tbuckley/cabot-search huggingface dataset:
Titin and diaphragm dysfunction in mechanically ventilated rats
Authors: Hieronymus W. H. van Hees, Willem-Jan M. Schellekens, Gilberto L. Andrade Acuña, Marianne Linkels, Theo Hafmans, Coen A. C. Ottenheijm, Henk L. Granzier, Gert-Jan Scheffer, Johannes G. van der Hoeven, P. N. Richard Dekhuijzen, Leo M. A. Heunks
Journal: Intensive Care Medicine (2012)

Diaphragm weakness induced by mechanical ventilation may contribute to difficult weaning from the ventilator. For optimal force generation the muscle proteins myosin and titin are indispensable. The present study investigated if myosin and titin loss or dysfunction are involved in mechanical ventilation-induced diaphragm weakness.Male Wistar rats were either assigned to a control group (n = 10) or submitted to 18 h of mechanical ventilation (MV, n = 10). At the end of the experiment, diaphragm and soleus muscle were excised for functional and biochemical analysis.Maximal specific active force generation of muscle fibers isolated from the diaphragm of MV rats was lower than controls (128 ± 9 vs. 165 ± 13 mN/mm(2), p = 0.02) and was accompanied by a proportional reduction of myosin heavy chain concentration in these fibers. Passive force generation upon stretch was significantly reduced in diaphragm fibers from MV rats by ca. 35%. Yet, titin content was not significantly different between control and MV diaphragm. In vitro pre-incubation with phosphatase-1 decreased passive force generation upon stretch in diaphragm fibers from control, but not from MV rats. Mechanical ventilation did not affect active or passive force generation in the soleus muscle.Mechanical ventilation leads to impaired diaphragm fiber active force-generating capacity and passive force generation upon stretch. Loss of myosin contributes to reduced active force generation, whereas reduced passive force generation is likely to result from a decreased phosphorylation status of titin. These impairments were not discernable in the soleus muscle of 18 h mechanically ventilated rats.
TFAP2B overexpression contributes to tumor growth and a poor prognosis of human lung adenocarcinoma through modulation of ERK and VEGF/PEDF signaling
Authors: Lingyi Fu, Ke Shi, Jingshu Wang, Wangbing Chen, Dingbo Shi, Yun Tian, Wei Guo, Wendan Yu, Xiangsheng Xiao, Tiebang Kang, Shusen Wang, Wenlin Huang, Wuguo Deng
Journal: Molecular Cancer (2014)

TFAP2B is a member of the AP2 transcription factor family, which orchestrates a variety of cell processes. However, the roles of TFAP2B in regulating carcinogenesis remain largely unknown. Here, we investigated the regulatory effects of TFAP2B on lung adenocarcinomas growth and identified the underlying mechanisms of actions in non-small cell lung cancer (NSCLC) cells. We first examined the expression of TFAP2B in lung cancer cell lines and tumor tissues. We also analyzed the prognostic predicting value of TFAP2B in lung adenocarcinomas. Then we investigated the molecular mechanisms by which TFAP2B knockdown or overexpression regulated lung cancer cell growth, angiogenesis and apoptosis, and further confirmed the role of TFAP2B in tumor growth in a lung cancer xenograft mouse model. TFAP2B was highly expressed in NSCLC cell lines and tumor tissues. Strong TFAP2B expression showed a positive correlation with the poor prognoses of patients with lung adenocarcinomas (P < 0.001). TFAP2B knockdown by siRNA significantly inhibited cell growth and induced apoptosis in NSCLC cells in vitro and in a lung cancer subcutaneous xenograft model, whereas TFAP2B overexpression promoted cell growth. The observed regulation of cell growth was accompanied by the TFAP2B-mediated modulation of the ERK/p38, caspase/cytochrome-c and VEGF/PEDF-dependent signaling pathways in NSCLC cells. These results indicate that TFAP2B plays a critical role in regulating lung adenocarcinomas growth and could serve as a promising therapeutic target for lung cancer treatment.
Development of Tumors, Particularly Mammary Tumors, in Agent-Free Substrain RIIIeB/De Mice
Authors: Margaret K. Deringer
Journal: JNCI Journal of the National Cancer Institute (1969)

