tbuckley/cabot-search huggingface dataset:
Are dust mite allergens more abundant and/or more stable than other Dermatophagoides pteronyssinus proteins?
Authors: Ryenne N. Ogburn, Thomas A. Randall, Yingrong Xu, Julia H. Roberts, Betelihem Mebrahtu, Jaret M. Karnuta, S. Dean Rider, Grace E. Kissling, Robert E. London, Anna Pomés, Larry Arlian, Michael C. Fitzgerald, Geoffrey A. Mueller
Journal: Journal of Allergy and Clinical Immunology (2016)
Cost Effectiveness of Clinical Diagnosis, Venography, and Noninvasive Testing in Patients with Symptomatic Deep-Vein Thrombosis
Authors: Russell Hull, Jack Hirsh, David L. Sackett, Greg Stoddart
Journal: New England Journal of Medicine (1981)

Until the past decade, physicians were content to base therapeutic decisions on the clinical diagnosis of deep-vein thrombosis. Subsequently, numerous studies demonstrated that clinical diagnosis of this condition is nonspecific. Although many now use objective methods to diagnose venous thrombosis, their relative cost and effectiveness have not been adequately studied. We performed a cost-effectiveness analysis of 516 patients with clinically suspected venous thrombosis who were evaluated by clinical diagnosis, venography, and the less invasive combination of impedance plethysmography and leg scanning. We used this analysis to rank these alternative approaches in terms of both cost and effectiveness. The results indicate that clinical diagnosis is cost ineffective. Venography is cost effective — more so when applied as an outpatient investigation. Impedance plethysmography plus leg scanning is a practical, less invasive alternative to outpatient venography. The cost of inpatient diagnosis is likely to remain the major cost; thus, emphasis should be placed on outpatient diagnostic procedures. (N Engl J Med. 1981; 304:1561–7.)
Alum-Containing Vaccines Increase Total and Food Allergen-Specific IgE, and Cow's Milk Oral Desensitization Increases Bosd4 IgG4 While Peanut Avoidance Increases Arah2 IgE: The Complexity of Today's Child with Food Allergy
Authors: Alice E.W. Hoyt, Alexander J. Schuyler, Peter W. Heymann, Thomas A.E. Platts-Mills, Scott P. Commins
Journal: Journal of Allergy and Clinical Immunology (2016)
Nontraumatic Necrosis of Bone (Osteonecrosis)
Authors: Jane F. Desforges, Henry J. Mankin
Journal: New England Journal of Medicine (1992)

ALTHOUGH osteonecrosis, the in situ death of a segment of bone, has been recognized since the early part of this century, it still presents challenges to the biologist, the physician in the applied sciences, and especially the clinician. Since the first descriptions,1 2 3 we have learned what to call it; at least for lesions of the hip, how to classify it4 , 5; and through advanced radiologic imaging, how to diagnose it with certainty.6 , 7 The pathogenesis of osteonecrosis has been partially elucidated,8 , 9 but its natural history and the effective management of it remain in some ways as confusing and shrouded in mystery . . .
Androgen regulated immunosuppression in prostate cancer through arginase expression
Authors: P. O. Gannon, J. Godin-Ethier, B. Peant, M. Aversa, M. Alam Fahmy, R. Lapointe, A. M. Mes-Masson, F. Saad
Journal: Journal of Clinical Oncology (2008)

