tbuckley/cabot-search huggingface dataset:
Regulatory T-Cell–Mediated Attenuation of T-Cell Responses to the NY-ESO-1 ISCOMATRIX Vaccine in Patients with Advanced Malignant Melanoma
Authors: Theo Nicholaou, Lisa M. Ebert, Ian D. Davis, Grant A. McArthur, Heather Jackson, Nektaria Dimopoulos, Bee Tan, Eugene Maraskovsky, Lena Miloradovic, Wendie Hopkins, Linda Pan, Ralph Venhaus, Eric W. Hoffman, Weisan Chen, Jonathan Cebon
Journal: Clinical Cancer Research (2009)

Abstract Purpose: NY-ESO-1 is a highly immunogenic antigen expressed in a variety of malignancies, making it an excellent target for cancer vaccination. We recently developed a vaccine consisting of full-length recombinant NY-ESO-1 protein formulated with ISCOMATRIX adjuvant, which generated strong humoral and T-cell–mediated immune responses and seemed to reduce the risk of disease relapse in patients with fully resected melanoma. This study examines the clinical and immunologic efficacy of the same vaccine in patients with advanced metastatic melanoma. Experimental Design: Delayed-type hypersensitivity responses, circulating NY-ESO-1–specific CD4+ and CD8+ T cells, and proportions of regulatory T cells (Treg) were assessed in patients. Results: In contrast to patients with minimal residual disease, advanced melanoma patients showed no clinical responses to vaccination. Although strong antibody responses were mounted, the generation of delayed-type hypersensitivity responses was significantly impaired. The proportion of patients with circulating NY-ESO-1–specific CD4+ T cells was also reduced, and although many patients had CD8+ T cells specific to a broad range of NY-ESO-1 epitopes, the majority of these responses were preexisting. Tregs were enumerated in the blood by flow cytometric detection of cells with a CD4+CD25+FoxP3+ and CD4+CD25+CD127− phenotype. Patients with advanced melanoma had a significantly higher proportion of circulating Treg compared with those with minimal residual disease. Conclusions: Our results point to a tumor-induced systemic immune suppression, showing a clear association between the stage of melanoma progression, the number of Treg in the blood, and the clinical and immunologic efficacy of the NY-ESO-1 ISCOMATRIX cancer vaccine.
DEPLETION OF T LYMPHOCYTES IN DONOR MARROW PREVENTS SIGNIFICANT GRAFT-VERSUS-HOST DISEASE IN MATCHED ALLOGENEIC LEUKAEMIC MARROW TRANSPLANT RECIPIENTS
Authors: H.G. Prentice, G. Janossy, L. Price-Jones, L.K. Trejdosiewicz, D. Panjwani, S. Graphakos, K. Ivory, H.A. Blacklock, M.J.M.L. Gilmore, N. Tidman, D.B.L. Skeggs, S. Ball, J. Patterson, A.V. Hoffbrand
Journal: The Lancet (1984)
Fluorine 18 Bone Scans in the Detection of Early Metastatic Bone Tumors
Authors: G. Bruce Hopkins
Journal: JAMA (1972)

Fluorine 18 bone scans are valuable adjuvants in the detection of early metastatic bone disease. In 104 patients with metastatic bone tumors, the scans and roentgenograms correlated in 75% of cases. Where discrepancies occurred, the scans were correct four times as often as the roentgenograms. Osteoblastic lesions were readily defined whereas osteolytic lesions yielded negative scans in four patients with bone metastases. Fluorine 18 scintiphotos also proved more sensitive than serum acid or alkaline phosphatase determinations.
Antiangiogenic Agents Can Increase Lymphocyte Infiltration into Tumor and Enhance the Effectiveness of Adoptive Immunotherapy of Cancer
Authors: Rajeev K. Shrimali, Zhiya Yu, Marc R. Theoret, Dhanalakshmi Chinnasamy, Nicholas P. Restifo, Steven A. Rosenberg
Journal: Cancer Research (2010)

