tbuckley/cabot-search huggingface dataset:
Aminoglycosides Increase Intracellular Calcium Levels and ERK Activity in Proximal Tubular OK Cells Expressing the Extracellular Calcium-Sensing Receptor
Authors: Donald T. Ward, Stuart J. McLarnon, Daniela Riccardi
Journal: Journal of the American Society of Nephrology (2002)

Aminoglycoside antibiotics (AGAs) are nephrotoxic, with most of the damage confined to the proximal tubule, but the mechanism for cellular toxicity is not clear. It has been previously shown that the extracellular-calcium sensing receptor (CaR) is expressed in intact rat proximal tubule and can be stimulated by the AGA neomycin. To investigate whether CaR could contribute to AGA-induced nephrotoxicity, the acute responses to various AGAs in the proximal tubule-derived opossum kidney (OK) cell line were examined. The presence in OK cells of CaR-related transcripts and protein was demonstrated by northern analyses, reverse transcriptase-PCR, immunocytochemistry, and immunoblotting. OK cells responded to elevated extracellular calcium (Ca(2+)(o)) and neomycin but also to gentamicin and tobramycin with an increase in cytosolic [Ca(2+)]. Ca(2+)(o), neomycin, and gentamicin also activated the extracellular signal-regulated kinases, ERK1 and ERK2. Neomycin-induced ERK activation was both dose- and time-dependent and was attenuated by inhibitors of phosphatidylinositol 3-kinase, phosphatidylinositol bisphosphate (PIP(2))-specific phospholipase C, and MEK1, but not of protein kinase C. Thus, proximal tubular OK cells express a CaR that mediates Ca(2+)(i) mobilization and PIP(2)-PLC-dependent ERK activation in response to AGAs and thus could play a role in AGA-induced nephrotoxicity.
Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus Latent Membrane Protein-1
Authors: Olivier Dellis, Atousa Arbabian, Jean-Philippe Brouland, Tünde Kovàcs, Martin Rowe, Christine Chomienne, Irène Joab, Béla Papp
Journal: Molecular Cancer (2009)

Abstract Background Calcium signaling plays an important role in B lymphocyte survival and activation, and is critically dependent on the inositol-1,4,5- tris -phosphate-induced release of calcium stored in the endoplasmic reticulum (ER). Calcium is accumulated in the ER by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes), and therefore these enzymes play an important role in ER calcium homeostasis and in the control of B of cell activation. Because Epstein-Barr virus (EBV) can immortalize B cells and contributes to lymphomagenesis, in this work the effects of the virus on SERCA-type calcium pump expression and calcium accumulation in the endoplasmic reticulum of B cells was investigated. Results Two Sarco-Endoplasmic Reticulum Calcium transport ATPase isoforms, the low Ca 2+ -affinity SERCA3, and the high Ca 2+ -affinity SERCA2 enzymes are simultaneously expressed in B cells. Latency type III infection of Burkitt's lymphoma cell lines with immortalization-competent virus expressing the full set of latency genes selectively decreased the expression of SERCA3 protein, whereas infection with immortalization-deficient virus that does not express the EBNA2 or LMP-1 viral genes was without effect. Down-modulation of SERCA3 expression could be observed upon LMP-1, but not EBNA2 expression in cells carrying inducible transgenes, and LMP-1 expression was associated with enhanced resting cytosolic calcium levels and increased calcium storage in the endoplasmic reticulum. Similarly to virus-induced B cell immortalisation, SERCA3 expression was also decreased in normal B cells undergoing activation and blastic transformation in germinal centers of lymph node follicles. Conclusion The data presented in this work indicate that EBV-induced immortalization leads to the remodelling of ER calcium homeostasis of B cells by LMP-1 that copies a previously unknown normal phenomenon taking place during antigen driven B cell activation. The functional remodelling of ER calcium homeostasis by down-regulation of SERCA3 expression constitutes a previously unknown mechanism involved in EBV-induced B cell immortalisation.
Effects of Pulmonary Artery Ligation on Pulmonary Surfactant and Pressure-Volume Characteristics of Dog Lung
Authors: Samuel T. Giammona, Isidore Mandelbaum, James Foy, Stuart Bondurant
Journal: Circulation Research (1966)

