tbuckley/cabot-search huggingface dataset:
Detection of Thymus Leukemia Antigens on the Surface Membranes of Murine Leukemia Cells Resistant to Thymus Leukemia Antibodies and Guinea Pig Complement2
Authors: Weitze Liang, Edward P. Cohen
Journal: JNCI Journal of the National Cancer Institute (1977)

The thymus leukemia (TL) antigens of ASL-1 murine leukemia reversibly disappeared from the membranes of cells exposed to TL antisera; the cells acquired resistance to fresh TL antiserum and complement (antigenic modulation). Three independent methods, however, indicated that the acquisition of complement resistance preceded the complete disappearance of TL antigens from the cell surface. Modulated cells reduced known titers of TL antisera by absorption; they stained positively in immunofluorescence studies involving TL antibodies and fluorescence-labeled rabbit anti-mouse immunoglobulin. TL antigens labeled previously with 125I were recovered by immunoprecipitation from cellular extracts prepared with non ionic detergent. Continued exposure of the cells to TL antiserum led to virtually complete disappearance of the antigens. Similar results were obtained for RADA-1 cells, another murine leukemia that forms TL antigens, although in this instance the cells were resistant to the cytolytic effects of TL antisera and guinea pig complement (GPC) without prior exposure to TL antibodies. The density of TL antigens remaining on the surfaces of different TL(+) cell types failed to correlate with resistance to TL antibodies and GPC. Cells from F1 hybrids of TL(+) and TL(−) mouse strains formed TL antigens and were susceptible to TL antibodies and GPC even though the density of TL antigens formed by the susceptible cells was less than the density of TL antigens formed by modulated cells. Stable somatic hybrids of RADA-1 cells and TL(−)LM cells formed TL antigens at lower density than did RADA-1 cells and lysed in the presence of aliquots of the TL antisera and GPC used in previous tests.
Barriers and facilitators to physical activity receiving chemotherapy for lung cancer: An exploratory study
Authors: Sebastien Mas, Xavier Quantin, Gregory Ninot
Journal: European Respiratory Journal (2013)

Background  Physical activities (PA) induce a positive effect on cardiorespiratory fitness, lung cancer symptoms and quality of life of patients suffering from lung cancer. While 92% of patients are interested in participating in a PA program, only 1/3 of them do sufficient amount of PA to provide important health benefits. The aim of our study was to identify barriers and facilitators to PA in patients with lung cancer receiving chemotherapy.  Methods  Our study provided data from patients diagnosed with primary NSCLC in advanced stages of the disease receiving chemotherapy. We chose a qualitative approach using a semi-structured interview. We conducted an exploratory analysis, using the thematic analysis technique to process the data.  Results  Seven barriers and facilitators to PA were identified (side effects of the disease/cancer-related treatment, other physiological limitation, timing/loss of meaning of projects, kinesiophobia, support/care, social usefulness/useless feeling, nature of the PA) and were grouped into 4 categories: physiological, psychological, social and environmental factors. These factors were identified to have different effects on the barriers to PA. Psychological and social factors mainly have an impact on the willingness and ability to practice PA; while physiological and environmental factors have an impact on the duration, intensity and regularity of PA.  Conclusion  Our study highlighted some of the effects that the barriers to PA have on the practice of PA in patients with NSCLC receiving chemotherapy. Our findings may be used by professionals to design an adapted PA program in this population.
Pharmacokinetics and myeloid effector cell engagement of an engineered IgA antibody against the epidermal growth factor receptor.
Authors: Thomas Valerius, Stefan Lohse, Saskia Meyer, Marco J.H. Jansen, Laura A.P. Meulenbroek, Maaike Nederend, Uwe Möginger, Anna Kretschmer, Katja Klausz, Stefanie Derer, Peter Sondermann, Daniel Kolarich, Matthias Peipp, Jeanette H. W. Leusen, Martin Gramatzki
Journal: Journal of Clinical Oncology (2015)

