tbuckley/cabot-search huggingface dataset:
The search for autoantibodies against elastin, collagen and decorin in COPD
Authors: C.A. Brandsma, H.A.M. Kerstjens, M. Geerlings, M. Kerkhof, M.N. Hylkema, D.S. Postma, W. Timens
Journal: European Respiratory Journal (2011)

To the Editors:

Several studies indicate that an autoimmune response may underlie the pathogenesis of chronic obstructive pulmonary disease (COPD). A high prevalence of anti-Hep-2 epithelial cell autoantibodies has been shown in patients with COPD 1, 2, as well as autoantibodies against airway epithelial cells 1, endothelial cells 3, lung elastin 4, several immunogenic peptides 5 and cytokeratin 18 6. The most convincing evidence for an autoimmune response in COPD was provided by Lee et al. 4. They showed a specific autoantibody and a specific T-cell response against elastin in COPD patients, as well as increased numbers of anti-elastin antibody-producing cells in the lungs of COPD patients. Recent studies 7, 8, however, could not confirm such an anti-elastin autoantibody response. Cottin et al. 7 found no evidence for an anti-elastin autoantibody response in patients with combined pulmonary fibrosis and emphysema. Additionally, Greene et al. 8 investigated the presence of autoantibodies against elastin- and collagen-derived proline–glycine–proline in patients with COPD and α1-antitrypsin deficiency, and also did not observe increased autoantibody levels.

We assessed the presence of autoantibodies against elastin, collagen and decorin in serum of COPD patients and healthy controls. In addition, and as an extension of previous studies, we included equal numbers of current, ex- and never-smokers, in order to investigate the effect of the smoking status on autoantibody levels. We chose to asses autoantibodies against elastin and collagen to confirm the previous results of Lee et al. 4 in two different patient groups. As we previously demonstrated a decreased presence of the extracellular …
Memory CD8<b>+</b> T Cells Are Required for Protection from Persistent Hepatitis C Virus Infection
Authors: Naglaa H. Shoukry, Arash Grakoui, Michael Houghton, David Y. Chien, John Ghrayeb, Keith A. Reimann, Christopher M. Walker
Journal: The Journal of Experimental Medicine (2003)

Few hepatitis C virus (HCV) infections resolve spontaneously but those that do appear to afford protective immunity. Second infections are usually shorter in duration and are less likely to persist but mechanisms of virus control in immune individuals have not been identified. In this study we investigated whether memory helper and/or cytotoxic T lymphocytes provide protection in chimpanzees serially reinfected with the virus. Clearance of the first infection took 3–4 mo and coincided with the delayed onset of CD4+ and CD8+ T cell responses. High frequencies of memory T cells targeting multiple HCV proteins were stable over 7 yr of follow-up. Animals were infected for a second time to assess the protective role of memory T cells. In contrast to the prolonged course of the first infection, viremia was terminated within 14 d. Control of this second infection was kinetically linked to rapid acquisition of virus-specific cytolytic activity by liver resident CD8+ T cells and expansion of memory CD4+ and CD8+ T cells in blood. The importance of memory CD8+ T cells in control of HCV infection was confirmed by antibody-mediated depletion of this lymphocyte subset before a third infection. Virus replication was prolonged despite the presence of memory CD4+ T helper cells primed by the two prior infections and was not terminated until HCV-specific CD8+ T cells recovered in the liver. These experiments demonstrate an essential role for memory CD8+ T cells in long-term protection from chronic hepatitis C.
Pulmonary rehabilitation; what's in a name?
Authors: Sally J Singh, Michael C Steiner
Journal: Thorax (2013)

The therapeutic efficacy of pulmonary rehabilitation is now well established and supported by a substantial body of clinical trial evidence.1 ,2 The place of pulmonary rehabilitation in the management of chronic obstructive pulmonary disease (COPD) and other chronic respiratory diseases has been enshrined in national and international guidelines including those recently produced by the British Thoracic Society.3 In recent years, attention has shifted from questions regarding the effectiveness of the intervention for those who successfully attend and complete a programme, to meeting challenges for the delivery of pulmonary rehabilitation to the wider population with disabling lung disease. A key driver of this focus is the perception in many quarters that uptake and adherence to rehabilitation is poor, and that a significant minority of patients do not fully respond, or quickly decline, once the programme is completed. As a result, there is considerable interest in developing and testing alternative delivery models of pulmonary rehabilitation and other behavioural interventions that aim to improve general health, knowledge of the disease and promote self-care.