The effects of pulmonary artery ligation upon pulmonary surfactant and upon the pressure-volume characteristics of the canine lung were studied. Four hours after ligation of one pulmonary artery the two lungs had similar deflation pressure-volume curves and extracts from these lungs had similar surface tension. Two weeks after ligation, the lungs with a ligated PA differed from the contralateral lungs in having a smaller fraction of total volume retained at each pressure during deflation, and extracts with a higher minimal surface tension, and a lower surfactant activity index. Low but significant correlations were observed between the fractional volume at 15 cm H 2 O transpulmonary pressure and the minimal surface tension of the lung extracts (Wilhelmy balance), between the fractional volume of 15 cm H 2 O transpulmonary pressure and the surfactant activity index, and between the surfactant activity index and the lung stability index. These data suggest a close relationship between altered surface forces and the pressure-volume characteristics of the lung after pulmonary artery ligation.
Finasteride to Prevent Prostate Cancer: Should All Men or Only a High-Risk Subgroup Be Treated?
Authors: Andrew J. Vickers, Caroline J. Savage, Hans Lilja
Journal: Journal of Clinical Oncology (2010)

PURPOSE Finasteride has been shown to reduce the incidence of prostate cancer. Yet the use of finasteride remains low, likely because of the risk of adverse effects. We sought to determine whether prostate-specific antigen (PSA) levels could identify a high-risk subgroup for which the benefits of finasteride treatment outweigh the potential harms. PATIENTS AND METHODS Raw data from the Prostate Cancer Prevention Trial were used to model chemopreventive treatment strategies: treat all men, treat no men, or treat a high-risk subgroup based on PSA level. We weighted the benefits (reduction in cancer rate) and harms (treatment rate) of each strategy using numbers-needed-to-treat thresholds-the maximum number of men a clinician would treat with finasteride to prevent one cancer. Results Of 9,058 men, 1,957 were diagnosed with prostate cancer during the 7-year study. For the end point of all cancers, including both for-cause and end-of-study biopsies, the optimal strategy is to treat all or nearly all men. To reduce risk of cancers detected through routine care, treating men with PSA > 1.3 or > 2 ng/mL is optimal. For example, treating only men with PSA > 2 ng/mL reduced the treatment rate by 83% and resulted in a cancer rate only 1.1% higher than treating all men. CONCLUSION Clinicians wishing to reduce the risk of any biopsy-detectable prostate cancer should recommend finasteride to all men. Clinicians who believe that it is unnecessary to prevent all cancers, but that preventing those readily detectable by screening would be desirable, would be best off recommending finasteride only to a high-risk subgroup.
IL-4 and IgE–anti-IgE modulation of 15(S)-hydroxyeicosatetraenoic acid release by mononuclear phagocytes
Authors: Mirella Profita, Antonio M. Vignola, Angela Mirabella, Liboria Siena, Angelo Sala, Mark Gjomarkaj, Jean Bousquet, Giovanni Bonsignore
Journal: Journal of Allergy and Clinical Immunology (1999)
Association of CCR5Delta32 with reduced risk of childhood but not adult asthma
Authors: P Srivastava
Journal: Thorax (2003)

<b>Background:</b> A number of potential candidate genes have been implicated in the pathogenesis of asthma. A 32 base pair deletion in the CCR5 gene renders this chemokine receptor non-functioning and has been shown to be associated with a reduced prevalence of asthma in childhood. The mechanism may be related to impairment of pathogen entry into cells and modified host inflammatory response. We sought to determine the influence of the CCR5Δ32 mutation on asthma and allergy in the transition from childhood to adulthood. <b>Methods:</b> 627 individuals first studied as part of a whole population schoolchildren cohort in 1989 when aged 8–12 years were followed up 10 years later for respiratory and allergy symptoms and laboratory markers of atopy. CCR5Δ32 status was also characterised and the association with childhood and adulthood symptoms determined. <b>Results:</b> The follow up sample was representative of the original cohort except for a slightly greater prevalence of symptomatic individuals. As children, none who were homozygous for the CCR5Δ32 mutation had a current physician's diagnosis of asthma. In multivariate analysis and controlling for known confounders, the protective effect of carrying the allele in childhood was highly significant (OR 0.31, 95% CI 0.14 to 0.72, p=0.006). There was no protective association with "current asthma" as classified in adulthood within the same population. Subjective or laboratory markers of atopy in childhood or adulthood were not associated with the CCR5Δ32 mutation. Methacholine bronchial hyperresponsiveness in adulthood was also unrelated to gene carrier status. <b>Conclusions:</b> In a population with a high allelic frequency for the CCR5Δ32 mutation, a significant protection against childhood asthma is evident which is independent of atopy. This protection is lost in the transition between childhood and early adulthood. The contribution of different genetic candidates to the expression of asthma may change with advancing maturity and confound the interpretation of association and linkage studies unless age is taken into account.
Mechanism of the enhanced epidermal growth factor-induced growth response of genetically hypertensive vascular myocytes.
Authors: R D Bukoski, P DeWan, J Bo
Journal: Circulation Research (1991)

