tbuckley/cabot-search huggingface dataset:
Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer
Authors: Elena Provasi, Pietro Genovese, Angelo Lombardo, Zulma Magnani, Pei-Qi Liu, Andreas Reik, Victoria Chu, David E Paschon, Lei Zhang, Jurgen Kuball, Barbara Camisa, Attilio Bondanza, Giulia Casorati, Maurilio Ponzoni, Fabio Ciceri, Claudio Bordignon, Philip D Greenberg, Michael C Holmes, Philip D Gregory, Luigi Naldini, Chiara Bonini
Journal: Nature Medicine (2012)
SUPPURATIVE OTITIS MEDIA TREATED BY ZINC IONIZATION
Authors: T. B. Jobson
Journal: BMJ (1924)

Several factors are known to be capable of inducing relatively selective dopaminergic cell death in the substantia nigra and inducing the clinical features that characterize Parkinson’s disease (PD). Neuronal toxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can induce parkinsonism in human and animal models, and rotenone, another specific mitochondrial complex I inhibitor, can induce similar effects in rodents to produce a model for PD. Studies in twins suggest a significant genetic component to young-onset PD, and several gene mutations have now been identified as causing familial autosomal dominant or autosomal recessive PD. Etiologic factors including free radical-mediated damage (including excitotoxicity), mitochondrial dysfunction, and inflammation-mediated cell damage can contribute to pathogenesis. In addition, the recent interest in protein misfolding, aggregation, and proteosomal activity has provided further insight into potential pathogenetic pathways in PD. Against this background there has been increasing interest in the development of drugs to modify these biochemical abnormalities and thus alter the course of PD, either by retarding the rate of cell death or by restoring function to neurons that are likely to be damaged but not dead. In this context, dopamine agonists have shown significant promise. Not only do these drugs provide symptomatic relief of PD but they also appear to be associated with a significant decrease in the rate of motor complications and to be capable of protecting against some of the adverse consequences of levodopa use. However, evidence is now emerging that dopamine agonists may have additional neuroprotective properties. As a group, they have antioxidant actions in vitro and in vivo. More specifically, the D<sub>2</sub>/D<sub>3</sub> dopamine agonist pramipexole may have neuroprotective activity that is, at least in part, unrelated to its dopamine agonist action. Protection in cell and animal models against a variety of toxins, including MPTP and 6-hydroxydopamine, confirms that this agonist has in vitro and in vivo neuroprotective action. Evidence is now emerging that some of this may be mediated by direct action on mitochondrial membrane potential and the inhibition of apoptosis. If the neuroprotective action of this drug is confirmed in patients with PD, this will have important implications for its early use in patients.
Maternal employment and atopic dermatitis in children: a prospective cohort study
Authors: I.J. Wang, H.J. Wen, T.L. Chiang, S.J. Lin, P.C. Chen, Y.L. Guo
Journal: British Journal of Dermatology (2013)

Journal Article Maternal employment and atopic dermatitis in children: a prospective cohort study Get access I.J. Wang, I.J. Wang Department of Pediatrics, Taipei Hospital, Department of Health, Taipei, TaiwanChina Medical University, Taichung, TaiwanNational Yang‐Ming University, Taipei, TaiwanFu Jen Catholic University, Taipei, Taiwan Search for other works by this author on: Oxford Academic Google Scholar H.J. Wen, H.J. Wen Department of Environmental and Occupational Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan Search for other works by this author on: Oxford Academic Google Scholar T.L. Chiang, T.L. Chiang Institute of Health Policy and Management, National Taiwan University College of Public Health, Taipei, Taiwan Search for other works by this author on: Oxford Academic Google Scholar S.J. Lin, S.J. Lin Department of Pediatrics, National Cheng Kung University Hospital and College of Medicine, National Cheng Kung University, Tainan, Taiwan Search for other works by this author on: Oxford Academic Google Scholar P.C. Chen, P.C. Chen Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, TaiwanDepartment of Public Health, National Taiwan University College of Public Health, Taipei, TaiwanDepartment of Environmental and Occupational Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan Pau‐Chung Chen. E‐mail: pchen@ntu.edu.tw Yueliang Leon Guo. E‐mail: leonguo@ntu.edu.tw Search for other works by this author on: Oxford Academic Google Scholar Y.L. Guo Y.L. Guo Department of Environmental and Occupational Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 168, Issue 4, 1 April 2013, Pages 794–801, https://doi.org/10.1111/bjd.12195 Published: 01 April 2013 Article history Accepted: 02 December 2012 Published: 01 April 2013
Nuclear Factor-κB Is Central to the Expression of Truncated Neurokinin-1 Receptor in Breast Cancer: Implication for Breast Cancer Cell Quiescence within Bone Marrow Stroma
Authors: Shakti H. Ramkissoon, Prem S. Patel, Marcelo Taborga, Pranela Rameshwar
Journal: Cancer Research (2007)

