tbuckley/cabot-search huggingface dataset:
Activation of v-Myb avian myeloblastosis viral oncogene homolog-like2 (MYBL2)-LIN9 complex contributes to human hepatocarcinogenesis and identifies a subset of hepatocellular carcinoma with mutant p53
Authors: Diego F. Calvisi, Maria M. Simile, Sara Ladu, Maddalena Frau, Matthias Evert, Maria L. Tomasi, Maria I. Demartis, Lucia Daino, Maria A. Seddaiu, Stefania Brozzetti, Francesco Feo, Rosa M. Pascale
Journal: Hepatology (2011)

Up-regulation of the v-Myb avian myeloblastosis viral oncogene homolog-like2 B-Myb ( MYBL2 ) gene occurs in human hepatocellular carcinoma (HCC) and is associated with faster progression of rodent hepatocarcinogenesis. We evaluated, in distinct human HCC prognostic subtypes (as defined by patient survival length), activation of MYBL2 and MYBL2 -related genes, and relationships of p53 status with MYBL2 activity. Highest total and phosphorylated protein levels of MYBL2, E2F1-DP1, inactivated retinoblastoma protein (pRB), and cyclin B1 occurred in HCC with poorer outcome (HCCP), compared to HCC with better outcome (HCCB). In HCCP, highest LIN9-MYBL2 complex (LINC) and lowest inactive LIN9-p130 complex levels occurred. MYBL2 positively correlated with HCC genomic instability, proliferation, and microvessel density, and negatively with apoptosis. Higher MYBL2/LINC activation in HCC with mutated p53 was in contrast with LINC inactivation in HCC harboring wildtype p53. Small interfering RNA (siRNA)-mediated MYBL2/LINC silencing reduced proliferation, induced apoptosis, and DNA damage at similar levels in HCC cell lines, irrespective of p53 status. However, association of MYBL2/LINC silencing with doxorubicin-induced DNA damage caused stronger growth restraint in p53-/- Huh7 and Hep3B cells than in p53+/+ Huh6 and HepG2 cells. Doxorubicin triggered LIN9 dissociation from MYBL2 in p53+/+ cell lines and increased MYBL2-LIN9 complexes in p53-/- cells. Doxorubicin-induced MYBL2 dissociation from LIN9 led to p21WAF1 up-regulation in p53+/+ but not in p53-/- cell lines. Suppression of p53 or p21WAF1 genes abolished DNA damage response, enhanced apoptosis, and inhibited growth in doxorubicin-treated cells harboring p53+/+. Conclusion: We show that MYBL2 activation is crucial for human HCC progression. In particular, our data indicate that MYBL2-LIN9 complex integrity contributes to survival of DNA damaged p53-/- cells. Thus, MYBL2 inhibition could represent a valuable adjuvant for treatments against human HCC with mutated p53. (HEPATOLOGY 2011;)
Complete hormonal blockade versus epirubicin-based chemotherapy in premenopausal, one to three node-positive, and hormone-receptor positive, early breast cancer patients: 7-year follow-up results of French Adjuvant Study Group 06 randomised trial
Authors: H. Roché, P. Kerbrat, J. Bonneterre, P. Fargeot, P. Fumoleau, A. Monnier, P. Clavère, M.-J. Goudier, P. Chollet, J.-P. Guastalla, D. Serin
Journal: Annals of Oncology (2006)
Improving the Quality of Abstract Reporting for Phase I Cancer Trials
Authors: Elizabeth L. Strevel, Nicole G. Chau, Gregory R. Pond, Anthony J. Murgo, Percy S. Ivy, Lillian L. Siu
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Conference abstracts of phase I trials (P1T) communicate important anticancer drug development information. Our objectives were to determine elements essential for good P1T abstract reporting, to assess the quality of P1T abstracts submitted to American Society of Clinical Oncology (ASCO) meetings, and to propose reporting guidelines. Experimental Design: A survey of developmental therapeutics experts established elements of P1T reporting quality, and a scoring system was generated. All P1T abstracts published in ASCO Annual Proceedings from 1997 to 2006 were reviewed, and the scoring system was applied. Results: A survey was distributed twice to 69 experts, with a response rate of 39% (27 of 69). Experts rated 37 elements using a five-point scale, and elements with mean ratings over 3.75 were included in the final scoring system. One thousand six hundred and eighty three P1T abstracts were reviewed. A positive and linear association was observed between average expert rating of the elements and the proportion of P1T abstracts including those elements (Spearman correlation coefficient, ρ = 0.60, P &amp;lt; 0.001). The median for all 1,683 abstracts was 62.5% (range, 25-95%; SD, 12.3%). Year of presentation was found to be significantly associated with higher quality scores (ρ = 0.20, P &amp;lt; 0.001), with later years possessing better quality scores. The quality score was statistically significant as a predictor of type of presentation (odds ratio, 1.10; 95% confidence interval, 1.02-1.19 per 10% increase; P = 0.014), with oral presentations having the highest scores. Conclusions: The quality of P1T abstract reporting at ASCO has improved over time, although there is room for optimization. The quality of P1T abstract reporting may be enhanced using guidelines derived from our expert consensus.
Frequenin—A novel calcium-binding protein that modulates synaptic efficacy in the drosophila nervous system
Authors: O. Pongs, J. Lindemeier, X.R. Zhu, T. Theil, D. Engelkamp, I. Krah-Jentgens, H.-. Lambrecht, K.W. Koch, J. Schwemer, R. Rivosecchi, A. Mallart, J. Galceran, I. Canal, J.A. Barbas, A. Ferrús
Journal: Neuron (1993)
THE USE OF FLUPHENAZINE (PROLIXIN) IN REHABILITATION OF CHRONIC SCHZOPHRENIC PATIENTS
Authors: LEON REZNIKOFF
Journal: American Journal of Psychiatry (1960)

