tbuckley/cabot-search huggingface dataset:
Factors affecting peak expiratory flow variability and bronchial reactivity in a random population sample.
Authors: B G Higgins, J R Britton, S Chinn, K K Lai, P G Burney, A E Tattersfield
Journal: Thorax (1993)

BACKGROUND--Bronchial reactivity measurements are widely used in epidemiological studies to provide an objective marker of asthma. There are, however, several potential advantages of measuring peak expiratory flow (PEF) variability instead, particularly in large studies. PEF variability and bronchial reactivity were compared in a population sample to assess the relationships of the two measurements to factors known to be associated with airways disease, and to compare their response rates. METHODS--Subjects aged 18-65 were randomly selected from the electoral register of an administrative area in eastern England and randomised to attend either for a bronchial challenge test measuring the provocative dose of methacholine producing a 20% fall in FEV1 (PD20), or to measure PEF at two hourly intervals during waking hours for one week. Skin tests with common allergens were performed and a smoking history obtained. PEF variability was expressed as the amplitude % mean (highest - lowest x 100/mean). RESULTS--A total of 273 subjects (69%) collected a PEF meter but a completed record sheet was returned by only 247 (62%); this was still significantly more than the 202 subjects (54%) who attended for and successfully completed a challenge test. Amplitude % mean was higher in women than in men (9.7% v 8.5%). In multiple regression analysis amplitude % mean increased significantly with age, mean skin weal diameter, and with current smoking. The odds of having a PD20 below 24.5 mumol increased with mean skin weal diameter and were greater in current smokers. Neither age nor sex had a significant effect on bronchial reactivity but there were significant interactions between age and the effects of both smoking and atopy. CONCLUSIONS--The higher response rate associated with the use of PEF variability measurement, and the association with factors implicated in the pathogenesis of airways disease, suggest that PEF variability would be a useful measurement to employ in epidemiological studies.
The Nature of Anaemia in Rheumatoid Arthritis: V. Red Cell Survival measured by Radioactive Chromium
Authors: J. Richmond, W. R. M. Alexander, J. L. Potter, J. J. R. Duthie
Journal: Annals of the Rheumatic Diseases (1961)

A number of studies have been undertaken to assess the importance of shortened red cell survival in the causation of anaemia complicating rheumatoid arthritis.Freireich, Ross, Bayles, Emerson, and Finch (1954), using the Ashby technique, found reduction of the life span of transfused erythrocytes from normal individuals in patients suffering from the disease.Alexander, Richmond, Roy, and Duthie (1956), using the same technique, confirmed this observation in all of eighteen patients, as did McCrea (1957) in ten out of fifteen patients and Freireich, Ross, Bayles, Emerson, and Finch (1957) in "more than half" of thirteen patients.However, Freireich and others (1954, 1957) observed that cells from patients with rheumatoid arthritis survived normally in the circulation of normal individuals; Alexander and others (1956) reported that the survival time of cells from patients with rheumatoid arthritis, although shorter than normal, exceeded that of cells from normal subjects when transfused to other patients with rheumatoid arthritis.
Maintaining benefits following pulmonary rehabilitation: a randomised controlled trial
Authors: L. M. Spencer, J. A. Alison, Z. J. McKeough
Journal: European Respiratory Journal (2009)

The aim of this study was to determine if weekly, supervised, outpatient-based exercise plus unsupervised home exercise following an 8-week pulmonary rehabilitation programme would maintain functional exercise capacity and quality of life at 12 months better than standard care of unsupervised home exercise training. Chronic obstructive pulmonary disease (COPD) subjects completed an 8-week pulmonary rehabilitation programme, were randomised to an intervention group (IG) of weekly, supervised, exercise plus home exercise or to a control group (CG) of unsupervised home exercise and followed for 12 months. Outcome measurements at baseline (after pulmonary rehabilitation), and 3, 6 and 12 months included the 6-min walk test and St George's Respiratory Questionnaire (SGRQ). 59 subjects with moderate COPD (Global Initiative for Chronic Obstructive Lung Disease stage II) were recruited and 48 subjects completed the study. 12-month mean difference showed no significant change from baseline in 6-min walk distance (IG -11 m, 95% CI -21–10 m; CG -6 m, 95% CI -34–11 m) or total SGRQ score (IG 3, 95% CI -0.8–7; CG -3, 95% CI -7–3). 12 months following pulmonary rehabilitation both weekly, supervised, outpatient-based exercise plus unsupervised home exercise and standard care of unsupervised home exercise successfully maintained 6-min walk distance and quality of life in subjects with moderate COPD.
Genomics in Multiple Myeloma
Authors: Nikhil C. Munshi, Hervé Avet-Loiseau
Journal: Clinical Cancer Research (2011)