Abstract Breast cancer is a leading cause of mortality among women in the United States. Tac1 and neurokinin-1 (NK1) are involved in autocrine stimulation of breast cancer cells (BCCs). The single NK1 gene produces full-length (NK1-FL) and truncated (NK1-Tr) forms. NK1-Tr mediates malignancy in breast cells. We now report a critical role for nuclear factor-κB (NF-κB) in the expression of NK1-Tr, but not NK1-FL, in human BCCs. By Western and Northern blot analyses, NK1-FL and NK1-Tr were coexpressed in BCCs but were undetectable in nontumorigenic cells. Loss of repressive activity within the 5′ flanking region of the NK1 partly accounts for constitutive expression of NK1 in BCCs but could not account for the presence of NK1-Tr. Transient transfections with dominant-negative and wild-type IκB show that activation of NF-κB is required for the expression of NK1-Tr. Tac1 gene was linked to the generation of NK1-Tr because its overexpression in BCCs led to the production of multiple cytokines that can activate NF-κB to mediate NK1-Tr expression. Studies with Tac1 knockdown BCCs and Tac1-expressing nontumorigenic breast cells verified a role for NF-κB in the expression of NK1-Tr. The quiescent phenotype of BCCs on contact with bone marrow stroma was partly explained by decreased NF-κB activation and undetectable NK1-Tr. In summary, this study shows a role for NF-κB in the expression of NK1-Tr in BCCs, which seems to be reversed by bone marrow stromal cells. [Cancer Res 2007;67(4):1653–9]
Mitochondrial Dysfunction and Reactive Oxygen Species Imbalance Promote Breast Cancer Cell Motility through a CXCL14-Mediated Mechanism
Authors: Helene Pelicano, Weiqin Lu, Yan Zhou, Wan Zhang, Zhao Chen, Yumin Hu, Peng Huang
Journal: Cancer Research (2009)

Although mitochondrial dysfunction and reactive oxygen species (ROS) stress have long been observed in cancer cells, their role in promoting malignant cell behavior remains unclear. Here, we show that perturbation of the mitochondrial respiratory chain in breast cancer cells leads to a generation of subclones of cells with increased ROS, active proliferation, high cellular motility, and invasive behaviors in vitro and in vivo. Gene expression analysis using microarrays revealed that all subclones overexpressed CXCL14, a novel chemokine with undefined function. We further show that CXCL14 expression is up-regulated by ROS through the activator protein-1 signaling pathway and promotes cell motility through elevation of cytosolic Ca(2+) by binding to the inositol 1,4,5-trisphosphate receptor on the endoplasmic reticulum. Abrogation of CXCL14 expression using a decoy approach suppressed cell motility and invasion. Our data suggest that mitochondrial dysfunction and ROS stress promote cancer cell motility through a novel pathway mediated by CXCL14.
Synergy between public health and veterinary services to deliver human and animal health interventions in rural low income settings
Authors: Esther Schelling, Kaspar Wyss, Mahamat Béchir, Daugla Doumagoum Moto, Jakob Zinsstag
Journal: BMJ (2005)

x An international accreditation mechanism operated by the Office International des Epizooties.x Guidelines for surveillance combined with performance indicators-the World Health Organization's pioneering work was taken as a model. 11 12 x Molecular characterisation of viruses had a seminal effect on both epidemiological understanding and the conduct of eradication programmes.Designation of a world reference laboratory, hosted by the UK Institute for Animal Health, was invaluable. ConclusionsMuch has been learnt since the start of GREP that merits consideration when mounting control or eradication efforts for human or animal diseases.Whether other diseases will follow for eradication or be singled out for progressive control in geographically defined areas, as are foot and mouth disease and classical swine fever in Latin America, depends largely on the outcome of the global rinderpest eradication programme and the attitude of the international community towards funding such endeavours.There is no shortage of candidates, and new ones constantly arise.Medical and veterinary epidemic disease control is becoming a single continuum.The recent zoonotic Rift Valley fever, severe acute respiratory syndrome (SARS), Hendra virus or Nipah virus, and avian influenza indicate that we need to move on from separate human and veterinary scenarios.Competing interests: None declared. Synergy between public health and veterinary services to deliver human and animal health interventions in rural low income settings
Cardiac autonomic function and oesophageal acid sensitivity in patients with non-cardiac chest pain
Authors: G Tougas
Journal: Gut (2001)

