tbuckley/cabot-search huggingface dataset:
Abstract 1794: TXNL2 is a key regulator of reactive oxygen species levels and NF-κB activity in cancer cells
Authors: Ying Qu, Jinhua Wang, Miyung Shin-Sim, Jiang Huang, Bingya Liu, Ning Zhang, Yukung Cui, Armando E. Giuliano, Ninghui Cheng, Xiaojiang Cui
Journal: Cancer Research (2010)

Abstract Cancer cells usually generate and maintain higher levels of reactive oxygen species (ROS) compared to normal cells, in part because of their higher metabolic rate and defects in the electron transport chain. Because most tumor cells possess stronger antioxidative defense mechanisms to counterbalance excessive ROS, redox proteins such as thioredoxins (TRXs) and glutaredoxins (GRXs) are potential targets of anticancer therapy. We recently found that a novel redox protein called thioredoxin-like 2 (TXNL2) is required for embryonic stem cell functions and is consistently overexpressed in many different cancers. It has a TRX-homology domain and two GRX-homology domains, suggesting that it may have redox function. Using immunohistochemical and cDNA microarray analyses, we found that levels of TXNL2 were significantly higher (P = 0.00036) in human breast cancers than in normal breast tissues; levels also were higher in human breast cancer cell lines than in normal mammary epithelial cell lines. Knockdown of TXNL2 by shRNA in breast cancer cell lines induced a 5-fold increase of ROS levels and inhibited cell proliferation, survival, invasion, and the expression of genes critically involved in these cellular processes. Breast cancer stem-like cell populations and stem-like properties such as mammosphere formation were reduced by TXNL2 silencing and induced by TXNL2 overexpression. Surprisingly, TXNL2 depletion in normal mammary epithelial cells did not significantly affect ROS levels and cell survival. Xenograft models of orthotopic injection indicated that TXNL2 knockdown inhibited mammary tumor growth and metastasis to the lung. Cell signaling studies showed that TXNL2 knockdown inhibited GSH synthase (GSS) expression, and thereby decreased GSH levels and increased ROS levels; N-acetylcysteine (NAC), a GSH precursor, partially reversed these effects. In addition, TXNL2 knockdown suppressed NF-κB activity by inactivating IKK and p65 via glutathionylation, whereas TXNL2 overexpression markedly increased NF-κB activity. Blockade of NF-κB using its small-molecule inhibitors and IκB overexpression mimicked the effect of TXNL2 depletion. Our results suggest that TXNL2 is a potentially promising target for ROS-based anticancer therapies and is a key regulator of the NF-κB pathway. Because high cellular antioxidant capacity is well-known to impair cellular responses to chemotherapy and radiation therapy, our study may also open up a new avenue of maximize the efficacy of conventional anticancer therapies by targeting TXNL2. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1794.
Ischemia–reperfusion injury-induced abnormal dendritic cell traffic in the transplanted kidney with delayed graft function
Authors: A. Loverre, C. Capobianco, G. Stallone, B. Infante, A. Schena, P. Ditonno, S. Palazzo, M. Battaglia, A. Crovace, G. Castellano, E. Ranieri, F.P. Schena, L. Gesualdo, G. Grandaliano
Journal: Kidney International (2007)
DIFFERENCES IN THE ELECTROPHORETIC MOBILITIES OF GUINEA PIG 7S ANTIBODIES OF DIFFERENT SPECIFICITIES
Authors: Victor Nussenzweig, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1964)

The electrophoretic mobilities of guinea pig γ1 and γ2 antibodies bearing different specificities were compared in agar gel at pH 8.2. Specifically purified antibodies bearing the same immunological specificity showed the same electrophoretic mobility, but significant differences in mobility were observed when antibodies with certain selected different specificities were compared. The specificity of the carrier protein appeared not to affect the mobilities of antihapten antibodies. Differences in mobility have also been shown between γ1 antihapten antibodies produced by individual guinea pigs immunized concomitantly with 2,4-dinitrophenyl bovine gamma globulin and arsanilic acid azo guinea pig albumin. The differences in the net electrophoretic charge between antibodies with different specificities roughly paralleled that of their S fragments produced by papain digestion.
Effects of pioglitazone and metformin on intracellular lipid content in liver and skeletal muscle of individuals with type 2 diabetes mellitus
Authors: Tetsuya Teranishi, Takeshi Ohara, Kengo Maeda, Masako Zenibayashi, Kunichi Kouyama, Yushi Hirota, Hideaki Kawamitsu, Masahiko Fujii, Kazuro Sugimura, Masato Kasuga
Journal: Metabolism (2007)
The Safety of Treating Rheumatoid Arthritis With Aspirin
Authors: Eric P. Gall
Journal: JAMA (1982)

