tbuckley/cabot-search huggingface dataset:
Antireflux Surgery in Patients With Chronic Cough and Abnormal Proximal Exposure as Measured by Hypopharyngeal Multichannel Intraluminal Impedance
Authors: Toshitaka Hoppo, Yoshihiro Komatsu, Blair A. Jobe
Journal: JAMA Surgery (2013)

Chronic cough is a laryngeal symptom that can be caused by gastroesophageal reflux disease; however, treatment outcome has been difficult to predict because of the lack of an objective testing modality that accurately detects reflux-related cough.To define the patterns of reflux and assess the outcome of antireflux surgery (ARS) in patients with chronic cough who were selected using hypopharyngeal multichannel intraluminal impedance (HMII).Review of prospectively collected data.Tertiary care university hospital.Patients with chronic cough, which was defined as persistent cough (≥8 weeks) of unknown cause.Hypopharyngeal multichannel intraluminal impedance with a specialized catheter to detect laryngopharyngeal reflux and high-esophageal reflux (reflux 2 cm distal to the upper esophageal sphincter) and ARS.Abnormal proximal exposure was defined as laryngopharyngeal reflux occurring 1 or more times per day and/or high-esophageal reflux occurring 5 or more times per day. The outcomes of ARS included symptomatic improvement.From October 2009 to June 2011, a total of 314 symptomatic patients underwent HMII. Of this population, 49 patients (15 men, 34 women; median age, 57 years) were identified as having chronic cough. Of the 49 participants, 23 of 44 patients (52%) had objective findings of gastroesophageal reflux disease, such as esophagitis. Abnormal proximal exposure was discovered in 36 of the 49 patients (73%). Of 16 patients with abnormal proximal exposure who subsequently underwent ARS, 13 patients (81%) had resolution of cough and 3 patients (19%) had significant improvement at a median follow-up of 4.6 months (range, 0.5-13 months).A highly selective group of patients with idiopathic chronic cough may have abnormal proximal exposure to gastroesophageal reflux documented by HMII that would have not been detected with conventional pH testing. Thus, HMII is likely to improve the sensitivity of laryngopharyngeal reflux diagnosis and better elucidate those who will respond to antireflux surgery.
Reply to A. Italiano
Authors: Amy R. Peck, Agnieszka K. Witkiewicz, Chengbao Liu, Ginger A. Stringer, Alexander C. Klimowicz, Edward C. Pequignot, Boris C. Freydin, Thai H. Tran, Ning Yang, Anne L. Rosenberg, Jeffrey A. Hooke, Albert J. Kovatich, Marja T. Nevalainen, Craig D. Shriver, Terry Hyslop, Guido Sauter, David L. Rimm, Anthony M. Magliocco, Hallgeir Rui
Journal: Journal of Clinical Oncology (2011)
The effect of cigarette smoking on asthma control during exacerbations in pregnant women
Authors: V. E. Murphy, V. L. Clifton, P. G. Gibson
Journal: Thorax (2010)