Acid reflux can elicit non-cardiac chest pain (NCCP), possibly through altered visceral sensory or autonomic function. The interactions between symptoms, autonomic function, and acid exposure are poorly understood.To examine autonomic function in NCCP patients during exposure to oesophageal acid infusion.Autonomic activity was assessed using power spectral analysis of heart rate variability (PSHRV), before and during oesophageal acidification (0.1 N HCl), in 28 NCCP patients (40.5 (10) years; 13 females) and in 10 matched healthy controls. Measured PSHRV indices included high frequency (HF) (0.15-0.5 Hz) and low frequency (LF) (0.06-0.15 Hz) power to assess vagal and sympathetic activity, respectively.A total of 19/28 patients had angina-like symptoms elicited by acid. There were no significant manometric changes observed in either acid sensitive or insensitive patients. Acid sensitive patients had a higher baseline heart rate (82.9 (3.1) v 66.7 (3.5) beats/min; p<0.005) and lower baseline vagal activity (HF normalised area: 31.1 (1.9)% v 38.9 (2.3)%; p< 0.03) than acid insensitive patients. During acid infusion, vagal cardiac outflow increased (p<0.03) in acid sensitive but not in acid insensitive patients.Patients with angina-like pain during acid infusion have decreased resting vagal activity. The symptoms elicited by perception of acid are further associated with a simultaneous increase in vagal activity in keeping with a vagally mediated pseudoaffective response.
Prevalence of faecal incontinence in adults aged 40 years or more living in the community
Authors: S Perry
Journal: Gut (2002)

Prevalence studies of faecal incontinence in the general population are rare and the impact of faecal incontinence on quality of life has not been previously addressed.To establish the prevalence of faecal incontinence in adults in terms of frequency of leakage, degree of soiling, and level of impact on quality of life.In a cross sectional postal survey, 15 904 adults aged 40 years or more (excluding residents of nursing and residential homes) were selected randomly by household from the Leicestershire Health Authority patient register. Participants were asked to complete a confidential health questionnaire. Major faecal incontinence was defined as soiling of underwear or worse with a frequency of several times a month or more. Respondents were also asked if bowel symptoms had an impact on their quality of life.From a total sample of 10 116 respondents, 1.4% reported major faecal incontinence and 0.7% major faecal incontinence with bowel symptoms that had an impact on quality of life. Major faecal incontinence was significantly associated with a lot of impact on quality of life (odds ratio 12.4, 95% confidence interval 7.5-20.6). Incontinence was more prevalent and more severe in older people but there was no significant difference between men and women.This study has confirmed that faecal incontinence is a fairly common symptom, particularly in older people. Faecal incontinence in men has received little attention in the past and the results from this study indicate that it is as much of a problem in men as it is in women while the level of unmet need in this group is high. Estimates of need for health care for this symptom should be multidimensional and assess both the severity of symptoms and the impact it has on quality of life.
MECHANISMS OF ENDOTOXIN TOLERANCE
Authors: Sheldon E. Greisman, Henry N. Wagner, Masahiro Iio, Richard B. Hornick
Journal: The Journal of Experimental Medicine (1964)