Dympna4 presents data from the PRINCE study which reports on the delivery of a structured education pulmonary rehabilitation programme (SEPRP) in a primary care setting. This is not the first study of pulmonary rehabilitation in the community,5 ,6 but the PRINCE study has taken an alternative approach. The authors describe a tightly controlled cluster ramdomised controlled trial (RCT) of a rehabilitation intervention versus best usual care in a group of participants with moderate to severe COPD. The authors should be congratulated on conducting such a rigorous randomised controlled trial in a large study population. Participants underwent an 8-week programme, comprising weekly sessions of exercise and education, followed by a telephone call at 4 weeks postdischarge, and a 1 h group …
ENVIRONMENTAL FACTORS THAT INCREASE THE FOOD INTAKE AND CONSUMPTION VOLUME OF UNKNOWING CONSUMERS
Authors: Brian Wansink
Journal: Annual Review of Nutrition (2004)

Package size, plate shape, lighting, socializing, and variety are only a few of the environmental factors that can influence the consumption volume of food far more than most people realize. Although such environmental factors appear unrelated, they generally influence consumption volume by inhibiting consumption monitoring and by suggesting alternative consumption norms. For researchers, this review suggests that redirecting the focus of investigations to the psychological mechanisms behind consumption will raise the profile and impact of research. For health professionals, this review underscores how small structural changes in personal environments can reduce the unknowing overconsumption of food.
Permanent and functional male-to-female sex reversal in d-rR strain medaka (Oryzias latipes) following egg microinjection of o,p'-DDT.
Authors: J S Edmunds, R A McCarthy, J S Ramsdell
Journal: Environmental Health Perspectives (2000)

Complete sex reversal of fish is accomplished routinely in aquaculture practices by exposing fish to exogenous sex steroids during gonadal differentiation. A variety of environmental chemicals are also active at sex steroid receptors and theoretically possess the potential to alter normal sexual differentiation in fish. However, in controlled environmental chemical exposures to date, only partial alterations of fish sexual phenotype have been observed. Here we report complete, permanent, and functional male-to-female sex reversal in the Japanese medaka (Oryzias latipes, d-rR strain) after a onetime embryonic exposure to the xenoestrogen o, p'-DDT. d-rR strain medaka are strict gonochorists that possesses both sex-linked pigmentation, which distinguishes genotypic sex, and sexually dimorphic external secondary sexual characteristics, which distinguish phenotypic sex. We directly microinjected the xenoestrogen o, p'-DDT into the egg yolks of medaka at fertilization to parallel the maternal transfer of lipophilic contaminants to the embryo. At 10 weeks of age, microinjected medaka were examined for mortality and sex reversal. A calculated embryonic dose of 511 +/- 22 ng/egg o, p'-DDT (mean +/- standard error) resulted in 50% mortality. An embryonic exposure of 227 +/- 22 ng/egg o, p'-DDT resulted in 86% (6 of 7) sex reversal of genetic males to a female phenotype (XY females). XY females were distinguished by sex-linked male pigmentation accompanying female secondary sexual characteristics. Histologic examination of the gonads confirmed active ovaries in 100% of the XY females. In 10-day breeding trials in which XY females were paired with normal XY males, 50% of the XY females produced fertilized embryos; this represents a comparable breeding success rate to normal XX females. Fertilized eggs produced from XY females hatched to viable larvae. These results clearly indicate that a weakly estrogenic pesticide, o, p'-DDT, when presented during the critical period of gonadal development, can profoundly alter sexual differentiation.
Is It Downhill from Here? Eliminating Leukemic Stem Cells and Curing Chronic Myeloid Leukemia
Authors: Catherine C. Smith, Neil P. Shah
Journal: Clinical Cancer Research (2011)

Patients with chronic phase chronic myeloid leukemia who respond to imatinib have a rapid initial decrease in BCR-ABL transcript levels (α), followed by a slow decline (β). The rate of β decrease is consistent with declining leukemic stem cells and may predict which patients may safely discontinue therapy.
Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma
Authors: J. H. Sampson, K. D. Aldape, G. E. Archer, A. Coan, A. Desjardins, A. H. Friedman, H. S. Friedman, M. R. Gilbert, J. E. Herndon, R. E. McLendon, D. A. Mitchell, D. A. Reardon, R. Sawaya, R. Schmittling, W. Shi, J. J. Vredenburgh, D. D. Bigner, A. B. Heimberger
Journal: Neuro-Oncology (2010)

Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation widely expressed in glioblastoma multiforme (GBM) and other neoplasms, but absent from normal tissues. Immunotherapeutic targeting of EGFRvIII could eliminate neoplastic cells more precisely but may be inhibited by concurrent myelosuppressive chemotherapy like temozolomide (TMZ), which produces a survival benefit in GBM. A phase II, multicenter trial was undertaken to assess the immunogenicity of an experimental EGFRvIII-targeted peptide vaccine in patients with GBM undergoing treatment with serial cycles of standard-dose (STD) (200 mg/m2 per 5 days) or dose-intensified (DI) TMZ (100 mg/m2 per 21 days). All patients receiving STD TMZ exhibited at least a transient grade 2 lymphopenia, whereas those receiving DI TMZ exhibited a sustained grade 3 lymphopenia (<500 cells/μL). CD3+ T-cell (P = .005) and B-cell (P = .004) counts were reduced significantly only in the DI cohort. Patients in the DI cohort had an increase in the proportion of immunosuppressive regulatory T cells (TReg; P = .008). EGFRvIII-specific immune responses developed in all patients treated with either regimen, but the DI TMZ regimen produced humoral (P = .037) and delayed-type hypersensitivity responses (P = .036) of greater magnitude. EGFRvIII-expressing tumor cells were also eradicated in nearly all patients (91.6%; CI95: 64.0%–99.8%; P < .0001). The median progression-free survival (15.2 months; CI95: 11.0–18.5 months; hazard ratio [HR] = 0.35; P = .024) and overall survival (23.6 months; CI95: 18.5–33.1 months; HR = 0.23; P = .019) exceeded those of historical controls matched for entry criteria and adjusted for known prognostic factors. EGFRvIII-targeted vaccination induces patient immune responses despite therapeutic TMZ-induced lymphopenia and eliminates EGFRvIII-expressing tumor cells without autoimmunity.
Resistance of cytolytic lymphocytes to perforin-mediated killing. Lack of correlation with complement-associated homologous species restriction.
Authors: S B Jiang, P M Persechini, A Zychlinsky, C C Liu, B Perussia, J D Young
Journal: The Journal of Experimental Medicine (1988)

CTL and NK cells resist self-mediated killing and lysis by their own pore-forming protein (PFP; perforin). Perforin, like C, lyses RBC. Efficient C-mediated lysis of RBC occurs when both C and RBC are from different species (homologous species restriction). A protective surface protein (C8-binding protein, homologous restriction factor) has been reported to mediate both homologous species restriction in C-dependent cytolysis and protection of some target cells against perforin-induced lysis. We show here that perforin, unlike C, lyses target cells across a variety of species, including the homologous one, while the same target cell populations resist the attack by homologous C. Perforin-containing extracts of CTL and LAK/NK cells from three species (rat, mouse, and human) and purified mouse perforin were tested against RBC from 10 different species, several nucleated target cell lines, and one primary cell population (thymocytes). While resisting lysis by homologous C, most of these cell types were lysed effectively by perforin without any homologous restriction pattern. CTL and NK cells, like other nucleated targets, are resistant to lysis by homologous but not heterologous C; however, these cell types are resistant to both homologous and heterologous perforin. Together, our results suggest that the protective mechanisms associated with C- and perforin-mediated lysis are distinct.
Clemastine causes immune suppression through inhibition of extracellular signal-regulated kinase–dependent proinflammatory cytokines
Authors: Pål Johansen, Andreas Weiss, Antonia Bünter, Ying Waeckerle-Men, Antonia Fettelschoss, Bernhard Odermatt, Thomas M. Kündig
Journal: Journal of Allergy and Clinical Immunology (2011)
A Comparison of the Vascular Dopamine Receptor with Other Dopamine Receptors
Authors: L I Goldberg, P H Volkman, J D Kohli
Journal: The Annual Review of Pharmacology and Toxicology (1978)