Abstract Adoptive cell transfer (ACT)–based immunotherapies can mediate objective cancer regression in animal models and in up to 70% of patients with metastatic melanoma; however, it remains unclear whether the tumor vasculature impedes the egress of tumor-specific T cells, thus hindering this immunotherapy. Disruption of the proangiogenic interaction of vascular endothelial growth factor (VEGF) with its receptor (VEGFR-2) has been reported to “normalize” tumor vasculature, enhancing the efficacy of chemotherapeutic agents by increasing their delivery to the tumor intersitium. We thus sought to determine whether disrupting VEGF/VEGFR-2 signaling could enhance the effectiveness of ACT in a murine cancer model. The administration of an antibody against mouse VEGF synergized with ACT to enhance inhibition of established, vascularized, B16 melanoma (P = 0.009) and improve survival (P = 0.003). Additive effects of an antibody against VEGFR-2 in conjunction with ACT were seen in this model (P = 0.013). Anti-VEGF, but not anti–VEGFR-2, antibody significantly increased infiltration of transferred cells into the tumor. Thus, normalization of tumor vasculature through disruption of the VEGF/VEGFR-2 axis can increase extravasation of adoptively transferred T cells into the tumor and improve ACT-based immunotherapy. These studies provide a rationale for the exploration of combining antiangiogenic agents with ACT for the treatment of patients with cancer. Cancer Res; 70(15); 6171–80. ©2010 AACR.
Paralogy and Orthology in the Malvaceae rpb2 Gene Family: Investigation of Gene Duplication in Hibiscus
Authors: B. E. Pfeil
Journal: Molecular Biology and Evolution (2004)

A sample of the second largest subunit of low-copy nuclear RNA polymerase II (rpb2) sequences from Malvaceae subfamily Malvoideae suggests that rpb2 has been duplicated early in the subfamily's history. Hibiscus and related taxa possess two rpb2 genes, both of which produce congruent phylogenetic patterns that are largely concordant with cpDNA topologies. No evidence of functional divergence or disruption was found among duplicated copies, suggesting that long-term maintenance of duplicated copies of rpb2 is usual in this lineage. Therefore, this gene may be suitable for the potential diagnosis of relatively old polyploid events. One probable pseudogene was found in Radyera farragei and a single chimeric sequence was recovered from Howittia trilocularis, suggesting that the rpb2 locus is not as prone to evolutionary processes that can confound phylogenetic inferences based on nDNA sequences. The pattern of relationships among rpb2 sequences, coupled with chromosome number information and Southern hybridization data, suggests that an early polyploid event was not the cause of the duplication, despite independent evidence of paleopolyploidy in some members of Malvoideae. Rpb2 exons and introns together are suitable for phylogenetic analysis, producing well-resolved and well-supported results that were robust to model permutation and congruent with previous studies of subfamily Malvoideae using cpDNA characters.
Case-control study of risk factors for human infection with influenza A(H7N9) virus in Jiangsu Province, China, 2013
Authors: J Ai, Y Huang, K Xu, D Ren, X Qi, H Ji, A Ge, Q Dai, J Li, C Bao, F Tang, G Shi, T Shen, Y Zhu, M Zhou, H Wang
Journal: Eurosurveillance (2013)

We describe a case-control study performed in Jiangsu, China, to evaluate risk factors for human infection with novel avian influenza A(H7N9) virus. Twenty-five cases and 93 controls matched by age, sex, and location were included in the study. Direct contact with poultry or birds in the two weeks before illness onset, chronic medical conditions (hypertension excluded), and environment-related exposures were significantly associated with A(H7N9) infection.
Cognitive Function Across Manic or Hypomanic, Depressed, and Euthymic States in Bipolar Disorder
Authors: Anabel Martínez-Arán, Eduard Vieta, María Reinares, Francesc Colom, Carla Torrent, Jose Sánchez-Moreno, Antonio Benabarre, José Manuel Goikolea, Mercè Comes, Manel Salamero
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The study aims were to address neuropsychological functioning across different states of bipolar illness and to determine relationships among clinical features, neuropsychological performance, and psychosocial functioning. METHOD: Several domains of cognitive function were examined in 30 depressed bipolar patients (DSM-IV criteria for major depression, Hamilton Depression Rating Scale score ≥17), 34 manic or hypomanic bipolar patients (DSM-IV criteria for manic or hypomanic episode, Young Mania Rating Scale score ≥12), and 44 euthymic bipolar patients (6 months of remission, Hamilton depression scale score ≤8, and Young Mania Rating Scale score ≤6). The comparison group consisted of 30 healthy subjects without history of neurological or psychiatric disorders. A neuropsychological battery assessed executive function, attention, and verbal and visual memory. RESULTS: The three groups showed cognitive dysfunction in verbal memory and frontal executive tasks in relation to the comparison group. Low neuropsychological performance was associated with poor functional outcome. Impairment of verbal memory was related to the duration of illness and the numbers of previous manic episodes, hospitalizations, and suicide attempts. CONCLUSIONS: A poorer performance was observed in all bipolar groups regarding executive function and verbal memory in relation to the healthy comparison subjects. These cognitive difficulties, especially related to verbal memory, may help explain the impairment regarding daily functioning, even during remission. Further studies should focus on testing, whether optimizing prophylactic pharmacological treatment and psychoeducation might reduce cognitive impairment, and whether bipolar patients would benefit from neuropsychological rehabilitation in order to reduce the impact of cognitive impairment in their overall functioning.
DIETARY n-6 AND n-3 FATTY ACID BALANCE AND CARDIOVASCULAR HEALTH
Authors: Vasuki Wijendran, K.C. Hayes
Journal: Annual Review of Nutrition (2004)

