tbuckley/cabot-search huggingface dataset:
P101 Effects Of Using A Mask Vs. Mouthpiece On The Multiple Breath Inert Gas Washout Technique
Authors: S. Lum, J. Stocks, W. Kozlowska, P. Aurora
Journal: Thorax (2014)

<h3></h3> Assessment of ventilation inhomogeneity using the multiple breath washout (MBW) technique has been shown to be more sensitive than spirometry in detecting early cystic fibrosis lung disease throughout childhood. The current “gold standard” interface for school age children and adults is a mouthpiece. Although masks are better tolerated by infants and younger children, their use increases equipment deadspace-which could influence measured values and hence interpretation of results. The aim of this study was to examine the effect of using a mask vs mouthpiece on values of functional residual capacity (FRC) and the lung clearance index (LCI) derived from MBW. <h3>Method</h3> Comparisons were performed in healthy adults. The study design incorporated repeated measures as well as interface comparison. The mask was selected to mimic measurement conditions in infants, the deadspace of 85 mL being approximately 1–2 ml/kg in adults. Mouthpiece (MP) deadspace was ~5 ml. Subjects were randomly allocated to group A (Mask-Mouthpiece-Mouthpiece) or group B (Mouthpiece-Mouthpiece-Mask) protocols. Each subject performed a total of 9 MBW runs, in 3 sets, each consisting of 3 runs, with a 5-minute break between each set. MBW was performed using a mass spectrometer as described previously (Aurora 2005 AJRCCM). Paired t-tests with 95% limits of agreement were used to establish repeatability (MP1 vs. MP2) and any differences between Mask vs. Mouthpiece. This study was approved by the local research ethics committee and written consent obtained from subjects. <h3>Results</h3> Technically satisfactory comparative data were obtained on 15 occasions in 14 adults (36% males; age: 22–56 years). Respiratory rate and tidal volume were similar using either approach. Repeatability: Both FRC and LCI were repeatable using the mouthpiece [(Mean (95% CI) diff: FRC: 0.012L (-0.05;0.07); LCI: -0.1(-0.3; 0.1)]; Figure 1A and B. Mask vs. Mouthpiece: FRC and LCI were both significantly higher when assessments were made using a mask compared with a mouthpiece: FRC: 0.101L (0; 0.202); LCI: 0.4 (0.2;0.7); Figure 1C and D. <h3>Conclusion</h3> The increase in LCI when using a facemask exceeded normal within test variability in adults and could influence interpretation of results especially if different patient interfaces are used when collecting data in younger children.
A Case-Control Study of the Effectiveness of Bicycle Safety Helmets
Authors: Robert S. Thompson, Frederick P. Rivara, Diane C. Thompson
Journal: New England Journal of Medicine (1989)

Bicycling accidents cause many serious injuries and, in the United States, about 1300 deaths per year, mainly from head injuries. Safety helmets are widely recommended for cyclists, but convincing evidence of their effectiveness is lacking. Over one year we conducted a case-control study in which the case patients were 235 persons with head injuries received while bicycling, who sought emergency care at one of five hospitals. One control group consisted of 433 persons who received emergency care at the same hospitals for bicycling injuries not involving the head. A second control group consisted of 558 members of a large health maintenance organization who had had bicycling accidents during the previous year. Seven percent of the case patients were wearing helmets at the time of their head injuries, as compared with 24 percent of the emergency room controls and 23 percent of the second control group. Of the 99 cyclists with serious brain injury only 4 percent wore helmets. In regression analyses to control for age, sex, income, education, cycling experience, and the severity of the accident, we found that riders with helmets had an 85 percent reduction in their risk of head injury (odds ratio, 0.15; 95 percent confidence interval, 0.07 to 0.29) and an 88 percent reduction in their risk of brain injury (odds ratio, 0.12; 95 percent confidence interval, 0.04 to 0.40). We conclude that bicycle safety helmets are highly effective in preventing head injury. Helmets are particularly important for children, since they suffer the majority of serious head injuries from bicycling accidents. (N Engl J Med 1989;320:1361–7.)
Abstract 3898: NOSH-aspirin: A novel nitric oxide- and hydrogen sulfide-releasing hybrid for treatment of colon cancer
Authors: Diana H. Lee, Diandra E. Nesbitt, Mitali Chattopadhyay, Ravinder Kodela, Khosrow Kashfi
Journal: Cancer Research (2012)