High-dose aspirin has long been considered first-choice therapy for the treatment of rheumatoid arthritis and other inflammatory rheumatic diseases.<sup>1</sup>Recently some clinicians have challenged this premise and suggested that the newer nonsteroidal anti-inflammatory agents, while more costly, are equally efficacious and less toxic.<sup>2</sup>They have emphasized less gastrointestinal toxic reaction and have suggested that these drugs be substituted for aspirin as a foundation of medical therapy. We have disagreed, noting the relatively short experience with the newer agents, as well as the emergence of a number of side effects with their continued use.<sup>3</sup>The subject of renal toxic reaction of aspirin and other nonsteroidal agents has been discussed in the literature. The article by Emkey and Mills in this issue ofThe Journal(p 55) examines the safety of long-term ingestion of large cumulative doses of aspirin from the standpoint of significant renal parenchymal disease. To decide
Abstract P2-09-23: Investigating VAV3 Expression as a Novel Biomarker and Indicator of Chemosensitivity in Basal-Like Breast Cancer
Authors: JE Getz, EM Anderson, Y Balagurunathan, MA Black, IA Hedenfalk, AL Willis, P Ramos, CM Mancini, HE. Cunliffe
Journal: Cancer Research (2010)

Abstract Background: Basal-like breast (BLB) cancer accounts for ∼15% of all breast cancers diagnosed. Patients with BLB cancer are typically younger, present with higher tumor grade and despite recent advances in therapy, still have a poor outcome. BLB cancers are the most proliferative breast tumor sub-type, are commonly triple-negative (ER-, PgR-, HER2/neu-), and often harbor mutations in TP53 and BRCA1. The biological drivers of disease progression in this tumor subtype remains poorly understood. Recently, VAV3, a guanine nucleotide exchange factor and a member of the of the Rho/Rac/Cdc42 GTPase superfamily, has been reported as overexpressed and oncogenic in ER+ breast cancer cells. Our preliminary studies using publicly available microarray data indicates a consistent lack of VAV3 in BLB cancer, particularly those patients with shorter survival time following chemotherapy. We therefore hypothesize that VAV3 is a novel biomarker of BLB cancer and potential predictor of chemosensitivity in this subtype. Materials and Methods: Gene expression microarray technology, qRTPCR and western blotting was used to investigate relative expression of VAV3 in a panel of breast cancer cell lines and tumors. Array Comparative Genomic Hybridization and Fluorescence in Situ Hybridization were used to evaluate VAV3 gene copy number. BLB cancer cell lines stably overexpressing VAV3 were developed to evaluate the role of VAV3 in sensitivity to chemotherapy. Results: Unsupervised hierarchical clustering revealed low VAV3 expression in BLB tumors compared to all other intrinsic subtypes. Consistently lower VAV3 mRNA and protein expression were observed in BLB cancer cell lines compared to luminal epithelial cell lines, consistent with our in silico observations. We confirmed that low VAV3 expression in the BLB cancer cell lines is not due to gene copy number loss. Ectopic expression of VAV3 in MDA-MB-231 BLB cancer cells significantly enhanced their sensitivity to cisplatin. Discussion: A consistent lack of VAV3 gene expression is evident in BLB tumors, however the mechanism underlying this loss is yet to be elucidated. Our findings support a hypothesis that low VAV3 expression is a potential diagnostic biomarker of BLB cancer, and that VAV3 expression may be a predictor of response to chemotherapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-23.
Hierarchical approach to replication and selection
Authors: Alexei A. Sharov
Journal: Behavioral and Brain Sciences (1999)

The major merit of Rose's book is the elaboration of the idea of multilevel causation in different explanatory languages. Yet Rose's critique of “ultra-Darwinism” is not convincing. Rose argues that activity and self-replication are properties of organisms rather than genes, which contradicts his idea of multilevel causation. Also, Rose fails to develop the concept of multilevel selection.
Spirolactone Effect on Postoperative Electrolytes and Adrenal Activity
Authors: Robert H. Seller, Osvaldo Ramirez-Muxo, Charles Swartz, Nicholas Pitha, Albert N. Brest
Journal: JAMA (1963)