Tumor development has been studied in mice of substrain RIIIeB/De, which was produced by transfer of fertilized ova from strain RIII/AnDe to strain C57BL/HeDe. Compared with RIII/AnDe, in which 97% of virgin females and 98.5% of breeding females developed mammary tumors at average ages of 11.6 and 7.7 months, mammary tumors developed in 23% of virgin females at an average age of 22.3 months; in 41% of breeding females at an average age of 20.1 months, and in 40% of forcebred females at an average age of 19.9 months. As in other agent-free lines, the incidence of mammary tumors was reduced from that of the line carrying the agent, and the average tumor age was increased. The development of various other tumors has been noted also.
Stents versus Coronary-Artery Bypass Grafting for Left Main Coronary Artery Disease
Authors: Ki Bae Seung, Duk-Woo Park, Young-Hak Kim, Seung-Whan Lee, Cheol Whan Lee, Myeong-Ki Hong, Seong-Wook Park, Sung-Cheol Yun, Hyeon-Cheol Gwon, Myung-Ho Jeong, Yangsoo Jang, Hyo-Soo Kim, Pum Joon Kim, In-Whan Seong, Hun Sik Park, Taehoon Ahn, In-Ho Chae, Seung-Jea Tahk, Wook-Sung Chung, Seung-Jung Park
Journal: New England Journal of Medicine (2008)

Several studies have compared the treatment effects of coronary stenting and coronary-artery bypass grafting (CABG). However, there are limited data regarding the long-term outcomes of these two interventions for patients with unprotected left main coronary artery disease.We evaluated 1102 patients with unprotected left main coronary artery disease who underwent stent implantation and 1138 patients who underwent CABG in Korea between January 2000 and June 2006. We compared adverse outcomes (death; a composite outcome of death, Q-wave myocardial infarction, or stroke; and target-vessel revascularization) with the use of propensity-score matching in the overall cohort and in separate subgroups according to type of stent.In the overall matched cohort, there was no significant difference between the stenting and CABG groups in the risk of death (hazard ratio for the stenting group, 1.18; 95% confidence interval [CI], 0.77 to 1.80) or the risk of the composite outcome (hazard ratio for the stenting group, 1.10; 95% CI, 0.75 to 1.62). The rates of target-vessel revascularization were significantly higher in the group that received stents than in the group that underwent CABG (hazard ratio, 4.76; 95% CI, 2.80 to 8.11). Comparisons of the group that received bare-metal stents with the group that underwent CABG and of the group that received drug-eluting stents with the group that underwent CABG produced similar results, although there was a trend toward higher rates of death and the composite end point in the group that received drug-eluting stents.In a cohort of patients with unprotected left main coronary artery disease, we found no significant difference in rates of death or of the composite end point of death, Q-wave myocardial infarction, or stroke between patients receiving stents and those undergoing CABG. However, stenting, even with drug-eluting stents, was associated with higher rates of target-vessel revascularization than was CABG.
Reduced-intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment for myeloid malignancies in patients older than 55 years
Authors: Raymond Wong, Sergio A. Giralt, Thomas Martin, Daniel R. Couriel, Athanasios Anagnostopoulos, Chitra Hosing, Borje S. Andersson, Pedro Cano, Munir Shahjahan, Cindy Ippoliti, Elihu H. Estey, John McMannis, James L. Gajewski, Richard E. Champlin, Marcos de Lima
Journal: Blood (2003)
A Phase II Trial of Intraperitoneal Photodynamic Therapy for Patients with Peritoneal Carcinomatosis and Sarcomatosis
Authors: Stephen M. Hahn, Douglas L. Fraker, Rosemarie Mick, James Metz, Theresa M. Busch, Debbie Smith, Timothy Zhu, Carmen Rodriguez, Andreea Dimofte, Francis Spitz, Mary Putt, Stephen C. Rubin, Chandrakala Menon, Hsing-Wen Wang, Daniel Shin, Arjun Yodh, Eli Glatstein
Journal: Clinical Cancer Research (2006)

