tbuckley/cabot-search huggingface dataset:
A Novel HLA-A*0201 Restricted Peptide Derived from Cathepsin G Is an Effective Immunotherapeutic Target in Acute Myeloid Leukemia
Authors: Mao Zhang, Pariya Sukhumalchandra, Atim A. Enyenihi, Lisa S. St. John, Sally A. Hunsucker, Elizabeth A. Mittendorf, Anna Sergeeva, Kathryn Ruisaard, Zein Al-Atrache, Patricia A. Ropp, Haroon Jakher, Tania Rodriguez-Cruz, Gregory Lizee, Karen Clise-Dwyer, Sijie Lu, Jeffrey J. Molldrem, Gary L. Glish, Paul M. Armistead, Gheath Alatrash
Journal: Clinical Cancer Research (2012)

Immunotherapy targeting aberrantly expressed leukemia-associated antigens has shown promise in the management of acute myeloid leukemia (AML). However, because of the heterogeneity and clonal evolution that is a feature of myeloid leukemia, targeting single peptide epitopes has had limited success, highlighting the need for novel antigen discovery. In this study, we characterize the role of the myeloid azurophil granule protease cathepsin G (CG) as a novel target for AML immunotherapy.We used Immune Epitope Database and in vitro binding assays to identify immunogenic epitopes derived from CG. Flow cytometry, immunoblotting, and confocal microscopy were used to characterize the expression and processing of CG in AML patient samples, leukemia stem cells, and normal neutrophils. Cytotoxicity assays determined the susceptibility of AML to CG-specific cytotoxic T lymphocytes (CTL). Dextramer staining and cytokine flow cytometry were conducted to characterize the immune response to CG in patients.CG was highly expressed and ubiquitinated in AML blasts, and was localized outside granules in compartments that facilitate antigen presentation. We identified five HLA-A*0201 binding nonameric peptides (CG1-CG5) derived from CG, and showed immunogenicity of the highest HLA-A*0201 binding peptide, CG1. We showed killing of primary AML by CG1-CTL, but not normal bone marrow. Blocking HLA-A*0201 abrogated CG1-CTL-mediated cytotoxicity, further confirming HLA-A*0201-dependent killing. Finally, we showed functional CG1-CTLs in peripheral blood from AML patients following allogeneic stem cell transplantation.CG is aberrantly expressed and processed in AML and is a novel immunotherapeutic target that warrants further development.
Asthma and Posttraumatic Stress Symptoms 5 to 6 Years Following Exposure to the World Trade Center Terrorist Attack
Authors: Robert M. Brackbill
Journal: JAMA (2009)

The World Trade Center Health Registry provides a unique opportunity to examine long-term health effects of a large-scale disaster.To examine risk factors for new asthma diagnoses and event-related posttraumatic stress (PTS) symptoms among exposed adults 5 to 6 years following exposure to the September 11, 2001, World Trade Center (WTC) terrorist attack.Longitudinal cohort study with wave 1 (W1) enrollment of 71,437 adults in 2003-2004, including rescue/recovery worker, lower Manhattan resident, lower Manhattan office worker, and passersby eligibility groups; 46,322 adults (68%) completed the wave 2 (W2) survey in 2006-2007.Self-reported diagnosed asthma following September 11; event-related current PTS symptoms indicative of probable posttraumatic stress disorder (PTSD), assessed using the PTSD Checklist (cutoff score > or = 44).Of W2 participants with no stated asthma history, 10.2% (95% confidence interval [CI], 9.9%-10.5%) reported new asthma diagnoses postevent. Intense dust cloud exposure on September 11 was a major contributor to new asthma diagnoses for all eligibility groups: for example, 19.1% vs 9.6% in those without exposure among rescue/recovery workers (adjusted odds ratio, 1.5 [95% CI, 1.4-1.7]). Asthma risk was highest among rescue/recovery workers on the WTC pile on September 11 (20.5% [95% CI, 19.0%-22.0%]). Persistent risks included working longer at the WTC site, not evacuating homes, and experiencing a heavy layer of dust in home or office. Of participants with no PTSD history, 23.8% (95% CI, 23.4%-24.2%) reported PTS symptoms at either W1 (14.3%) or W2 (19.1%). Nearly 10% (9.6% [95% CI, 9.3%-9.8%]) had PTS symptoms at both surveys, 4.7% (95% CI, 4.5%-4.9%) had PTS symptoms at W1 only, and 9.5% (95% CI, 9.3%-9.8%) had PTS symptoms at W2 only. At W2, passersby had the highest rate of PTS symptoms (23.2% [95% CI, 21.4%-25.0%]). Event-related loss of spouse or job was associated with PTS symptoms at W2.Acute and prolonged exposures were both associated with a large burden of asthma and PTS symptoms 5 to 6 years after the September 11 WTC attack.
Phase II EORTC trial with 5-fluorouracil, cisplatin and interferon-α as second-line treatment of advanced transitional cell cancer of the urothelial tract
Authors: P.H.M. De Mulder, C. Theodore, A. Sella, O. Koriakine, C.N. Sternberg, L. Collette, C. de Balincourt
Journal: Annals of Oncology (2000)
Thrombopoietin and Thrombopoietin Mimetics in the Treatment of Thrombocytopenia
Authors: David J. Kuter
Journal: Annual Review of Medicine (2008)

