tbuckley/cabot-search huggingface dataset:
Phase I Study of Adoptive T-Cell Therapy Using Antigen-Specific CD8<sup>+</sup> T Cells for the Treatment of Patients With Metastatic Melanoma
Authors: Andreas Mackensen, Norbert Meidenbauer, Sandra Vogl, Monika Laumer, Jana Berger, Reinhard Andreesen
Journal: Journal of Clinical Oncology (2006)

The adoptive transfer of in vitro generated tumor antigen-specific cytotoxic T lymphocytes (CTL) provides a promising approach to the immunotherapy of cancer. A phase I study was conducted to test the feasibility, safety, and survival of adoptively transferred Melan-A-specific CTL lines in melanoma patients.Eleven HLA-A2+ patients with metastatic melanoma received at least three intravenous infusions of Melan-A-specific CTL at 2-week intervals. CTL were generated by four rounds of in vitro stimulation of purified CD8+ peripheral blood lymphocytes with autologous dendritic cells pulsed with an HLA-A2 binding Melan-A peptide. Each T-cell infusion was accompanied by a 6-day course of low-dose interleukin-2.A total of 52 T-cell infusions were administered, averaging 2.1 x 10(8) Melan-A-specific CTL per infusion. Clinical adverse effects were mild and consisted of chills and low-grade fever in seven of 11 patients. Clinical and immunologic responses revealed an antitumor response in three of 11 patients (one complete regression, one partial regression, one mixed response), an elevated frequency of circulating Melan-A tetramer+ T cells up to 2 weeks in all the patients with a maximal frequency of 2% of total CD8+ T cells, an increase in eosinophils to up to 50% in seven of 11 patients, and a selective loss of Melan-A expression in lymph node metastases in two evaluated patients after T-cell transfer.Our data indicate that the adoptive transfer of antigen-specific T cells in melanoma patients can induce clinical tumor-specific immune responses without major adverse effects.
Fludarabine treatment favors the retention of miR-485-3p by prostate cancer cells: implications for survival
Authors: Serena Lucotti, Giuseppe Rainaldi, Monica Evangelista, Milena Rizzo
Journal: Molecular Cancer (2013)