The dopamine (DA) receptor has had an interesting history. Unusual actions were attributed to the catecholamine for many years, but these effects were generally considered to be manifestations of activation of 0.and ,8-adrenergic receptors rather thap results of action of DA on a specific receptor (1). The pendulum now has swung the other way. The literature is replete with papers reporting the existence of DA receptors subserving specialized functions in a wide variety of organs and species (2-4). A pertinent question which must be answered is whether the same DA receptor subserves all reported functions or whether there is a family of specific, but different, DA receptors (5). In this review we are concerned primarily with similari­ ties and differences in the effects of agonists and antagonists acting on the DA receptor in the canine renal vascular bed and on selected DA receptors described in other organs and species. The actions of DA on a specific vascular receptor and on other receptors in the cardiovascular system have been the subject of previous reviews (1, 6, 7).
A comparison of the sensitivity of diagnostic criteria for polymyalgia rheumatica
Authors: H A Bird
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To compare the performance of the several different diagnostic criteria sets currently in use for polymyalgia rheumatica (PMR). <b>Methods:</b> 213 patients attending eight rheumatological centres in eight different European countries were studied. All had recently been referred and were considered by the senior investigator at each centre, selected because of their experience in treatment of PMR, to have this condition. By use of a standard international proforma, the requisite diagnostic points in each criteria set were sought. Sensitivity for each criterion from each set was then calculated, as well as the sensitivity of each criteria set as a whole. <b>Results:</b> Of four criteria sets compared, the Bird (1979) criteria performed best with a sensitivity of 99.5%, and the Hunder (1982) criteria second best, with sensitivity of 93.3%. These both performed significantly better than the two other criteria sets, though each of these was admittedly developed for rather specialised reasons. <b>Conclusions:</b> Although this study compares homogeneity, we suggest the Bird 1979 or Hunder 1982 criteria should be used whenever possible. Studies that have used alternative criteria may have less sensitivity in diagnosis.
Assessing the Liverpool Respiratory Symptom Questionnaire in children with cystic fibrosis
Authors: R. Trinick, K.W. Southern, P.S. McNamara
Journal: European Respiratory Journal (2011)

Monitoring respiratory status in cystic fibrosis (CF) is challenging, particularly in young children. We aimed to test whether the Liverpool Respiratory Symptom Questionnaire (LRSQ) could distinguish well, pre-school and older children with and without CF, whether it could distinguish well and unwell children with CF and, finally, whether LRSQ scores in older children with CF correlated with established measures of disease severity. 20 stable pre-school children with CF had significantly higher total LRSQ scores than 51 pre-school controls, and higher scores in two out of eight domains. Similarly, 21 stable 6- to 12-yr-old children with CF had higher total scores than 97 6- to 12-yr-old controls, and higher scores in seven out of eight domains. In older children with CF, LRSQ scores correlated negatively with Shwachman score and forced expiratory volume in 1 s (r= -0.58, p&lt;0.001, n=31; and r= -0.46, p&lt;0.010, n=34, respectively). Within the CF group, patients who cultured Pseudomonas aeruginosa , who used more “back-up” antibiotics or whose school attendance was lower also had higher LRSQ scores. The LRSQ differentiates well children from those with CF in both pre-school and the 6- to 12-yr-old age group, even at a point of stability. It also differentiates stable from unwell children with CF, and scores correlate with other measures of respiratory disease, highlighting its potential as a clinical monitoring tool in paediatric CF.
Human tumor fluorouracil trapping: clinical correlations of in vivo 19F nuclear magnetic resonance spectroscopy pharmacokinetics.
Authors: C A Presant, W Wolf, M J Albright, K L Servis, R Ring, D Atkinson, R L Ong, C Wiseman, M King, D Blayney
Journal: Journal of Clinical Oncology (1990)

We previously reported that fluorouracil (5FU) accumulation and metabolism in human livers and tumors can be studied by in vivo nuclear magnetic resonance spectroscopy (NMRS). We have extended these observations by evaluating the pharmacokinetics of 5FU in the tumors of 11 patients with carcinoma of the breast, colon, endometrium, cervix, and kidney, using 19F-NMRS in a 1.5 Magnetom (Siemens Medical Systems, Cerrito, CA) magnetic resonance imaging unit (MRI). These NMRS measurements detected a long-lived tumor pool of 5FU in six of 11 tumors in our patients including carcinomas in the pelvis, breast, lung, and liver. The half-life (T1/2) of this tumor pool of "trapped" 5FU was 0.33 to 1.3 hours (20 to 78 minutes), much longer than the T1/2 of 5FU in blood (5 to 15 minutes). Neither the anabolites of 5FU (fluorinated nucleosides, nucleotides, 5FU-RNA, or 5FU-thymidylate synthase) nor the catabolites (eg, fluorobetaalanine [FBAL]) were detectable by 19F NMRS. Patient response to chemotherapy appeared to correlate with the extent of trapping of free 5FU in the human tumors: in the seven patients receiving 5FU, or 5FU or FUdR plus leucovorin, four of four patients whose tumors trapped 5FU responded to fluorinated pyrimidine chemotherapy, whereas three patients in whom there was a failure to detect tumor trapping were resistant to 5FU. We conclude that NMRS is clinically feasible, and enables investigators to study 5FU pharmacokinetics and metabolism in tumors in vivo. 19F-NMRS of 5FU allows for in vivo evaluation of 5FU metabolic modulation and might be able to guide therapeutic decisions.
M267 Health Status And Quality Of Life In Idiopathic Pulmonary Fibrosis And Sarcoidosis: Effect Of Fatigue
Authors: C. Atkins, D. Gilbert, C. Brockwell, S. Robinson, A. Wilson
Journal: Thorax (2014)

