (NuBCP-9/PLA-PEG) or PEG-polypropylene glycol-PEG-modified PLA—tetrablock copolymer (NuBCP-9/PLA-PEG-PPG-PEG). We found that peptide encapsulation was enhanced by increasing the PEG chain length in the block copolymers. NuBCP-9 release from the nanoparticles was controlled by both PEG chain length and the PLA molecular weight, permitting time-release over sustained periods. Treatment of human cancer cells with these nanoparticles in vitro triggered apoptosis by NuBCP-9–mediated mechanism, with a potency similar to NuBCP-9 linked to a cell-penetrating poly-Arg peptide. Strikingly, in vivo administration of NuBCP-9/nanoparticles triggered complete regressions in the Ehrlich syngeneic mouse model of solid tumor. Our results illustrate an effective method for sustained delivery of anticancer peptides, highlighting the superior qualities of the novel PLA-PEG-PPG-PEG tetrablock copolymer formulation as a tool to target intracellular proteins. Cancer Res; 74(12); 3271–81. ©2014 AACR.
In vitro metabolism of creatinine, methylamine and amino acids by intestinal contents of normal and uraemic subjects.
Authors: C W Owens, Z P Albuquerque, G M Tomlinson
Journal: Gut (1979)

An original method which uses in vitro anaerobic incubation at 37 degrees C followed by centrifugation, ultrafiltration, and ion exchange chromatography is described; it shows that faecal material suspended in physiological saline can destroy added creatinine. The rate of breakdown by suspensions from uraemic subjects (mean 780 mumol h-1kg-1 SEM 70) was slightly faster than in normal subjects (mean 550 mumol h-1kg-1 SEM 80). Methylamine concentration increased over eight hours as creatinine was metabolised and sarcosine appeared as an intermediate. The rates of these reactions varied within and between individuals and were inhibited by oxygen and centrifugation but not by oxytetracycline. Concentrations of free amino acids did not change significantly despite the formation of ammonia. This approach should be useful in studying the metabolic inter-relationships between intestinal contents and the host organism in health and disease.
Management of spontaneous pneumothorax: British Thoracic Society pleural disease guideline 2010
Authors: A. MacDuff, A. Arnold, J. Harvey
Journal: Thorax (2010)

CLINICAL EVALUATION< Symptoms in PSP may be minimal or absent.In contrast, symptoms are greater in SSP, even if the pneumothorax is relatively small in size.(D) < The presence of breathlessness influences the management strategy.(D) < Severe symptoms and signs of respiratory distress suggest the presence of tension pneumothorax.(D) The typical symptoms of chest pain and dyspnoea may be relatively minor or even absent, 23 so that
Characteristics and Outcomes of AKI Treated with Dialysis during Pregnancy and the Postpartum Period
Authors: Ainslie M. Hildebrand, Kuan Liu, Salimah Z. Shariff, Joel G. Ray, Jessica M. Sontrop, William F. Clark, Michelle A. Hladunewich, Amit X. Garg
Journal: Journal of the American Society of Nephrology (2015)