5150 Background: The significant immunological boost following androgen depletion therapy (ADT) illustrates the immunosuppressive potential of androgens in prostate cancer. As the expression of arginase II (ArgII) appears to be one possible mode of immunosuppression in prostate cancer, it is of interest to determine whether the expression of ArgII in prostate cancer cells is regulated by androgens. Our objectives are to evaluate the in vitro and in vivo expression of ArgII in prostate cancer cell lines and primary tumors. Methods: The androgen-regulated expression of ArgII was evaluated in vivo on a tissue micro-array containing cores from a cohort of 40 control patients (radical prostatectomy only) and 36 ADTx patients (ADT prior to radical prostatectomy). Two independent observers evaluated data from the immunohistochemistry staining against ArgII. The in vitro expression was evaluated in LNCaP cells stimulated for 72 hours with 10nM of R1881. PBMCs from healthy donors were stimulated by 0.250ng/ml of OKT3 in the presence of conditioned media from LNCaP expressing a siRNA against ArgII. PBMCs activation was monitored by ELISA against IFNγ. Results: By immunohistochemistry, in vivo expression of ArgII in ADTx patients was 2x lower in normal adjacent tissues (p6x more ArgII than control LNCaP (p2.5x in the presence of R1881. These results suggest that the presence of androgens favors the expression of ArgII both in vitro and in vivo. PBMCs activated by OTK3 for 24 hours in the presence of conditioned media of LNCaP + SiArgII demonstrated that the absence of ArgII was associated with increased IFNγ secretion: 1,681pg/ml with LNCaP + SiCtrl vs 537pg/ml with LNCaP + SiArgII (p<0.05, Mann-U, n=4). Conclusions: Our results demonstrate that the pro-inflammatory boost following ADT is associated with a lower expression of ArgII. Moreover, our in vitro data suggest an androgen regulation of ArgII expression. Finally, conditioned media from LNCaP transfected with a siRNA against ArgII had improved immunostimulatory potential leading to an increased activation of PBMCs. Our data supports the notion that, in the presence of androgens, prostate cancer cells are directly involved in the development of an immunosuppressive tumor environment through the up-regulation of ArgII. No significant financial relationships to disclose.
Extraction of Tumor-Specific Antigen From Cells and Plasma Membranes of Line-10 Hepatoma
Authors: Edward J. Leonard, Arleen K. Richardson, Alison S. Hardy, Herbert J. Rapp
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Extraction of Tumor-Specific Antigen From Cells and Plasma Membranes of Line-10 Hepatoma Get access Edward J. Leonard, Edward J. Leonard Search for other works by this author on: Oxford Academic PubMed Google Scholar Arleen K. Richardson, Arleen K. Richardson Search for other works by this author on: Oxford Academic PubMed Google Scholar Alison S. Hardy, Alison S. Hardy Search for other works by this author on: Oxford Academic PubMed Google Scholar Herbert J. Rapp Herbert J. Rapp Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 55, Issue 1, July 1975, Pages 73–79, https://doi.org/10.1093/jnci/55.1.73 Published: 01 July 1975 Article history Received: 13 November 1974 Accepted: 14 March 1975 Published: 01 July 1975
Abstract A34: EWS/FLI regulates transcriptional activation in Ewing sarcoma via length dependent GGAA microsatellites
Authors: Kirsten M. Johnson, Kunal Gangwal, James Robertson, Thomas E. Cheatham, Stephen L. Lessnick
Journal: Cancer Research (2016)