<h3>Background</h3> Smoking and severe asthma exacerbations in pregnancy are risk factors for low birth weight babies. No studies have assessed the clinical implications of smoking on asthma exacerbations in pregnancy. <h3>Methods</h3> Pregnant women with current asthma (n=80) were prospectively assessed at clinic visits (18, 30, 36 weeks), during exacerbations and with fortnightly phone calls. The asthma control questionnaire was administered at each contact and exacerbations classified as severe (requiring medical intervention) or mild (self-managed). Medications, self-management skills, smoking history, fractional exhaled nitric oxide (FENO), exhaled carbon monoxide (ECO) and lung function were assessed. Pregnant women without asthma (controls, n=46) were assessed prospectively at clinic visits. <h3>Results</h3> Women with asthma were more likely to smoke (34% current smokers) than women without asthma (15% current smokers). In women with asthma, the median (IQR) exacerbation rate during pregnancy was 2.0 (1.0–3.0) in current smokers, 2.0 (1.0–3.0) in ex-smokers and 1.5 (1.0–2.0) in never smokers. The asthma control score during exacerbations was higher in current smokers (median (IQR) 2.17 (1.17–2.7)) compared with never smokers (1.17 (0.8–2.17), p=0.056). An adjusted linear regression model found that smoking was significantly associated with higher asthma control score during exacerbation (p=0.04). Birth weights were lower among children of smokers than non-smokers (p=0.023 control group, p=0.086 asthma group). <h3>Conclusions</h3> During pregnancy, asthma exacerbations are more common and more severe in current smokers than never smokers. The risk of effects of maternal asthma on the fetus may be greater among smokers.
Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study
Authors: Owen A. O'Connor, Steven Horwitz, Tamás Masszi, Achiel Van Hoof, Peter Brown, Jeannette Doorduijn, Georg Hess, Wojciech Jurczak, Poul Knoblauch, Shanta Chawla, Gajanan Bhat, Mi Rim Choi, Jan Walewski, Kerry Savage, Francine Foss, Lee F. Allen, Andrei Shustov
Journal: Journal of Clinical Oncology (2015)

Peripheral T-cell lymphomas (PTCLs) represent a diverse group of non-Hodgkin lymphomas with a poor prognosis and no accepted standard of care for patients with relapsed or refractory disease. This study evaluated the efficacy and tolerability of belinostat, a novel histone deacetylase inhibitor, as a single agent in relapsed or refractory PTCL.Patients with confirmed PTCL who experienced progression after ≥ one prior therapy received belinostat 1,000 mg/m(2) as daily 30-minute infusions on days 1 to 5 every 21 days. Central assessment of response used International Working Group criteria. Primary end point was overall response rate. Secondary end points included duration of response (DoR) and progression-free and overall survival.A total of 129 patients were enrolled, with a median of two prior systemic therapies. Overall response rate in the 120 evaluable patients was 25.8% (31 of 120), including 13 complete (10.8%) and 18 partial responses (15%). Median DoR by International Working Group criteria was 13.6 months, with the longest ongoing patient at ≥ 36 months. Median progression-free and overall survival were 1.6 and 7.9 months, respectively. Twelve of the enrolled patients underwent stem-cell transplantation after belinostat monotherapy. The most common grade 3 to 4 adverse events were anemia (10.8%), thrombocytopenia (7%), dyspnea (6.2%), and neutropenia (6.2%).Monotherapy with belinostat produced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across the major subtypes, irrespective of number or type of prior therapies. These results have led to US Food and Drug Administration approval of belinostat for this indication.
ACE-inhibition prevents postischemic coronary leukocyte adhesion and leukocyte-dependent reperfusion injury
Authors: Christian Kupatt, Helmut Habazettl, Stefan Zahler, Christian Weber, Bernhard F Becker, Konrad Messmer, Eckehart Gerlach
Journal: Cardiovascular Research (1997)