Although the thrombopoietin receptor was discovered in 1991 and thrombopoietin (TPO) was purified in 1994, the development of a clinically useful TPO was hampered by the appearance of neutralizing antibodies to some forms of recombinant TPO. However, in 2008 two new drugs that mimic the effect of TPO became available to treat thrombocytopenia. Romiplostim is a TPO peptide mimetic given by subcutaneous injection that activates the TPO receptor by binding to the distal hematopoietic receptor domain just like TPO. Eltrombopag is a TPO nonpeptide mimetic administered orally that activates the TPO receptor by binding to the transmembrane domain. Both increase the platelet count in healthy humans as well as in >80% of patients with immune thrombocytopenic purpura (ITP). Although initially restricted to the second-line treatment of ITP, both agents could help treat many thrombocytopenic disorders. Both agents are well tolerated, with mild headache being the most common complaint. Potential long-term complications include thrombosis, increased bone marrow reticulin, rebound worsening of thrombocytopenia upon discontinuation, and increased blast formation. Ongoing studies should establish the incidence of these complications and determine the efficacy of these new agents in a variety of other thrombocytopenic conditions.
The sequence of the Mycoplasma arthritidis superantigen, MAM: identification of functional domains and comparison with microbial superantigens and plant lectin mitogens.
Authors: B C Cole, K L Knudtson, A Oliphant, A D Sawitzke, A Pole, M Manohar, L S Benson, E Ahmed, C L Atkin
Journal: The Journal of Experimental Medicine (1996)

Mycoplasma arthritidis, an agent of chronic proliferative arthritis of rodents, secretes a potent soluble superantigen, MAM, that is active for both murine and human T and B lymphocytes. We now report the complete nucleotide and amino acid sequence of MAM and show it to be distinct from other proteins and not closely related phylogenetically to other superantigens. Two functional domains on MAM are identified based on the ability of peptides encompassing these regions to inhibit lymphocyte proliferation by the intact MAM molecule. One of these domains shares short sequences or epitopes with other microbial superantigens. The second domain contains the consensus legume lectin motif-beta, which is important for T cell activation by concanavalin (Con) A. MAM and Con A peptides containing this motif are functionally cross reactive, suggesting a novel secondary pathway for T cell activation by MAM.
Convulsions Complicating Colectomy in Inflammatory Bowel Disease
Authors: W. Stover Wiggins
Journal: JAMA (1977)