3037 Background: IgA antibodies play an important role in bridging adaptive and innate immunity. There is increasing evidence that FcαRI-dependent engagement of myeloid cells appears to be crucial to activate mechanisms like phagocytosis or antibody-dependent cell-mediated cytotoxicity and that myeloid cells constitute important effector cells in cancer and cancer immunotherapy. Here, we describe an Fc engineering approach to further improve the immunotherapeutic potential of IgA antibodies. Methods: Recombinant IgA antibodies against the epidermal growth factor receptor (EGFR) were produced by co-transfecting CHO-K1 cells with vectors encoding the 225 variable and Igα heavy and κ light chain constant regions, respectively. An Fc engineered IgA2 antibody was generated by mutating two N-glycosylation sites and by removing two free cysteines. The resulting antibody was compared to wild type IgA2 regarding biochemical characteristics as well as Fab and Fc-mediated effector functions. Additionally, serum half-life and in vivo efficacy in a xenogeneic FcαRI-transgenic tumor model were evaluated. Results: Rational engineering of an IgA2 antibody resulted in monomeric molecules with improved biochemical characteristics, identical Fab- and Fc- mediated effector functions, but with significantly lower levels of terminal galactose. This molecule demonstrated lower asialoglycoprotein-receptor (ASGPR) binding and subsequently improved pharmacokinetics in mice. Compared to wild type IgA, this novel molecule displayed enhanced therapeutic efficacy against A431 tumor cells in vivo, which required human FcαRI-dependent myeloid effector cell engagement. Conclusions: These results demonstrate that an Fc engineered IgA antibody against EGFR displayed improved immunotherapeutic efficacy, which may overcome limitations (stability, pharmacokinetics, in vivo efficacy) of wild type IgA antibodies. Thus, these results promote the concept of FcαRI-dependent engagement of myeloid effector cells as a promising approach for antibody-based tumor immunotherapy.
Measurement technique influences the response of transfer factor (TICO) to salbutamol in patients with airflow limitation
Authors: DJ Chinn, J Askew, L Rowley, JE Cotes
Journal: European Respiratory Journal (1988)

Single-breath transfer factor obtained using a multibreath estimate of alveolar volume (TI) was measured before and after salbutamol in twenty patients with reversible airflow limitation. The effective breathholding time was calculated by four methods due respectively to Ogilvie and colleagues as modified by the American Thoracic Society (ATS), ATS Epidemiological Standardization Project (ESP), Jones and Meade in which allowance was made for the time of sample collection and a simplified method in which the allowance for sampling was in terms of volume, not time. Two patients could perform the test procedure only after salbutamol. Amongst the remainder the transfer factor calculated using a single-breath estimate of alveolar volume (TI') was on average 12% less than TI. Carbon monoxide transfer coefficient (KCO), TI and TI' were highest by the ESP method and lowest by the Ogilvie method. Inhalation of salbutamol (200 gamma) did not affect TI' by any method or TI and KCO by the Jones and Meade method but results by the other methods were reduced; in the case of the modified Ogilvie method the reduction was 3.9%. This error was due to overestimation of effective breathholding time by neglecting the reduction of 39% which occurred in the time of sample collection. The time of inspiration was unchanged whilst the time of deadspace washout was reduced by 16%. After bronchodilatation the absence of a change in TI' was due to the overestimation of effective breathholding time being offset by an increase in the proportion of alveolar volume measured by the single-breath procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
Increase of Induced Skin Tumors in the Mouse by the Lethal Yellow Gene (&lt;italic&gt;A&lt;/italic&gt;&lt;sup&gt;&lt;italic&gt;v&lt;/italic&gt;&lt;/sup&gt;)
Authors: George Vlahakis, W. E. Heston
Journal: JNCI Journal of the National Cancer Institute (1963)

The lethal yellow gene (Av) increased susceptibility to skin tumors induced in the mouse by painting with methylcholanthrene. This was most clearly shown by the statistically significant greater average number of papillomas and carcinomas of the skin in the yellow (AvA) mice than in the agouti (Aa) mice. The final incidence of papillomas and epidermoid carcinomas was greater in the yellow than in the agouti mice of both the male and female groups. All these incidences, however, approached 100 percent and the individual differences were only borderline or not highly significant statistically. There was a shorter latent period in the yellow mice than in the agouti mice of both the male and female groups and a shorter time between the appearance of the first tumor and the time the animal was autopsied. All these differences were in the same direction, although some of the individual differences were not highly significant statistically. Females showed a greater tumor response to the painting of the skin with methylcholanthrene than did males.
Risk Stratification for Acute Pulmonary Embolism
Authors: Jeffrey A. Kline, David W. Miller
Journal: Journal of the National Comprehensive Cancer Network (2011)