Abstract Multiple myeloma (MM) is a complex disease that is driven by numerous genetic and epigenetic alterations. Comprehensive oncogenomic analysis indicates the presence of many highly recurrent and highly focal amplifications and/or deletions in the MM genome. Integrated oncogenomic analyses of human MM have identified candidates resident within regions of amplification and/or deletions that are predicted to be involved in MM pathogenesis and progression. The biological behavior and clinical outcome in MM are dependent on these molecular determinants, which are also attractive therapeutic targets. The data obtained from extensive analysis of patient samples, with annotated clinical outcomes, are providing insights into molecular mechanisms of disease behavior, helping to develop sensitive prognostic models, identifying novel therapeutic targets, providing the framework for the development of molecularly based therapies, and, eventually, will help in developing individualized therapy to improve outcomes, with reduced toxicity. Clin Cancer Res; 17(6); 1234–42. ©2011 AACR.
Surfactant composition reflects lung overinflation and arterial oxygenation in patients with acute lung injury
Authors: AD Bersten, IR Doyle, KG Davidson, HA Barr, TE Nicholas, F Kermeen
Journal: European Respiratory Journal (1998)

Pulmonary surfactant abnormalities have consistently been documented in patients with acute lung injury (ALI), however, there is little evidence directly correlating them to altered respiratory mechanics. To explore this further, surfactant composition was measured in lung aspirate fluid collected on 15 occasions from 10 patients with ALI. The composition was compared with lung aspirate fluid from 11 intubated patients prior to elective cardiac surgery (CS), and bronchoalveolar lavage fluid from 16 normal subjects. In both the ALI and cardiac groups the proportion of disaturated phospholipids (DSP) and phosphatidylcholine was reduced. Plasma levels of surfactant proteins-A and -B (SP-A and -B) were elevated, but were unrelated to alveolar surfactant levels. In the ALI group, and the ALI + CS group, DSP, normalized to the total phospholipid content, sphingomyelin (SPH), and urea, showed strong direct correlations with arterial oxygen tension/inspiratory oxygen fraction (all p &lt; or = 0.01). In the ALI group, normalized DSP was also directly related to the elastance of the positive end-expiratory pressure-induced increase in the end-expiratory lung volume (all p &lt; or = 0.02), and indirect correlations were found with a measure of lung overinflation (%E2; all p &lt; or = 0.01). We conclude that surfactant composition correlates with lung function abnormalities in acute lung injury and cardiac patients, and that both groups had elevated plasma surfactant proteins-A and -B levels, consistent with a concurrent increase in alveolocapillary permeability.
Advances in Radiation Oncology
Authors: Mohamed Elshaikh, Mats Ljungman, Randall Ten Haken, Allen S. Lichter
Journal: Annual Review of Medicine (2005)

Advances in radiation oncology have been made on three major fronts: biology, physics, and clinical application. Our biological understanding of how radiation kills cells and how malignant cells avoid damage has identified new targets for therapeutic manipulation. Research in physics has yielded sophisticated methods to direct the deposition of radiation energy in ways that enhance target coverage while minimizing dose to normal structures as much as possible. Intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy represent new paradigms in treatment planning and dose delivery. Clinical management of the cancer patient is multidisciplinary. Increasingly, combinations of radiation and chemotherapy, with or without surgery, are enhancing cure rates, often with preservation of organ function. Taken together, these advances have increased the effectiveness of radiation therapy and promise better treatment results in the future.
Validation of EncephalApp, Smartphone-Based Stroop Test, for the Diagnosis of Covert Hepatic Encephalopathy
Authors: Jasmohan S. Bajaj, Douglas M. Heuman, Richard K. Sterling, Arun J. Sanyal, Muhammad Siddiqui, Scott Matherly, Velimir Luketic, R. Todd Stravitz, Michael Fuchs, Leroy R. Thacker, HoChong Gilles, Melanie B. White, Ariel Unser, James Hovermale, Edith Gavis, Nicole A. Noble, James B. Wade
Journal: Clinical Gastroenterology and Hepatology (2014)
Advances in Clinical Trials in the Twentieth Century
Authors: Lloyd D. Fisher
Journal: Annual Review of Public Health (1999)

