tbuckley/cabot-search huggingface dataset:
CD8+ T Cell Profiles in Patients With Rheumatoid Arthritis and Their Relationship to Disease Activity
Authors: Helena Carvalheiro, Cátia Duarte, Sandra Silva‐Cardoso, José A. P. da Silva, M. Margarida Souto‐Carneiro
Journal: Arthritis & Rheumatology (2014)

Objective CD8+ T cells are abundant in rheumatoid arthritis (RA). However, their role in disease pathogenesis is poorly defined. This study was undertaken to investigate the relationship between disease activity and CD8+ T cell phenotypes, production of cytokines, and production of cytotoxic molecules in the peripheral blood (PB) and synovial fluid (SF) of patients with RA. Methods CD8+ T cell phenotypes were determined in 96 patients with RA (44 with disease in remission, 34 with active disease, 18 with low disease activity) and in 64 sex‐ and age‐matched healthy controls. Ten paired PB and SF samples from patients with active RA were analyzed. The expression of surface markers, cytokines, and proteolytic enzymes in CD8+ T cells was evaluated using flow cytometry. Results PB CD8+ T cells from RA patients with active disease exhibited an effector (CD27−CD62L−) phenotype ( P = 0.005), with elevated expression of proinflammatory cytokines (tumor necrosis factor α [TNFα], interferon‐γ [IFNγ], interleukin‐6 [IL‐6], IL‐17A) when compared to healthy controls. In a state of remission, the same phenotype observed in patients with active disease persisted, including a significant increase in the frequency of CD69 ( P &lt; 0.001), but lower cytokine production was observed. SF CD8+ T cells from RA patients expressed more robust effector memory (CD27+CD62L−) and activated (CD69+) profiles compared to the T cell subsets in paired PB samples. Production of cytokines (IL‐6, IL‐17A, and IFNγ) by CD8+ T cells from RA PB was positively correlated within individual donors. Moreover, production of cytokines (TNFα, IFNγ, and IL‐17A) by CD8+ T cells from RA PB positively correlated with the Disease Activity Score in 28 joints. Conclusion The activation status and proinflammatory potential of CD8+ T cell subsets observed in the RA patients in this study strongly suggest that a phenotype of local and systemic cytotoxic effector T cells plays a role in this disease.
Assessment of Bronchodilator Responsiveness in Infants with Bronchiolitis
Authors: MANFRED MODL, ERNST EBER, ELISABETH WEINHANDL, WILFRIED GRUBER, MAXIMILIAN S. ZACH
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Whether bronchodilators should be used for the treatment of infants with bronchiolitis is subject to debate, partly because of the low sensitivity of the methods for assessing lung function changes in infants. In the present study, we compared the recently introduced raised volume (RVRTC) with the conventional end-tidal rapid thoracoabdominal compression (ETRTC) technique in infants with acute viral bronchiolitis. In 17 infants lung function was assessed by both methods, at baseline values and after salbutamol inhalation. Forced expiratory volumes (FEV(0.5), FEV(0.75), FEV(1.0)) were used for the quantification of RVRTC measurement, and maximal expiratory flow at functional residual capacity (Vmax (FRC)) for ETRTC measurements. A significant individual change was defined by a mean postbronchodilator value that differed from baseline value by more than twice the within-subject coefficient of variation (CV). Group mean intrasubject CVs ranged from 4.7% to 5.3% for FEV parameters; it was 14.0% for Vmax (FRC). For the group, post-bronchodilator measurements did not differ significantly from baseline measurements. For the majority of infants, however, the within-subject comparison of responses revealed substantial differences between both techniques; while no infant demonstrated a significant increase in Vmax (FRC), eight (47%) infants responded with significantly improved timed volumes. The RVRTC technique provides the investigator with a more sensitive diagnostic tool for documenting the effectiveness of therapeutic interventions on an individual basis. Furthermore, the findings of the present study provide a rationale for the application of bronchodilators in a subgroup of infants with acute bronchiolitis.
Asthma severity and duration influence to fetoplacental circulation
Authors: Olga Lavrova, Maria Petrova, Elena Shapovalova
Journal: European Respiratory Journal (2011)

Hemodynamic of fetoplacental circulation in Asthmatic patients is not studied enough yet. Modern data on asthma severity duration and its control influence to fetoplacental circulation are still lack and controversial.

The goal of our study was investigation of fetoplacental circulation with ultrasonic dopplerography. Pregnants with different asthma severity and treatment were studied at 34 week of gestation.