1. Fifty chronic schizophrenic patients with an average duration of mental illness of over 12 years and refractory to any other treatment had been treated with fluphenazine for a period of 3 to 4 months. 2. Twenty-nine patients (58%) improved and 21 (42%) remained unimproved. 3. The dose of fluphenazine varied from 2.5 mg. to 20 mg. per day. When the dose of fluphenazine was raised over 10 mg. per day, 50% of patients developed extrapyramidal symptoms. 4. Fluphenazine is a valuable adjunct in the total program of rehabilitation of chronic schizophrenic patients.
Transcellular biosynthesis contributes to the production of leukotrienes during inflammatory responses in vivo
Authors: Jean-Etienne Fabre, Jennifer L. Goulet, Estelle Riche, MyTrang Nguyen, Kenneth Coggins, Steven Offenbacher, Beverly H. Koller
Journal: Journal of Clinical Investigation (2002)

Leukotrienes are lipid mediators that evoke primarily proinflammatory responses by activating receptors present on virtually all cells. The production of leukotrienes is tightly regulated, and expression of 5-lipoxygenase, the enzyme required for the first step in leukotriene synthesis, is generally restricted to leukocytes. Arachidonic acid released from the cell membrane of activated leukocytes is rapidly converted to LTA(4) by 5-lipoxygenase. LTA(4) is further metabolized to either LTC(4) or LTB(4) by the enzyme LTC(4) synthase or LTA(4) hydrolase, respectively. Unlike 5-lipoxygenase, these enzymes are expressed in most tissues. This observation previously has led to the suggestion that LTA(4) produced by leukocytes may, in some cases, be delivered to other cell types before being converted into LTC(4) or LTB(4). While in vitro studies indicate that this process, termed transcellular biosynthesis, can lead to the production of leukotrienes, it has not been possible to determine the significance of this pathway in vivo. Using a series of bone marrow chimeras generated from 5-lipoxygenase- and LTA(4) hydrolase-deficient mice, we show here that transcellular biosynthesis contributes to the production of leukotrienes in vivo and that leukotrienes produced by this pathway are sufficient to contribute significantly to the physiological changes that characterize an ongoing inflammatory response.
Determination of azithromycin in raw materials and pharmaceutical formulations by HPLC coupled with an evaporative light scattering detector
Authors: Aiguo Zeng, Xia Liu, Siruo Zhang, Yan Zheng, Ping Huang, Kangli Du, Qiang Fu
Journal: Asian Journal of Pharmaceutical Sciences (2014)