To the Editor.—  We read the article by Schulak et al (Convulsions Complicating Colectomy in Inflammatory Bowel Disease, 237:1456) with interest, as we had the opportunity recently to see a patient who had generalized seizures in the same setting. This article points out many of the potential causes for seizures in these patients and was of value to us in approaching our patient.  We find it ironic that colectomy, once a procedure prescribed for and accepted as a treatment for epilepsy in major medical centers,1should now begin to receive attention as a cause.
Differential recognition of a protective filarial antigen by antibodies from humans with bancroftian filariasis.
Authors: J W Kazura, H Cicirello, K Forsyth
Journal: Journal of Clinical Investigation (1986)

The objectives of this study were to identify filarial antigens which induce enhanced clearance of circulating microfilariae and to establish if human antibody reactivity with these molecules correlates with the apparent parasite burdens of residents of an endemic area of Bancroftian filariasis. Mice immunized with an extract of Brugia malayi microfilariae develop IgG antibodies to four major filarial antigens with an apparent molecular weight (Mr) of approximately 112,000, 60,000, 45,000, and 25,000. Animals immunized with gel slices containing the approximately 25,000-Mr antigen are resistant to intravenous challenge with live microfilariae (78-98% reduction in parasitemia vs. controls, P less than 0.01). A group of 22 amicrofilaremic humans had a significantly higher (P less than 0.025) mean antibody titer to the Mr 25,000-Mr antigen (1: 424) than 16 microfilaremic individuals (1:95). There were no significant differences between the two groups in antibody titers to filarial antigens of Mr approximately 112,000, 60,000, and 45,000 Mr. These data suggest that a high degree of reactivity to the 25,000-Mr antigen in humans with lymphatic filariasis correlates with a parasitologic status that is least conducive to transmission of infection.
Sex differences in thoracic adaptation to pulmonary hyperinflation in cystic fibrosis
Authors: F. Bellemare, A. Jeanneret
Journal: European Respiratory Journal (2006)

Sex differences in thoracic adaptation have been reported in patients with cystic fibrosis (CF). The interplay between the pattern of thoracic adaptation and the function of the respiratory muscles in male and female CF patients with pulmonary hyperinflation was investigated. Thoracic dimensions and diaphragm length were measured at residual volume, functional residual capacity and total lung capacity using chest radiography in 23 CF (12 males) and 18 normal (11 males) subjects. Respiratory muscle recruitment during resting breathing was assessed by recording intrathoracic and intra-abdominal pressures. In female CF patients, ribcage expansion was predominant, tending to preserve diaphragm length. In male CF patients, thoracic configuration was normal and diaphragm shortening consequently greater. Ribcage cross-sectional area for a given rib inclination was greater in CF patients, indicating a structural expansion of the ribcage 2.5 times greater in females than males. The contribution of inspiratory ribcage muscles to inspiratory pressure was also greater relative to the diaphragm in the CF group. In conclusion, a structural expansion of the ribcage occurs in cystic fibrosis patients with lung hyperinflation that is greater in females than males. This is associated with an apparent greater contribution of inspiratory ribcage muscles to inspiratory pressure.
Why take up rheumatology?
Authors: F D Hart
Journal: Annals of the Rheumatic Diseases (1980)

<h3>Abstract</h3> Spike-based neural network models have so far not been able to reproduce the capability of the brain to learn from very few, often even from just a single example. We show that this deficiency of models disappears if one allows synaptic weights to store priors and other information that optimize the learning process, while using the network state to quickly absorb information from new examples. For that, it suffices to include biologically realistic neurons with spike frequency adaptation in the neural network model, and to optimize the learning process through meta-learning. We demonstrate this on a variety of tasks, including fast learning and deletion of attractors, adaptation of motor control to changes in the body, and solving the Morris water maze task – a paradigm for fast learning of navigation to a new goal. <h3>Significance Statement</h3> It has often been conjectured that STDP or other rules for synaptic plasticity can only explain some of the learning capabilities of brains. In particular, learning a new task from few trials is likely to engage additional mechanisms. Results from machine learning show that artificial neural networks can learn from few trials by storing information about them in their network state, rather than encoding them in synaptic weights. But these machine learning methods require neural networks with biologically unrealistic LSTM (Long Short Term Memory) units. We show that biologically quite realistic models for neural networks of the brain can exhibit similar capabilities. In particular, these networks are able to store priors that enable learning from very few examples.
Structure-Guided Design of a High-Affinity Platelet Integrin α <sub>IIb</sub> β <sub>3</sub> Receptor Antagonist That Disrupts Mg <sup>2+</sup> Binding to the MIDAS
Authors: Jieqing Zhu, Won-Seok Choi, Joshua G. McCoy, Ana Negri, Jianghai Zhu, Sarasija Naini, Jihong Li, Min Shen, Wenwei Huang, Daniel Bougie, Mark Rasmussen, Richard Aster, Craig J. Thomas, Marta Filizola, Timothy A. Springer, Barry S. Coller
Journal: Science Translational Medicine (2012)