Materials & methods: 73 Asthmatic pregnants were studied (5 - severe persistent, 18 - moderate persistent, 22 - mild persistent & 28 - mild intermittent). 64 females without lung pathology were studied also as a control group (K). ICS were administered to 55 patients. Among them 17 rejected ICS use and were administered SABA with other medications instead. Systolo-diastolic ratio (SD) in uterine (UA), umbilical (UmA) and fetus medial cerebral (ACM) arteries was measured.

Results: SD was increased in UA and ACM within asthmatics, but with no significantly differences. In moderate persistent asthma SD was significantly higher in UA (2,51±0,29) in comparison with mild persistent (1,91±0,18) and with K (1,95±0,13) (p<0,05). In pregnants, who undergone asthma relapse during the first trimester SD in UA (2,69±0,12) differed (p<0,05) in comparison with K. Reliable UA and ACM SD level differences were accepted in patients with moderate persistent asthma, who were administered ICS to ICS free patients (1,91±0,15 to 2,82±0,59) and (4,39±0,43 to 5,98±0,68) respectively (p<0,05).

Conclusions: Relapse of Asthma in the first trimester of pregnancy, severity of Asthma and absence of basic therapy influence level of the blood flow in UA. Absence of basic therapy leads to increase of blood pressure in ACM of fetus.
RRP22 Is a Farnesylated, Nucleolar, Ras-Related Protein with Tumor Suppressor Potential
Authors: Candice Elam, Luke Hesson, Michele D. Vos, Kristin Eckfeld, Chad A. Ellis, Aaron Bell, Dietmar Krex, Michael J. Birrer, Farida Latif, Geoffrey J. Clark
Journal: Cancer Research (2005)

Abstract Ras proteins are members of a superfamily of related small GTPases. Some members, such as Ras, are oncogenic. However, other members seem to serve as tumor suppressors, such as Rig and Noey2. We now identify and characterize a novel member of the Ras superfamily, RRP22. Like Ras, RRP22 can be posttranslationally modified by farnesyl. Unlike Ras, RRP22 inhibits cell growth and promotes caspase-independent cell death. Examination of human tumor cells shows that RRP22 is frequently down-regulated due to promoter methylation. Moreover, reexpression of RRP22 in an RRP22-negative neural tumor cell line impairs its growth in soft agar. Unusually for a Ras-related protein, RRP22 localizes to the nucleolus in a GTP-dependent manner, suggesting a novel mechanism of action. Thus, we identify a new member of the Ras superfamily that can serve as a potential tumor suppressor.
Positive effects of inspiratory muscle training (IMT) on ventilatory response to progressive hypercapnia in healthy subjects
Authors: David Dörfler, Milos Petrovic, Wolfgang Pohl, Theodor Wanke
Journal: European Respiratory Journal (2011)

Inspiratory muscle training (IMT) is known to improve inspiratory muscle capacity, whole body exercise capacity and the sensation of dyspnea.  Until now the effects of IMT on respiration during ventilatory stress, induced by hyperoxic progressive hypercapnia, have not been examined. We speculate that IMT, by improving inspiratory pump capacity, may affect ventilatory response during CO2-rebreathing.   Aim of the study:  The aim of our study was to analyze the effects of IMT on the ventilatory response during CO2-rebreathing tests in healthy subjects.   Methods:  Eight healthy subjects (4 males, 4 females) performed specific IMT for 6 weeks. Maximal inspiratory pressure (Pi max) and endurance time during resistive breathing manoeuvres (tlim) served as parameters for inspiratory muscle capacity.The ventilatory response to CO2, using the Read9s rebreathing technique, was analysed twice before commencement of IMT and once on the day after stopping IMT.  Breathing pattern (Vt/VE),maximal achieved VE, as well as the sensation of dyspnea (BORG Scale) during CO2-rebreathing were analysed.   Results:  After 6 weeks of IMT, inspiratory muscle capacity increased significantly.  Maximal achieved VE (minute volume) as well as Vt (tidal volume) also increased significantly, while the level of dyspnea (Borg Scale) was lower.  Breathing pattern during ventilatory stress changed in that the proportion of tidal volume on minute volume increased significantly.   Conclusions:  IMT leads to more effective respiration under ventilatory stress,even in healthy subjects.  This might be of clinical relevance for patients with lung diseases.
Sensitivity to &lt;sc&gt;L&lt;/sc&gt;-Asparaginase and Amino Acid Metabolism&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Herbert K. Miller, Irwin H. Krakoff, Josephine S. Salser, M. Earl Balis
Journal: JNCI Journal of the National Cancer Institute (1970)