▪ Abstract This article considers the rise of the randomized clinical trial during the twentieth century. Before such development could begin, probability and statistics needed to merge. Sir RA Fisher introduced randomization in the 1920s and, beginning in the 1930s and 1940s, randomized clinical trials in humans were being performed by using the statistical-hypothesis-testing paradigm. Randomization gave unbiased comparisons and a way to perform hypothesis testing without model assumptions. To preserve the benefits of randomization, a type of analysis called intent-to-treat analysis is appropriate. Needed development has occurred and is occurring in refining ethical standards, monitoring trials of serious irreversible endpoints while preserving type-I error, and instituting independent data- and safety-monitoring boards. Recent methodology has also been concerned with the appropriateness of using surrogate endpoints. A current area of debate is the appropriateness of using Bayesian statistical methods in this context.
Cisplatin Preferentially Binds Mitochondrial DNA and Voltage-Dependent Anion Channel Protein in the Mitochondrial Membrane of Head and Neck Squamous Cell Carcinoma: Possible Role in Apoptosis
Authors: Zejia Yang, Lisa M. Schumaker, Merrill J. Egorin, Eleanor G. Zuhowski, Zhongmin Guo, Kevin J. Cullen
Journal: Clinical Cancer Research (2006)

Cisplatin adducts to nuclear DNA (nDNA) are felt to be the molecular lesions that trigger apoptosis, but the mechanism linking nDNA adduct formation and cell death is unclear. Some literature in the last decade has suggested a possible direct effect of cisplatin on mitochondria independent of nDNA interaction. In this study, we define separately the sequelae of cisplatin interactions with nDNA and with mitochondria in head and neck squamous cell carcinoma (HNSCC) cell lines.Cisplatin binding to mitochondrial DNA (mtDNA) and proteins was analyzed by atomic absorption spectroscopy and other methods.Following 1 hour of exposure to cisplatin, platinum adducts to mtDNA were 300- to 500-fold more abundant than adducts to nDNA; these differences were not due to differences in rates of adduct repair. Whereas HNSCC cell cytoplasts free of nDNA retained the same dose-dependent cisplatin sensitivity as parental cells, HNSCC rho(0) cells free of mtDNA were 4- to 5-fold more resistant to cisplatin than parental cells. Isolated mitochondria released cytochrome c within minutes of exposure to cisplatin, and ultrastructural analysis of intact HNSCC cells by electron microscopy showed marked mitochondrial disruption after 4 hours of cisplatin treatment, whereas the nucleus and other cellular structures remain intact. The very prompt release of cytochrome c from isolated mitochondria implies that apoptosis does not require alteration in mitochondrial gene transcription. Further, cisplatin binds preferentially to mitochondrial membrane proteins, particularly the voltage-dependent anion channel.Cisplatin binding to nDNA is not necessary for induction of apoptosis in HNSCC, which can result from direct action of cisplatin on mitochondria.
Temporal Arteritis
Authors: David B Hellmann
Journal: JAMA (2002)

Temporal arteritis, the most common form of systemic vasculitis in adults, is a panarteritis that chiefly involves the extracranial branches of the carotid artery. The condition is illustrated in this article by the case of a 79-year-old woman with a dry cough, toothache, tongue infarction, and vision loss. The mean age of onset is 72 years and the disease rarely occurs in persons younger than 50 years. The most common presenting manifestations are headache, jaw claudication, polymyalgia rheumatica, and visual symptoms. Eighty-nine percent of patients have an erythrocyte sedimentation rate greater than 50 mm/h. However, about 40% of patients present with atypical manifestations, including fever of unknown origin, respiratory tract symptoms (especially dry cough), and large artery involvement. Familiarity with such unusual manifestations of temporal arteritis facilitates early diagnosis and treatment, thereby reducing the risk of vision loss.
Gene expression profiling of normal and malignant CD34-derived megakaryocytic cells
Authors: Elena Tenedini, Maria Elena Fagioli, Nicola Vianelli, Pier Luigi Tazzari, Francesca Ricci, Enrico Tagliafico, Paolo Ricci, Luigi Gugliotta, Giovanni Martinelli, Sante Tura, Michele Baccarani, Sergio Ferrari, Lucia Catani
Journal: Blood (2004)
Genome-Wide Promoter Analysis Uncovers Portions of the Cancer Methylome
Authors: Mohammad Obaidul Hoque, Myoung Sook Kim, Kimberly Laskie Ostrow, Junwei Liu, G. Bea A. Wisman, Hannah Lui Park, Maria Luana Poeta, Carmen Jeronimo, Rui Henrique, Ágnes Lendvai, Ed Schuuring, Shahnaz Begum, Eli Rosenbaum, Maté Ongenaert, Keishi Yamashita, Joseph Califano, William Westra, Ate G.J. van der Zee, Wim Van Criekinge, David Sidransky
Journal: Cancer Research (2008)