Abstract Background Circulating microRNAs (miRNAs) have been found in many body fluids and represent reliable markers of several physio-pathological disorders, including cancer. In some cases, circulating miRNAs have been evaluated as markers of the efficacy of anticancer treatment but it is not yet clear if miRNAs are actively released by tumor cells or derive from dead tumor cells. Results We showed that a set of prostate cancer secretory miRNAs (PCS-miRNAs) were spontaneously released in the growth medium by DU-145 prostate cancer cells and that the release was greater after treatment with the cytotoxic drug fludarabine. We also found that the miRNAs were associated with exosomes, implying an active mechanism of miRNA release. It should be noted that in fludarabine treated cells the release of miR-485-3p, as well as its association with exosomes, was reduced suggesting that miR-485-3p was retained by surviving cells. Monitoring the intracellular level of miR-485-3p in these cells, we found that miR-485-3p was stably up regulated for several days after treatment. As a possible mechanism we suggest that fludarabine selected cells that harbor high levels of miR-485-3p, which in turn regulates the transcriptional repressor nuclear factor-Y triggering the transcription of topoisomerase IIα, multidrug resistance gene 1 and cyclin B2 pro-survival genes. Conclusions Cytotoxic treatment of DU-145 cells enhanced the release of PCS-miRNAs with the exception of miR-485-3p which was retained by surviving cells. We speculate that the retention of miR-485-3p was a side effect of fludarabine treatment in that the high intracellular level of miR-485-3p plays a role in the sensitivity to fludarabine.
Skin Prick Test with Heated Fruit for Differentiating Fruit Allergy with Systemic Reaction from That with Oral Reaction
Authors: Osamu Natsume, Tatsuki Fukuie, Ryuhei Yasuoka, Iwao Tajima, Takeshi Chiba, Mai Kondo, Tomohide Taguchi, Masami Narita, Masaki Futamura, Hiroshi Kitazawa, Yukihiro Ohya
Journal: Journal of Allergy and Clinical Immunology (2015)
A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging
Authors: Mark A. McCormick, Joe R. Delaney, Mitsuhiro Tsuchiya, Scott Tsuchiyama, Anna Shemorry, Sylvia Sim, Annie Chia-Zong Chou, Umema Ahmed, Daniel Carr, Christopher J. Murakami, Jennifer Schleit, George L. Sutphin, Brian M. Wasko, Christopher F. Bennett, Adrienne M. Wang, Brady Olsen, Richard P. Beyer, Theodor K. Bammler, Donna Prunkard, Simon C. Johnson, Juniper K. Pennypacker, Elroy An, Arieanna Anies, Anthony S. Castanza, Eunice Choi, Nick Dang, Shiena Enerio, Marissa Fletcher, Lindsay Fox, Sarani Goswami, Sean A. Higgins, Molly A. Holmberg, Di Hu, Jessica Hui, Monika Jelic, Ki-Soo Jeong, Elijah Johnston, Emily O. Kerr, Jin Kim, Diana Kim, Katie Kirkland, Shannon Klum, Soumya Kotireddy, Eric Liao, Michael Lim, Michael S. Lin, Winston C. Lo, Dan Lockshon, Hillary A. Miller, Richard M. Moller, Brian Muller, Jonathan Oakes, Diana N. Pak, Zhao Jun Peng, Kim M. Pham, Tom G. Pollard, Prarthana Pradeep, Dillon Pruett, Dilreet Rai, Brett Robison, Ariana A. Rodriguez, Bopharoth Ros, Michael Sage, Manpreet K. Singh, Erica D. Smith, Katie Snead, Amrita Solanky, Benjamin L. Spector, Kristan K. Steffen, Bie Nga Tchao, Marc K. Ting, Helen Vander Wende, Dennis Wang, K. Linnea Welton, Eric A. Westman, Rachel B. Brem, Xin-guang Liu, Yousin Suh, Zhongjun Zhou, Matt Kaeberlein, Brian K. Kennedy
Journal: Cell Metabolism (2015)
Phase III Trial Comparing 4-Day Chronomodulated Therapy Versus 2-Day Conventional Delivery of Fluorouracil, Leucovorin, and Oxaliplatin As First-Line Chemotherapy of Metastatic Colorectal Cancer: The European Organisation for Research and Treatment of Cancer Chronotherapy Group
Authors: Sylvie Giacchetti, Georg Bjarnason, Carlo Garufi, Dominique Genet, Stefano Iacobelli, Marco Tampellini, Rune Smaaland, Christian Focan, Bruno Coudert, Yves Humblet, Jean Luc Canon, Antoine Adenis, Giovanni Lo Re, Carlos Carvalho, Johannes Schueller, Nicole Anciaux, Marie-Ange Lentz, Benoît Baron, Thierry Gorlia, Francis Lévi
Journal: Journal of Clinical Oncology (2006)