Objective: Polymorphonuclear leukocytes (PMN), retained in the microvascular bed, can contribute to postischemic myocardial reperfusion injury. Since a beneficial effect of ACE-inhibition on reperfusion injury has been reported, we investigated the impact of cilazaprilat on PMN dependent reperfusion injury in isolated guinea pig hearts. Methods: Hearts (n = 5 per group) were subjected to 15 min of ischemia. Immediately thereafter, a bolus of PMN was injected into the coronary system. External heart work (EHW) and total cardiac nitric oxide release were measured. For microscopic evaluation, hearts received rhodamine 6G labelled PMN after ischemia, were arrested 5 min later and further perfused with FITC dextran (0.1%). Localization of retained PMN was assessed by fluorescence microscopy. Leukocyte activation was studied by FACS analysis of the adhesion molecule CD11b before and after coronary passage of the PMN. The ACE-inhibitor cilazaprilat (Cila, 2 μM) and the NO-synthase inhibitor nitro-l-arginine (NOLAG, 10 μM) were used to modulate nitric oxide formation of the heart. Results: Postischemic EHW recovered to 67±5% (controls) and 64±6% (Cila) of the preischemic value. Addition of PMN severely depressed recovery of EHW (39±2%) and NO release (39±6% of the preischemic value). Simultaneously, ischemia led to a substantial increase in postcapillary PMN adhesion (from 21±5 to 172±27 PMN/mm2 surface) and CD11b-expression of the recovered PMN (3-fold). Cila attenuated postischemic PMN adhesion (83±52 PMN/mm2) and activation of PMN, whereas it improved recovery of work performance (64±4%) and NO release (65±4%) in the presence of PMN. Conversely, NOLAG increased PMN adhesion (284±40 PMN/mm2) and myocardial injury. We conclude that ACE-inhibition prevents leukocyte dependent reperfusion injury mainly by inhibition of postcapillary leukocyte adhesion. The effect may be mediated by NO, given the proadhesive effect of NOLAG.
Mice lacking inhibitory leptin receptor signals are lean with normal endocrine function
Authors: Marie Björnholm, Heike Münzberg, Rebecca L. Leshan, Eneida C. Villanueva, Sarah H. Bates, Gwendolyn W. Louis, Justin C. Jones, Ryoko Ishida-Takahashi, Christian Bjørbaek, Martin G. Myers
Journal: Journal of Clinical Investigation (2007)

The adipose-derived hormone, leptin, acts via its receptor (LRb) to convey the status of body energy stores to the brain, decreasing feeding and potentiating neuroendocrine energy expenditure. The failure of high levels of leptin in most obese individuals to promote weight loss defines a state of diminished responsiveness to increased leptin, termed leptin resistance. Leptin stimulates the phosphorylation of several tyrosine residues on LRb to mediate leptin action. We homologously replaced LRb in mice with a receptor with a mutation in one of these sites (Tyr985) in order to examine its role in leptin action and signal attenuation in vivo. Mice homozygous for this mutation are neuroendocrinologically normal, but females demonstrate decreased feeding, decreased expression of orexigenic neuropeptides, protection from high-fat diet–induced obesity, and increased leptin sensitivity in a sex-biased manner. Thus, leptin activates autoinhibitory signals via LRb Tyr985 to attenuate the anti-adiposity effects of leptin, especially in females, potentially contributing to leptin insensitivity in obesity.
Haemoglobin Bart's hydrops syndrome in Greece.
Authors: C Kattamis, A Metaxotou-Mavromati, E Tsiarta, C Metaxatou, P Wasi, W G Wood, L Pressley, D R Higgs, J B Clegg, D J Weatherall
Journal: BMJ (1980)

A case of haemoglobin Bart9s hydrops syndrome was characterised in a Greek family with a history of three other fetuses with hydrops. Family studies showed that both the mother and father carried alpha-thalassaemia genes, and globin-chain synthesis analysis of the present fetus showed a total absence of alpha-chain production. The haemoglobin composition of the fetus was similar to that seen in cases in south-east Asia, and analysis of DNA from the Greek case confirmed the total deletion of the alpha-chain genes. The extent of the deletion, however, differed from that seen in south-east Asian cases and included the loss of one of the embryonic zeta-chain genes. Thus the severe form of alpha-thalassaemia occurs in Greece but has arisen independently from the similar condition in south-east Asia. The condition must be considered in any woman of this racial background who gives a history of unexplained stillbirths.
The RIP1-Kinase Inhibitor Necrostatin-1 Prevents Osmotic Nephrosis and Contrast-Induced AKI in Mice
Authors: Andreas Linkermann, Jan-Ole Heller, Ágnes Prókai, Joel M. Weinberg, Federica De Zen, Nina Himmerkus, Attila J. Szabó, Jan H. Bräsen, Ulrich Kunzendorf, Stefan Krautwald
Journal: Journal of the American Society of Nephrology (2013)