Healthy male volunteers were rendered tolerant to the pyrogenic and toxic activities of bacterial endotoxin by daily intravenous injections. Five subjects were given 0.5 µg Salmonella typhosa endotoxin for 7 days; four subjects were given Pseudomonas endotoxin, increasing over a period of 30 days from 25 to 250 µg. Reticuloendothelial system (RES) phagocytic activity was assessed by serial measurements of the clearance of I131-labeled aggregated human serum albumin. In no subject was an increase in RES phagocytic activity detectable. Such negative findings could not be attributed to decreased RES blood flow.—Additional studies on the pyrogenic responses of man to various schedules of endotoxin administration revealed: (a) Hyperreactivity of some subjects to a second injection of endotoxin administered 24 hours after the initial dose; (b) prevention of such hyperreactivity by plasma from donors tolerant to a heterologous endotoxin, but not from normal donors; (c) reduced reactivity to a second injection of endotoxin given 7 days after the initial dose; (d) reversal of induced tolerance by administration of half the dose of endotoxin followed 2 hours later by the second half; (e) reversal of induced tolerance 24 hours after administration of a heterologous endotoxin; (f) enhanced dermal reactivity to endotoxin induced inflammation during tolerance. The observations are consistent with the hypothesis that tolerance to the pyrogenic activity of endotoxin in man is not based upon generalized enhancement of RES phagocytic activity or exhaustion of host reactivity but rather involves the participation of specific antibody which assists the RES in the clearance and inactivation of the endotoxin molecule.
Two Important Determinants May Play a Role in the Success of the FinHer Trial
Authors: Metin Isik, Omer Dizdar, Kadri Altundag
Journal: Journal of Clinical Oncology (2010)

We read with great interest the article by Joensuu et al, 1 in which the authors demonstrated that a brief course of trastuzumab for 9 weeks administered concomitantly with docetaxel followed by three cycles of fluorouracil, epirubicin, and cyclophosphamide was safe and effective in women with human epidermal growth factor receptor 2-positive cancer with axillary nodepositive or high-risk node-negative breast cancer.We propose two important determinants that may play a role in the success of this regimen.Compared with other adjuvant trastuzumab trials, trastuzumab was administered earlier.In two US trials, trastuzumab was administered after completion of four cycles of adriamycine and cyclophosphamide. 2,3In the HERA (Herceptin Adjuvant) trial, trastuzumab was used after completion of all chemotherapy. 4Second, there has been concern about the sequencing of taxanes and anthracyclines.In a recent randomized phase III study by the Hellenic Oncology Research Group, docetaxel administered every 3 weeks followed by combination epirubicin/cyclophosphamide (E/C) was compared with a regimen of epirubicin/cyclophosphamide/fluorouracil as adjuvant chemotherapy in women with axillary node-positive early breast cancer. 5Five-year disease-free survival was found to be better in the group receiving sequential docetaxel followed by E/C (72.6% v 67.2%; P ϭ .041).Furthermore, the first report of the Neo-tAnGo (Neoadjuvant Study of Sequential Epirubicin with Cyclophosphamide and Paclitaxel With or Without Gemcitabine) study, a neoadjuvant randomized phase III trial of E/C and paclitaxel Ϯ gemcitabine in high-risk early breast cancer also concluded that the sequence of the taxane-first regimen had a significant advantage in pathologic com-plete response rate compared with the sequence of the anthracyclinefirst regimen (20% v 15%; P ϭ .03). 6 Therefore, administration of taxane followed by anthracycline in the FinHer (Finland Herceptin) trial may also lead to better results.
Exploring the Effects of Omalizumab in Allergic Asthma
Authors: Nicola A. Hanania, Sally Wenzel, Karin Rosén, Hsin-Ju Hsieh, Sofia Mosesova, David F. Choy, Preeti Lal, Joseph R. Arron, Jeffrey M. Harris, William Busse
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: For many patients with asthma, allergic airway inflammation is primarily a Th2-weighted process; however, heterogeneity in patterns of inflammation suggests phenotypic distinctions exist that influence disease presentation and treatment effects.Objectives: To assess the potential of fractional exhaled nitric oxide (FeNO), peripheral blood eosinophil count, and serum periostin as biomarkers of Th2 inflammation and predictors of treatment effects of omalizumab.Methods: The EXTRA omalizumab study enrolled patients (aged 12–75 yr) with uncontrolled severe persistent allergic asthma. Analyses were performed evaluating treatment effects in relation to FeNO, blood eosinophils, and serum periostin at baseline. Patients were divided into low- and high-biomarker subgroups. Treatment effects were evaluated as number of protocol-defined asthma exacerbations during the 48-week treatment period (primary endpoint).Measurements and Main Results: A total of 850 patients were enrolled. Data were available from 394 (46.4%), 797 (93.8%), and 534 (62.8%) patients for FeNO, blood eosinophils, and serum periostin, respectively. After 48 weeks of omalizumab, reductions in protocol-defined exacerbations were greater in high versus low subgroups for all three biomarkers: FeNO, 53% (95% confidence interval [CI], 37–70; P = 0.001) versus 16% (95% CI, −32 to 46; P = 0.45); eosinophils, 32% (95% CI, 11–48; P = 0.005) versus 9% (95% CI, −24 to 34; P = 0.54); and periostin, 30% (95% CI, −2 to 51; P = 0.07) versus 3% (95% CI, −43 to 32; P = 0.94).Conclusions: The difference in exacerbation frequency between omalizumab and placebo was greatest in the three high-biomarker subgroups, probably associated with the greater risk for exacerbations in high subgroups. Additional studies are required to explore the value of these biomarkers in clinical practice.Clinical trial registered with www.clinicaltrials.gov (NCT00314574).
Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease.
Authors: P N Dekhuijzen, K K Aben, I Dekker, L P Aarts, P L Wielders, C L van Herwaarden, A Bast
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