In two previous randomized trials, the adjustment of chemotherapy delivery to circadian rhythms improved tolerability and anticancer activity compared with constant-rate infusion during 5 days in patients with metastatic colorectal cancer.For this multicenter randomized trial, it was hypothesized that a chronomodulated infusion of fluorouracil, leucovorin, and oxaliplatin for 4 days (chronoFLO4) would improve survival by 10% compared with conventional 2-day delivery of the same drugs (FOLFOX2). Patients were treated every 2 weeks with intrapatient dose escalation.Baseline characteristics were similar in both arms for the 564 patients (36 institutions, 10 countries). Median survival was 19.6 months (95% confidence limit [CL] = 18.2, 21.2) with chronoFLO4 and 18.7 months with FOLFOX2 (95% CL = 17.7, 21.0; P = .55). The main dose-limiting toxicities were diarrhea for chronoFLO4 and neutropenia for FOLFOX2. The analysis of survival predictors showed that sex was the single most important factor (P = .001). In women, the risk of an earlier death with chronoFLO4 was increased by 38% compared with FOLFOX2, with median survival times of 16.3 and 19.1 months (P = .03), respectively. In men, the risk of death was decreased by 25% with chronoFLO4 compared with FOLFOX2, with median survival times of 21.4 and 18.3 months (P = .02), respectively.Both regimens achieved similar median survival times more than 18 months with an acceptable toxicity. The chronomodulated schedule produced a survival advantage over FOLFOX in men. The strong sex dependency of optimal scheduling of fluorouracil, leucovorin, and oxaliplatin calls for translational investigations of determinants related to the patient's molecular clock.
Abrupt Discontinuation of Clonidine Therapy
Authors: C. Venkata S. Ram
Journal: JAMA (1979)

Clonidine therapy was discontinued abruptly in seven patients. Blood pressure was recorded every hour or two hours throughout the study. Clonidine therapy was reinstituted 48 hours after its discontinuation in all except two patients, in whom it was reinstituted at 36 hours. During the withdrawal phase, blood pressure tended to return rapidly to nontreatment levels, but there was no "overshoot" in blood pressure. Apprehension, insomnia, palpitations, and sweating were experienced by two patients. These symptoms were relieved promptly by reinstituting clonidine therapy. In this prospective study, no blood pressure overshoot was noted with abrupt discontinuation of clonidine.
Therapeutic Strategies Utilized in the Setting of Acquired Resistance to EGFR Tyrosine Kinase Inhibitors
Authors: Helena A. Yu, Gregory J. Riely, Christine M. Lovly
Journal: Clinical Cancer Research (2014)

Patients with EGFR-mutant lung cancer derive significant therapeutic benefit from treatment with EGFR tyrosine kinase inhibitors (TKI). Unfortunately, acquired resistance is an inevitable consequence of this treatment strategy, with a broad variety of resistance mechanisms including acquired EGFR mutations (e.g., T790M) and activation of bypass signaling pathways, such as MET and HER2. Several therapeutic strategies hypothesized to delay or overcome resistance have been tested in clinical trials, including "next-generation" EGFR TKIs and rational combinations of targeted agents. However, to date, there are no FDA-approved therapies for patients with acquired resistance to first-line EGFR TKI therapy. There remains a critical need for more effective and better tailored treatments in this setting to match treatments to the individual patient and specific resistance mechanism at hand. In this review, we discuss known mechanisms of resistance to first-line EGFR TKI therapy and describe previous and ongoing strategies to overcome resistance.
Evidence that Lyb-2 is critical to specific activation of B cells before they become responsive to T cell and other signals.
Authors: H Yakura, F W Shen, E Bourcet, E A Boyse
Journal: The Journal of Experimental Medicine (1982)

The generation of plaque-forming cells (PFC) to T-dependent antigen, but not to T-independent antigen, is reduced in vitro by Lyb-2 antibody. Monoclonal Lyb-2 antibody, added to Mishell-Dutton cultures within the first 2 d, but not later, greatly reduces the generation of alpha-sheep erythrocyte (SRBC) PFC from T-depleted spleen cells whether help is provided in the form of intact T cells or as soluble factors contained in mixed lymphocyte culture (MLC) supernatants. Generation of alpha-SRBC PFC from purified B cells, assisted by soluble factors in MLC and macrophage (P388D.1 cell) supernatants, is similarly reduced by Lyb-2 antibody. The initial 2-d period, during which cultures are diminishingly sensitive to reduction of PFC generation by Lyb-2 antibody, is not affected by the time at which such soluble factors are added. Thus, Lyb-2 cell surface molecules evidently do not function as receptors for these differentiative signals. Reduction of PFC generation by Lyb-2 antibody is antigen dependent in the sense that reduction of the PFC response to one antigen (SRBC) does not affect subsequent generation of PFC to a second antigen (horse erythrocytes) from the same cell population. These findings accord with the view that the Lyb-2 molecule participates in a B cell differentiative phase, probably proliferative, which begins with binding of antigen and precedes the phase in which B cells become fully receptive to signals from T and other cells.
Functional Imaging in Lung Cancer
Authors: Lalitha K. Shankar, Daniel C. Sullivan
Journal: Journal of Clinical Oncology (2005)