Acute kidney injury (AKI) is a rare complication of pregnancy, but may be associated with significant morbidity and mortality in young and often otherwise healthy women. We conducted a retrospective population-based cohort study of all consecutive pregnancies over a 15-year period (1997-2011) in Ontario, Canada, and describe the incidence and outcomes of AKI treated with dialysis during pregnancy or within 12 weeks of delivery. Of 1,918,789 pregnancies, 188 were complicated by AKI treated with dialysis (incidence: 1 per 10,000 [95% confidence interval, 0.8 to 1.1]). Only 21 of 188 (11.2%) women had record of a preexisting medical condition; however, 130 (69.2%) women experienced a major pregnancy-related complication, including preeclampsia, thrombotic microangiopathy, heart failure, sepsis, or postpartum hemorrhage. Eight women died (4.3% versus 0.01% in the general population), and seven (3.9%) women remained dialysis dependent 4 months after delivery. Low birth weight (<2500 g), small for gestational age, or preterm birth (<37 weeks' gestation) were more common in pregnancies in which dialysis was initiated (35.6% versus 14.0%; relative risk, 3.40; 95% confidence interval, 2.52 to 4.58). There were no stillbirths and fewer than five neonatal deaths (<2.7%) in affected pregnancies compared with 0.1% and 0.8%, respectively, in the general population. In conclusion, AKI treated with dialysis during pregnancy is rare and typically occurs in healthy women who acquire a major pregnancy-related medical condition such as preeclampsia. Many affected women and their babies have good short-term outcomes.
Ultrafine Particles Affect Experimental Thrombosis in an <i>In Vivo</i> Hamster Model
Authors: Abderrahim Nemmar, Marc F. Hoylaerts, Peter H. M. Hoet, David Dinsdale, Tim Smith, Haiyan Xu, Jozef Vermylen, Benoit Nemery
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Particulate air pollution is associated with cardiovascular morbidity and mortality. To investigate this association, we studied the effect of ultrafine (60 nm) polystyrene particles on thrombus formation in a hamster model after intravenous and intratracheal administration of unmodified, carboxylate-polystyrene, or amine-polystyrene particles. Unmodified particles had no effect on thrombosis up to 5 mg/kg. Carboxylate-polystyrene particles significantly inhibited thrombus formation at 500 and 100 μg/kg body weight but not at 50 μg/kg body weight. In contrast, amine-polystyrene particles significantly enhanced thrombosis at 500 and 50 μg/kg body weight but not at 5 μg/kg body weight. Similarly, the intratracheal instillation of 5,000 μg of amine-polystyrene particles significantly increased thrombus formation. The unmodified particles and carboxylate-polystyrene particles had no effect. During platelet aggregation in human platelet-rich plasma, induced with 1.25 μM ADP, unmodified particles had no effect up to 100 μg/ml, and carboxylate-polystyrene particles weakly enhanced platelet aggregation at 25 to 100 μg/ml. However, amine-polystyrene particles (50 and 100 μg/ml) induced platelet aggregation themselves and strongly increased the ADP-induced aggregation. We conclude that the presence of (ultrafine) particles in the circulation may affect hemostasis. The observed in vivo prothrombotic tendency results, at least in part, from platelet activation by positively charged amine-polystyrene particles.
Percutaneous gall bladder aspiration as an alternative to laparoscopic cholecystectomy in Child-Pugh C cirrhotic patients with acute cholecystitis
Authors: G Curro
Journal: Gut (2006)

Cholelithiasis is a common disease in patients with cirrhosis due to intravascular haemolysis and functional alterations of the gall bladder.1 Acute cholecystitis (AC) results from obstruction of the cystic duct, usually by a gall stone, followed by distension and subsequent chemical or bacterial inflammation of the gall bladder. Approximately 95% of people with AC have gall stones (calcolous cholecystitis) and 5% lack gall stones (acalcolous cholecystitis). Severe AC may lead to necrosis of the gall bladder wall and to perforation, more commonly in patients with chronic diseases such as diabetes mellitus, renal failure, or cirrhosis.2 Early cholecystectomy is the standard treatment for AC in the general population and laparoscopic cholecystectomy (LC) is generally a safe and effective procedure even in cases of acute inflammation of the gall bladder.3,4 Although there is increasing evidence that patients with early cirrhosis may undergo LC with low morbidity and no mortality even when presenting with AC, patients with advanced cirrhosis are at high risk for surgery.3,4 Those with AC who have multiple comorbid conditions and relative contraindications for surgery may be treated conservatively with antibiotics and drip infusion and, more recently, by radiological interventional procedures in order to decompress the gall bladder and to interrupt the pathogenic mechanism of cystic duct obstruction, distension, and infection of the bile which may lead to gangrenous cholecystitis.5,6

Gall bladder decompression by a sonografically guided percutaneous cholecystostomy was firstly reported by Radder in 1980 for gall bladder empyema and later on several studies confirmed the safety and …
Why the empirical literature fails to support or disconfirm modular or dual-process models
Authors: David Trafimow
Journal: Behavioral and Brain Sciences (2007)