Epidemiological and clinical studies have established that the n-6 fatty acid, linoleic acid (LA), and the n-3 fatty acids, linolenic acid (LNA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) collectively protect against coronary heart disease (CHD). LA is the major dietary fatty acid regulating low-density lipoprotein (LDL)-C metabolism by downregulating LDL-C production and enhancing its clearance. Further, the available mass of LA is a critical factor determining the hyperlipemic effects of other dietary fat components, such as saturated and trans fatty acids, as well as cholesterol. By contrast, n-3 fatty acids, especially EPA and DHA, are potent antiarryhthmic agents. EPA and DHA also improve vascular endothelial function and help lower blood pressure, platelet sensitivity, and the serum triglyceride level. The distinct functions of these two families make the balance between dietary n-6 and n-3 fatty acids an important consideration influencing cardiovascular health. Based on published literature describing practical dietary intakes, we suggest that consumption of ~6% en LA, 0.75% en LNA, and 0.25% en EPA + DHA represents adequate and achievable intakes for most healthy adults. This corresponds to an n-6/n-3 ratio of ~6:1. However, the absolute mass of essential fatty acids consumed, rather than their n-6/n-3 ratio, should be the first consideration when contemplating lifelong dietary habits affecting cardiovascular benefit from their intake.
Value of the 24 hour intraoesophageal pH monitoring in children.
Authors: S Cucchiara, A Staiano, L Gobio Casali, A Boccieri, F M Paone
Journal: Gut (1990)

Twenty four hour oesophageal intraluminal pH probe studies were performed in 114 children (range age: one month-12 years) referred for symptoms or signs compatible with gastroesophageal reflux. Forty five patients had reflux disease alone, 69 had evidence of oesophagitis which was assessed endoscopically and histologically. Recordings were also performed in 63 control patients. The occurrence of reflux was analysed for the total study period and particularly while awake, asleep, fasting, and during postcibal periods. Oesophageal acid exposure time and the number of reflux episodes lasting greater than five minutes during the total study period provided the best discrimination between patients and controls; however, 20% and 30% of all reflux patients had both normal (with 2 SD of control) acid exposure time and number of long lasting reflux episodes, respectively. Patients with oesophagitis had significantly more acid reflux than those with simple uncomplicated disease during postcibal, fasting, awake periods, but not during sleep; however, increasing severity of oesophagitis was not associated with increasing acid exposure. The ability of the intraluminal oesophageal pH test to discriminate patients with various degrees of reflux disease decreased if only postprandial pH variables were taken into account. We conclude that: (1) the 24 hour intraoesophageal pH monitoring may present false negative results that limit overall sensitivity of the test; (2) the presence of oesophagitis does not seem to be associated with increased oesophageal acid exposure during sleep; (3) limiting the pH recording to postprandial periods reduces the discriminatory power of the test.
Ultrasound Increases Nanoparticle Delivery by Reducing Intratumoral Pressure and Increasing Transport in Epithelial and Epithelial–Mesenchymal Transition Tumors
Authors: Katherine D. Watson, Chun-Yen Lai, Shengping Qin, Dustin E. Kruse, Yueh-Chen Lin, Jai Woong Seo, Robert D. Cardiff, Lisa M. Mahakian, Julie Beegle, Elizabeth S. Ingham, Fitz-Roy Curry, Rolf K. Reed, Katherine W. Ferrara
Journal: Cancer Research (2012)