The serum amino acid levels of mice carrying L-aspara-ginase-sensitive and resistant tumors were determined. Citrulline and glutamine levels were consistently lower in the sera of tumor-bearing mice; aspartic acid levels were higher. Levels of asparagine were below normal in the sensitive series and above normal in the resistant series. Rats carrying Walker 256 tumors cleared large intravenous doses of L-asparagine faster than rats carrying RFS-1 and normals. The uptake of amino acids and the incorporation of labeled thymidine and formate by leukemic mouse cells in vitro were also measured. These studies suggest that the turnover of asparagine in human patients might be predictive of sensitivity to L-asparaginase. L-Asparagine label disappeared from the blood of all patients with great rapidity. The first part of the decay curve showed a half-life of about 10 minutes in all cases. In the second part of the decay curve, half-life periods varied from about 3-5 hours, with a patient with an L-asparaginase-sensitive neoplasm showing a somewhat shorter half-life than the remaining group. The radioactive label in the red cell “asparagine fraction” was roughly about one-third of the plasma label throughout this study.
Investigation and Management of Loss of Efficacy of an Antiepileptic Medication Using Carbamazepine as an Example
Authors: K K Jain
Journal: Journal of the Royal Society of Medicine (1993)

Cases reported as loss of efficacy (secondary failure) of carbamazepine (CBZ) for epilepsy were analysed to determine the cause. In these cases, seizures previously controlled with CBZ, recurred or increased in frequency. The following causes were identified in 131 cases where adequate information was available: use for types of epilepsy where this drug is not recommended, lowering of the blood levels of the drug on switching over from branded to a generic CBZ, change in the galenic form, drug interactions, progression of the underlying brain pathology such as a brain tumor, and unexplained increase in the blood levels of the drug. In cases where the increase in seizures was transient no special measures or changes in therapy were required. Unexplained failure occurred only in seven cases (5.3%). Based on this information, a flow chart was designed to evaluate such a problem step by step and to take appropriate measures. Only when true therapeutic failure is identified, should another antiepileptic drug be substituted for CBZ. Similar approach can be used for other antiepileptic drugs.
Commentary: Present system could be improved
Authors: C Smith, S Adam
Journal: BMJ (1994)

This paper raises several important issues about current clinical practice guidelines for the investigation and treatment of women with abnormal cervical smears. Equipment to excise the abnormal cervical transformation zone while preserving specimens for histolog (loop excision, laser miniconisation) is now widely available for outpatient use. Downey et al propose a policy of see and treat for women in prison, but it could be extended to women in whom factors other than imprisonment identify them as being at high risk. Careful examination is needed to establish the costs and benefits of this approach, to define criteria for its use, and to ensure that women and their general practitioners are clear what to expect and which policy is followed by the local service. Four points require comment.

We assume that the high prevalence of cervical abnormalities in these women is real. It may, however, be exaggerated by the relative frequency of …
Effect of Hormone Stimulation, Dose, and Time of Administration of Carcinogen on Carcinogen-Induced Mammary Tumors From Preneoplastic Nodule Outgrowths&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Daniel Medina
Journal: JNCI Journal of the National Cancer Institute (1971)

The tumorigenic effect of two chemical carcinogens, 7,12-dimethylbenz[a]anthracene (DMBA) and urethan, and of γ-irradiation were analyzed further on the nodule outgrowth line D1. Nodule outgrowth line D1 treated with DMBA and urethan produced 68 and 83% tumors, respectively, whereas irradiated outgrowths produced only 23%. Prolonged hormone stimulation by a single pituitary isograft enhanced the tumorigenic effect of DMBA, had no effect on urethan-induced tumorigenesis, and inhibited irradiation-induced tumorigenesis. Nodule outgrowths were exposed to various doses of DMBA and urethan. Outgrowths exposed to 1.0 mg and 1.5 mg DMBA produced the same tumor incidence (68%), whereas outgrowths exposed to 0.5 mg produced only 50% tumors. The various doses of urethan produced mammary tumors in the following order: 200 mg >100 mg = 80 mg >60 mg = 40 mg >20 mg. The time of administration of urethan was important in determination of the ultimate tumor incidence and the rate of tumor formation. Outgrowths exposed to urethan between 3 and 5 weeks after transplantation produced tumors earlier and at a higher incidence than outgrowths exposed to urethan at later periods. The implications of these results are discussed as to similar findings of D1 nodule outgrowths treated with 3-methycholanthrene.
Effects of Mild Chronic Obstructive Pulmonary Disease on Gas Exchange during Cycling and Walking
Authors: Alejandro A. Diaz, Orlando Diaz
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

