tbuckley/cabot-search huggingface dataset:
In vitro comparison of different gall stone dissolution solvents.
Authors: H Vergunst, O T Terpstra, H G Nijs, G Steen
Journal: Gut (1991)

Extracorporeal shockwave lithotripsy (ESWL) of gall bladder stones leaves residual fragments that need to be dissolved by chemical solvents. In this study we compared the in vitro dissolving capacity of methyl tert-butyl ether (MTBE), mono-octanoin, limonene, and limonene/mono-octanoin (70%/30%). From nine sets of five human gall stones obtained at cholecystectomy, four stones were used for dissolution and the fifth was used for chemical analysis of cholesterol, calcium, and bilirubin contents. Eight sets were cholesterol stones with a mean (SD) cholesterol content of 89.9 (5.6)%. These stones dissolved completely in either solvent, often leaving sand-like debris, with the exception of one stone. MTBE dissolved cholesterol gall stones 100 times faster than mono-octanoin and 10 times faster than limonene or the limonene/mono-octanoin mixture (p less than 0.001). The combination of limonene and mono-octanoin was as effective as limonene alone. Of the four solvents, MTBE is the best one to evaluate for dissolution of residual fragments after ESWL treatment of gall bladder stones.
Mechanisms regulating cytochrome c release in pancreatic mitochondria
Authors: I V Odinokova, K-F Sung, O A Mareninova, K Hermann, Y Evtodienko, A Andreyev, I Gukovsky, A S Gukovskaya
Journal: Gut (2008)

<h3>Objective.</h3> To systematically review the literature on the safety of using nonsteroidal antiinflammatory drugs (NSAID) and/or paracetamol in people receiving methotrexate (MTX) for inflammatory arthritis (IA), as an evidence base for generating clinical practice recommendations. <h3>Methods.</h3> A systematic literature review was performed using the Cochrane Library, Medline, Embase, and conference proceedings for the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) for 2008–2009. The search aimed to identify studies describing adverse events (AE) with the concurrent use of paracetamol and/or NSAID in people taking MTX for IA. Articles fulfilling our predefined inclusion criteria were systematically reviewed and quality appraised. <h3>Results.</h3> Seventeen publications out of 8681 identified studies were included in the review, all of which included people with rheumatoid arthritis (RA) using various NSAID; there were no identified studies for other forms of IA or with paracetamol. Of the studies examining concurrent use of MTX and NSAID, there were no reported adverse effects on lung, liver, or renal function, and no increase in MTX withdrawal or in major toxic reactions. However, transient thrombocytopenia was demonstrated in 1 study. Looking at specific NSAID, there were no clinically significant AE with concomitant piroxicam or etodolac, and only mild AE with celecoxib or etoricoxib. Antiinflammatory dose aspirin was demonstrated to have an adverse effect on liver and renal function. <h3>Conclusion.</h3> In the management of RA, concurrent use of NSAID with MTX appears to be safe, provided appropriate monitoring is performed. The use of antiinflammatory doses of aspirin should be avoided.
Regulation of smooth muscle cell migration and integrin expression by the Gax transcription factor
Authors: Bernhard Witzenbichler, Yasuko Kureishi, Zhengyu Luo, Aude Le Roux, Didier Branellec, Kenneth Walsh
Journal: Journal of Clinical Investigation (1999)

Homeobox transcription factors specify body plan by regulating differentiation, proliferation, and migration at a cellular level. The homeobox transcription factor Gax is expressed in quiescent vascular smooth muscle cells (VSMCs), and its expression is downregulated by vascular injury or other conditions that lead to VSMC proliferation. Previous investigations demonstrate that Gax may regulate VSMC proliferation by upregulating the cyclin-dependent kinase (cdk) inhibitor p21. Here we examined whether Gax influences VSMC migration, a key feature in the development of stenotic lesions after balloon injury. Transduction of a Gax cDNA inhibited the migratory response of VSMCs toward PDGF-BB, basic fibroblast growth factor, or hepatocyte growth factor/scatter factor. Gax expression also inhibited migration of NIH.3T3 fibroblasts and embryonic fibroblasts lacking p53. Gax was unable to inhibit the migration of fibroblasts lacking p21, but this effect could be restored in these cells by providing exogenous p21 or by overexpressing another cdk inhibitor, p16. Flow cytometric analysis implicated a Gax-mediated downregulation of alpha(v)beta(3) and alpha(v)beta(5) integrin expression in VSMCs as a potential cause for reduced cell motility. Gax specifically downregulated beta(3) and beta(5) in VSMCs in culture and after acute vascular injury in vivo. Repression of integrin expression was also found in NIH 3T3 cells and p53 knockout fibroblasts, but not in p21-knockout fibroblasts, unless these cells express exogenous p21 or p16. These data suggest that cycle progression, integrin expression, and cell migration can be regulated in VSMCs by the homeobox gene product Gax.
Substance P‐induced pulmonary vascular remodelling in precision cut lung slices
Authors: J. Springer, A. Fischer
Journal: European Respiratory Journal (2003)