Although enhanced growth of the vascular myocyte is believed to play a role in hypertensive cardiovascular disease, the cellular basis of altered growth regulation is not completely understood. The present study demonstrates that in the presence of 10% fetal calf serum, the logarithmic growth rate of cultured mesenteric artery myocytes of the spontaneously hypertensive rat (SHR) is similar to that of the normotensive Wistar-Kyoto (WKY) control rat. However, in the presence of low levels of fetal calf serum, SHR myocytes respond to epidermal growth factor (EGF) with increased growth, whereas WKY cells do not. This difference does not result from different numbers or affinities of EGF receptors in these cell lines. Examination of EGF-induced growth responses of SHR and WKY myocytes in the presence of varying levels of insulin or fetal calf serum indicates that, compared with WKY myocytes, SHR myocytes have a lower requirement for factors that confer competence to respond to EGF. Another property of the SHR myocytes is an elevation of free intracellular Ca2+. To determine whether a difference in cellular Ca2+ metabolism might play a role in the differential growth response, growth of myocytes in medium containing 0.25, 0.75, or 1.25 mM extracellular Ca2+ and 5% fetal calf serum was examined. Myocytes of SHR showed enhanced growth in the presence of 5% fetal calf serum at all levels of extracellular Ca2+. It is concluded that, although vascular myocytes of SHR and WKY rats have the capacity to grow at similar rates, under limiting conditions, the SHR myocyte growth response is enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)
Temozolomide in Elderly Patients With Newly Diagnosed Glioblastoma and Poor Performance Status: An ANOCEF Phase II Trial
Authors: Jaime Gállego Pérez-Larraya, François Ducray, Olivier Chinot, Isabelle Catry-Thomas, Luc Taillandier, Jean-Sébastien Guillamo, Chantal Campello, Annick Monjour, Stéphanie Cartalat-Carel, Maryline Barrie, Aymeri Huchet, Patrick Beauchesne, Mona Matta, Karima Mokhtari, Marie-Laure Tanguy, Jérôme Honnorat, Jean-Yves Delattre
Journal: Journal of Clinical Oncology (2011)

The management of glioblastoma multiforme (GBM) in elderly patients with poor performance status is not well established. A trial evaluating the efficacy and safety of temozolomide alone in this population was undertaken.Patients age 70 years or older with newly diagnosed GBM and postoperative Karnofsky performance score (KPS) less than 70 were eligible for this nonrandomized phase II trial. Treatment consisted of 150 to 200 mg/m(2)/d temozolomide for 5 days every 4 weeks until disease progression. Radiotherapy was not administered. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), safety, quality of life, and cognition.Seventy patients (median age, 77 years; median KPS, 60) were enrolled between July 2007 and February 2009. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 13% and 14% of patients, respectively. Median PFS was 16 weeks (95% CI, 10 to 20 weeks), and median OS was 25 weeks (95% CI, 19 to 28 weeks), comparing favorably with a 12- to 16-week OS expected from a purely supportive approach. Twenty-three patients (33%) improved their KPS by 10 or more points, and 18 (26%) became capable of self-care (KPS ≥ 70). Overall quality of life and cognition improved over time before disease progression. In the 31 tumors evaluated for O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation, a methylated status indicated longer PFS (26 v 11 weeks; P = .03) and OS (31 v 19 weeks; P = .03).Temozolomide has an acceptable tolerance in elderly patients with GBM and KPS less than 70. It is associated with improvement of functional status in 33% of patients and appears to increase survival compared with supportive care alone, especially in patients with methylated MGMT promoter.
Chemotherapy should not be withheld from patients with an indwelling pleural catheter for malignant pleural effusion
Authors: A. Morel, E. Mishra, L. Medley, N. M. Rahman, J. Wrightson, D. Talbot, R. J. O. Davies
Journal: Thorax (2010)