Abstract Purpose: A previous phase I trial of i.p. photodynamic therapy established the maximally tolerated dose of Photofrin (Axcan Pharma, Birmingham, AL)-mediated photodynamic therapy and showed encouraging efficacy. The primary objectives of this phase II study were to determine the efficacy and toxicities of i.p. photodynamic therapy in patients with peritoneal carcinomatosis and sarcomatosis. Experimental Design: Patients received Photofrin 2.5 mg/kg i.v. 48 hours before debulking surgery. Intraoperative laser light was delivered to the peritoneal surfaces of the abdomen and pelvis. The outcomes of interest were (a) complete response, (b) failure-free survival time, and (c) overall survival time. Photosensitizer levels in tumor and normal tissues were measured. Results: One hundred patients were enrolled into one of three strata (33 ovarian, 37 gastrointestinal, and 30 sarcoma). Twenty-nine patients did not receive light treatment. All 100 patients had progressed by the time of statistical analysis. The median failure-free survival and overall survival by strata were ovarian, 2.1 and 20.1 months; gastrointestinal cancers, 1.8 and 11.1 months; sarcoma, 3.7 and 21.9 months. Substantial fluid shifts were observed postoperatively, and the major toxicities were related to volume overload. Two patients died in the immediate postoperative period from bleeding, sepsis, adult respiratory distress syndrome, and cardiac ischemia. Conclusions: Intraperitoneal Photofrin-mediated photodynamic therapy is feasible but does not lead to significant objective complete responses or long-term tumor control. Heterogeneity in photosensitizer uptake and tumor oxygenation, lack of tumor specificity for photosensitizer uptake, and the heterogeneity in tissue optical properties may account for the lack of efficacy observed.
ATP-dependent closure and reactivation of inward rectifier K+ channels in endothelial cells.
Authors: S P Olesen, M Bundgaard
Journal: Circulation Research (1993)

This report presents the results of a patch-clamp study examining the role of intracellular ATP in the regulation of endothelial inward rectifier K+ channels. Administration of ATP to the cytosolic surface of inside-out patches reversibly activated the K+ channel within seconds. ATP (1 mM) increased the mean open probability by a factor of 3.5, primarily by increasing the number of openings. Administration of the nonhydrolyzable ATP analogue ATP-gamma-S failed to modulate channel activity. Inhibition of ATP synthesis by administration of cyanide plus iodoacetate resulted in channel closure within 1 to 6 minutes. In experiments in which ATP was coadministered with the metabolic blockers, the channel activity continued unchanged for up to 30 minutes, but when ATP was removed, the activity rapidly decayed. We propose that normal functioning of the inward rectifier K+ channel is ATP dependent. Phosphorylation of the channel molecule is probably essential for maintaining activity.
RNAi-Mediated Silencing of Myc Transcription Inhibits Stem-like Cell Maintenance and Tumorigenicity in Prostate Cancer
Authors: Gianluca Civenni, Anastasia Malek, Domenico Albino, Ramon Garcia-Escudero, Sara Napoli, Stefano Di Marco, Sandra Pinton, Manuela Sarti, Giuseppina M. Carbone, Carlo V. Catapano
Journal: Cancer Research (2013)