Abstract Barbey &amp; Sloman (B&amp;S) present five models that account for performance in Bayesian inference tasks, and argue that the data disconfirm four of them but support one model. Contrary to B&amp;S, I argue that the cited data fail to provide strong confirmation or disconfirmation for any of the models.
Serum carcinoembryonic antigen in clinical disorders
Authors: S. N. Booth, J. P. G. King, J. C. Leonard, P. W. Dykes
Journal: Gut (1973)

Carcinoembryonic antigen (CEA) levels have been measured in the serum of 490 patients and 93 normal controls using the double antibody radioimmunoassay technique. Levels were elevated in 71 of patients with carcinomata of the gastrointestinal tract and in 42% with other types of malignancy. In patients with non-neoplastic disease of the gastrointestinal tract and liver, elevated levels were found in 14 and 66% respectively. In general the CEA level tends to be higher in cancer patients with haematogenous dissemination. Following complete surgical removal of a tumour, levels fall to normal within 14 days in the majority of patients. Of 33 patients studied during follow up, elevated levels were found in 12, 10 of whom had evidence of recurrence. The significance of these findings and the possible application of CEA assay in clinical practice are discussed.
Apoptosis and inflammation
Authors: W VAN VENROOY
Journal: Annals of the Rheumatic Diseases (2000)

Apoptosis and inflammation . Ed James D Winkler. (Pp 256; DM228.) Basel: Birkhauser Verlag, 1999. ISBN 3-7643-5795-9.

Apoptosis is one of the hottest topics in present day research, offering an umbrella for studies in the fields of general biochemistry, cell biology, cellular differentiation, molecular biology, and immunology. A few years ago it became clear that there is also a strong link between apoptosis and autoimmunity. In some autoimmune diseases it has been shown that there is a defect at some step in the apoptotic cascade of events which, in genetically susceptible people, may lead to a change in the …
Identification of a Macromolecule Containing an Anticarcinoembryonic Antigen-Reactive Substance and Immunoglobulin M in Human Pancreatic Cancer2
Authors: S. R. Harvey, L. R Van Dusen, H. O. Douglass, E. D. Holyoke, T. M. Chu
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Identification of a Macromolecule Containing an Anticarcinoembryonic Antigen-Reactive Substance and Immunoglobulin M in Human Pancreatic Cancer Get access S. R. Harvey, S. R. Harvey 3Department of Diagnostic Immunology Research and Biochemistry, Roswell Park Memorial Institute, 666 Elm St., Buffalo, N.Y. 14263. Search for other works by this author on: Oxford Academic PubMed Google Scholar L. R Van Dusen, L. R Van Dusen 3Department of Diagnostic Immunology Research and Biochemistry, Roswell Park Memorial Institute, 666 Elm St., Buffalo, N.Y. 14263. Search for other works by this author on: Oxford Academic PubMed Google Scholar H. O. Douglass, H. O. Douglass 4Department of General Surgery, Roswell Park Memorial Institute. Search for other works by this author on: Oxford Academic PubMed Google Scholar E. D. Holyoke, E. D. Holyoke 4Department of General Surgery, Roswell Park Memorial Institute. Search for other works by this author on: Oxford Academic PubMed Google Scholar T. M. Chu T. M. Chu 5 3Department of Diagnostic Immunology Research and Biochemistry, Roswell Park Memorial Institute, 666 Elm St., Buffalo, N.Y. 14263. 6We thank Ms. J. Ogledzinski for preparation of this manuscript. 5Address reprint requests to Dr. Chu. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 61, Issue 5, November 1978, Pages 1199–1204, https://doi.org/10.1093/jnci/61.5.1199 Published: 01 November 1978 Article history Received: 29 March 1978 Accepted: 02 June 1978 Published: 01 November 1978
Induction of Adipophilin-Specific Cytotoxic T Lymphocytes Using a Novel HLA-A2-Binding Peptide That Mediates Tumor Cell Lysis
Authors: Susanne M. Schmidt, Kerstin Schag, Martin R. Müller, Toni Weinschenk, Silke Appel, Oliver Schoor, Markus M. Weck, Frank Grünebach, Lothar Kanz, Stefan Stevanovic, Hans-Georg Rammensee, Peter Brossart
Journal: Cancer Research (2004)