This article discusses state-of-the-art techniques for predicting risk of death after acute pulmonary embolism (PE), with special attention to how underlying malignancy adversely affects survival after an episode. Current methods of risk stratification generally categorize patients with PE as low-, moderate-, and high-risk for in-hospital adverse outcomes of respiratory failure, circulatory shock, and death. Published risk stratification studies find that patients with PE and an underlying malignancy have a worse prognosis, but no validated risk stratification criteria have been published specifically for these patients. Standard treatment is full-dose heparin followed by oral anticoagulation. The term escalated treatment refers to the use of systemic or intrapulmonary fibrinolytic agents, catheter-based treatment, or surgical embolectomy. Most patients with low-risk PE (normal vital signs and normal serum troponin, brain natriuretic peptide, and normal echocardiography) are treated successfully with standard anticoagulation, and many can be treated as outpatients. In contrast, patients with high-risk PE (systolic blood pressure < 90 mm Hg and no contraindications) often benefit from escalated treatment. Treatment decisions for patients with moderate-risk PE (normotension with evidence of right ventricular damage or dysfunction) are most controversial. Most patients in this category of risk recover with standard therapy, but some benefit from escalated treatment. Patients with cancer with an incidentally discovered PE should be risk stratified the same as those who have clinically suspected PE.
The mesenchymal stem cell profile in psoriasis
Authors: M. Orciani, A. Campanati, E. Salvolini, G. Lucarini, G. Di Benedetto, A. Offidani, R. Di Primio
Journal: British Journal of Dermatology (2011)

The expression of inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) and the level of total oxyradical scavenging capacity have been evaluated extensively in the cutaneous cells of patients with psoriasis. As yet, no indications are available about the undifferentiated cells, the mesenchymal stem cells (MSCs), isolated from skin.To isolate MSCs in patients with psoriasis and to compare them with those obtained from atopic and healthy subjects, in order to analyse whether MSCs show some typical psoriatic profiles and to understand whether pathophysiological events leading to psoriasis start early at the stem cell level.MSCs isolated from seven patients with psoriasis, seven patients with acute atopic dermatitis and seven healthy subjects were characterized by fluorescence-activated cell sorting analysis. VEGF and nitric oxide (NO) content was measured in conditioned medium, the expression of VEGF and iNOS was analysed by immunohistochemistry, and the total oxyradical scavenging capacity towards peroxynitrite was tested.VEGF content was highest in the medium conditioned by psoriatic perilesional MSCs, whereas NO concentration was maximally increased in medium conditioned by MSCs isolated from lesional psoriatic skin. The ability to neutralize the oxidizing effects of peroxynitrite was lower for MSCs isolated from lesional psoriatic skin compared with other MSCs, except for MSCs of lesional atopic skin.The microenvironment in psoriasis differs from those of atopic dermatitis and healthy skin; it could induce resident MSCs to produce angiogenic and proinflammatory mediators which lead to a reduction in the antioxidant capacity of these cells, contributing to the development of skin lesions in psoriasis.
Treatment of Children With Medulloblastomas With Reduced-Dose Craniospinal Radiation Therapy and Adjuvant Chemotherapy: A Children's Cancer Group Study
Authors: Roger J. Packer, Joel Goldwein, H. Stacy Nicholson, L. Gilbert Vezina, Jeffrey C. Allen, M. Douglas Ris, Karin Muraszko, Lucy B. Rorke, William M. Wara, Bruce H. Cohen, James M. Boyett
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Medulloblastoma is the most common malignant brain tumor of childhood. After treatment with surgery and radiation therapy, approximately 60% of children with medulloblastoma are alive and free of progressive disease 5 years after diagnosis, but many have significant neurocognitive sequelae. This study was undertaken to determine the feasibility and efficacy of treating children with nondisseminated medulloblastoma with reduced-dose craniospinal radiotherapy plus adjuvant chemotherapy. PATIENTS AND METHODS: Over a 3-year period, 65 children between 3 and 10 years of age with nondisseminated medulloblastoma were treated with postoperative, reduced-dose craniospinal radiation therapy (23.4 Gy) and 55.8 Gy of local radiation therapy. Adjuvant vincristine chemotherapy was administered during radiotherapy, and lomustine, vincristine, and cisplatin chemotherapy was administered during and after radiation. RESULTS: Progression-free survival was 86% ± 4% at 3 years and 79% ± 7% at 5 years. Sites of relapse for the14 patients who developed progressive disease included the local tumor site alone in two patients, local tumor site and disseminated disease in nine, and nonprimary sites in three. Brainstem involvement did not adversely affect outcome. Therapy was relatively well tolerated; however, the dose of cisplatin had to be modified in more than 50% of patients before the completion of treatment. One child died of pneumonitis and sepsis during treatment. CONCLUSION: These overall survival rates compare favorably to those obtained in studies using full-dose radiation therapy alone or radiation therapy plus chemotherapy. The results suggest that reduced-dose craniospinal radiation therapy and adjuvant chemotherapy during and after radiation is a feasible approach for children with nondisseminated medulloblastoma.
Abstract 113: Mast Cell Plays Pivotal Role in Nicotine-Induced Atherosclerotic Plaque Progress and Instability
Authors: Han Chen, Chen Wang, Yinchuan Xu, Xinyang Hu, Jian-an Wang
Journal: Circulation Research (2014)