Abstract The purpose of this study is to investigate how EWS/FLI transcriptionally activates gene targets via polymorphic GGAA microsatellites. Ewing Sarcoma is a pediatric bone malignancy initiated by a t(11;22) chromosomal translocation that produces the EWS/FLI oncoprotein. EWS/FLI transcriptionally activates and represses its target genes to mediate oncogenic reprogramming. Expression of its up-regulated targets correlates with EWS/FLI binding to associated GGAA microsatellites. These microsatellites show length polymorphisms, suggesting that microsatellite polymorphisms may have critical effects on EWS/FLI-responsiveness of key gene targets. For example, NR0B1 is necessary for EWS/FLI mediated oncogenic transformation, and we found a “sweet-spot” of 24-25 repeat length as optimal for EWS/FLI mediated transcriptional activity at NR0B1. The mechanism underlying this optimal length is unknown. We therefore explored the stoichiometry and binding affinity of EWS/FLI for different repeat lengths through biochemical studies combined with molecular modeling simulation. Our data demonstrate a complex relationship between microsatellite length and transcriptional activity. Fluorescence anisotropy studies demonstrate that FLI binding affinity is independent of GGAA microsatellite length. In contrast, the stoichiometry of protein to DNA binding increases in specific incremental patterns with increasing microsatellite repeats. Gel shift binding assays elucidate the minimal microsatellite length critical for binding. Overall our data suggests a model in which the DNA binding domain of multiple monomers of FLI function as independent binding units to facilitate transcriptional activity in a length-dependent fashion. We propose that GGAA microsatellites are necessary and sufficient for EWS/FLI-mediated oncogenic transformation and that repeat length affects optimal DNA binding stoichiometry and transcriptional activity. Citation Format: Kirsten M. Johnson, Kunal Gangwal, James Robertson, Thomas E. Cheatham, Stephen L. Lessnick. EWS/FLI regulates transcriptional activation in Ewing sarcoma via length dependent GGAA microsatellites. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr A34.
Successful Use of Regitine (Phentolamine) in the Diagnosis and Surgical Management of a Case of Pheochromocytoma
Authors: Thomas H. Newton, Gilbert I. Smith, Felix O. Kolb, Donald R. Smith
Journal: New England Journal of Medicine (1955)

IT is estimated that 800 persons die yearly in the United States of complications of hypertension due to pheochromocytoma.1 , 2 Smithwick and his associates3 found 5 unsuspected cases of pheochromocytoma among a group of 1000 patients subjected to sympathectomy and adrenal exploration for hypertension. The increasing recognition that such a tumor may cause sustained as well as paroxysmal hypertension has led to the continued search for a simple and safe diagnostic agent for screening hypertensive patients. The recent introduction of Regitine by Grimson4 and others5 , 6 has made available an agent that has shown no serious side reactions to date.7 To this . . .
P129 What is the patient’s preference: tiotropium monotherapy or fixed-dose indacaterol/glycopyrronium combination therapy? - the FAVOUR study
Authors: P Kardos, I Hagedorn
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Shared decision-making for drug and inhaler-device use improves adherence and outcomes in COPD. Physicians are encouraged to involve patient’s opinion in choosing drugs and inhalers. It remains unclear, however, whether the superior effect on FEV1 shown for the fixed-dose combination of indacaterol/glycopyrronium (IND/GLY) compared to tiotropium (TIO) translates into medication preference by patients. The present study was conducted to evaluate the overall preference for IND/GLY and TIO respectively, in patients who are still symptomatic under a TIO treatment. <h3>Method</h3> This multicenter, cross-over, open-label study randomised COPD patients with moderate to severe airflow limitation and a CAT score of ≥10 to either receive 4 weeks o.d. IND/GLY (110/50 µg) followed by 4 weeks o.d. TIO (18 µg) or <i>vice versa </i>in a 1:1 ratio. To determine patient’s treatment preference and satisfaction as secondary and explorative objectives, respectively, several validated and new questionnaires were used. As primary endpoint, FEV1 1 h post-inhalation after 4 weeks was investigated. <h3>Results</h3> Of 88 patients (mean age, 65 years; post-bronchodilator FEV1, 57.7% predicted; mean CAT score, 17.6) randomised, 87 patients completed the study. After 4 weeks treatment, 1 h post-inhalation FEV1 was significantly higher with IND/GLY compared to TIO (LSM difference, 81 ml; p = 0.0017). Importantly, a higher proportion of patients preferred IND/GLY (69.4%) over TIO (30.6%) at the end of the study. Reduction of dyspnea was mentioned as an important or very important reason for favouring IND/GLY by 91.5% of the patients. <h3>Conclusion</h3> This study indicated that beyond FEV1, patients reported outcomes improve with the dual bronchodilator IND/GLY compared to TIO monotherapy. Further studies are needed to investigate how the favoured treatment option translates into improved adherence and long term treatment outcomes.
P43 How appropriately is NIV used as a ceiling of treatment?
Authors: S Woolf, J Jitan, J Robinson, J Suntharalingam
Journal: Thorax (2015)