A new drug blocks platelet aggregation by interacting with the integrin receptor differently from current drugs that cause adverse side effects.
Heart rate response to ultraendurance cycling
Authors: G Neumayr, R Pfister, G Mitterbauer, H Gaenzer, W Sturm, H Hoertnagl
Journal: British Journal of Sports Medicine (2003)

The heart rate (HR) response to ultraendurance cycling is poorly understood. This case report describes the exercise intensity of ultraendurance cycling by means of HR monitoring in a well trained male amateur cyclist performing the Ötztal Radmarathon twice en bloque in a circuit of two identical laps (distance 460 km; cumulative altitude difference 11 000 m). The overall intensity was moderate (HR mean = 130 beats/min; HR mean /HR max = 0.71) corresponding to an average individual workload of 47% of V o 2 max . Almost the whole race was performed under aerobic conditions (99.6%); high intensity work was negligible (0.4%). The average speed and the HR response also declined in the course of the two laps, average speed by 17.2% (23.8 to 19.7 km/h), HR mean by 10.1% (138 to 124 beats/min), and HR mean /HR max by 10.7% (0.75 to 0.67). This scale of HR decrease corresponds to comparable data gained in the field of triathlon and represents a specific cardiac feature of ultraendurance exercise in general.
Leukocyte depletion filters: A comparison of efficiency
Authors: David C. Bodensteiner
Journal: American Journal of Hematology (1990)

Abstract Four commercially available leukocyte depletion filters were evaluated using a flow cytometric technique to determine the efficiency of each type of filter. The Sepacell R‐500A® and the PALL RC50® were the most efficient in leukocyte depletion having a mean depletion percentage of 99.3% and 99.5%, respectively. The PALL RC100® which is used for two units also had a 99.3% depletion with the first unit but with the second unit the depletion dropped to 94.2%. The Imugard IG‐500® had a 97.3% depletion. Red cell recovery ranged from 87.4% for the PALL RC50® to 92.2% for the Sepacell R‐500A®.
MicroRNA-708 Induces Apoptosis and Suppresses Tumorigenicity in Renal Cancer Cells
Authors: Sharanjot Saini, Soichiro Yamamura, Shahana Majid, Varahram Shahryari, Hiroshi Hirata, Yuichiro Tanaka, Rajvir Dahiya
Journal: Cancer Research (2011)

Abstract Cancer pathogenesis is restricted by stresses that compromise cell division and survival. In this study, we identify miR-708, a little studied member of a set of microRNAs that have been implicated in stress control, as an important tumor suppressor in renal cell carcinoma (RCC). miR-708 expression was attenuated widely in human RCC specimens. Restoration of miR-708 expression in RCC cell lines decreased cell growth, clonability, invasion, and migration and elicited a dramatic increase in apoptosis. Moreover, intratumoral delivery of miR-708 was sufficient to trigger in vivo regression of established tumors in murine xenograft models of human RCC. Investigation of the targets of miR-708 identified the inhibitor of apoptosis protein survivin as important. siRNA-mediated knockdown of survivin partially phenocopied miR-708 overexpression suggesting that the proapoptotic role of miR-708 may be mediated primarily through survivin regulation. Additionally, we identified the E-cadherin regulators ZEB2 and BMI1 as likely miR-708 targets. Taken together, our findings define a major tumor suppressive role for miR-708, which may offer an attractive new target for prognostic and therapeutic intervention in RCC. Cancer Res; 71(19); 6208–19. ©2011 AACR.
Pressor Substances in Arterial Hypertension
Authors: DEAN F. DAVIES, NORMAN S. OLSEN, HENRY A. SCHROEDER
Journal: Circulation (1952)