presence of procoagulant factors (macrophages and activated leucocytes are known to increase activation of thrombin and fibrin formation) and co-existence of sarcoidosis and antiphospholipid syndrome. 5Antiphospholipid antibodies occur in 2e5% of the general population, but in up to 38% patients with sarcoidosis, correlating with poorer prognosis. 5verall, our findings would be viewed as hypothesis generating, providing a platform for further study, and supportive of the anecdotal observations made in our Sarcoidosis Clinic.Despite the limitations discussed above, PE should be considered in patients with sarcoidosis when there is sudden deterioration in dyspnoea.
Anti-inflammatory effects of inhaled carbon monoxide in patients with COPD: a pilot study
Authors: E. Bathoorn, D-J. Slebos, D. S. Postma, G. H. Koeter, A. J. M. van Oosterhout, M. van der Toorn, H. M. Boezen, H. A. M. Kerstjens
Journal: European Respiratory Journal (2007)

<i>In vitro</i> and <i>in vivo</i> studies have shown that carbon monoxide (CO) has both anti-inflammatory and anti-oxidant capacities. Since chronic obstructive pulmonary disease (COPD) is characterised by inflammation and oxidative stress, low-dose CO could be of therapeutic use. The aim of the present study was to investigate the feasibility and anti-inflammatory effects of 100–125 ppm CO inhalation in patients with stable COPD. In total, 20 ex-smoking COPD patients with post-bronchodilator forced expiratory volume in one second (FEV<sub>1</sub>) &gt;1.20 L and FEV<sub>1</sub>/forced vital capacity &lt;70% were enrolled in a randomised, placebo-controlled, crossover study. Effects on inflammation were measured in induced sputum and blood. CO inhalation was feasible and patients9 vital signs were unaffected; 2 h·day<sup>−1</sup> inhalation of low-dose CO on 4 consecutive days led to a maximal individual carboxyhaemoglobin level of 4.5%. Two exacerbations occurred in the CO period. CO inhalation led to trends in reduced sputum eosinophils (median reduction 0.25% point) and improved responsiveness to methacholine (median provocative concentration causing a 20% fall in FEV<sub>1</sub> 0.85 <i>versus</i> 0.63 mg·mL<sup>−1</sup>). Inhalation of 100–125 ppm carbon monoxide by patients with chronic obstructive pulmonary disease in a stable phase was feasible and led to trends in reduction of sputum eosinophils and improvement of responsiveness to methacholine. Further studies need to confirm the safety and efficacy in inflammatory lung diseases.
Compression garments and recovery from exercise-induced muscle damage: a meta-analysis
Authors: Jessica Hill, Glyn Howatson, Ken van Someren, Jonathan Leeder, Charles Pedlar
Journal: British Journal of Sports Medicine (2013)

The purpose of the study was to determine the effects of compression garments on recovery following damaging exercise. A systematic review and meta-analysis was conducted using studies that evaluated the efficacy of compression garments on measures of delayed onset muscle soreness (DOMS), muscular strength, muscular power and creatine kinase (CK). Studies were extracted from a literature search of online databases. Data were extracted from 12 studies, where variables were measured at baseline and at 24 or 48 or 72 h postexercise. Analysis of pooled data indicated that the use of compression garments had a moderate effect in reducing the severity of DOMS (Hedges’ g=0.403, 95% CI 0.236 to 0.569, p&lt;0.001), muscle strength (Hedges’ g=0.462, 95% CI 0.221 to 0.703, p&lt;0.001), muscle power (Hedges’ g=0.487, 95% CI 0.267 to 0.707, p&lt;0.001) and CK (Hedges’ g=0.439, 95% CI 0.171 to 0.706, p&lt;0.001). These results indicate that compression garments are effective in enhancing recovery from muscle damage.
Prospective study about two modes of sedation in endobronchial ultrasound transbronchial needle aspiration
Authors: Sabrina Lenel, Damien Basile, Florence Le Meunier, Coraline Hybiak, Remi Suguenot, Houcine Bentayeb, Emmanuelle Lecuyer, Bénédicte Toublanc, Vincent Jounieaux, Charles Dayen, Youcef Douadi
Journal: European Respiratory Journal (2013)