Abstract Introduction: In our search for a better non-steroidal anti-inflammatory drug (NSAID) we have synthesized a series of nitric oxide-, and hydrogen sulfide-releasing hybrid compounds that have IC50s for cell growth inhibition in the low nano-molar range. We have termed these NOSH compounds. Our lead agent, NOSH-aspirin is in the order of 100,000 to 250,000-fold more potent than aspirin in inhibiting colon cancer cell growth over a 24-72h time period. NOSH-aspirin although highly potent, has very limited cyto-toxicity, lactate dehydrogenase (LDH) release at 4 times its IC50 for cell growth inhibition was less than 10% at 24h. Here we report our results on the effects of NOSH-aspirin treatment on established tumors in a xenograft model of human colon cancer cells. Methods: Compound: NOSH-aspirin was synthesized and purified by us with 1H-NMR verification. Cell line: HT-29 human adenocarcimoma; Xenografts: Male athymic SKID mice were implanted s.c. in the right flank with HT-29 (2 x 106) cells suspended in 50% Matrigel, after 10 days the animals were randomly divided into 4 groups (N = 7/group) and gavaged daily with NOSH-aspirin (25 or 50 or 100 mg/kg body weight) or vehicle. Tumor volume and animal weight were recorded every 3 days. After 3 weeks of treatment, mice were sacrificed, tumors excised, weighed, and fixed in 10% buffered formalin for immunohistochemical studies. Results: NOSH-aspirin had no effect on the weight of the mice even at the highest concentration used. There were no overt signs of toxicity. It dose-dependently reduced tumor mass by 50 ± 7%, 75 ± 5%, 90 ± 3 % at 25, 50, and 100 mg/kg, respectively. Tumor volume was also dose-dependently reduced as a function of time. NOSH-aspirin inhibited growth of HT-29 colon cancer cells xenografts as a result of reduced proliferation (decreased PCNA expression), and induction apoptosis (increased number of TUNEL positive cells). NF-κB, activated in control xenografts was significantly inhibited by NOSH-aspirin. Conclusions: NOSH-aspirin has potent anti-cancer affects and merits further evaluation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3898. doi:1538-7445.AM2012-3898
P01 The effect of intraoperative N-acetylcysteine on hepatocellular injury during laparoscopic bariatric surgery: a randomised controlled trial
Authors: A. P. Belgaumkar, K. A. Carswell, R. R. Mitry, R. D. Hughes, A. Dhawan, A. G. Patel
Journal: Gut (2011)

<h3>Introduction</h3> The combination of pneumoperitoneum and intraoperative retraction of the left lobe of the liver leads to hepatocellular injury during laparoscopic oesophago-gastric surgery, with often more than a sixfold rise in serum transaminases. Fatty livers are more susceptible to ischaemic insults and increased oxidative stress. <h3>Aim</h3> The aim of the study was to investigate whether the antioxidant N-acetylcysteine (NAC) could reduce liver injury during laparoscopic sleeve gastrectomy. <h3>Method</h3> Patients undergoing laparoscopic sleeve gastrectomy were allocated to receive intraoperative NAC infusion or standard anaesthetic treatment in a single blind randomised controlled trial. Blood samples were taken before and at the end of surgery and on post-operative days 1–4. Primary endpoints included serum aminotransferases and clinical outcomes. Secondary measures were markers of oxidative stress (superoxide dismutase, lipid peroxidation (TBARS) and liver injury (cytokeratin-18 M30 and M65) and plasma TRAIL and FasL for apoptosis. <h3>Results</h3> 20 patients (14 females, median age 44 (27–64) years, median BMI 62 (39–83) kg/m<sup>2</sup>) were recruited; NAC n=10, control n=10. Demographic parameters and baseline liver function were similar [pre-op ALT NAC median 25 U/ml (IQR 24–42) vs control 30.5 (29–44)]. The peak rise in liver enzymes was on day 1, but the levels were not significantly different between the groups? ALT: NAC median 126 (IQR 73–627) vs control 136 (107–239); AST: NAC 130 IU/l (68–504) vs Control 124 (72–237). There were no significant differences in day 1 superoxide dismutase (NAC 0.48 pg/ml vs Control 0.66), TBARS (NAC 8.84 nmol/ml vs Control 12.47), CK18-M30 (NAC 340U/l vs 471) and CK18-M65 (NAC 803.5 U/l vs 878). There was a significant reduction in TRAIL and FasL after POD1 (TRAIL pre-op 100.6 pg/ml day 1_ 38.8, p&lt;0.01; FasL pre-op 94.6 pg/ml vs POD1 67.5, p&lt;0.01), but there were no significant differences between the treatment groups. Rates of complications and length of stay were not significantly different. <h3>Conclusion</h3> NAC was not shown reduce intraoperative liver injury in this small number of patients. The heterogenous nature of the bariatric patient population, with differences in comorbidities, body mass index and intra-abdominal anatomy, makes this difficult. Significant hepatocyte injury does occur through both necrosis and apoptosis, which does not appear to be mediated by TRAIL or FasL.
Abstract 4274: Prolidase directly binds and activates epidermal growth factor receptor and stimulates downstream signaling.
Authors: Lu Yang
Journal: Cancer Research (2013)