A simple high-performance liquid chromatography (HPLC) method coupled with an evaporative light scattering detector (ELSD) was developed for the determination of azithromycin in raw materials and pharmaceutical formulations (injections, capsules and tablets) without any pretreatment or derivatization step. Azithromycin, degradation products and formulation ingredients were separated efficiently by using the mobile phase consisted of ammonium acetate (0.05 M, pH 8.0) and acetonitrile (60:40, v/v) in an isocratic mode at 0.8 ml/min flow rate. Parameters of ELSD were 60 °C for evaporation temperature and 50 psi for pressure of carrier gas (air). A logarithmic calibration curve was obtained from 50.93 to 509.30 μg/ml (r = 0.9996) for azithromycin, with the limit of detection (LOD) of 6.75 μg/ml (S/n = 3) and the limit of quantification of 22.50 μg/ml (S/n = 10). The developed method was validated and applied with satisfactory accuracy and precision for the determination of azithromycin in raw materials and pharmaceutical formulations (recovery 99–102%, RSD <1.2%, n = 3). No significant difference (t-test) was found between the results of the developed HPLC–ELSD method and the HPLC–UV or microbiological method.
Generalized acquired cutis laxa associated with coeliac disease: evidence of immunoglobulin A deposits on the dermal elastic fibres
Authors: V. GARCÍA-PATOS, R.M. PUJOL, M.A. BARNADAS, M. PÉREZ, A. MORENO, J. CONDOMINES, C. GELPI, J.L. RODRÍGUEZ, J.M. DE MORAGAS
Journal: British Journal of Dermatology (1996)

Acquired cutis laxa (ACL) is an uncommon elastolytic disorder of unknown aetiology. In rare instances. ACL has been reported in association with autoimmune diseases and dermal deposit of immunoglobulins, suggesting that destruction of elastic tissue may be immunologically mediated. We report a 35‐year‐old man with generalized acquired cutis laxa (GACL) associated with a persistent papular erythematous eruption that histopathologically showed some resemblance to dermatitis herpetiformis. A marked reduction and degeneration of dermal elastic fibres was noted in biopsies from loose‐hanging skin. Direct immunofluorescence from non‐inflammatory loose skin revealed granular immunoglobulin A (IgA) deposits at the basement membrane zone and fibrillar IgA deposits in the dermal papillae. IgA deposits were also observed on the elastic fibres of the reticular dermis. Electron microscopy of skin from the submammary fold revealed fragmented elastic fibres, partial absence of peripheral microfibrils and abundant neutrophils, some of which were degranulated and adjacent to elastic fibres. Immunoelectron microscopy of an erythematous papule revealed IgA deposits around dermal elastic fibres. Antigliadin, antireticulin and antiendomysium antibodies were present. Jejunal biopsies showed a gluten‐sensitive enteropathy. A possible IgA‐mediated immune mechanism for the development of GACL in our patient is suggested.
Increased Adipose Tissue Oxygen Tension in Obese Compared With Lean Men Is Accompanied by Insulin Resistance, Impaired Adipose Tissue Capillarization, and Inflammation
Authors: Gijs H. Goossens, Alessandro Bizzarri, Nicolas Venteclef, Yvonne Essers, Jack P. Cleutjens, Ellen Konings, Johan W.E. Jocken, Merima Čajlaković, Volker Ribitsch, Karine Clément, Ellen E. Blaak
Journal: Circulation (2011)