Accurate detection of the presence and extent of disease is vital in the management of non–small-cell lung cancer. While computed tomography and magnetic resonance imaging tend to be the routine diagnostic modalities used in the management of lung cancer, there have been significant advances in the field of functional and molecular imaging. In this article, we review the performance of the functional imaging techniques that are currently available for the evaluation of non–small-cell lung cancer. The techniques range from evaluation of glucose metabolism in tumors with fluorodeoxyglucose, to evaluation of proliferation with fluorothymidine and evaluation of tumor hypoxia with agents such as fluoromisonidazole. Magnetic resonance imaging with an emphasis on dynamic contrast enhancement of tumors as well as detecting of malignant lymph nodes with targeted contrast agents is discussed. Emerging technologies such as lung imaging fluorescence endoscopy are considered. The role of functional imaging in planning, predicting response to, and evaluating effects of, various therapies is explored.
Transformation of Visual Signals by Inhibitory Interneurons in Retinal Circuits
Authors: Pablo D. Jadzinsky, Stephen A. Baccus
Journal: Annual Review of Neuroscience (2013)

One of the largest mysteries of the brain lies in understanding how higher-level computations are implemented by lower-level operations in neurons and synapses. In particular, in many brain regions inhibitory interneurons represent a diverse class of cells, the individual functional roles of which are unknown. We discuss here how the operations of inhibitory interneurons influence the behavior of a circuit, focusing on recent results in the vertebrate retina. A key role in this understanding is played by a common representation of the visual stimulus that can be applied at different stages. By considering how this stimulus representation changes at each location in the circuit, we can understand how neuron-level operations such as thresholds and inhibition yield circuit-level computations such as how stimulus selectivity and gain are controlled by local and peripheral visual stimuli.
Salmeterol/fluticasone combination instead of indacaterol or<i>vice-versa</i>?
Authors: Andrea Rossi, Thys van der Molen, Ricardo del Olmo, Luis Wehbe
Journal: European Respiratory Journal (2015)

We read with interest the comments by L.M. Fabbri and A. Augusti on our article entitled "INSTEAD: a randomised switch trial of indacaterol versus salmeterol/fluticasone in moderate COPD" [1]. However, we believe that those comments go well beyond the conclusion of the study, which is well supported by the data. This study shows that inhaled corticosteroids are not needed in COPD patients at low risk of exacerbations <http://ow.ly/IkmDF>
Functional Role of Glucose Metabolism, Osmotic Stress, and Sodium-Glucose Cotransporter Isoform-Mediated Transport on Na+/H+ Exchanger Isoform 3 Activity in the Renal Proximal Tubule
Authors: Thaissa Dantas Pessoa, Luciene Cristina Gastalho Campos, Luciene Carraro-Lacroix, Adriana C.C. Girardi, Gerhard Malnic
Journal: Journal of the American Society of Nephrology (2014)