Abstract DNA methylation has a role in mediating epigenetic silencing of CpG island genes in cancer and other diseases. Identification of all gene promoters methylated in cancer cells “the cancer methylome” would greatly advance our understanding of gene regulatory networks in tumorigenesis. We previously described a new method of identifying methylated tumor suppressor genes based on pharmacologic unmasking of the promoter region and detection of re-expression on microarray analysis. In this study, we modified and greatly improved the selection of candidates based on new promoter structure algorithm and microarray data generated from 20 cancer cell lines of 5 major cancer types. We identified a set of 200 candidate genes that cluster throughout the genome of which 25 were previously reported as harboring cancer-specific promoter methylation. The remaining 175 genes were tested for promoter methylation by bisulfite sequencing or methylation-specific PCR (MSP). Eighty-two of 175 (47%) genes were found to be methylated in cell lines, and 53 of these 82 genes (65%) were methylated in primary tumor tissues. From these 53 genes, cancer-specific methylation was identified in 28 genes (28 of 53; 53%). Furthermore, we tested 8 of the 28 newly identified cancer-specific methylated genes with quantitative MSP in a panel of 300 primary tumors representing 13 types of cancer. We found cancer-specific methylation of at least one gene with high frequency in all cancer types. Identification of a large number of genes with cancer-specific methylation provides new targets for diagnostic and therapeutic intervention, and opens fertile avenues for basic research in tumor biology. [Cancer Res 2008;68(8):2661–70]
Loss of E-Cadherin Promotes Ovarian Cancer Metastasis via α5-Integrin, which Is a Therapeutic Target
Authors: Kenjiro Sawada, Anirban K. Mitra, A. Reza Radjabi, Vinay Bhaskar, Emily O. Kistner, Maria Tretiakova, Sujatha Jagadeeswaran, Anthony Montag, Amy Becker, Hilary A. Kenny, Marcus E. Peter, Vanitha Ramakrishnan, S. Diane Yamada, Ernst Lengyel
Journal: Cancer Research (2008)

E-cadherin loss is frequently associated with ovarian cancer metastasis. Given that adhesion to the abdominal peritoneum is the first step in ovarian cancer dissemination, we reasoned that down-regulation of E-cadherin would affect expression of cell matrix adhesion receptors. We show here that inhibition of E-cadherin in ovarian cancer cells causes up-regulation of alpha(5)-integrin protein expression and transcription. When E-cadherin was blocked, RMUG-S ovarian cancer cells were able to attach and invade more efficiently. This greater efficiency could, in turn, be inhibited both in vitro and in vivo with an alpha(5)beta(1)-integrin-blocking antibody. When E-cadherin is silenced, alpha(5)-integrin is up-regulated through activation of an epidermal growth factor receptor/FAK/Erk1-mitogen-activated protein kinase-dependent signaling pathway and not through the canonical E-cadherin/beta-catenin signaling pathway. In SKOV-3ip1 ovarian cancer xenografts, which express high levels of alpha(5)-integrin, i.p. treatment with an alpha(5)beta(1)-integrin antibody significantly reduced tumor burden, ascites, and number of metastasis and increased survival by an average of 12 days when compared with IgG treatment (P < 0.0005). alpha(5)-Integrin expression was detected by immunohistochemistry in 107 advanced stage ovarian cancers using a tissue microarray annotated with disease-specific patient follow-up. Ten of 107 tissues (9%) had alpha(5)-integrin overexpression, and 39% had some level of alpha(5)-integrin expression. The median survival for patients with high alpha(5)-integrin levels was 26 months versus 35 months for those with low integrin expression (P < 0.05). Taken together, we have identified alpha(5)-integrin up-regulation as a molecular mechanism by which E-cadherin loss promotes tumor progression, providing an explanation for how E-cadherin loss increases metastasis. Targeting this integrin could be a promising therapy for a subset of ovarian cancer patients.
Six-Minute Walk, Maximal Exercise Tests
Authors: Tam Eaton, Pam Young, David Milne, Athol U. Wells
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Resting pulmonary function and exercise variables are widely used to stage and monitor idiopathic interstitial pneumonia (IIP). However, the variability of exercise data (maximal exercise and the 6-minute walk test) has not been evaluated definitively. We have prospectively quantified the reproducibility of resting and exercise functional data in fibrotic IIP (idiopathic pulmonary fibrosis, fibrotic nonspecific interstitial pneumonia) and have evaluated interrelationships between variables. Thirty consecutive patients with fibrotic IIP underwent serial resting pulmonary function tests, 6-minute walk (n = 29), and maximal exercise (n = 24) at an interval of 1 week, with all testing performed in accordance with American Thoracic Society standards. Within-subject reproducibility was excellent for 6-minute walk distance (SD/mean = 4.2%) and clinically acceptable for resting pulmonary function indices and VO2max on maximal exercise testing. However, the amplitude of oxygen desaturation at the end of exercise was poorly reproducible in both 6-minute walk and maximal exercise testing (SD/mean > 25%). There was a highly significant relationship between VO2max on maximal exercise testing and 6-minute walk distance (rs = 0.78, p < 0.0001). In fibrotic IIP, the excellent reproducibility of the 6-minute walk distance is a major advantage in routine staging and monitoring, whereas maximal exercise variables are poorly reproducible.
Malignant lymphomas in coeliac disease: evidence of increased risks for lymphoma types other than enteropathy-type T cell lymphoma
Authors: K E Smedby
Journal: Gut (2004)