Several studies link disease progression, recurrence, and treatment failures to the cancer stem-like cell (CSC) subpopulation within the heterogeneous tumor cell population. Myc is a transcription factor having a central function in stem cell biology and in human cancers. Hence, Myc represents an attractive target to develop CSC-specific therapies. Recent findings suggest that Myc transcription can be silenced using an RNA interference (RNAi)-based strategy that targets noncoding promoter-associated RNA (paRNA) overlapping the transcription start site. In this study, we investigated the effects of silencing Myc transcription on prostate CSC in cell culture and xenograft models of human prostate cancer. Treatment with an effective promoter-targeting siRNA reduced the fraction of CSCs, leading to reduced self-renewal, tumor-initiating, and metastatic capability. Combined analysis of stem-like cells and senescence markers indicated that Myc silencing triggered a phenotypic shift and senescence in the CSC subpopulation. Notably, systemic delivery of the promoter-targeting siRNA in the xenograft model produced a striking suppression in the development of prostate tumors. Our results support a pivotal role for Myc in CSC maintenance and show that Myc targeting via RNAi-based transcriptional silencing can trigger CSC senescence and loss of their tumor-initiating capability. More generally, our findings demonstrate the efficacy of RNAi-based transcriptional strategies and the potential to target regulatory noncoding paRNAs for therapeutic applications.
Effects of body fat distribution on regional lipolysis in obesity.
Authors: M L Martin, M D Jensen
Journal: Journal of Clinical Investigation (1991)

To determine the contribution of the major body fat depots to systemic free fatty acid (FFA) availability, palmitate ([1-14C]-palmitate) release was measured from leg (lower body) and non-leg (upper body) fat in eight upper body obese (UB Ob), six lower body obese (LB Ob), and six nonobese (Non Ob) age-matched premenopausal women in the overnight postabsorptive state. Splanchnic palmitate release was determined in 16 of these subjects. Results: total palmitate release was greater in UB Ob (P less than 0.005) than LB Ob or Non Ob women (161 +/- 16 vs. 111 +/- 9 vs. 92 +/- 9 mumol/min, respectively). Despite increased leg fat mass in obese women, leg palmitate release was similar in each group. Therefore, leg fat palmitate release was greater in Non Ob women than LB Ob (P less than 0.01) or UB Ob (P = 0.06) women (3.7 +/- 0.3 vs. 2.4 +/- 0.2 vs. 2.7 +/- 0.2 mumol.kg fat-1.min-1, respectively). Upper body fat palmitate release was less (P less than 0.01) in LB Ob than Non Ob or UB Ob women (3.0 +/- 0.4 vs. 5.0 +/- 0.3 vs. 4.9 +/- 0.4 mumol.kg fat-1.min-1, respectively). Splanchnic palmitate release accounted for 20-32% of upper body fat palmitate release in each group (P = NS between groups). Leg fat palmitate release was significantly less than upper body fat palmitate release. We conclude that the major difference in resting FFA metabolism between UB Ob and LB Ob women is the ability of the later to down-regulate upper body fat lipolysis to maintain normal FFA availability.
Mineralocorticoid Receptor Blockade Reverses Obesity-Related Changes in Expression of Adiponectin, Peroxisome Proliferator-Activated Receptor-γ, and Proinflammatory Adipokines
Authors: Christine Guo, Vincent Ricchiuti, Bill Q. Lian, Tham M. Yao, Patricia Coutinho, José R. Romero, Jianmin Li, Gordon H. Williams, Gail K. Adler
Journal: Circulation (2008)