Background— Adipose tissue (AT) dysfunction in obesity contributes to chronic, low-grade inflammation that predisposes to type 2 diabetes mellitus and cardiovascular disease. Recent in vitro studies suggest that AT hypoxia may induce inflammation. We hypothesized that adipose tissue blood flow (ATBF) regulates AT oxygen partial pressure (AT P o 2 ), thereby affecting AT inflammation and insulin sensitivity. Methods and Results— We developed an optochemical measurement system for continuous monitoring of AT P o 2 using microdialysis. The effect of alterations in ATBF on AT P o 2 was investigated in lean and obese subjects with both pharmacological and physiological approaches to manipulate ATBF. Local administration of angiotensin II (vasoconstrictor) in abdominal subcutaneous AT decreased ATBF and AT P o 2 , whereas infusion of isoprenaline (vasodilator) evoked opposite effects. Ingestion of a glucose drink increased ATBF and AT P o 2 in lean subjects, but these responses were blunted in obese individuals. However, AT P o 2 was higher (hyperoxia) in obese subjects despite lower ATBF, which appears to be explained by lower AT oxygen consumption. This was accompanied by insulin resistance, lower AT capillarization, lower AT expression of genes encoding proteins involved in mitochondrial biogenesis and function, and higher AT gene expression of macrophage infiltration and inflammatory markers. Conclusions— Our findings establish ATBF as an important regulator of AT P o 2 . Nevertheless, obese individuals exhibit AT hyperoxia despite lower ATBF, which seems to be explained by lower AT oxygen consumption. This is accompanied by insulin resistance, impaired AT capillarization, and higher AT gene expression of inflammatory cell markers. Clinical Trial Registration— URL: http://www.trialregister.nl . Unique identifier: NTR2451.
Hierarchical analysis of population genetic variation in mitochondrial and nuclear genes of Daphnia pulex.
Authors: T J Crease, M Lynch, K Spitze
Journal: Molecular Biology and Evolution (1990)

The geographic structure of Daphnia pulex populations from the central United States is analyzed with respect to isozyme and mitochondrial DNA variation. The species complex consists of cyclic and obligate parthenogens. A hierarchical analysis of population structure in the cyclic parthenogens by using a fixation-index approach indicates that this is one of the most extremely subdivided species yet studied. This genetic structure, much of which accrues within 100 km, is certainly due in part to the limited dispersal ability of Daphnia. However, previous work has shown that fluctuating selection can account for the spatial heterogeneity in isozyme frequencies in these populations. This may explain why the population subdivision for the mitochondrial genome increases approximately three times as rapidly with distance as does that for nuclear genes, which is slower than the neutral expectation. The obligate parthenogens are shown to be polyphyletic in origin, evolutionarily young, and, in some cases, geographically widespread.
Abstract 2073: Neutrophil serine proteases, cathepsin-G and elastase, promote metastasis through cleavage of thrombospondin-1
Authors: Tina E. Rayes, Raul Catena, Sharrell Lee, Dingcheng Gao, Marcin Stawowczyk, Nasser Altorki, Vivek Mittal
Journal: Cancer Research (2014)