An imbalance between oxidative stress and antioxidative capacity is thought to play an important role in the development and progression of chronic obstructive pulmonary disease (COPD). To assess the lung oxidative status in patients with COPD, we studied whether exhaled hydrogen peroxide (H2O2) is increased in breath condensate of patients with stable COPD (n = 12, mean FEV1 51% pred) and in patients with exacerbated COPD (n = 19, actual FEV1 36% pred) compared with a healthy control group (n = 10, FEV1 108% pred). Expired breath condensate during 15 min of tidal breathing was collected by cooling. The concentration of H2O2 was measured spectrophotometrically by means of horse radish peroxidase-catalyzed oxidation of tetramethylbenzidine. Concentrations of H2O2 (mean +/- SEM) were significantly elevated at 0.205 +/- 0.054 microM in patients with stable COPD compared with 0.029 +/- 0.012 microM in the control group (p < 0.05) and were further increased to 0.600 +/- 0.075 microM in patients with acutely exacerbated COPD (p < 0.001 compared with patients with stable COPD). Patients with pulmonary infiltrates on chest radiograph showed similar values compared with patients without obvious infiltrates. These findings demonstrate that patients with stable COPD exhibit increased oxidant production in the airways and that oxidant production increases further during exacerbations.
Correlation of Early Metastatic Response by<sup>123</sup>I-Metaiodobenzylguanidine Scintigraphy With Overall Response and Event-Free Survival in Stage IV Neuroblastoma
Authors: Katherine K. Matthay, Veronique Edeline, Jean Lumbroso, Marie Laure Tanguy, Bernard Asselain, Jean Michel Zucker, Dominique Valteau-Couanet, Olivier Hartmann, Jean Michon
Journal: Journal of Clinical Oncology (2003)

Purpose: Metaiodobenzylguanidine (MIBG), specifically taken up in cells of sympathetic origin, provides a highly sensitive and specific indicator for the detection of metastases in neuroblastoma. The aim of this study was to correlate early response to therapy by MIBG scan, using a semiquantitative scoring method, with the end induction response and event-free survival (EFS) rate in stage IV neuroblastoma. Patients and Methods: Seventy-five children older than 1 year and with stage IV neuroblastoma had 123 I-MIBG scans at diagnosis, after two and four cycles of induction therapy, and before autologous stem-cell transplantation. The scans were read by two independent observers (concordance &gt; 95%) using a semiquantitative method. Absolute and relative (score divided by initial score) MIBG scores were then correlated with overall pretransplantation response, bone marrow response, and EFS. Results: The pretransplantation response rate was 81%, and the 3-year EFS rate was 32%, similar to a concomitant group of 375 stage IV patients. The median relative MIBG scores after two, four, and six cycles were 0.5, 0.24, and 0.12, respectively. The probability of having a complete response or very good partial response before transplantation was significantly higher if the relative score after two cycles was ≤ 0.5, or, if after four cycles, the relative score was ≤ 0.24. Patients with a relative score of ≤ 0.5 after two cycles or a score of ≤ 0.24 after four cycles had an improved EFS rate (P = .053 and .045, respectively). Conclusion: Semiquantitative MIBG score early in therapy provides valuable prognostic information for overall response and EFS, which may be useful in tailoring treatment.
Telomerase inhibition with an oligonucleotide telomerase template antagonist: in vitro and in vivo studies in multiple myeloma and lymphoma
Authors: Eunice S. Wang, Kaida Wu, Allison C. Chin, Selina Chen-Kiang, Krisztina Pongracz, Sergei Gryaznov, Malcolm A. S. Moore
Journal: Blood (2003)