Objectives: Nicotine has been identified to promote atherosclerosis. But the mechanism of nicotine induced atherogenesis has not been well elucidated. This study focus on the role of mast cell in nicotine induced atherogenesis and plaque instability. Methods: Peritoneal administration of 100mM disodium cromoglicate (DSCG) was introduced to inhibit mast cell degranulation. 45 ApoE deficient mice were divided into 3 groups: high-fat diet, high-fat diet + nicotine, and high-fat diet + nicotine + DSCG. After 12 weeks of treatments, atherosclerotic lesion size of the aortas were quantified. Toluidine blue and tryptase staining identified mast cell count and activation at the lesion. Immuno-staining were used to evaluate the inflammatory filtration, smooth muscle cell proliferation and collagen content in the lesion. In vitro , bone marrow-derived mast cells (BMMCs) were harvested and treated with PBS as a negative control, compound 48/80 as a positive control,100μg/ml nicotine, nicotine with 100mM DSCG pretreatment and nicotine with 10μg/ml mecamylamine pretreatment. At 0.5hr,1hr and 2hrs, supernatants were harvested to analyze the mast cell degranulation. Futhermore, conditioned medium were also used to induce the macrophage migration and foam cell formation. Results: Nicotine increases plaque size, and macrophage infiltration, decreases smooth muscle collagen content along with the increases in mast cells count and activation ratio at the lesion, which could be inhibited by DSCG.Nicotine induced mast cell degranulation at 2 hours comparing to PBS (43.60% vs 2.3%) , which could be inhibited by mast cell stablizer DSCG (23.7%) and nAChR blocker mecamylamine (20.35%). Macrophage migration ability in the compound 48/80 and nicotine conditional medium group were significantly higher comparing to PBS, DSCG and mecamylamine group. Foam cell formation ratio in the compound 48/80 and nicotine conditional group were significantly higher comparing to PBS, DSCG and mecamylamine group. Conclusions: Nicotine induces mast cell degranulation through nAChR and then increases macrophages function, which leads to plaque instability. Administration of mast cell stabilizer showed potential of preventing nicotine induced atherogenesis.
Spacer cleaning: Nurse and patient survey examines current UK practice
Authors: Mark Sanders, Mark Levy, Keely Thompson, Ron Bruin
Journal: European Respiratory Journal (2012)

Introduction:  Washing spacers improves drug delivery by reduction of electrostatic charges, and is hygienic .  Contamination of spacers and masks has been shown ( JAMA 2003;290: 2, 195-196).  The ERS/ISAM guideline (ERJ 2011;37:1308-1331) identified a lack of standard instructions for good spacer cleaning practice.   Methods:  Online structured interview questionnaires by a market research agency, 100 asthma patients (Pts) using pMDI with spacer and 50 respiratory nurses (RN) to establish current practice. Pts: 49 adults, parents of child aged 2-9 yrs (n=30) or 10-15 yrs (n=21).   Results:  74% of RN told Pts to wash spacers weekly, 4% instruct daily and 22% instruct    Conclusions:  RN spacer washing instructions frequently conform to manufacturer9s instructions. Many Pts wash spacers more frequently than instructed but some do not wash at all; many dry with a cloth which may dissipate the electrostatic benefits of air-drying and encourage contamination.
The CT emphysema index is a predictor for exertional desaturation in COPD patients without resting hypoxemia
Authors: Changhwan Kim, Yong Bum Park, Joon Beom Seo, Yeon-Mok Oh, Sang-Do Lee
Journal: European Respiratory Journal (2012)

Background : Although numerous studies have attempted to correlate various clinical tests with exertional desaturation in patients with COPD, no test has shown significant positive predictive value. The aim of this study was to identify clinical predictors of exertional desaturation focusing on the CT indices, and to determine whether an association exists between exertional desaturation and a particular COPD phenotype.