needed for such cases.Multiple studies have proven EBUS-TBNA to be an effective means of providing adequate samples for molecular analysis (2-5).In most of these studies, EBUS-TBNA was, in fact, performed under moderate sedation.The number of samples required from a lymph node to obtain adequate material for molecular testing remains unclear.The only available study is a retrospective review from Yarmus and colleagues that evaluated 85 patients with adenocarcinoma of the lung who underwent EBUS-TBNA (6).Molecular analysis was successfully performed in 93.5% of the cases with a median of four needle passes.In our study, we routinely performed between three and six passes per lymph node in both groups without difficulty, sampling a similar amount of targets in both groups (1).On the basis of the current literature showing that EBUS-TBNA performed under moderate sedation can provide enough material for molecular testing, and the study from Yarmus and coworkers showing that four needle passes may provide sufficient material, I respectfully disagree with Dr. Song's suggestion of the need of general anesthesia for such cases.I do, however, recognize that the influence of the type of sedation on the ability to obtain adequate material for molecular testing with EBUS-TBNA remains unclear and needs to be studied in prospective trials.
Influence of a distractive auditory stimulus on 6 minute walking test in COPD patients
Authors: Gregory Reychler, Charlotte Duranceau, Anne-Sophie Aubriot, Gilles Caty, Thierry Pieters, Giuseppe Liistro
Journal: European Respiratory Journal (2013)

Introduction: The 6MWT evaluates exercise tolerance and functional capacity. It was demonstrated that the encouragements influence the walked distance and that the music improve dyspnea. The aim of this study was to evaluate the effect of different distractive auditory stimuli on the 6MWT in COPD patients.

Method: 11 COPD patients (FEV1 = 39.1 ± 7.6% of predicted values) performed randomly the same day a walking test in 3 different conditions: without music (WM), with a slow music (SM) and with a fast music (FM). The 6MWD, the cardio-respiratory parameters and the dyspnea were measured.

Results: No difference was observed on the walking distance depending on the conditions (WM: 350 m - SM: 366 m - FM: 358; p=0.924). Cardio-respiratory parameters and dyspnea were not influenced by the kind of distractive auditory stimulus.

Conclusion: In this sample of COPD patients, a distractive auditory stimulus did not modify the results of the 6MWT. The tempo of the listened music is not influent.
Lectin Potentiation of BCG-Contact-Mediated Antitumor Action&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: T. B. Poduval, M. Seshadri, K. Sundaram
Journal: JNCI Journal of the National Cancer Institute (1980)

Concanavalin A (Con A) potentiated the BCG-contact-mediated antitumor action when both Con A (10 microgram) and BCG (50 micrograms) were injected with fibrosarcoma cells (5 x 10(4)) into inbred Swiss mice. BCG (50 micrograms) alone had no antitumor effect. The Con A-potentiated BCG-contact-mediated phenomenon was shown to be immunologically mediated, inasmuch as tumors developed in immunosuppressed mice inoculated with tumor cells mixed with Con A and BCG. The same dose of 50 micrograms BCG was effective in controlling the growth of 10(6) fibrosarcoma cells in the presence of Con A. The specific inhibitor of Con A, alpha-methyl D-mannoside, abrogated the potentiation of the BCG effect seen with Con A. Con A also increased the antitumor effect of BCG in sarcoma 180 ascites tumor. Another lectin, peanut agglutinin, also induced an antitumor effect in the presence of BCG only when the tumor cells were treated with Vibrio cholerae neuraminidase.
Reslizumab for Poorly Controlled, Eosinophilic Asthma
Authors: Mario Castro, Sameer Mathur, Frederick Hargreave, Louis-Philippe Boulet, Fang Xie, James Young, H. Jeffrey Wilkins, Timothy Henkel, Parameswaran Nair
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Eosinophilic asthma is a phenotype of asthma characterized by the persistence of eosinophils in the airways. IL-5 is involved in the activation and survival of eosinophils.To evaluate the effect of the antibody to IL-5, reslizumab, in patients with eosinophilic asthma that is poorly controlled with high-dose inhaled corticosteroid.Patients were randomly assigned to receive infusions of reslizumab at 3.0 mg/kg (n = 53) or placebo (n = 53) at baseline and at Weeks 4, 8, and 12, with stratification by baseline Asthma Control Questionnaire (ACQ) score less than or equal to 2 or greater than 2. The primary efficacy measure was the difference between the reslizumab and placebo groups in the change in ACQ score from baseline to end of therapy (Week 15 or early withdrawal).Mean changes from baseline to end of therapy in ACQ score were -0.7 in the reslizumab group and -0.3 in the placebo group (P = 0.054) and in FEV(1) were 0.18 and -0.08 L, respectively (P = 0.002). In those patients with nasal polyps, the changes in ACQ score were -1.0 and -0.1, respectively (P = 0.012). Median percentage reductions from baseline in sputum eosinophils were 95.4 and 38.7%, respectively (P = 0.007). Eight percent of patients in the reslizumab group and 19% of patients in the placebo group had an asthma exacerbation (P = 0.083). The most common adverse events with reslizumab were nasopharyngitis, fatigue, and pharyngolaryngeal pain.Patients receiving reslizumab showed significantly greater reductions in sputum eosinophils, improvements in airway function, and a trend toward greater asthma control than those receiving placebo. Reslizumab was generally well tolerated.
Additional benefit of cryotechnique in transbronchial biopsies for histological diagnosis in interstitial lung disease (ILD)
Authors: Henrik Wurps, Sergej Griff, Wim Ammenwerth, Torsten Blum, Nicolas Schönfeld, Thomas Mairinger, Torsten T. Bauer, Wolfram Grüning
Journal: European Respiratory Journal (2012)