NOT LONG AFTER intravenous sodium chloride solutions became available for human use, they were administered to surgical patients. It soon became apparent that salt was retained during the postoperative period to such a degree that some patients became edematous and a few developed overt congestive heart failure after sodium chloride administration. In 1945, Coller and associates quantitated postoperative salt retention by the use of a sodium chloride solution infusion. They found that patients retained approximately 50% of an intravenous sodium chloride solution load during the first 30 hours after an abdominoperineal resection.<sup>1</sup>Although stress-induced adrenal cortical hyperactivity was postulated as a cause of postoperative salt retention, the minimal mineralo-corticoid activity of cortisone or cortisol did not appear to account for the marked salt retention. In 1952 aldosterone, a corticosteroid which possesses one thousand times the salt-retaining potency of cortisone, was isolated.<sup>2</sup>Subsequently the role of aldosterone as
PMO-073 Post-operative enteral nutrition and recirculation of jejunal effluent in the management of a paraduodenal hernia: a case report
Authors: D Mcgrogan, S McCain, A Harris, K McCallion
Journal: Gut (2012)

<h3>Introduction</h3> Short gut secondary to surgical resection often requires post-operative total parenteral nutrition. We present a case of ischaemic gut secondary to a paraduodenal hernia. Post-operative nutritional requirements were met using enteral feeding via a feeding jejunostomy and recycling end jejunostomy effluent. <h3>Methods</h3> Case: A female presented with abdominal pain and metabolic acidosis. A double contrast abdominal computer topography scan revealed necrotic small bowel secondary to an internal hernia into the right paraduodenal fossa. She was found to have 180 cm of infarcted jejunum and ileum. After resection of this segment an end jejunostomy was formed along with a closed mucus fistula from proximal ileum. 50 cm proximal to this a feeding jejunostomy/ileostomy was constructed. Early jejunal feeding with elemental feed was commenced on day 1. Loperamide and codeine were added to slow intestinal transit and promote absorption. On day 5, bile excreted via her jejunostomy was recycled via her feeding jejunostomy. Her enteral feed was changed from elemental to modular on day 8 and sandostatin commenced. Her nutritional markers improved on this regime and despite having only 50 cm of jejunum proximal to her stoma, outputs were low and her electrolytes remained normal. She put on weight post-operatively and proceded to closure of her stomas at 6 months. <h3>Results</h3> N/A. <h3>Conclusion</h3> Discussion: Internal hernias are rare and commonly present with small bowel obstruction. Paraduodenal hernias are the most common form and can be either left or right sided. Normal small intestinal length varies between about 275 cm to 850 cm with nutritional or fluid supplementation required for patients with &lt;200 cm. This lady had a post-operative bowel length of 225 cm. The majority of gastrointestinal secretions are reabsorbed in the upper jejunum and patients with jejunostomies often have large volume stomal output. We used loperamide and codeine to slow intestinal transit, aid absorption and prevent fluid and electrolyte imbalance. Limited reports of bile-jejunostomy recycling were found in the literature and to our knowledge no cases have been reported of patients with short bowel being managed using recirculation of jejunal effluent and enteral nutrition in isolation. In this case, jejunostomy fluid was collected and immediately recycled via a feeding ileostomy eliminating the need for parenteral nutrition. Success was shown by improvement in nutritional status and weight gain. <h3>Conclusion</h3> This case exemplifies the effective use of jejunostomy output recycling to reduce water and electrolyte loss and aid fat absorption in a patient with short gut thus preventing the use of parenteral nutrition. <h3>Competing interests</h3> None declared.
Assessment of Upper Airway Dynamics in Awake Patients with Sleep Apnea Using Phrenic Nerve Stimulation
Authors: FRÉDÉRIC SÉRIÈS, CHRISTIAN STRAUS, ALEXANDRE DEMOULE, VALÉRIE ATTALI, ISABELLE ARNULF, JEAN-PHILIPPE DERENNE, THOMAS SIMILOWSKI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Phrenic nerve stimulation can reproduce during wakefulness the dissociation between upper airway and inspiratory muscles that is associated with obstructive sleep-related breathing disorders. This could provide a useful management tool in the study of passive upper airway (UA) dynamics during wakefulness in patients with the obstructive sleep apnea–hypopnea syndrome (OSAHS). To assess the feasibility of the technique in this setting, we studied the dynamics of diaphragm twitch-associated inspiratory flow in eight patients with OSAHS. Cervical magnetic stimulation (CMS) and bilateral anterior magnetic phrenic stimulation (BAMPS) were applied at end-expiration during exclusive nasal breathing. Electrical phrenic nerve stimulation (ES) proved not feasible. The driving pressure and the respiratory resistance at peak twitch esophageal pressure obtained at maximal stimulation intensity were significantly higher with BAMPS than with CMS. A twitch-flow limitation pattern was observed in seven of eight subjects; Vi max values of flow-limited twitches obtained at 100% stimulation intensity was 0.81 ± 0.5 L/s with BAMPS and 0.87 ± 0.5 L/s with CMS (p = 0.4). The number of flow-limited BAMPS twitches dropped from an average 77.5% to 18.4% with nasal continuous positive airway pressure (CPAP) levels corresponding to the patient's home treatment. We conclude that (1) BAMPS is potentially a useful tool to evaluate the dynamics of flow through the passive UA in awake OSAHS patients, (2) BAMPS may be superior to CMS in evaluating UA properties in OSAHS.
Mind wandering and driving: responsibility case-control study
Authors: C. Galera, L. Orriols, K. M'Bailara, M. Laborey, B. Contrand, R. Ribereau-Gayon, F. Masson, S. Bakiri, C. Gabaude, A. Fort, B. Maury, C. Lemercier, M. Cours, M.-P. Bouvard, E. Lagarde
Journal: BMJ (2012)