Endobronchial ultrasound with real-time guided transbronchial needle aspiration (EBUS-TBNA) sedation are available in two modes: sedation with midazolam (MID) and general anesthesia with propofol (PRO). The purpose of this study was to evaluate the tolerance according to sedation. This is a prospective, two-center, observational, non randomized study. The aim of the study is to evaluate the safety of patients according to the method of sedation. The main objective primary endpoint is to evaluate the tolerance on the one hand with the pain on a VAS from 0 (no pain) to 100 (unbearable pain). On the other hand, a questionnaire is given to the patient at the end of the investigation on cough, worst time of the examination, the pain during the move of the ultrasound endoscope through the mouth, the desire to repeat the examination under the same conditions. The secondary endpoint of the trial is evaluating the stress according to hemodynamic parameters (CF and AT). Results: Over a period of three months, 40 patients were included in the study: 20 in the MID group, 20 patients in the PRO. Among the 40 patients included, 34 were male (85%) and 6 women (15%). The average age was 61 years + / - 12 (27-81). Tolerance of ultrasound bronchoscopy is considered better under general anesthesia with propofol sedation as midazolam. EVA and all other parameters are the best in the PRO group. Hemodynamic parameters were similar. No complications were noted. The informativeness of punctures, the failure rate, the average number of punctures and the exam duration is comparable in the two groups.
Prognostic Value of Tumor-Infiltrating CD4+ T-Cell Subpopulations in Head and Neck Cancers
Authors: Cécile Badoual, Stéphane Hans, José Rodriguez, Severine Peyrard, Christophe Klein, Nour El Houda Agueznay, Véronique Mosseri, Ollivier Laccourreye, Patrick Bruneval, Wolf H. Fridman, Daniel F. Brasnu, Eric Tartour
Journal: Clinical Cancer Research (2006)

Abstract Purpose: CD4+ T cells play a central role in initiating and maintaining anticancer immune responses. However, regulatory CD4+CD25+ T cells which express Foxp3 have also been shown to inhibit antitumor effector T cells. In view of these heterogeneous CD4+ T-cell populations, this study was designed to determine the prognostic value of various tumor-infiltrating CD4+ T-cell populations in head and neck squamous cell carcinoma. Experimental Design: Eighty-four newly diagnosed untreated patients with histologically proven primary head and neck squamous cell carcinoma were included in this study. Double or triple immunofluorescence staining was done to assess and quantify the activated CD4+CD69+ T cells, regulatory CD4+Foxp3+ T cells, and mixed CD4+CD25+ T cells comprising both activated and regulatory T cells. Results: On univariate analysis, high levels of tumor-infiltrating CD4+CD69+ T cells were correlated with both better locoregional control (P = 0.01) and longer survival (P = 0.01). Infiltration by regulatory Foxp3+CD4+ T cells was positively associated with a better locoregional control of the tumor. Multivariate analysis showed that the only significant prognostic factors related to locoregional control were T stage (P = 0.02) and CD4+Foxp3+ T-cell infiltration of the tumor (P = 0.02). In the Cox multivariate analysis, only two variables influenced overall survival probability: T stage (P = 0.036) and CD4+CD69+ T-cell infiltration (P = 0.017). Conclusion: This study shows that tumor-infiltrating activated CD4+CD69+ T cells are associated with a good prognosis in head and neck squamous cell carcinoma. In addition, regulatory Foxp3+CD4+ T cells are positively correlated with locoregional control may be through down-regulation of harmful inflammatory reaction, which could favor tumor progression.
Reconstruction of the trachea: Experience in 100 consecutive cases
Authors: H. C. Grillo
Journal: Thorax (1973)

<b>Grillo, H. C. (1973).</b><i>Thorax</i>, <b>28</b>, 667-679. <b>Reconstruction of the trachea. Experience in 100 consecutive cases.</b> Anatomic mobilization of the trachea permits resection of one-half or more with primary anastomosis. An anterior approach by a cervical or cervicomediastinal route utilizes cervical flexion to devolve the larynx and tracheal mobilization with preservation of the lateral blood supply. The transthoracic route is employed for lower tracheal lesions. Over 100 tracheal resections have been done using these methods of direct reconstruction. Eighty-four patients suffered from benign strictures, 79 resulting from intubation injuries. Eleven primary tracheal tumours and five secondary tumours are included. The majority of lesions following intubation occurred at the level of the cuff. It was possible to repair 78 of the 84 stenotic lesions through a cervical or cervicomediastinal approach. Seventy-three of the 84 patients with inflammatory lesions obtained an excellent or good functional and anatomic result. Nine of 11 patients with primary neoplasms who underwent reconstruction are alive and without known disease. There were five early postoperative deaths in these 100 consecutive patients who underwent tracheal reconstruction.