Abstract Prolidase, also known as Xaa-Pro dipeptidase or peptidase D (PEPD), is a ubiquitously expressed enzyme that hydrolyzes dipeptides with proline or hydroxyproline at the carboxy terminus. Unexpectedly, we have found that recombinant human PEPD directly binds and activates epidermal growth factor receptor (EGFR), and that EGFR activation by PEPD in turn leads to activation of multiple signaling molecules downstream of EGFR, including but may not be limited to AKT, ERK and STAT3. EGFR is a cell surface receptor that plays a major role in a variety of cellular responses, and EGFR activation is known to result in increase in DNA synthesis, cell growth, cell proliferation and cell migration, which perhaps are most clearly demonstrated in cancer cells. The ability of PEPD to activate EGFR signaling is neither cell-specific nor dependent on its enzymatic activity; in the latter case, an enzymatically inactive PEPD mutant was similarly effective in activating EGFR, AKT, ERK and STAT3. PEPD is also a novel inducer of cyclooxygenase-2 (Cox-2), known to play an important role in cancer, inflammation and other diseases, but Cox-2 induction by PEPD also depends on EGFR activation. In line with the pro-survival and pro-proliferation activities of EGFR and Cox-2, PEPD stimulates cell proliferation and DNA synthesis in cultured cells. However, PEPD could activate EGFR only when it was present in the extracellular space, as forced expression of human PEPD via transient gene transfection failed to activate EGFR and the downstream signaling proteins. This result is nonetheless consistent with EGFR being a cell surface receptor. Although PEPD is normally a cytosolic protein, it is apparently released from injured cells and tissues in vivo, and such release appears to result in EGFR activation and activation of its downstream signals. PEPD differs from all known EGFR ligands in that it does not possess an epidermal growth factor (EGF) motif and is not synthesized as a transmembrane precursor. Indeed, there are several notable differences between PEPD and EGF with regard to binding and activation of EGFR and activation of downstream signaling molecules. In conclusion, PEPD is a new ligand of EGFR and presents a novel mechanism of EGFR activation. Citation Format: Lu Yang. Prolidase directly binds and activates epidermal growth factor receptor and stimulates downstream signaling. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4274. doi:10.1158/1538-7445.AM2013-4274
Abstract 5147: Glutamine addiction: Recognizing and harnessing the pathometabolic potential of Ras-mediated macropinocytosis
Authors: Cosimo Commisso, Rengin G. Soydaner-Azeloglu, Dafna Bar-Sagi
Journal: Cancer Research (2012)