The pathophysiology of contrast-induced AKI (CIAKI) is incompletely understood due to the lack of an appropriate in vivo model that demonstrates reduced kidney function before administration of radiocontrast media (RCM). Here, we examine the effects of CIAKI in vitro and introduce a murine ischemia/reperfusion injury (IRI)–based approach that allows induction of CIAKI by a single intravenous application of standard RCM after injury for in vivo studies. Whereas murine renal tubular cells and freshly isolated renal tubules rapidly absorbed RCM, plasma membrane integrity and cell viability remained preserved in vitro and ex vivo, indicating that RCM do not induce apoptosis or regulated necrosis of renal tubular cells. In vivo, the IRI-based CIAKI model exhibited typical features of clinical CIAKI, including RCM-induced osmotic nephrosis and increased serum levels of urea and creatinine that were not altered by inhibition of apoptosis. Direct evaluation of renal morphology by intravital microscopy revealed dilation of renal tubules and peritubular capillaries within 20 minutes of RCM application in uninjured mice and similar, but less dramatic, responses after IRI pretreatment. Necrostatin-1 (Nec-1), a specific inhibitor of the receptor-interacting protein 1 (RIP1) kinase domain, prevented osmotic nephrosis and CIAKI, whereas an inactive Nec-1 derivate (Nec-1i) or the pan-caspase inhibitor zVAD did not. In addition, Nec-1 prevented RCM-induced dilation of peritubular capillaries, suggesting a novel role unrelated to cell death for the RIP1 kinase domain in the regulation of microvascular hemodynamics and pathophysiology of CIAKI.
Impaired left atrial function in heart failure with preserved ejection fraction
Authors: Angela B.S. Santos, Elisabeth Kraigher‐Krainer, Deepak K. Gupta, Brian Claggett, Michael R. Zile, Burkert Pieske, Adriaan A. Voors, Marty Lefkowitz, Toni Bransford, Victor Shi, Milton Packer, John J.V. McMurray, Amil M. Shah, Scott D. Solomon
Journal: European Journal of Heart Failure (2014)
Effect of metoclopramide on transport in the small intestine of the dog
Authors: J. Tinker, A. G. Cox
Journal: Gut (1969)

A method is described for the simultaneous measurement of flow rate, mean transit time, and volume of the intestine during the transport of fluid through a segment of the small intestine of the dog. Using this method, the effect of metoclopramide on motility of the small bowel was assessed. The drug resulted in a decrease in transit time and volume in the test segment of bowel while the flow rate remained constant. This finding suggests that metoclopramide-stimulated contraction of intestinal smooth muscle.
Nitrative Inactivation of Thioredoxin-1 and Its Role in Postischemic Myocardial Apoptosis
Authors: Ling Tao, Xiangying Jiao, Erhe Gao, Wayne B. Lau, Yuexing Yuan, Bernard Lopez, Theodore Christopher, Satish P. RamachandraRao, William Williams, Garry Southan, Kumar Sharma, Walter Koch, Xin L. Ma
Journal: Circulation (2006)