Substance P (SP) levels have been reported to be elevated in animal models of pulmonary hypertension (PH) and chronic administration of SP has been shown to induce PH. In the present study, the role of reactive oxygen species (ROS) as mediators of SP-induced vascular remodelling and PH was analysed. Vascular remodelling was induced in precision cut lung slices by treatment with [Sar9,Met11(O2)]-SP and by hypoxia. Functional analyses were used to study the chronic [Sar9,Met11(O2)]-SP-mediated effects on proliferation and generation of ROS, which is involved in the pathogenesis of PH. The nonpeptide NK-1 receptor antagonist CP 96345 was used to block [Sar9,Met11(O2)]-SP effects. ROS generation and proliferation was assayed by the dichloroflourescein-diacetate method and incorporation of 5-Bromo-2'-Deoxyuridine, respectively. ROS generation was induced by either 1% oxygen (5.8-fold) or [Sar9,Met11(O2)]-SP (8-fold) in normoxia in the alveolar region. [Sar9,Met11(O2)]-SP did not further elevate ROS levels in hypoxia, suggesting an oxygen-dependent mechanism. High ROS levels stabilised hypoxia inducible factor-1alpha and induced proliferation in small vessels (4.3-fold in hypoxia and [Sar9,Met11(O2)]-SP). Both ROS generation and proliferation were blocked in the presence of CP 96345, nitroblue-tetrazolium, N-acetylcysteine- and diphenylene-iodonium. The results presented in this study indicate a role of SP in proliferative events associated with vascular remodelling in pulmonary hypertension.
Cardiac Output by Thermodilution
Authors: R. William McIntyre
Journal: JAMA (1985)

<h3>To the Editor.—</h3> It has been estimated that between 1 and 2 million pulmonary artery catheters were inserted for hemodynamic monitoring in the last decade.<sup>1</sup>The prevalence of the procedure has increased substantially over the past few years. It is therefore of interest that the methodology of a clinical hemodynamic measurement, cardiac output by thermodilution, which is made less frequently than blood pressure and heart rate only, be the subject of continued investigation. Some of the errors associated with the early use of this technique have been eliminated by improved technology. For example, those due to alterations in injectate temperature<sup>2</sup>are now minimized by the use of both a proximal and distal thermistor. The question of the importance of the respiratory effect on the measurement of cardiac output appears to have now been settled by a report inThe Journal.<sup>3</sup>The data presented in this article demonstrate
Intracoronary Injection of Mononuclear Bone Marrow Cells in Acute Myocardial Infarction
Authors: Ketil Lunde, Svein Solheim, Svend Aakhus, Harald Arnesen, Michael Abdelnoor, Torstein Egeland, Knut Endresen, Arnfinn Ilebekk, Arild Mangschau, Jan G. Fjeld, Hans Jørgen Smith, Eli Taraldsrud, Haakon Kiil Grøgaard, Reidar Bjørnerheim, Magne Brekke, Carl Müller, Einar Hopp, Asgrimur Ragnarsson, Jan E. Brinchmann, Kolbjørn Forfang
Journal: New England Journal of Medicine (2006)