Abstract Oncogenic mutations in Ras-encoding genes are found in approximately 30% of all human tumors and are most prevalent in carcinomas of the pancreas, colon, lung and bladder. Oncogenic forms of Ras are trapped in a constitutively active state and, as a consequence, promote the persistent stimulation of effector pathways that control cell growth, survival and proliferation. A prominent phenotypic feature associated with oncogenic Ras expression is the stimulation of macropinocytosis, an endocytic process that mediates the uptake of extracellular fluid via large, heterogeneous vesicles known as macropinosomes. While in amoeboid organisms this process has been linked to nutrient internalization, the functional significance of oncogenic Ras-mediated macropinocytosis is unknown. We have found that cancer cells harboring oncogenic Ras utilize macropinocytosis to internalize extracellular albumin, a major constituent of extracellular fluids and a potentially rich source of amino acids. Furthermore, we have established that tumor cells harboring oncogenic Ras mutations display robust macropinocytosis in vivo. Utilizing cell biological approaches and amino acid quantification, we determined that extracellular albumin that is internalized via oncogenic Ras-stimulated macropinosomes is targeted for degradation leading to the intracellular production of albumin-derived amino acids. Cancer cells display a heightened dependence on glutamine due to their need to sustain rapid proliferation, bioenergetics and macromolecular biosynthesis. We have observed that in cells expressing oncogenic Ras, the adverse effects of glutamine deprivation on cell growth can be rescued by macropinocytosis-mediated uptake of extracellular albumin. Moreover, the capacity of macropinocytic inhibition to diminish this growth advantage is dependent on both glutamine and glutamine-derived metabolites. These results indicate that macropinocytosis may serve as a glutamine supply mechanism that is particularly critical under conditions where free glutamine is limiting. Together, these data implicate oncogenic Ras-mediated macropinocytosis in the regulation of cancer cell metabolism and point to the possibility of exploiting this process in the design of anti-cancer therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5147. doi:1538-7445.AM2012-5147
SP0199 Overcoming the outside and Inner Barriers – A Personal Experience of Travelling with an Rmd
Authors: L. Kyriakides
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> I am Litsa Kyriakides and I come from Cyprus. Although since I was a kid I suffer from severe RMD I am very fond of travelling. I am motivated by the challenge, the adventure, the knowledge I acquire, the people I meet, making new friends, the experience of different cultures, but most of all the change of environment from the everyday routine. So far I visited many countries in all continents and had very interesting experiences. From these experiences I was taught many tips and ways to overcome most outside and inner barriers so that I can have enjoyable holidays. Good organization and planning makes travelling with RMD easier. I always Start planning my holidays early. I make realistic plans and I consider all factors, internal and external, that may determine any decision for travelling. I do my own research based on my own needs and decide which is best for me i.e. whether to use a travel agent or organize everything on my own. I collect and save all useful information in a folder or my lap-top. I try to avoid fatigue and stress, stay healthy and safe, before and during my trip. Over the time, I adapt my holiday plans to my health condition and age. The importance of having support. However, setbacks may occur before or during my travel. I feel I always gain and benefit from my trips. Travelling with RMD is all about challenge, achievement and accomplishment. Always make dreams, set goals and make plans. Live the day. There may never be a better opportunity than today so accomplish what you can, NOW. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6149
SAT0178 IGA+ plasmablasts contribute to the expansion of peripheral plasmablasts in SLE
Authors: S. Schmidt, B.F. Hoyer, H.E. Mei, T. Dörner
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Active systemic lupus erythematosus (SLE) is associated with increased levels of peripheral blood antibody-secreting plasmablasts which correlate with autoantibody production and disease activity. Plasmablasts which circulate in healthy individuals at very low levels in steady-state express a mucosal phenotype and secrete IgA, but are conditionally expanded by additional IgG-secreting plasmablasts during systemic immune responses. The dynamics of plasmablasts generated in mucosal IgA vs. systemic IgG responses underlying the expanded plasmablast subset in SLE patients and its implication in SLE immunopathogenesis remain unexplored. <h3>Objectives</h3> To analyse the blood of SLE patients for the presence and characteristics of IgA+ plasmablasts and to evaluate their potential relation to SLE disease activity. <h3>Methods</h3> Peripheral blood plasmablasts from 30 SLE patients and 20 healthy controls (HD) were enumerated and analysed by multi-parametric flow cytometry using antibodies directed against CD19, CD27, CD20, and analysed for surface co-expression of IgA, CCR10 and beta7 Integrin. Disease activity was assessed by SLEDAI scores. <h3>Results</h3> IgA+ plasmablasts were detected in the blood of all controls and at significantly higher numbers in SLE patients (HD, IgA+ 1,2 cells/μl; SLE, IgA+ 3,2 cells/μl; p=0.0017). Patients with high disease activity (SLEDAI ≥6) showed significantly higher numbers of circulating IgA+ plasmablasts when compared with less active patients at SLEDAI&lt;6 (p=0.0442). In both patients and controls, the majority of plasmablasts expressed at least one of the mucosal markers, i.e. IgA, beta7 Integrin or CCR10, suggesting their generation in mucosal immune responses. In SLE patients, expression of CCR10 and beta7 integrin was associated with IgA expression. However, we found that a unique IgA+/CCR10-/beta7- plasmablast subset disproportionately contributed to the expansion of IgA+ plasmablasts in the blood of SLE patients (HD, 25%; SLE, 38%). In contrast, IgA+ plasmablasts expressing CCR10 but not beta7 Integrin were significantly reduced in SLE patients compared to healthy controls (HD, 48%; SLE, 29%; p=0,0182). <h3>Conclusions</h3> Our data demonstrate that IgA+ plasmablasts contribute to the expanded plasmablast subset in SLE patients related to disease activity. The data implicate enhanced activation and differentiation of mucosal B cells, although the expansion of a distinct IgA+ plasmablast subset lacking mucosal homing receptors beta7 Integrin and CCR10 indicates abnormalities of mucosal B cell activation in these patients. <h3>Disclosure of Interest</h3> None Declared
Abstract 3319: CD44 standard isoform regulates the mesenchymal phenotype in hepatocellular carcinoma cells, and associates with a poor prognosis in patients.
Authors: Kosuke Mima, Hirohisa Okabe, Takatsugu Ishimoto, Toru Beppu, Hideo Baba
Journal: Cancer Research (2012)