Abstract Acquisition of the epithelial–mesenchymal transition (EMT) tumor phenotype is associated with impaired chemotherapeutic delivery and a poor prognosis. In this study, we investigated the application of therapeutic ultrasound methods available in the clinic to increase nanotherapeutic particle accumulation in epithelial and EMT tumors by labeling particles with a positron emission tomography tracer. Epithelial tumors were highly vascularized with tight cell–cell junctions, compared with EMT tumors where cells displayed an irregular, elongated shape with loosened cell–cell adhesions and a reduction in E-cadherin and cytokeratins 8/18 and 19. Without ultrasound, the accumulation of liposomal nanoparticles administered to tumors in vivo was approximately 1.5 times greater in epithelial tumors than EMT tumors. When ultrasound was applied, both nanoaccumulation and apparent tumor permeability were increased in both settings. Notably, ultrasound effects differed with thermal and mechanical indices, such that increasing the thermal ultrasound dose increased nanoaccumulation in EMT tumors. Taken together, our results illustrate how ultrasound can be used to enhance nanoparticle accumulation in tumors by reducing their intratumoral pressure and increasing their vascular permeability. Cancer Res; 72(6); 1485–93. ©2012 AACR.
A thymic stromal lymphopoietin gene variant is associated with asthma and airway hyperresponsiveness
Authors: Jian-Qing He, Teal S. Hallstrand, Darryl Knight, Moira Chan-Yeung, Andrew Sandford, Ben Tripp, David Zamar, Yohan Bossé, Anita L. Kozyrskyj, Alan James, Catherine Laprise, Denise Daley
Journal: Journal of Allergy and Clinical Immunology (2009)
IRON, COPPER, ZINC, AND MANGANESE IN MILK
Authors: Bo Lönnerdal, Carl L. Keen, Lucille S. Hurley
Journal: Annual Review of Nutrition (1981)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
Update on Medical Practices That Should Be Questioned in 2015
Authors: Daniel J. Morgan, Sanket S. Dhruva, Scott M. Wright, Deborah Korenstein
Journal: JAMA Internal Medicine (2015)

Overuse of medical care, consisting primarily of overdiagnosis and overtreatment, is a common clinical problem.To identify and highlight articles published in 2014 that are most likely to influence medical overuse, organized into the categories of overdiagnosis, overtreatment, and methods to avoid overuse, and to review these articles and interpret them for their importance to clinical medicine.A structured review of English-language articles in PubMed published in 2014 and a review of tables of contents of relevant journals to identify potential articles that related to medical overuse in adults.We reviewed 910 articles, of which 440 addressed medical overuse. Of these, 104 were deemed most relevant based on the presentation of original data, quality of methods, magnitude of clinical effect, and number of patients potentially affected. The 10 most influential articles were selected by author consensus using the same criteria. Findings included lack of benefit for screening pelvic examinations (positive predictive value <5%), carotid artery screening (no reduction in stroke), and thyroid ultrasonography (15-fold increase in thyroid cancer). The harms of cancer screening included unnecessary surgery and complications. Head computed tomography was an overused diagnostic test (clinically significant findings in 4% [7 of 172] of head computed tomographic scans). Overtreatment included acetaminophen for low back pain, perioperative aspirin use, medications to increase high-density lipoprotein cholesterol level, stenting for renal artery stenosis, and prolonged opioid use after surgery (use >90 days in 3% [1229 of 39,140] of patients).Many common medical practices should be reconsidered. It is anticipated that our review will promote reflection on these 10 articles and lead to questioning of other non-evidence-based practices.
Comparison of a limited computerized diagnostic system (ResCare Autoset) with polysomnography in the diagnosis of obstructive sleep apnoea syndrome
Authors: JL Kiely, C Delahunty, S Matthews, WT McNicholas
Journal: European Respiratory Journal (1996)

The increasing numbers of patients referred for evaluation of suspected obstructive sleep apnoea (OSA) places a growing burden on available sleep laboratory resources. A number of limited diagnostic systems have been developed in an effort to cope with this clinical problem. In this study, the diagnostic capabilities of one limited diagnostic system (ResCare Autoset) were compared with full polysomnography (PSG), using the Oxford SAC computerized system. Thirty six patients with suspected OSA had simultaneous studies performed both with the Autoset and Oxford PSG systems. The apnoea plus hypopnoea index (AHI) (events x h(-1)) scored by the Autoset system was compared with the AHI scored from the PSG raw tracings by an experienced sleep technician. There were highly significant correlations between the Autoset AHI and the AHI scored by the manual PSG scoring method (r=0.92; p&lt;0.001). The positive predictive value for diagnosis of OSA for the Autoset was 86% when compared with manual PSG scoring, based on an AHI threshold for OSA of 15 events x h(-1). However, the agreement between Autoset and PSG was poor in severe cases of OSA, although not sufficiently so as to result in mistaken diagnosis in any of these cases. We conclude that the Autoset system is a sensitive and easy to use system, which facilitates screening for obstructive sleep apnoea with a reasonable degree of accuracy.
GLUCOCORTICOID AND MINERALOCORTICOID RECEPTORS: Biology and Clinical Relevance
Authors: John W. Funder, MD
Journal: Annual Review of Medicine (1997)