Background— Intracellular proteins involved in oxidative stress and apoptosis are nitrated in diseased tissues but not in normal tissues; definitive evidence to support a causative link between a specific protein that is nitratively modified with tissue injury in a specific disease is limited, however. The aims of the present study were to determine whether thioredoxin (Trx), a novel antioxidant and antiapoptotic molecule, is susceptible to nitrative inactivation and to establish a causative link between Trx nitration and postischemic myocardial apoptosis. Methods and Results— In vitro exposure of human Trx-1 to 3-morpholinosydnonimine resulted in significant Trx-1 nitration and almost abolished Trx-1 activity. 3-morpholinosydnonimine–induced nitrative Trx-1 inactivation was completely blocked by MnTE-2-PyP 5+ (a superoxide dismutase mimetic) and markedly attenuated by PTIO (a nitric oxide scavenger). Administration of either reduced or oxidized Trx-1 in vivo attenuated myocardial ischemia/reperfusion injury (&gt;50% reduction in apoptosis and infarct size, P &lt;0.01). However, administration of nitrated Trx-1 failed to exert a cardioprotective effect. In cardiac tissues obtained from ischemic/reperfused heart, significant Trx-1 nitration was detected, Trx activity was markedly inhibited, Trx-1/ASK1 (apoptosis signal-regulating kinase-1) complex formation was abolished, and apoptosis signal-regulating kinase-1 activity was increased. Treatment with either FP15 (a peroxynitrite decomposition catalyst) or MnTE-2-PyP 5+ 10 minutes before reperfusion blocked nitrative Trx inactivation, attenuated apoptosis signal-regulating kinase-1 activation, and reduced postischemic myocardial apoptosis. Conclusions— These results strongly suggest that nitrative inactivation of Trx plays a proapoptotic role under those pathological conditions in which production of reactive nitrogen species is increased and that antinitrating treatment may have therapeutic value in those diseases, such as myocardial ischemia/reperfusion, in which pathological apoptosis is increased.
Differential Response of Human Ovarian Cancer Cells to Induction of Apoptosis by Vitamin E Succinate and Vitamin E Analogue, α-TEA
Authors: Kristen Anderson, Marla Simmons-Menchaca, Karla A. Lawson, Jeffrey Atkinson, Bob G. Sanders, Kimberly Kline
Journal: Cancer Research (2004)

Abstract A vitamin E derivative, vitamin E succinate (VES; RRR-α-tocopheryl succinate), and a vitamin E analogue, 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid (α-TEA), induce human breast, prostate, colon, lung, cervical, and endometrial tumor cells in culture to undergo apoptosis but not normal human mammary epithelial cells, immortalized, nontumorigenic breast cells, or normal human prostate epithelial cells. Human ovarian and cervical cancer cell lines are exceptions, with α-TEA exhibiting greater proapoptotic effects. Although both VES and α-TEA can induce A2780 and subline A2780/cp70 ovarian cancer cells to undergo DNA synthesis arrest within 24 h of treatment, only α-TEA is an effective inducer of apoptosis. VES or α-TEA treatment of cp70 cells with 5, 10, or 20 μg/ml for 3 days induced 5, 6, and 19% versus 9, 36, and 71% apoptosis, respectively. Colony formation data provide additional evidence that cp70 cells are more sensitive to growth inhibition by α-TEA than VES. Differences in stability of the ester-linked succinate moiety of VES versus the ether-linked acetic acid moiety of α-TEA were demonstrated by high-performance liquid chromatography analyses that showed α-TEA to remain intact, whereas VES was hydrolyzed to the free phenol, RRR-α-tocopherol. Pretreatment of cp70 cells with bis-(p-nitrophenyl) phosphate, an esterase inhibitor, before VES treatment, resulted in increased levels of intact VES and apoptosis. Taken together, these data show α-TEA to be a potent and stable proapoptotic agent for human ovarian tumor cells and suggest that endogenous ovarian esterases can hydrolyze the succinate moiety of VES, yielding RRR-α-tocopherol, an ineffective apoptotic-inducing agent.
CTLA-4 Ablation and Interleukin-12–Driven Differentiation Synergistically Augment Cardiac Pathogenicity of Cytotoxic T Lymphocytes
Authors: Victoria A. Love, Nir Grabie, Paurene Duramad, George Stavrakis, Arlene Sharpe, Andrew Lichtman
Journal: Circulation Research (2007)