Abstract Purpose: Cancer stem cells (CSCs) in many tumors have been identified using CD44, either individually or in combination with other markers and are involved in tumor progression and metastasis. Epithelial-mesenchymal transition (EMT) is known to induce cancer invasion, metastasis, and CSCs properties. However, the underlying molecular mechanisms which integrate EMT and CSCs properties remain largely unknown. In this study, we test the hypothesis that CSCs markers play an important role in regulating EMT in hepatocellular carcinoma (HCC). Experimental Design: The relationship between the CSCs markers and EMT markers was investigated in HCC cell lines. The EMT markers, invasive phenotype, the relevant transcriptional factors and signaling pathways induced by CD44 were examined in vitro. The clinicopathological importance of CD44 standard isoform (CD44s) expression was analyzed by an immunohistochemical analysis, and the correlation of CD44s and EMT markers was determined in 150 patients with hepatocellular carcinoma. Results: HCC cell lines with high CD44 expression showed decreased E-cadherin expression and increased vimentin expression. CD44s mRNA was dominant form of CD44 mRNA present in HCC cell lines with the mesenchymal phenotype. Overexpression of CD44s in HCC cells induced the mesenchymal phenotype and increased tumor cell invasion, whereas knockdown of CD44s in HCC cells led to loss the mesenchymal phenotype and decreased tumor cell invasion. CD44s expression was associated with E-cadherin low expression (P=0.039) and vimentin high expression (P&amp;lt;0.001). CD44s expression was related to a large tumor size (P=0.003), multiple tumors (P=0.032), and poor tumor differentiation (P=0.020), and a shorter disease-free (P=0.023) and overall survival (P=0.013) in patients with HCC. Conclusions: our study will be valuable for understanding the relationship between CSCs and EMT, and the identification of new treatment targets for future HCC treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3319. doi:1538-7445.AM2012-3319
Case 30-2015
Authors: Thurman M. Wheeler, Joshua N. Baker, David A. Chad, Jodi L. Zilinski, Stacey Verzosa, Daniel A. Mordes
Journal: New England Journal of Medicine (2015)

A 50-year-old man with a history of cardiomyopathy and progressive muscle weakness was admitted with cardiogenic shock. Electroencephalography showed total suppression of cerebral activity; ventilator support was withdrawn, and he died. An autopsy was performed.
Neural Degeneration and Regeneration in Human Renal Transplants
Authors: A. F. Gazdar, G. J. Dammin
Journal: New England Journal of Medicine (1970)

Neural degeneration and regeneration were studied histologically with hematoxylin–eosin and Bodian stains in 33 human renal transplants. By the fifteenth day after transplantation few intact axons were recognizable, and by the twenty-sixth day, only axonal debris remained. As early as the twenty-eighth day, regenerating axons appeared distal to the graft's arterial anastomosis. Regenerating axons could be traced to the nerves accompanying the interlobular arteries, but the axon population did not reach the number observed in normal nerves of comparable size. Allografts and isografts exhibited comparable patterns of neural regeneration.