Previous studies have shown improvement in left ventricular function after intracoronary injection of autologous cells derived from bone marrow (BMC) in the acute phase of myocardial infarction. We designed a randomized, controlled trial to further investigate the effects of this treatment.
Structural and Functional Features of the B-Cell Receptor in IgG-Positive Chronic Lymphocytic Leukemia
Authors: Kathleen N. Potter, C. Ian Mockridge, Louise Neville, Isla Wheatley, Michael Schenk, Jennifer Orchard, Andrew S. Duncombe, Graham Packham, Freda K. Stevenson
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To determine the origin and relationship of the rare IgG+ variant of chronic lymphocytic leukemia (CLL) to the two common IgM+IgD+ subsets that are distinguished by expression of unmutated or mutated VH genes, with the former having a worse prognosis. Experimental Design: IgG+ CLL cells were characterized using phenotypic, functional, and immunogenetic analyses. Results: IgG+ CLL was phenotypically similar to mutated IgM+IgD+ CLL (M-CLL) and variably expressed CD38 (4 of 14). ZAP-70, a tyrosine kinase preferentially expressed in unmutated CLL, was found in only 2 of 14 cases. The ability to signal via surface IgM (sIgM) varies between the main subsets of CLL and is associated with expression of ZAP-70. In IgG+ CLL, 9 of 14 responded to engagement of sIgG with no apparent requirement for expression of CD38 or ZAP-70. However, signal capacity correlated with intensity of sIgG expression. Most switched immunoglobulin variable region genes were somatically mutated without intraclonal variation, and no case expressed activation-induced cytidine deaminase. Derivation from a postgerminal center B cell is, therefore, likely, and a relationship with M-CLL is suggested. This is supported by a shared biased usage of the V4-34 gene. Similar bias in normal B cells developed with age, providing an expanded population for transforming events. However, conserved sequences detected in the CDR3 of V4-34-encoded γ chains were not found M-CLL, indicating no direct path of isotype switch from M-CLL. Conclusion: IgG+ CLL is likely to arise from an age-related expanded pool of B cells, on a path parallel to M-CLL, and perhaps with a similar clinical course.
DT-Diaphorase Expression and Tumor Cell Sensitivity to 17-Allylamino,17-demethoxygeldanamycin, an Inhibitor of Heat Shock Protein 90
Authors: L. R. Kelland, S. Y. Sharp, P. M. Rogers, T. G. Myers, P. Workman
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: To our knowledge, 17-allylamino,17-demethoxygeldanamycin (17AAG) is the first inhibitor of heat shock protein 90 (Hsp90) to enter a phase I clinical trial in cancer. Inhibition of Hsp90, a chaperone protein (a protein that helps other proteins avoid misfolding pathways that produce inactive or aggregated states), leads to depletion of important oncogenic proteins, including Raf-1 and mutant p53 (also known as TP53). Given its ansamycin benzoquinone structure, we questioned whether the antitumor activity of 17AAG was affected by expression of the NQO1 gene, which encodes the quinone-metabolizing enzyme DT-diaphorase. METHODS: The antitumor activity of 17AAG and other Hsp90 inhibitors was determined by use of a sulforhodamine B-based cell growth inhibition assay in culture and by the arrest of xenograft tumor growth in nude mice. DT-diaphorase activity was determined by use of a spectrophotometric assay, and protein expression was determined by means of western immunoblotting. RESULTS: In two independent in vitro human tumor cell panels, we observed a positive relationship between DT-diaphorase expression level and growth inhibition by 17AAG. Stable, high-level expression of the active NQO1 gene transfected into the DT-diaphorase-deficient (by NQO1 mutation) BE human colon carcinoma cell line resulted in a 32-fold increase in 17AAG growth-inhibition activity. Increased sensitivity to 17AAG in the transfected cell line was also confirmed in xenografts. The extent of depletion of Raf-1 and mutant p53 protein confirmed that the Hsp90 inhibition mechanism was maintained in cells with high and low levels of DT-diaphorase. 17AAG was shown to be a substrate for purified human DT-diaphorase. CONCLUSION: These results suggest that the antitumor activity and possibly the toxicologic properties of 17AAG in humans may be influenced by the expression of DT-diaphorase. Careful monitoring for NQO1 polymorphism and the level of tumor DT-diaphorase activity is therefore recommended in clinical trials with 17AAG.
A comparison of cleat types during two football-specific tasks on FieldTurf
Authors: R M Queen, B L Charnock, W E Garrett, W M Hardaker, E L Sims, C T Moorman
Journal: British Journal of Sports Medicine (2007)