<h3>Background</h3> Treatment Escalation Plans (TEPs) were introduced at the Royal United Hospitals Bath (RUH) in 2013 to help physicians document decisions regarding ceilings of treatment. In implementing a TEP, a patient may be deemed unsuitable for resuscitation and/or Intensive Care Unit (ICU) but remain a potential candidate for ward-based non-invasive ventilation (NIV). However as ward-based NIV is indicated in relatively few respiratory conditions this option should only be available to a small cohort of patients. This study examines how appropriately patients have NIV cited as a ceiling of treatment, using 2002 BTS acute NIV guidelines as a benchmark. <h3>Method</h3> We collected data from medical, surgical and geriatric wards at the RUH on three separate days between November 2014 and June 2015. In patients with a TEP who were deemed unsuitable for CPR, we recorded a) the ceiling of treatment decision b) reason for admission and c) co-morbidities. We reviewed how many patients with NIV as a ceiling of treatment had an indication in accordance with BTS guidelines. <h3>Results</h3> 658 patient notes were reviewed. 109/658 patients were deemed not suitable for ICU but had NIV as a ceiling of treatment. 64/109 patients (59%) had an indication in accordance with BTS guidelines, while 45/109 patients (41%) were non-compliant. There was variation in compliance between specialties (General Medicine 60% compliant, Elderly Care 54% compliant and Surgery 33% compliant). The Respiratory ward was the most compliant (100%). <h3>Conclusions</h3> Whilst NIV can offer significant survival benefits to patients with certain conditions (eg COPD exacerbations, obesity hypoventilation syndrome and chest wall disease) national BTS audits have repeatedly shown that ward-based NIV is often used unsuccessfully outside of these indications. The current study demonstrates that over 40% of patients admitted to our hospital inappropriately have NIV set as their ceiling of treatment, albeit with some variability between wards and specialties. This suggests that further education is required about the potential limitations of NIV, particularly for non-respiratory specialists who often make TEP decisions.
Patients' attitudes toward behavior therapy and psychotherapy
Authors: B Sloane, F R Staples, K Whipple, A H Cristol
Journal: American Journal of Psychiatry (1977)

A questionnaire survey of 50 patients treated by behavior therapy or short-term, analytically oriented psychotherapy revealed that both groups, as well as those patients who improved the most, placed a high value on insight, the patient-therapist relationship, catharsis, and trust. The findings suggest that behavior therapy patients tend to place more emphasis than do their therapists on factors that have traditionally been thought important in analytic psychotherapy.
Molecular and Immunological Characterization of Gamma Gliadins As Major Allergens in Wheat Food Allergy
Authors: Sandra Wieser, Alexandra Baar, Bharani Srinivasan, Nikolaos G. Papadopoulos, Stavroula Giavi, Mika Makela, Anna Pelkonen, Christof Ebner, Josef Thalhamer, Susanne Vrtala, Rudolf Valenta
Journal: Journal of Allergy and Clinical Immunology (2016)
Flow Rate and Composition of Thoracic-Duct Lymph in Patients with Cirrhosis
Authors: Allan E. Dumont, John H. Mulholland
Journal: New England Journal of Medicine (1960)