CD8+ cytotoxic T lymphocytes contribute to viral and autoimmune myocarditis and cardiac allograft rejection. The role of cytotoxic T-lymphocyte-associated antigen (CTLA)-4 as a negative regulator of CD4+ T cells is well defined, yet CTLA-4 regulation of CD8+ T cells is less clear. We studied CTLA-4 regulation of cytotoxic T lymphocytes in a transgenic model of CD8+ T-cell-mediated myocarditis. We generated CTLA-4(-/-) Rag 2(-/-) OT-1 mice, the CD8+ T cells of which express an ovalbumin (OVA) peptide-specific, class I major histocompatibility complex-restricted T-cell receptor. CTLA-4(-/-Tc12) OT-1 effectors, differentiated with interleukin-12 present, are hyperproliferative in vitro, compared with CTLA-4(+/+)Tc12 OT-1 controls. Transfer of low doses of CTLA-4(-/-Tc12) OT-1 cells to cMy-mOVA mice, which express OVA on cardiac myocytes, causes severe myocarditis, with 99% mortality, compared with no mortality after transfer of low doses of CTLA-4(+/+)Tc12 OT-1 cells. High doses of CTLA-4(+/+)Tc12 cells cause lethal myocarditis in cMy-mOVA mice, but high doses of CTLA-4(+/+)Tc0 CTL, generated without interleukin-12, are hypoproliferative within the cardiac-draining lymph node and do not significantly infiltrate the heart. In contrast, CTLA-4(-/-Tc0) cytotoxic T lymphocytes do proliferate in the cardiac-draining lymph node and diffusely infiltrate the heart. Nonetheless, high doses of CTLA-4(-/-Tc0) cells cause only limited tissue damage, and the disease is not lethal. These data show that CTLA-4 regulates myocarditic CD8+ T cell responses and that CTLA-4 deficiency partly overcomes a differentiation block that exists when naïve CD8+ T cells are stimulated without interleukin-12. Therefore, targeting CTLA-4 solely or in conjunction with interleukin-12 could influence effector CD8+ T cell responses in therapeutically beneficial ways.
Bioenergetic and Functional Consequences of Cellular Therapy
Authors: Qiang Xiong, Lei Ye, Pengyuan Zhang, Michael Lepley, Cory Swingen, Liying Zhang, Dan S. Kaufman, Jianyi Zhang
Journal: Circulation Research (2012)

Rationale: The mechanism by which endogenous progenitor cells contribute to functional and beneficial effects in stem cell therapy remains unknown. Objective: Utilizing a novel 31 P magnetic resonance spectroscopy–2-dimensional chemical shift imaging method, this study examined the heterogeneity and bioenergetic consequences of postinfarction left ventricular (LV) remodeling and the mechanisms of endogenous progenitor cell contribution to the cellular therapy. Methods and Results: Human embryonic stem cell–derived vascular cells (hESC-VCs) that stably express green fluorescent protein and firefly luciferase (GFP + /Luc + ) were used for the transplantation. hESC-VCs may release various cytokines to promote angiogenesis, prosurvival, and antiapoptotic effects. Both in vitro and in vivo experiments demonstrated that hESC-VCs effectively inhibit myocyte apoptosis. In the mouse model, a fibrin patch–based cell delivery resulted in a significantly better cell engraftment rate that was accompanied by a better ejection fraction. In the swine model of ischemia-reperfusion, the patch-enhanced delivery of hESC-VCs resulted in alleviation of abnormalities including border zone myocardial perfusion, contractile dysfunction, and LV wall stress. These results were also accompanied by a pronounced recruitment of endogenous c-kit + cells to the injury site. These improvements were directly associated with a remarkable improvement in myocardial energetics, as measured by a novel in vivo 31 P magnetic resonance spectroscopy–2-dimensional chemical shift imaging technology. Conclusions: The findings of this study demonstrate that a severely abnormal heterogeneity of myocardial bioenergetics in hearts with postinfarction LV remodeling can be alleviated by the hESC-VCs therapy. These findings suggest an important therapeutic target of peri-scar border zone and a promising therapeutic potential for using hESC-VCs together with the fibrin patch–based delivery system.