▪ Abstract Mineralocorticoid and glucocorticoid receptors act as homodimers via canonical pentadecamer hormone response elements to regulate transcription. Glucocorticoid, but as yet not mineralocorticoid, receptors have been shown also to modulate AP-1- and NFκB-induced transcription by direct protein-protein interactions. The role of 11β-hydroxysteroid dehydrogenase in conferring aldosterone specificity on epithelial mineralocorticoid receptors has been proven by the demonstration of sequence mutations in all cases of apparent mineralocorticoid excess examined to date. The autosomal form of aldosterone resistance (pseudohypoaldosteronism) has been shown to reflect loss-of-function mutations in epithelial sodium channel subunit sequence. (Patho)physiological roles for aldosterone and glucocorticoid membrane receptors, and for the recently described nuclear receptors for 11–ketosteroids in 11β–hydroxysteroid dehydrogenase–protected epithelia, remain to be established.
Classifying leukemia types with chromatin conformation data
Authors: Mathieu Rousseau, Maria A Ferraiuolo, Jennifer L Crutchley, Xue Qing David Wang, Hisashi Miura, Mathieu Blanchette, Josée Dostie
Journal: Genome biology (2014)

Although genetic or epigenetic alterations have been shown to affect the three-dimensional organization of genomes, the utility of chromatin conformation in the classification of human disease has never been addressed.Here, we explore whether chromatin conformation can be used to classify human leukemia. We map the conformation of the HOXA gene cluster in a panel of cell lines with 5C chromosome conformation capture technology, and use the data to train and test a support vector machine classifier named 3D-SP. We show that 3D-SP is able to accurately distinguish leukemias expressing MLL-fusion proteins from those expressing only wild-type MLL, and that it can also classify leukemia subtypes according to MLL fusion partner, based solely on 5C data.Our study provides the first proof-of-principle demonstration that chromatin conformation contains the information value necessary for classification of leukemia subtypes.
Change in Basal Ganglia Volume Over 2 Years in Patients With Schizophrenia: Typical Versus Atypical Neuroleptics
Authors: Patricia Westmoreland Corson, Peg Nopoulos, Del D. Miller, Stephan Arndt, Nancy C. Andreasen
Journal: American Journal of Psychiatry (1999)

For many years, it has been assumed that medications affect brain chemistry and physiology but not structure. Recent reports suggest that neuroleptic medication changes basal ganglia volume. To explore this possibility, the authors assessed for basal ganglia volume change in individuals who had their basal ganglia structures delineated and measured on magnetic resonance scans at the beginning and end of a 2-year period and who received neuroleptic medication during this time.The basal ganglia volumes of 23 male patients with schizophrenia spectrum disorders were measured from manual traces delineating the caudate and lenticular nucleus on magnetic resonance images at admission and 2 years later. Patients' neuroleptic exposure was calculated over the 2 years by using a dose-year formula.During the 2-year period, mean basal ganglia volume of patients receiving predominantly typical neuroleptics increased, while the opposite was observed for patients receiving mostly atypical neuroleptics. Correlation analysis for the entire group showed a positive relationship between the 2-year exposure to typical neuroleptic medication and change in basal ganglia volume and the reverse for exposure to atypical neuroleptics.In this group, basal ganglia volume increased following exposure to typical neuroleptics and decreased following exposure to atypical neuroleptics.
Chronic graft-versus-host disease after allogeneic blood stem cell transplantation: long-term results of a randomized study
Authors: Mohamad Mohty, Mathieu Kuentz, Mauricette Michallet, Jean-Henri Bourhis, Noël Milpied, Laurent Sutton, Jean-Pierre Jouet, Michel Attal, Pierre Bordigoni, Jean-Yves Cahn, Jean-Michel Boiron, Didier Blaise
Journal: Blood (2002)