IN the 1908 Christian Herter Lectures at Bellevue Hospital, Starling1 emphasized the important influence of changes in hepatic interstitial-fluid formation on flow and composition of thoracic-duct lymph. More recently, alterations in both hepatic and thoracic-duct lymph have been demonstrated in experimentally produced liver disease in animals.2 3 4 In patients with hepatic cirrhosis formation of interstitial fluid in the liver is also considered to be abnormal and associated with recognized changes in the transport of water, electrolytes and large molecules across capillary membranes.5 , 6 Thoracic-duct lymph from human patients, however, has not been studied as that from animals with experimentally produced liver disease. . . .
Telomere Length and Treatment Outcome In Chronic Lymphocytic Leukemia: Results From The CLL8 Trial
Authors: Billy Michael Chelliah Jebaraj, Raymonde Busch, Thorsten Zenz, Andreas Bühler, Dirk Winkler, Andrea Schnaiter, Jennifer Edelmann, Daniel Mertens, Sebastian Böttcher, Michael Kneba, Ulrich Jäger, Michael K Wenger, Guenter Fingerle-Rowson, Clemens Wendtner, Anna-Maria Fink, Kirsten Fischer, Michael Hallek, Hartmut Döhner, Stephan Stilgenbauer
Journal: Blood (2013)
Adrenocortical 11β-Hydroxylase Deficiency and Virilism First Manifest in the Adult Woman
Authors: J. L. Gabrilove, D. C. Sharma, R. I. Dorfman
Journal: New England Journal of Medicine (1965)

THIS report is concerned with the delineation and biochemical demonstration of a clinical syndrome first manifest in the adult woman and resulting from an 11β-hydroxylase deficiency in the adrenal cortex.Experimental ProcedureDetermination of Urinary SteroidsThe urinary excretion of the neutral 17-ketosteroids has been measured by a modification of the method of Drekter and Heisler1 and of the 17-hydroxycorticoids by the Peterson modification2 of the method of Silber and Porter.3 The partition of the glucocorticoids and of the neutral 17-ketosteroids was carried out by methods previously described.4 , 5 Pregnanetriol was assayed by the method of Bongiovanni and Eberlein.6 For the . . .
Mutations of the<i>Connexin43</i>Gap-Junction Gene in Patients with Heart Malformations and Defects of Laterality
Authors: Scott H. Britz-Cunningham, Maithili M. Shah, Craig W. Zuppan, William H. Fletcher
Journal: New England Journal of Medicine (1995)

Gap junctions are thought to have a crucial role in the synchronized contraction of the heart and in embryonic development. Connexin43, the major protein of gap junctions in the heart, is targeted by several protein kinases that regulate myocardial cell–cell coupling. We hypothesized that mutations altering sites critical to this regulation would lead to functional or developmental abnormalities of the heart.
Evaluating the Health Impact of Large-Scale Public Policy Changes: Classical and Novel Approaches
Authors: Sanjay Basu, Ankita Meghani, Arjumand Siddiqi
Journal: Annual Review of Public Health (2017)

Large-scale public policy changes are often recommended to improve public health. Despite varying widely—from tobacco taxes to poverty-relief programs—such policies present a common dilemma to public health researchers: how to evaluate their health effects when randomized controlled trials are not possible. Here, we review the state of knowledge and experience of public health researchers who rigorously evaluate the health consequences of large-scale public policy changes. We organize our discussion by detailing approaches to address three common challenges of conducting policy evaluations: distinguishing a policy effect from time trends in health outcomes or preexisting differences between policy-affected and -unaffected communities (using difference-in-differences approaches); constructing a comparison population when a policy affects a population for whom a well-matched comparator is not immediately available (using propensity score or synthetic control approaches); and addressing unobserved confounders by utilizing quasi-random variations in policy exposure (using regression discontinuity, instrumental variables, or near-far matching approaches).
Association between primary tumor protein expression and response to sunitinib in patients with metastatic renal cell carcinoma.
Authors: Moshe Chaim Ornstein, Vlado Knezevic, Brian I. Rini, Ulka N. Vaishampayan
Journal: Journal of Clinical Oncology (2015)