Methods : A total of 224 subjects were selected from the Korean Obstructive Lung Disease cohort. Exertional desaturation was defined as a post-exercise oxygen saturation (SpO2) of <90% or a ≥4% decrease. The cohort was divided into desaturator (n=47) and non-desaturator (n=177) groups

Results : Significant differences were observed between the groups in terms of age, BODE index, forced expiratory volume in 1 second (FEV1), diffusing capacity, and resting SpO2. The CT emphysema index was significantly higher in the desaturator group. Multivariate analysis showed that the CT emphysema index (RR, 1.028; 95% CI, 1.001 to 1.056; p =0.046) and resting SpO2 (RR, 0.790; 95% CI, 0.648 to 0.965; p =0.021) were significant independent predictors. In the desaturator group, the rate of decline in FEV1 was more rapid and health-related quality of life worsened faster than in the non-desaturator group over a 3-year period of follow-up. Conclusions : In patients with COPD, exertional desaturation possibly occurs in parallel with an increase in the CT emphysema index. Exertional desaturation may be a manifestation of emphysema phenotype, and COPD patients with exertional desaturation are associated with a more rapid decline in lung function and poorer health-related quality of life.
A 4-min, self-paced step test to assess exercise impairment in COPD patients GOLD I-to-IV
Authors: Mauro Gomes, Beatriz Amorim, Miguel Rodrigues, Mayron Oliveira, Melline Almeida, Adriano Acedo, Aline Souza, Thulio Cunha, J. Alberto Neder
Journal: European Respiratory Journal (2012)

Background : There is a long-standing interest in developing “field” exercise tests for patients with chronic obstructive pulmonary disease (COPD) which can be easily performed in the consulting room with a minimum of technical support. Objectives : To investigate whether a 4-min, self paced step test (4MST) would be useful to assess exercise tolerance and oxyhemoglobin desaturation by pulse oximetry (SpO2) in a large group of outpatients with COPD. Methods : 191 patients (GOLD stages: I= 16, II= 63, III= 79, IV= 33) prospectively underwent the 4MST. Patients were allowed to stop the test as needed and re-start it within the allowed 4-min. Results : There were no significant test-related complications. There was a large variability in the steps climbed (ranging from low 20's to more than 100). Based on the tertiles of steps climbed, patients were separated into sub-groups of progressive impairment (Group A, N= 62; Group B, N= 61; Group C, N= 68). Group A patients were significantly younger than those of Group B and C (p<0.05). The number of interruptions during the tests increased from Group A to C; in addition, this variable and the steps climbed were significantly correlated (r= -0.53; p<0.01). 11/16 GOLD I patients were on Group A whereas 30/33 GOLD IV patients were on Groups B or C (p<0.05). In addition, from 36 patients with disabling breathlessness (MRC scores IV to V) 30 of them were on Groups B or C (p<0.05). Decreases in SpO2 corrected by steps climbed decreased as exercise tolerance diminished (p<0.05). Conclusions : A 4-min, self paced step test (4MST) was useful in discriminating COPD patients into progressive levels of exercise and pulmonary gas exchange impairment.
Abstract 2355: Targeting of Ischemic/reperfused Myocardium by Liposomal Amiodarone Reduced Ventricular Fibillilation in Rats
Authors: Hiroyuki Takahama, Masafumi Kitakaze, Tomohiro Asai, Tetsuo Minamino
Journal: Circulation (2009)

Background: Liposomes are nanoparticles that can deliver various agents to target tissues and delay degradation of these agents. Recently, we reported that liposomes could accumulate in and selectively deliver drugs to ischemic/reperfused myocardium. Although amiodarone has strong anti-arrhythimic effects, it causes significant adverse effects, e.g. interstinal pnumoniae, hypothyroidism. We hypothesized that amiodarone in liposomes specifically accumulate in ischemic/reperfused (I/R) myocardium, leading to augmented anti-arrhythimic effects. Methods and Results: We prepared liposomal amiodarone (mean diameter: 113±8nm) by the thin film method and investigated acute effects of liposomal amiodarone on lethal arrhythmia after myocardial infarction (MI) in rats. Left coronary artery was occluded for 5 minutes followed by reperfusion. First, we examined whether liposomes could accumulate in ischemic/reperfused myocardium in such a brief duration of ischemia. Using ex vivo bioluminescence imaging, it could be o...