Objective: To examine the effect of different cleat plate configurations on plantar pressure during two tasks. Design: Thirty-six athletes ran an agility course 5 times while wearing 4 different types of Nike Vitoria cleats: (1) bladed, (2) elliptical firm ground, (3) hard ground and (4) turf. Plantar pressure data were recorded during a side cut and a cross cut using Pedar-X insoles. Setting: Controlled laboratory study Participants: No history of lower extremity injury in the past 6 months, no previous foot or ankle surgery, not currently wearing foot orthotics and play a cleated sport at least twice a week. Main outcome measurements: Total foot contact time, contact area, maximum force, peak pressure and the force-time integral (FTI) in the medial, middle and lateral regions of the forefoot were collected. A 1×4 ANOVA (α = 0.05) was performed on each dependent variable. A Bonferroni adjustment was conducted (α = 0.008). Results: In the cross cut task, statistical differences between cleats were observed in three variables: total foot peak pressure, lateral forefoot FTI, and lateral forefoot normalised maximum force. In the side cut task, statistical differences between cleats were observed in 4 variables: total foot peak pressure, the medial and middle forefoot FTI, and the medial and middle forefoot normalised maximum force. Conclusions: Significant differences in forefoot loading patterns existed between cleat types. Based on the results of this study, it might be beneficial to increase the forefoot cushioning in cleats in an attempt to decrease loading in these regions of the foot.
Lanatoside C sensitizes glioblastoma cells to tumor necrosis factor–related apoptosis-inducing ligand and induces an alternative cell death pathway
Authors: Christian E. Badr, Thomas Wurdinger, Jonas Nilsson, Johanna M. Niers, Michael Whalen, Alexei Degterev, Bakhos A. Tannous
Journal: Neuro-Oncology (2011)

Human glioblastoma (GBM) cells are notorious for their resistance to apoptosis-inducing therapeutics. We have identified lanatoside C as a sensitizer of GBM cells to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–induced cell death partly by upregulation of the death receptor 5. We show that lanatoside C sensitizes GBM cells to TRAIL-induced apoptosis in a GBM xenograft model in vivo. Lanatoside C on its own serves as a therapeutic agent against GBM by activating a caspase-independent cell death pathway. Cells treated with lanatoside C showed necrotic cell morphology with absence of caspase activation, low mitochondrial membrane potential, and early intracellular ATP depletion. In conclusion, lanatoside C sensitizes GBM cells to TRAIL-induced cell death and mitigates apoptosis resistance of glioblastoma cells by inducing an alternative cell death pathway. To our knowledge, this is one of the first examples of use of caspase-independent cell death inducers to trigger tumor regression in vivo. Activation of such mechanism may be a useful strategy to counter resistance of cancer cells to apoptosis.
The role of healthcare delivery in the outcome of meningococcal disease in children: case-control study of fatal and non-fatal cases
Authors: Nelly Ninis, Claire Phillips, Linda Bailey, Jon I Pollock, Simon Nadel, Joseph Britto, Ian Maconochie, Andrew Winrow, Pietro G Coen, Robert Booy, Michael Levin
Journal: BMJ (2005)