Background— In obesity, decreases in adiponectin and increases in proinflammatory adipokines are associated with heart disease. Because adipocytes express mineralocorticoid receptor (MR) and MR blockade reduces cardiovascular inflammation and injury, we tested the hypothesis that MR blockade reduces inflammation and expression of proinflammatory cytokines in adipose tissue and increases adiponectin expression in adipose tissue and hearts of obese mice. Methods and Results— We determined the effect of MR blockade (eplerenone, 100 mg/kg per day for 16 weeks) on gene expression in retroperitoneal adipose and heart tissue from obese, diabetic db / db mice (n=8) compared with untreated obese, diabetic db / db mice (n=10) and lean, nondiabetic db /+ littermates (n=11). Expression of tumor necrosis factor-α, monocyte chemoattractant protein-1, plasminogen activator inhibitor type 1, and macrophage protein CD68 increased, and expression of adiponectin and peroxisome proliferator-activated receptor-γ decreased in retroperitoneal adipose tissue from obese versus lean mice. In addition, adiponectin expression in heart was reduced in obese versus lean mice. MR blockade prevented these obesity-related changes in gene expression. Furthermore, treatment of undifferentiated preadipocytes with aldosterone (10 −8 mol/L for 24 hours) increased mRNA levels of tumor necrosis factor-α and monocyte chemoattractant protein-1 and reduced mRNA and protein levels of peroxisome proliferator-activated receptor-γ and adiponectin, supporting a direct aldosterone effect on gene expression. Conclusions— MR blockade reduced expression of proinflammatory and prothrombotic factors in adipose tissue and increased expression of adiponectin in heart and adipose tissue of obese, diabetic mice. These effects on adiponectin and adipokine gene expression may represent a novel mechanism for the cardioprotective effects of MR blockade.
STUDIES ON OXIDATION AND REDUCTION BY PNEUMOCOCCUS
Authors: Oswald T. Avery, James M. Neill
Journal: The Journal of Experimental Medicine (1924)

1. Sterile broth extracts of unwashed pneumococci, entirely free from living or intact cells, actively reduce methylene blue. 2. Sterile extracts prepared by extracting washed pneumococci in phosphate solution are unable by themselves to reduce methylene blue. Upon the addition of meat infusion or yeast extract, these washed cell extracts actively reduce methylene blue. 3. The system or systems in pneumococcus extracts responsible for methylene blue reduction are destroyed by exposure to temperatures practically identical with those which have been previously found to destroy the peroxide-forming activity of the same extracts. 4. It is suggested that peroxide formation and methylene blue reduction by pneumococcus extracts are functions of the same or closely related systems, the particular reaction induced depending upon whether molecular oxygen or methylene blue serves as hydrogen acceptor or oxygen donator.
Out-of-Pocket Medication Costs and Use of Medications and Health Care Services Among Children With Asthma
Authors: Pinar Karaca-Mandic, Anupam B. Jena, Geoffrey F. Joyce, Dana P. Goldman
Journal: JAMA (2012)

Health plans have implemented policies to restrain prescription medication spending by shifting costs toward patients. It is unknown how these policies have affected children with chronic illness.To analyze the association of medication cost sharing with medication and hospital services utilization among children with asthma, the most prevalent chronic disease of childhood.Retrospective study of insurance claims for 8834 US children with asthma who initiated asthma control therapy between 1997 and 2007. Using variation in out-of-pocket costs for a fixed "basket" of asthma medications across 37 employers, we estimated multivariate models of asthma medication use, asthma-related hospitalization, and emergency department (ED) visits with respect to out-of-pocket costs and child and family characteristics.Asthma medication use, asthma-related hospitalizations, and ED visits during 1-year follow-up.The mean annual out-of-pocket asthma medication cost was $154 (95% CI, $152-$156) among children aged 5 to 18 years and $151 (95% CI, $148-$153) among those younger than 5 years. Among 5913 children aged 5 to 18 years, filled asthma prescriptions covered a mean of 40.9% of days (95% CI, 40.2%-41.5%). During 1-year follow-up, 121 children (2.1%) had an asthma-related hospitalization and 220 (3.7%) had an ED visit. Among 2921 children younger than 5 years, mean medication use was 46.2% of days (95% CI, 45.2%-47.1%); 136 children (4.7%) had an asthma-related hospitalization and 231 (7.9%) had an ED visit. An increase in out-of-pocket medication costs from the 25th to the 75th percentile was associated with a reduction in adjusted medication use among children aged 5 to 18 years (41.7% [95% CI, 40.7%-42.7%] vs 40.3% [95% CI, 39.4%-41.3%] of days; P = .02) but no change among younger children. Adjusted rates of asthma-related hospitalization were higher for children aged 5 to 18 years in the top quartile of out-of-pocket costs (2.4 [95% CI, 1.9-2.8] hospitalizations per 100 children vs 1.7 [95% CI, 1.3-2.1] per 100 in bottom quartile; P = .004) but not for younger children. Annual adjusted rates of ED use did not vary across out-of-pocket quartiles for either age group.Greater cost sharing for asthma medications was associated with a slight reduction in medication use and higher rates of asthma hospitalization among children aged 5 years or older.
`Vineyard sprayer's lung': a new occupational disease
Authors: J. C. Pimentel, F. Marques
Journal: Thorax (1969)