<h3>Introduction and Objective</h3> Sarcoidosis and Idiopathic Pulmonary Fibrosis (IPF) are two common forms of interstitial lung disease. Sarcoidosis frequently causes extra-pulmonary disease whereas IPF specifically affects the lungs. Fatigue is a common feature of sarcoidosis, but an association between fatigue and IPF has not been investigated. We investigated the frequency and severity of fatigue in sarcoidosis and IPF, how it correlates with quality of life (QOL) scores, and whether fatigue is affected by disease severity. <h3>Methods</h3> This was a cross-sectional questionnaire study of patients with sarcoidosis and IPF. Questionnaire data was analysed to investigate health status, QOL, and symptom prevalence (fatigue, depression and sleepiness). Comparison of scores between groups, and an analysis of the effect of markers of disease severity on fatigue, was undertaken. <h3>Results</h3> Questionnaires were administered to 235 participants; 82 healthy volunteers, 76 sarcoidosis patients and 77 IPF patients. IPF patients had statistically higher St George’s Respiratory Questionnaire (p = 0.034) and Epworth Sleepiness Scale scores (p = 0.003) than sarcoidosis patients, but there was no difference in mean fatigue scores. When stratified by questionnaire scores (Table 1), including pathological fatigue levels, no statistical difference was seen between IPF and sarcoidosis, although there was a trend towards a higher frequency of ‘severe fatigue’ in sarcoidosis. Fatigue scores correlated strongly with quality of life scores (King’s Brief Interstitial Lung Disease score and St George’s Respiratory Questionnaire) in both IPF (<i>r</i>=-0.615 and 0.659 respectively) and sarcoidosis (<i>r</i>=-0.529 and 0.502). In sarcoidosis, no measures of dyspnoea or disease severity (spirometry abnormality, immunosuppression use or extrapulmonary disease) were associated with fatigue scores. In IPF increasing dyspnoea scores were associated with increased fatigue scores (p &lt; 0.001). <h3>Conclusions</h3> Both sarcoidosis and IPF patients suffer with high levels of fatigue, although the sarcoidosis cohort showed a trend towards greater frequency of severe fatigue compared with IPF. In IPF patients increasing fatigue was associated with worsening dyspnoea, suggesting an association with disease progression, but no similar relationship was seen in sarcoidosis. This suggests that fatigue in sarcoidosis occurs independently of common markers of disease activity, whereas it occurs as a sequelae of progressive disease in IPF.
In vitro generation of cytotoxic lymphocytes against radiation- and radiation leukemia virus-induced tumors. III. Suppression of anti-tumor immunity in vitro by lymphocytes of mice undergoing radiation leukemia virus-induced leukemogenesis.
Authors: E Yefenof, A Meidav, E Kedar
Journal: The Journal of Experimental Medicine (1980)

Adult C57BL/6 mice exposed to fractionated irradiation or inoculated with the radiation leukemia virus (RadLV), develop high incidence (80-100%) of lymphatic leukemias within 3-6 mo. RadLV-induced lymphomas can elicit cytotoxic responses in vitro in lymphocytes of preimmunized syngeneic mice, a reaction that is dependent on the expression of membrane-associated viral antigenicity. As soon as 5 d after RadLV inoculation, and during the entire leukemogenic process, suppressor T cells are detectable in the spleen that are capable of specifically abrogating generation of syngeneic anti-tumor cytotoxic cells in vitro. Mice exposed to fractionated x irradiation do not develop suppressor cells and their splenocytes may be stimulated in vitro to generate cytotoxicity toward RadLV-induced leukemias. These findings suggest that although RadLV has been isolated from radiation-induced leukemias, x-ray- and RadLV-induced leukemogenesis do not seem to involve a common viral etiology, and that induction of suppressor cells during RadLV leukemogenesis may be essential for tumor progression.