Abstract Inflammation is known to be inextricably associated with tumor progression. However, the role of inflammation in metastatic initiation and outgrowth remains largely unexplored. In our study, we show that CXCR2-CXCL2-dependent recruitment of neutrophils supported a pro-metastatic phenotype in acutely inflamed lungs. The increased influx of Ly6G+ neutrophils into inflamed lungs was accompanied by a loss of thrombospondin-1 (Tsp-1) protein. In vitro, the degranulation of neutrophils was marked by an increase in the activity of the neutrophil proteases elastase and cathepsin-G, leading to degradation of Tsp-1, which was protected by using the protease inhibitor Sivelestat. Whereas genetic ablation of either cathepsin-G or elastase in vivo partially impaired metastasis, pharmacological inhibition of both neutrophil proteases, using the small molecule drug Sivelestat, dramatically suppressed metastasis. We have uncovered a novel pathway in which the serine proteases, cathepsin-G and elastase produced by degranulating neutrophils, promote a metastasis-conducive microenvironment through the cleavage of Tsp-1. Our results provide mechanistic insights into how inflammatory components of the premetastatic niche can support metastatic outgrowth, and they suggest that the neutrophil protease-Tsp-1 axis presents a therapeutic target against metastatic cancers. Citation Format: Tina El Rayes, Raul Catena, Sharrell Lee, Dingcheng Gao, Marcin Stawowczyk, Nasser Altorki, Vivek Mittal. Neutrophil serine proteases, cathepsin-G and elastase, promote metastasis through cleavage of thrombospondin-1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2073. doi:10.1158/1538-7445.AM2014-2073
Role of Leukotrienes in Bronchial Hyperresponsiveness and Cellular Responses in Airways
Authors: ALAN R. LEFF
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Among constitutively present cells, bronchoactive leukotrienes are produced predominantly by mast cells (1) and macrophages (2). A unique characteristic of asthmatic inflammation is the migration of leukocytes from the peripheral blood to the conducting airways of the lung. This is especially true of the eosinophil, which is not present in the airways of normal individuals, but may be found in massive numbers during periods of airway hyperresponsiveness in asthmatic individuals [Figure 1 (3)] (4-6). Most experimental models indicate that eosinophils are an invariable component of asthmatic hyperresponsiveness, although some studies suggest that bronchoconstriction can occur in the relative absence of these cells. For the purposes of this discussion, the eosinophil is viewed as a leukotriene transport system capable of providing a substantial reservoir of bronchoactive leukotrienes to airways in a relatively short time. They may be delivered to conducting airways in large numbers and have the capacity to produce cysteinyl-leukotriene C 4  (Cys-LTC 4 ), which cannot be produced by neutrophils, but also migrate into conducting airways in some circumstances (7, 8). This discussion deals first with the mechanism by which eosinophils, a minority constituent of the circulating blood, are homed selectively to the conducting airways of the lung in human asthma. The mechanism by which the recruitment process of cellular adhesion primes migrating eosinophils for augmented leukotriene synthesis is discussed with particular reference to interactions between surface integrins on eosinophils and their counterligands, the immunoglobulin supergenes on the endothelial surface (9, 10) and fibronectin within the airway wall (11). The potential physiological significance of augmented secretion caused by adhesive interactions is suggested by experiments elucidated in this discussion. Finally, some new preliminary evidence for an autocrine mechanism of eosinophil recruitment that is mediated through the secretion of Cys-leukotrienes is considered.
Rhinitis and the severity of OSA
Authors: P Michael
Journal: Thorax (2004)

▴ Kramer MF, de la Chaux R, Fintelmann R, Rasp G. NARES: a risk factor for obstructive sleep apnea. Am J Otolaryngol2004;25:173–7 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] There is controversy regarding whether nasal congestion is a risk factor for the obstructive sleep apnoea syndrome (OSAS). NARES (non-allergic rhinitis with eosinophilia) is a rare form of rhinitis, presenting with typical … [1]: {openurl}?query=rft.jtitle%253DAmerican%2Bjournal%2Bof%2Botolaryngology%26rft.stitle%253DAm%2BJ%2BOtolaryngol%26rft.aulast%253DKramer%26rft.auinit1%253DM.%2BF.%26rft.volume%253D25%26rft.issue%253D3%26rft.spage%253D173%26rft.epage%253D177%26rft.atitle%253DNARES%253A%2Ba%2Brisk%2Bfactor%2Bfor%2Bobstructive%2Bsleep%2Bapnea%253F%26rft_id%253Dinfo%253Adoi%252F10.1016%252Fj.amjoto.2003.12.004%26rft_id%253Dinfo%253Apmid%252F15124166%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/j.amjoto.2003.12.004&link_type=DOI [3]: /lookup/external-ref?access_num=15124166&link_type=MED&atom=%2Fthoraxjnl%2F59%2F8%2F661.atom [4]: /lookup/external-ref?access_num=000221530900005&link_type=ISI
Multicenter comparative trial of the V-scope system for therapeutic ERCP
Authors: A. Joyce, N. Ahmad, M. Beilstein, M. Kochman, W. Long, T. Baron, S. Sherman, E. Fogel, G. Lehman, L. McHenry Jr, J. Watkins, G. Ginsberg
Journal: Endoscopy (2006)