Na(+)-glucose cotransporter 1 (SGLT1)-mediated glucose uptake leads to activation of Na(+)-H(+) exchanger 3 (NHE3) in the intestine by a process that is not dependent on glucose metabolism. This coactivation may be important for postprandial nutrient uptake. However, it remains to be determined whether SGLT-mediated glucose uptake regulates NHE3-mediated NaHCO3 reabsorption in the renal proximal tubule. Considering that this nephron segment also expresses SGLT2 and that the kidneys and intestine show significant variations in daily glucose availability, the goal of this study was to determine the effect of SGLT-mediated glucose uptake on NHE3 activity in the renal proximal tubule. Stationary in vivo microperfusion experiments showed that luminal perfusion with 5 mM glucose stimulates NHE3-mediated bicarbonate reabsorption. This stimulatory effect was mediated by glycolytic metabolism but not through ATP production. Conversely, luminal perfusion with 40 mM glucose inhibited NHE3 because of cell swelling. Notably, pharmacologic inhibition of SGLT activity by Phlorizin produced a marked inhibition of NHE3, even in the absence of glucose. Furthermore, immunofluorescence experiments showed that NHE3 colocalizes with SGLT2 but not SGLT1 in the rat renal proximal tubule. Collectively, these findings show that glucose exerts a bimodal effect on NHE3. The physiologic metabolism of glucose stimulates NHE3 transport activity, whereas, supraphysiologic glucose concentrations inhibit this exchanger. Additionally, Phlorizin-sensitive SGLT transporters and NHE3 interact functionally in the proximal tubule.
BEHAVIORAL CATEGORIES OF CHILDHOOD
Authors: J. FRANKLIN ROBINSON, LOUIS J. VITALE, CARL J. NITSCHE
Journal: American Journal of Psychiatry (1961)

1. Five descriptive categories of behavior in childhood have been outlined. 2. These categories have proven useful in intra-staff communication, and in the organization of work with parents. 3. These or other groupings of symptoms or behavioral features may lead to the recognition of clinical conditions, which can achieve general recognition or acceptance leading toward a practical classification of childhood disorders.
Maternal and cord blood hormone levels in the United States and China and the intrauterine origin of breast cancer
Authors: P. Lagiou, E. Samoli, W. Okulicz, B. Xu, A. Lagiou, L. Lipworth, C. Georgila, L. Vatten, H.O. Adami, D. Trichopoulos, C.C. Hsieh
Journal: Annals of Oncology (2010)
Surgical Ablation of Atrial Fibrillation during Mitral-Valve Surgery
Authors: A. Marc Gillinov, Annetine C. Gelijns, Michael K. Parides, Joseph J. DeRose, Alan J. Moskowitz, Pierre Voisine, Gorav Ailawadi, Denis Bouchard, Peter K. Smith, Michael J. Mack, Michael A. Acker, John C. Mullen, Eric A. Rose, Helena L. Chang, John D. Puskas, Jean-Philippe Couderc, Timothy J. Gardner, Robin Varghese, Keith A. Horvath, Steven F. Bolling, Robert E. Michler, Nancy L. Geller, Deborah D. Ascheim, Marissa A. Miller, Emilia Bagiella, Ellen G. Moquete, Paula Williams, Wendy C. Taddei-Peters, Patrick T. O'Gara, Eugene H. Blackstone, Michael Argenziano
Journal: New England Journal of Medicine (2015)

Among patients undergoing mitral-valve surgery, 30 to 50% present with atrial fibrillation, which is associated with reduced survival and increased risk of stroke. Surgical ablation of atrial fibrillation has been widely adopted, but evidence regarding its safety and effectiveness is limited.We randomly assigned 260 patients with persistent or long-standing persistent atrial fibrillation who required mitral-valve surgery to undergo either surgical ablation (ablation group) or no ablation (control group) during the mitral-valve operation. Patients in the ablation group underwent further randomization to pulmonary-vein isolation or a biatrial maze procedure. All patients underwent closure of the left atrial appendage. The primary end point was freedom from atrial fibrillation at both 6 months and 12 months (as assessed by means of 3-day Holter monitoring).More patients in the ablation group than in the control group were free from atrial fibrillation at both 6 and 12 months (63.2% vs. 29.4%, P<0.001). There was no significant difference in the rate of freedom from atrial fibrillation between patients who underwent pulmonary-vein isolation and those who underwent the biatrial maze procedure (61.0% and 66.0%, respectively; P=0.60). One-year mortality was 6.8% in the ablation group and 8.7% in the control group (hazard ratio with ablation, 0.76; 95% confidence interval, 0.32 to 1.84; P=0.55). Ablation was associated with more implantations of a permanent pacemaker than was no ablation (21.5 vs. 8.1 per 100 patient-years, P=0.01). There were no significant between-group differences in major cardiac or cerebrovascular adverse events, overall serious adverse events, or hospital readmissions.The addition of atrial fibrillation ablation to mitral-valve surgery significantly increased the rate of freedom from atrial fibrillation at 1 year among patients with persistent or long-standing persistent atrial fibrillation, but the risk of implantation of a permanent pacemaker was also increased. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00903370.).
Kirsner's Inflammatory Bowel Disease, 6th edn
Authors: D A van Heel
Journal: Gut (2005)