<h3>OBJECTIVE</h3> Early recanalisation by thrombolysis is a conclusive therapy for acute ischaemic stroke. But this therapy may increase the risk of intracerebral haemorrhage or severe brain oedema. The purpose was to evaluate usefulness of quantitative measurement of cerebral blood flow by single photon emission computed tomography (SPECT) in predicting the risk of haemorrhage or oedema, and determining the therapeutic options in acute hemispheric ischaemic stroke. <h3>METHODS</h3> The relation was studied retrospectively between initial regional cerebral blood flow (rCBF) quantitatively measured by technetium-99m-labelled hexamethylpropyleneamine oxime (<sup>99m</sup>Tc-HMPAO) SPECT and final clinical and radiological outcome in 20 patients who presented hemispheric ischaemic stroke and were treated conservatively or received early recanalisation by local intra-arterial thrombolysis. The non-invasive Patlak plot method was used for quantitative measurement of rCBF by SPECT. <h3>RESULTS</h3> Regions where residual rCBF was preserved over 35 ml/100 g/min had a low possibility of infarction without recanalisation and regions where residual rCBF was preserved over 25 ml/100 g/min could be recovered by early recanalisation. However, regions where residual rCBF was severely decreased (&lt; 20 ml/100 g/min) had a risk of intracerebral haemorrhage and severe oedema. <h3>CONCLUSIONS</h3> A quantitative assessment of residual rCBF by <sup>99m</sup>Tc-HMPAO SPECT is useful in predicting the risk of haemorrhage or severe oedema in acute ischaemic stroke. Therapeutic options should be determined based on the results of rCBF measurement.
Phase I Safety and Pharmacokinetic Study of the PI3K/mTOR Inhibitor SAR245409 (XL765) in Combination with Erlotinib in Patients with Advanced Solid Tumors
Authors: Pasi A. Jänne, Roger B. Cohen, A. Douglas Laird, Sandrine Macé, Jeffrey A. Engelman, Rodrigo Ruiz-Soto, Kevin Rockich, Jianbo Xu, Geoffrey I. Shapiro, Pablo Martinez, Enriqueta Felip
Journal: Journal of Thoracic Oncology (2014)
Surgical management of nystagmus
Authors: J. Lee
Journal: Journal of the Royal Society of Medicine (2002)

All nystagmus degrades visual acuity by reducing the stability of fixation and lessening foveation time. In addition, adults with acquired nystagmus may complain of oscillopsia, a subjective impression of movement of the perceived world. Surgery may be performed for congenital nystagmus (CN), for latent or manifest-latent nystagmus (LN, MLN) or for acquired nystagmus. Nystagmus surgery aims to reduce the amplitude of nystagmus with either improvement of visual acuity or a reduction of a bothersome head posture. The commonest reason for patients' seeking surgical treatment is to allow them to acquire a driving licence. Regrettably, this is frequently not possible.
Letter: Increased serum iron in acute leukaemia.
Authors: D H Parry, M Worwood, A Jacobs
Journal: BMJ (1975)