Background and study aims: A new duodenoscope (the V-scope), with a modified elevator used in combination with a dedicated short guide wire, constitutes the V-system. This system is intended to allow fixation of the guide wire at the elevator lever, thereby enhancing the speed and reliability of accessory exchange over a guide wire during ERCP. The aim of this study was to evaluate the extent to which the V-system provides improved efficiency in comparison with conventional duodenoscope and guide wire combinations. Patients and methods: This was an industry-sponsored multicenter randomized trial. Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) procedures in which treatment was anticipated were randomly assigned to the V-system or to a conventional duodenoscope and accessories used routinely in each center. The parameters recorded included the total case time, fluoroscopy time, catheter/guide wire exchange time, guide wire repositioning, loss of guide wire access, and success or failure of guide wire fixation when using the V-system.
A role for a glibenclamide-sensitive, relatively ATP-insensitive K+ current in regulating membrane potential and current in rat aorta
Authors: S Mishra
Journal: Cardiovascular Research (1999)

Objective: ATP-sensitive K+ channels have been classified based on their inhibition by cytoplasmic ATP. Recent evidence in vascular smooth muscle has suggested that these channels show weak sensitivity to intracellular ATP. However, it is not known whether these channels regulate the resting K+ conductance in vascular smooth muscles. Therefore, the aim of the present investigation was to characterize this current in rat aorta myocytes and to examine whether it contributes to setting the membrane potential. Methods: The conventional and nystatin-permeablised whole cell patch clamp techniques were used to characterize the effect of glibenclamide on membrane potential and K+ current in enzymatically dispersed rat aorta myocytes. Results: The mean resting potential measured in current clamp mode using the permeabilized patch approach was −54±5 mV (n=8). Glibenclamide (10 μM) caused a reversible 24-mV depolarization in these cells. In symmetrical K+ (135 mM) solution an inward glibenclamide-sensitive (10 μM) current (−4.1±0.7 pA/pF; n=5), hereafter termed Iglib, was observed at a membrane potential of −80 mV when cells held at −60 mV were ramped from −80 to +80 mV. In the absence of any nucleotide in the pipette solution, Iglib measured by the conventional whole-cell method was −23.69±4.65 pA/pF (n=9). With 1 and 3 mM ATP in the pipette, the average current density was −25±6.3 pA/pF (n=8), and −9.4±2.7 pA/pF (n=9), respectively. In the absence of ATP, 1 mM GDP significantly (P<0.01) increased Iglib (−44.8±8.4 pA/pF; n=13). Inclusion of 1 mM ATP in the GDP-containing pipette solution had no significant effect on the current amplitude (−56.4±10.7 pA/pF; n=7). Iglib fell to −11.0±2.9 pA/pF (n=10) if 1 mM GDP and 3 mM ATP were present. In symmetrical K+, the Iglib observed in the presence of 1 mM ATP in the pipette was increased by more than two-fold in the presence of 10 μM levcromakalim. In PSS containing 5 mM K+, a significant glibenclamide-sensitive current was observed at −45 mV membrane potential when cells dialyzed with 1 mM ATP were ramped between −80 to 30 mV. Conclusion: These results demonstrate that Iglib channels in rat aorta myocytes differ from classical KATP channels, being relatively insensitive to intracellular ATP. Iglib therefore appears to have an important role in contributing to the maintenance of the resting potential in rat aortic smooth muscle.
Enhanced Antigen-Specific Antitumor Immunity with Altered Peptide Ligands that Stabilize the MHC-Peptide-TCR Complex
Authors: Jill E Slansky, Frédérique M Rattis, Lisa F Boyd, Tarek Fahmy, Elizabeth M Jaffee, Jonathan P Schneck, David H Margulies, Drew M Pardoll
Journal: Immunity (2000)