<b>Background:</b> Numerous studies have reported on the association between coeliac disease and the otherwise uncommon enteropathy-type T cell lymphoma (ETTL). A systematic risk assessment of more prevalent lymphoma entities, such as B cell and non-intestinal lymphomas, in coeliac disease has not been performed. <b>Aims:</b> In light of the increasing number of patients diagnosed with coeliac disease and the unknown aetiology of malignant lymphomas, we aimed to estimate the distribution and risk of lymphoma subtypes in coeliac disease. <b>Methods:</b> We reviewed and reclassified 56 cases of incident malignant lymphomas occurring in a Swedish population based cohort of 11 650 patients hospitalised with coeliac disease. The observed numbers of lymphoma subtypes were compared with those expected in the Swedish population. <b>Results:</b> The majority (n = 32, 57%) of lymphomas in the cohort were <i>not</i> intestinal T cell lymphomas. Significantly increased risks were observed for B cell non-Hodgkin lymphoma (NHL) (standardised incidence ratio (SIR) 2.2 (95% confidence interval (CI) 1.2–3.6); 11 non-intestinal and five intestinal) and for lymphomas of non-intestinal origin (SIR 3.6 (95% CI 2.3–5.2), 11 B and 14 T cell). Furthermore, 44% of patients with B cell NHL had a history of other autoimmune/inflammatory diseases. The relative risks for T cell NHL (SIR 51 (95% CI 35–68); n = 37) and for primary gastrointestinal lymphomas (SIR 24 (95% CI 16–34); five B and 25 T cell) were markedly increased, as anticipated. <b>Conclusion:</b> Most lymphomas complicating coeliac disease are indeed related to the disease and are not of the ETTL-type. There was a remarkable aggregation of autoimmune/inflammatory disorders, female sex, coeliac disease, and B cell lymphoma.
Development of stem cell-based therapy for Parkinson’s disease
Authors: Fabin Han, Deborah Baremberg, Junyu Gao, Jing Duan, Xianjie Lu, Nan Zhang, Qingfa Chen
Journal: Translational Neurodegeneration (2015)

Parkinson's disease (PD) is one of the most common neurodegenerative disorders of aging, characterized by the degeneration of dopamine neurons (DA neurons) in the substantial nigra, leading to the advent of both motor symptoms and non-motor symptoms. Current treatments include electrical stimulation of the affected brain areas and dopamine replacement therapy. Even though both categories are effective in treating PD patients, the disease progression cannot be stopped. The research advance into cell therapies provides exciting potential for the treatment of PD. Current cell sources include neural stem cells (NSCs) from fetal brain tissues, human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs) and directly induced dopamine neurons (iDA neurons). Here, we evaluate the research progress in different cell sources with a focus on using iPSCs as a valuable source and propose key challenges for developing cells suitable for large-scale clinical applications in the treatment of PD.