The mildew of the vineyards is prevented by the use of sprays with a solution of copper sulphate neutralized with hydrated lime. The inhalation of this solution while spraying may give rise to predominantly interstitial pulmonary lesions which may lead to respiratory insufficiency. These lesions, which were experimentally reproduced in guinea-pigs, have a well-defined histological picture characterized by three stages—intra-alveolar desquamation of macrophages, formation of predominantly histiocytic granulomas in the septa, and the healing of these lesions generally under the form of fibro-hyaline nodules very similar to those found in silicosis. These lesions contain variable amounts of copper. The pathogenesis of these lesions and the possibility of their regression when the offending agent is removed are discussed; and the value of lung biopsy and the necessity of protecting these workers are stressed.
Cardiac transplantation after the Fontan or Glenn procedure
Authors: K. Anitha Jayakumar, Linda J. Addonizio, Maryanne R. Kichuk-Chrisant, Mark E. Galantowicz, Jacqueline M. Lamour, Jan M. Quaegebeur, Daphne T. Hsu
Journal: Journal of the American College of Cardiology (2004)
A Central Role for Free Heme in the Pathogenesis of Severe Sepsis
Authors: Rasmus Larsen, Raffaella Gozzelino, Viktória Jeney, László Tokaji, Fernando A. Bozza, André M. Japiassú, Dolores Bonaparte, Moisés Marinho Cavalcante, Ângelo Chora, Ana Ferreira, Ivo Marguti, Sílvia Cardoso, Nuno Sepúlveda, Ann Smith, Miguel P. Soares
Journal: Science Translational Medicine (2010)

Heme from red blood cells released in septic shock worsens organ dysfunction and increases the risk of death, but can be overcome by a scavenger of free heme.
Normal Regulatory α/β T Cells Effectively Eliminate Abnormally Activated T Cells Lacking the Interleukin 2 Receptor β in Vivo
Authors: Haruhiko Suzuki, Yan Wen Zhou, Masashi Kato, Tak W. Mak, Izumi Nakashima
Journal: The Journal of Experimental Medicine (1999)

Although interleukin 2 (IL-2) has been thought to be the most important cytokine for T cell growth, animals lacking IL-2 or a component of its receptor molecules have more expanded T cells with activated memory phenotype, indicating an indispensable role for the IL-2/IL-2 receptor system in regulating the size and activity of the T cell population. In this study, we investigated the possible mechanism of abnormal expansion of activated T cells in IL-2 receptor β chain (IL-2Rβ)−/− mice using the systems of bone marrow transplantation and T cell transfer. Here, we show that IL-2Rβ2/− T cells in mice reconstituted with a mixture of IL-2Rβ2/− and IL-2Rβ1/+ bone marrow cells did not develop into an abnormally activated stage, and that already activated IL-2Rβ2/− T cells were effectively eliminated by IL-2Rβ1/+ T cells when both cells were cotransferred to T cell–deficient host mice. This regulation and/or elimination was dependent on T cells bearing α/β type T cell receptor, especially on CD8+ T cells and independent of the Fas–Fas ligand (FasL) system. IL-2Rβ1/+ T cells that eliminated activated IL-2Rβ2/− T cells expressed FasL, perforin, granzyme B, and tumor necrosis factor α/β. These results indicate a novel function of IL-2Rβ that is necessary for the induction of regulatory T cells acting to eliminate activated T cells.