Background: Due to the small specimen size of transbronchial forcepsbiopsy, the histological diagnosis of interstitial lung disease is often difficult. In comparison transbronchial cryobiopsies were shown to be bigger and to contain more often and larger amount of alveolar tissue.  Methods: Since 2009, all histological results of patients suspicious of ILD (clinical signs, pulmonary function, CT-scan-criteria) who underwent bronchocoscopy with transbronchial forceps- and cryobiopsy were analysed concerning the impact of the additional use of cryotechnique.  Results: We evaluated data of 34 patients (age 60.0 ± 13.2 years) who underwent forceps- and cryobiopsy. For 10 patients (29.4%) neither forceps- nor cryobiopsy assured a histological diagnosis. In 11 cases (32.4%) both methods ensured a diagnosis. In 12 cases (35.3%) a histological classification was found only in the cryobiopsy, in 1 case (2.9%) only in the forcepsbiopsy.  Conclusion: By additiononal use of the cryoprobe in transbronchial biopsy, in this prospective case series up to today we were able to increase the amount of ensured histological diagnoses in ILD from 12/34 = 35,3 % without cryobiopsy to 23/34 = 67,6% with cryobiopsy. This shows the high potential of cryotechnique as a tool in transbronchial biopsy in the diagnostic of ILD.
Tuning Sensitivity of CAR to EGFR Density Limits Recognition of Normal Tissue While Maintaining Potent Antitumor Activity
Authors: Hillary G. Caruso, Lenka V. Hurton, Amer Najjar, David Rushworth, Sonny Ang, Simon Olivares, Tiejuan Mi, Kirsten Switzer, Harjeet Singh, Helen Huls, Dean A. Lee, Amy B. Heimberger, Richard E. Champlin, Laurence J.N. Cooper
Journal: Cancer Research (2015)

Many tumors overexpress tumor-associated antigens relative to normal tissue, such as EGFR. This limits targeting by human T cells modified to express chimeric antigen receptors (CAR) due to potential for deleterious recognition of normal cells. We sought to generate CAR(+) T cells capable of distinguishing malignant from normal cells based on the disparate density of EGFR expression by generating two CARs from monoclonal antibodies that differ in affinity. T cells with low-affinity nimotuzumab-CAR selectively targeted cells overexpressing EGFR, but exhibited diminished effector function as the density of EGFR decreased. In contrast, the activation of T cells bearing high-affinity cetuximab-CAR was not affected by the density of EGFR. In summary, we describe the generation of CARs able to tune T-cell activity to the level of EGFR expression in which a CAR with reduced affinity enabled T cells to distinguish malignant from nonmalignant cells.
Erk Negative Feedback Control Enables Pre-B Cell Transformation and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia
Authors: Seyedmehdi Shojaee, Rebecca Caeser, Maike Buchner, Eugene Park, Srividya Swaminathan, Christian Hurtz, Huimin Geng, Lai N. Chan, Lars Klemm, Wolf-Karsten Hofmann, Yi Hua Qiu, Nianxiang Zhang, Kevin R. Coombes, Elisabeth Paietta, Jeffery Molkentin, H. Phillip Koeffler, Cheryl L. Willman, Stephen P. Hunger, Ari Melnick, Steven M. Kornblau, Markus Müschen
Journal: Cancer Cell (2015)