450 Background: Sunitinib is FDA-approved and widely used as frontline treatment for metastatic renal cell carcinoma (mRCC), but there is a large degree of variability in patient (pt) response to therapy. The association of baseline primary tumor expression of multiple proteins and objective response to sunitinib was investigated. Methods: Primary tumor samples from clear cell mRCC pts treated with sunitinib as frontline therapy at two academic institutions were retrieved. Layered immunohistochemical (LIHC) assay which allow the detection of multiple biomarkers in a single tissue section was used to evaluate the expression of 8 proteins (VEGFR1, VEGFR2, p-mTOR, p-4E-BP1 S65, VEGF A, 4E-BP1, PDGFRb, CAIX) on tumor cells. Pts were characterized as Responders (Complete Responders (CR), Partial Responders (PR) and Stable diseases (SD)) or Non-Responders (NR) based on investigator-assessment. The 8 proteins were tested separately and the area under the receiver operator characteristic (ROC) curve (AUC) analysis was used to compare the predictive power of each biomarker and their combinations. Results: 38 pts were eligible for evaluation; 29 responders and 9 non-responders. Of the 8 biomarkers tested individually, only PDGFRb and CAIX were statistically significant in providing a predictive value for response to sunitinib. Of the different possible biomarker combinations, the combination of increased levels of CAIX expression and decreased 4E-BP1 expression provided the highest ROC AUC (0.9) for predicting response. When stable disease cases were removed from the responders group, in addition to CAIX and 4E-BP1, increased levels of PDGFRb expression predicted response (AUC was 0.889). Conclusions: Baseline primary tumor expression of CAIX and 4E-BP1 is associated with an objective response to sunitinib in pts with mRCC.
A Phase II Study of Ofatumumab-High Dose Methylprednisolone Followed By Ofatumumab-Alemtuzumab in 17p Deleted or TP53 Mutated CLL
Authors: Matthew S. Davids, Haesook T. Kim, Stacey M. Fernandes, Jeffrey Hellman, Karen Francoeur, Jon E. Arnason, Eric Jacobsen, Ann S LaCasce, David C. Fisher, Jennifer R. Brown
Journal: Blood (2015)
Frequent Association of IgMλ with Crystalline Inclusions in Chronic Lymphatic Leukemic Lymphocytes
Authors: Connie Clark, Robert E. Rydell, Manuel E. Kaplan
Journal: New England Journal of Medicine (1973)

In four of 30 patients with chronic lymphocytic leukemia, studied by immunofluorescence, 1 to 31 per cent of peripheral blood lymphocytes were found to contain intracellular, rod-shaped inclusions that stained specifically for both μ and λ (IgMλ) determinants. Essentially all inclusion-containing lymphocytes exhibited monoclonal, membrane-bound IgMμ (M-IgM λ). However, only a minority of lymphocytes with M-IgM λcontained inclusions. On electron microscopy the homogeneous inclusions were found within the rough endoplasmic reticulum, and they exhibited an electrondense periodicity consistent with crystalline structure. In this series, the chance occurrence of crystals present solely in lymphocytes bearing M-IgMμ is 0.5 per cent. These studies indicate that in some patients with chronic lymphocytic leukemia, at least two morphologically distinct populations of neoplastic lymphocytes are present. (N Engl J Med 289:113–117, 1973)
Tumor-Induced Hypoglycemia
Authors: Derek Le Roith
Journal: New England Journal of Medicine (1999)

Hypoglycemia is a common medical emergency. Among hospitalized patients, it is most common in those with diabetes mellitus, but it also occurs in patients with renal insufficiency, liver disease, malnutrition, congestive heart failure, sepsis, or cancer.1,2 Among ambulatory patients, it is most common in patients with diabetes, particularly those treated with insulin. Factitious or surreptitious use of insulin or sulfonylurea drugs is probably the most common cause of hypoglycemia among patients who do not have diabetes. Occasionally, hypoglycemia can be induced by tumors, including pancreatic tumors that secrete insulin3 and non–islet-cell tumors that secrete insulin-like growth factors.4 Strict criteria . . .