It seems clear that the only spastic infant in our series would have been equally likely to be handicapped had it been delivered by caesarean section and, in our hands, prolonged resuscitation did not keep alive spastics caused by the mode of delivery, so depressing our perinatal loss rate.I thank Mr. E. 0.
Ventilation Asymmetry after Transplantation for Emphysema
Authors: Anne De Groote, Alain Van Muylem, Pietro Scillia, Guy Cheron, Geert Verleden, Manuel Paiva, Marc Estenne
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

After single-lung transplantation for emphysema, the hyperinflated native lung and the graft have different extents and rates of inflation and emptying. This requires that breathing produces asymmetrical expansion of the chest wall, displacement of the mediastinum, or both. In a first study in four seated transplant recipients, we measured the volumes of the two hemithoraces with optoelectronic plethysmography. Functional residual capacity and total lung capacity were identical on the native and transplanted sides, and changes in chest wall volume during CO(2)-induced hyperpnea and FVC maneuvers were similar on both sides. Studies with computerized tomography in three of these patients and in four additional patients in supine posture indicated that the mediastinum was shifted toward the graft at functional residual capacity and total lung capacity. The mediastinum moved toward the native lung during tidal and full inspiration and toward the graft during tidal and forced expiration; additional studies with fluoroscopy showed qualitatively similar changes in upright posture. In summary, the two hemithoraces assume identical static volumes and show similar volume changes during CO(2)-induced hyperpnea and FVC maneuvers in patients with single-lung transplantation for emphysema; displacement of the mediastinum accommodates part, if not all, of the unequal lung volumes and asymmetrical ventilation.
Evaluation of plitidepsin in patients with primary myelofibrosis and post polycythemia vera/essential thrombocythemia myelofibrosis: results of preclinical studies and a phase II clinical trial
Authors: A Pardanani, A Tefferi, P Guglielmelli, C Bogani, N Bartalucci, J Rodríguez, S Extremera, I Pérez, V Alfaro, A M Vannucchi
Journal: Blood Cancer Journal (2015)

Abstract Previous data established that plitidepsin, a cyclic depsipeptide, exerted activity in a mouse model of myelofibrosis (MF). New preclinical experiments reported herein found that low nanomolar plitidepsin concentrations potently inhibited the proliferation of JAK2V617F-mutated cell lines and reduced colony formation by CD34+ cells of individuals with MF, at least in part through modulation of p27 levels. Cells of MF patients had significantly reduced p27 content, that were modestly increased upon plitidepsin exposure. On these premise, an exploratory phase II trial evaluated plitidepsin 5 mg/m 2 3-h intravenous infusion administered on days 1 and 15 every 4 weeks (q4wk). Response rate (RR) according to the International Working Group for Myelofibrosis Research and Treatment consensus criteria was 9.1% (95% CI, 0.2–41.3%) in 11 evaluable patients during the first trial stage. The single responder achieved a red cell transfusion independence and stable disease was reported in nine additional patients (81.8%). Eight patients underwent a short-lasting improvement of splenomegaly. In conclusion, plitidepsin 5 mg/m 2 3-h infusion q4wk was well tolerated but had a modest activity in patients with primary, post-polycythaemia vera or post-essential thrombocythaemia MF. Therefore, this trial was prematurely terminated and we concluded that further clinical trials with plitidepsin as single agent in MF are not warranted.
Renal function in relation to low levels of cadmium exposure in a group of smelter workers.
Authors: G Kazantzis, B G Armstrong
Journal: Environmental Health Perspectives (1984)

Blood and urine samples were obtained from 274 smelter workers and urine samples from 48 controls. Cadmium, beta 2-microglobulin, and creatinine were estimated in blood and urine, and total protein in urine. Concentrations of cadmium in urine (mean 2.0 nmole/mmole creatinine) and blood (mean 21.8 nmole/L) observed in the smelter workers confirmed that this group had absorbed more cadmium than the general population, but less than most other occupationally exposed groups studied. Mean beta 2-microglobulin in urine was not significantly different in the smelter workers and the controls. The mean total protein in urine was 20% higher in the smelter workers, a difference which was significant (p congruent to 0.01). There was no consistent picture within the smelter workers of a relationship between history of cadmium exposure and the effect measures of beta 2-microglobulin in urine and blood, total protein in urine, creatinine clearance and relative beta 2-microglobulin clearance. Small but significant positive correlation coefficients were observed between cadmium in urine and beta 2-microglobulin in urine (r = 0.13), total protein in urine (r = 0.23) and beta 2-microglobulin clearance (r = 0.15), although these may be artifactual.