Abstract Identification of tumor-associated antigens and advances in tumor immunology resulted in the development of vaccination strategies to treat patients with malignant diseases. Using a novel approach that combines DNA chip analysis of tumor samples with isolation of peptides on the surface of tumor cells, a HLA-A*0201-binding peptide derived from the adipophilin protein was identified. Adipophilin is involved in lipid storage and was thought to be expressed only in adipocytes, but it can be found in other cell types such as macrophages or tumor cells. In the present study, we analyzed the possible use of this peptide as a T-cell epitope presented by malignant cells. To accomplish this, we induced CTL responses using this HLA-A*0201-binding peptide. The in vitro-induced CTLs efficiently lysed cells pulsed with the adipophilin peptide and HLA-matched tumor cell lines in an antigen-specific and HLA-restricted manner. Finally, the induced CTLs recognized autologous dendritic cells (DCs) pulsed with the antigenic peptide or transfected with tumor RNA purified from an adipophilin-expressing tumor cell line. To further analyze the possible use of this peptide in immunotherapies of human malignancies, we induced adipophilin-specific CTLs using peripheral blood mononuclear cells and DCs from HLA-A*0201-positive patients with chronic lymphatic leukemia and plasma cell leukemia. The in vitro-generated CTLs recognized autologous chronic lymphatic leukemia cells and malignant plasma cells, whereas they spared nonmalignant resting or activated B and T lymphocytes, monocytes, or DCs. Our results demonstrate that this peptide might represent an interesting candidate for the development of cancer vaccines designed to target adipophilin-derived epitopes in a wide range of malignancies.
Effects of Cigarette Smoking on the Angiographic Evolution of Coronary Atherosclerosis
Authors: David Waters, Jacques Lespe´rance, Peter Gladstone, Stephen J. Boccuzzi, Thomas Cook, Roger Hudgin, Gordon Krip, Lyall Higginson
Journal: Circulation (1996)

Background Although smoking increases both the risk of developing coronary disease and the risk of coronary events in patients with known coronary atherosclerosis, the effect of smoking on the evolution of coronary atherosclerosis as assessed by serial angiography is poorly defined. Methods and Results Ninety smokers with coronary atherosclerosis shown on a recent angiogram and with fasting cholesterol levels between 220 and 300 mg/dL were enrolled in a randomized, double-blind, placebo-controlled trial of cholesterol-lowering therapy, along with 241 nonsmokers and ex-smokers. Lovastatin at a mean dose of 36 mg/d lowered total and LDL cholesterol by 21±11% and 29±11%, respectively, but these levels changed by &lt;2% in placebo-treated patients. Coronary arteriography was repeated after 2 years in 72 smokers and their 557 lesions were measured blindly with an automated quantitative system, along with 1752 lesions in 227 nonsmokers. Coronary change score, the per-patient mean of the minimal lumen diameter changes for all qualifying lesions, worsened by 0.16±0.16 mm in smokers and by 0.07±0.15 mm in nonsmokers in the placebo group ( P &lt;.001). Lovastatin-treated smokers had less worsening (0.07±0.15 mm) than placebo-treated smokers ( P =.024). One or more coronary lesions progressed in 16 of 34 lovastatin-treated smokers and in 28 of 38 placebo-treated smokers (47% versus 74%, P &lt;.001). In the placebo group, new coronary lesions developed in 21 of 38 smokers and in 28 of 115 nonsmokers (55% versus 24%, P &lt;.001); fewer lovastatin-treated smokers developed new lesions (15% versus 55%, P &lt;.001). Conclusions Smoking accelerates coronary progression and new lesion formation as assessed by serial quantitative coronary arteriography. Lovastatin slows the progression of coronary atherosclerosis and prevents the development of new coronary lesions in smokers.