Management of acute pancreatitisNo account of the complications of acute pancreatitis (Gut 2005;54:426-36) would be complete without mention of diabetic ketoacidosis as an association, which is either fortuitous or one which exists as a complication in its own right.Recognition of this association has been inhibited by the complicated relationship between diabetic ketoacidosis, acute abdominal pain, and hyperamylassaemia, notwithstanding the
Possible Involvement of Stress-Activated Protein Kinase Signaling Pathway and Fas Receptor Expression in Prevention of Ischemia/Reperfusion-Induced Cardiomyocyte Apoptosis by Carvedilol
Authors: Tian-Li Yue, Xin-Liang Ma, Xinkang Wang, Anne M. Romanic, Gao-lin Liu, Calvert Louden, Juan-Li Gu, Sanjay Kumar, George Poste, Robert R. Ruffolo, Giora Z. Feuerstein
Journal: Circulation Research (1998)

Carvedilol, a new vasodilating beta-adrenoceptor antagonist and a potent antioxidant, produces a high degree of cardioprotection in a variety of experimental models of ischemic cardiac injury. Recent clinical studies in patients with heart failure have demonstrated that carvedilol reduces morbidity and mortality and inhibits cardiac remodeling. The present study was designed to explore whether the protective effects of carvedilol on the ischemic myocardium include inhibition of apoptosis of cardiomyocytes and, if so, to determine its mechanism of action. Anesthetized rabbits were subjected to 30 minutes of coronary artery occlusion followed by 4 hours of reperfusion. Detection of apoptosis of cardiomyocytes was based on the presence of nucleosomal DNA fragments on agarose gels (DNA ladder) and in situ nick end labeling. Carvedilol (1 mg/kg IV), administered 5 minutes before reperfusion, reduced the number of apoptotic myocytes in the ischemic area from 14.7 +/- 0.4% to 3.4 +/- 1.8% (77% reduction, P<.001). Propranolol, administered at equipotent beta-blocking dosage, reduced the number of apoptotic myocytes to 8.9 +/- 2.1% (39% reduction, P<.05). DNA ladders were observed in the hearts of all six vehicle-treated rabbits but only one of six carvedilol-treated rabbits (P<.01). Immunocytochemical analysis of rabbit hearts demonstrated an upregulation of Fas protein in ischemic cardiomyocytes, and treatment with carvedilol reduced both the intensity of staining as well as the area stained. Myocardial ischemia/reperfusion led to a rapid activation of stress-activated protein kinase (SAPK) in the ischemic area but not in nonischemic regions. SAPK activity was increased from 2.1 +/- 0.3 mU/mg (basal) to 8.9 +/- 0.8 mU/mg after 30 minutes of ischemia followed by 20 minutes of reperfusion. Carvedilol inhibited the activation of SAPK by 53.4 +/- 6.5% (P<.05). Under the same conditions, propranolol (1 mg/kg) had no effect on SAPK activation. Taken together, these results suggest that carvedilol prevents myocardial ischemia/reperfusion-induced apoptosis in cardiomyocytes possibly by downregulation of the SAPK signaling pathway, by inhibition of Fas receptor expression, and by beta-adrenergic blockade. The former two actions represent novel and important mechanisms that may contribute to the cardioprotective effects of carvedilol.