To determine whether suboptimal management in hospital could contribute to poor outcome in children admitted with meningococcal disease.Case-control study of childhood deaths from meningococcal disease, comparing hospital care in fatal and non-fatal cases.National statistics and hospital records.All children under 17 years who died from meningococcal disease (cases) matched by age with three survivors (controls) from the same region of the country.Predefined criteria defined optimal management. A panel of paediatricians blinded to the outcome assessed case records using a standardised form and scored patients for suboptimal management.We identified 143 cases and 355 controls. Departures from optimal (per protocol) management occurred more frequently in the fatal cases than in the survivors. Multivariate analysis identified three factors independently associated with an increased risk of death: failure to be looked after by a paediatrician, failure of sufficient supervision of junior staff, and failure of staff to administer adequate inotropes. Failure to recognise complications of the disease was a significant risk factor for death, although not independently of absence of paediatric care (P = 0.002). The odds ratio for death was 8.7 (95% confidence interval 2.3 to 33) with two failures, increasing with multiple failures.Suboptimal healthcare delivery significantly reduces the likelihood of survival in children with meningococcal disease. Improved training of medical and nursing staff, adherence to published protocols, and increased supervision by consultants may improve the outcome for these children and also those with other life threatening illnesses.
Response to Letter Regarding Article, “Rosiglitazone and Outcomes for Patients With Diabetes Mellitus and Coronary Artery Disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial”
Authors: Richard G. Bach, Maria Mori Brooks, Manuel Lombardero, Saul Genuth, Thomas W. Donner, Alan Garber, Laurence Kennedy, E. Scott Monrad, Rodica Pop-Busui, Sheryl F. Kelsey, Robert L. Frye
Journal: Circulation (2014)
Impaired Th1 cytokine production in spondyloarthropathy is restored by anti-TNFalpha
Authors: D Baeten
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> We have previously reported an increase of interleukin (IL)-17 levels during the first weeks of rheumatoid arthritis (RA) onset. <h3>Objectives</h3> Our main goal here was to investigate whether administration of digoxin, a specific inhibitor of Th17 cells polarization, is able to attenuate inflammation in a rat model of adjuvant-induced arthritis (AIA). <h3>Methods</h3> Digoxin was administered to AIA rats in the early phase (4 days after disease induction) or in the established phase of arthritis (11 days after disease induction). The inflammatory score, paw perimeter and body weight were evaluated during the period of treatment. Rats were sacrificed after 19 days of disease evolution and paw samples were collected for histological and immunohistochemical evaluation. <h3>Results</h3> We found that digoxin administration significantly suppressed joint inflammation if administrated in the early phase of disease course. The histological and immunohistochemical evaluation revealed that digoxin treatment was not efficient in inhibiting the infiltration of immune cells within the joint, but it was able to reduce local immune cells proliferation, if administrated in the early phase of arthritis. <h3>Conclusions</h3> Early inhibition of Th17 polarization ameliorates AIA but does not inhibit immune cell infiltration into the joints. <h3>Disclosure of Interest</h3> None Declared
Properties and protective value of the secondary versus primary T helper type 1 response to airborne <i>Mycobacterium tuberculosis</i> infection in mice
Authors: Yu-Jin Jung, Lynn Ryan, Ronald LaCourse, Robert J. North
Journal: The Journal of Experimental Medicine (2005)

Mice immunized against Mycobacterium tuberculosis (Mtb) infection by curing them of a primary lung infection were compared with naive mice in terms of the ability to generate a Th1 cell immune response and to control growth of an airborne Mtb challenge infection. Immunized mice generated and expressed Th1 cell immunity several days sooner than naive mice, as demonstrated by an earlier increase in the synthesis in the lungs of mRNA for Th1 cytokines and for inducible nitric oxide synthase, an indicator of macrophage activation. This Th1 cytokine/mRNA synthesis was accompanied by an earlier accumulation of Mtb-specific Th1 cells in the lungs and the presence of CD4 T cells in lesions. An earlier generation of immunity was associated with an earlier inhibition of Mtb growth when infection was at a 1-log lower level. However, inhibition of Mtb growth in immunized, as well as in naive, mice was not followed by resolution of the infection, but by stabilization of the infection at a stationary level. The results indicate that there is no reason to believe that the secondary response to an Mtb infection is quantitatively or qualitatively superior to the primary response.
Value of cancer antigen 125 for diagnosis of pleural endometriosis in females with recurrent pneumothorax
Authors: P. Bagan, P. Berna, J. Assouad, V. Hupertan, F. Le Pimpec Barthes, M. Riquet
Journal: European Respiratory Journal (2007)

The thorax is the most frequent extrapelvic location of endometriosis. Thoracic endometriosis is probably responsible for the high rate of recurrent pneumothoraces in females. The goal of the present prospective study was to assess the value of cancer antigen (CA)125 measurement in the detection of endometriosis in order to further enable early and adequate treatment of catamenial pneumothorax. Between January 2004 and March 2006, 31 females (mean age 32 yrs) underwent pneumothorax surgery. The control group comprised 17 males (mean age 27 yrs), who underwent videothoracoscopic pleural abrasion. Serum CA125 was measured around a menstrual period in females and before surgery in males. Videothoracoscopically diagnosed endometriosis occurred in 29% of females. The CA125 concentration was significantly higher in females with endometriosis compared to disease-free females (76.1 versus 16 U x mL(-1)). The mean value in males was similar to that observed in disease-free females. The frequency of thoracic endometriosis-related pneumothorax corresponds to, on average, a third of females presenting with recurrent pneumothorax. Early detection can be achieved with serum cancer antigen 125 measurement and may be helpful in indicating videothoracoscopic surgery.