Pherentasin is the only pressor substance found in blood of hypertensive patients which is not found in normal blood. This study defines its unit and compares its concentration with diastolic blood pressure level, type of hypertension, and age of patients. Lack of correlation between blood pressure level and pherentasin content suggests considerable variation in the amount of depressor substances in these patients. Chemical studies of pherentasin and its partial, tentative formula are discussed. Demonstration of the existence of an additional pressor fraction from blood which is volatile in alkaline solution is described.
Erratum to: Plasma soluble thrombomodulin levels are associated with mortality in the acute respiratory distress syndrome
Authors: Anil Sapru, Carolyn S. Calfee, Kathleen D. Liu, Kirsten Kangelaris, Helen Hansen, Ludmila Pawlikowska, Lorraine B. Ware, Mustafa F. Alkhouli, Jason Abbott, Michael A. Matthay
Journal: Intensive Care Medicine (2015)
Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin.
Authors: P C Brooks, S Strömblad, R Klemke, D Visscher, F H Sarkar, D A Cheresh
Journal: Journal of Clinical Investigation (1995)

Angiogenesis plays a fundamental role in human breast tu- mor progression.In fact, recent findings indicate that vascu- lar density is a prognostic indicator of breast cancer disease status.Evidence is presented that the integrin avfi3 is not only a marker of human breast tumor-associated blood vessels, but that it plays a significant role in human angiogenesis and breast tumor growth.To assess the role of avvp3dependent angiogenesis in the progression of human breast cancer, we examined a SCID mouse/human chimeric model with transplanted full thickness human skin containing avfi3-negative human breast tumor cells.This tumor in- duced a human angiogenic response as measured by vascu- lar cell immunoreactivity with monoclonal antibodies LM609 and P2B1 directed to human avj33 and CD31, re- spectively.Intravenous administration of LM609 either pre- vented tumor growth or markedly reduced tumor cell proliferation within the microenvironment of the human skin.These LM609-treated tumors not only contained significantly fewer human blood vessels but also appeared consid- erably less invasive than tumors in control animals.These findings demonstrate that atvP3 antagonists may provide an effective antiangiogenic approach for the treatment of human breast cancer.(
Disseminated strongyloidiasis. Diagnosis made by sputum examination
Authors: Robert A. Harris, Daniel M. Musher, Victor Fainstein, Edward J. Young, Jill Clarridge
Journal: JAMA (1980)

Two immune-compromised patients had pulmonary and intestinal infection due to Strongyloides stercoralis. Diagnosis was facilitated in both cases when the parasites were found in the sputum. Treatment with thiabendazole appeared to eradicate the infection, but repeated follow-up examinations are needed because of the likelihood of relapse.
The New Technology Assessment
Authors: V R Fuchs, A M Garber
Journal: New England Journal of Medicine (1990)

Technology assessment is not a new phenomenon in medicine. The most able and conscientious physicians have always sought to understand the effects of the interventions they apply.1 With the development of clinical research, attempts to establish safety and efficacy became more systematic and scientific, culminating in the crown jewel of traditional technology assessment, the randomized clinical trial.The determination of safety and efficacy remains an essential element of technology assessments, but in recent years such assessments have broadened in scope. They now encompass the measurement of effectiveness, considerations of quality of life and patients' preferences,2 , 3 and especially the evaluation of . . .
TGFβ receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension: results from a multicentre EUSTAR study of European Caucasian patients
Authors: Eugénie Koumakis, Julien Wipff, Philippe Dieudé, Barbara Ruiz, Matthieu Bouaziz, Lucile Revillod, Mickaël Guedj, Jörg H W Distler, Marco Matucci-Cerinic, Marc Humbert, Gabriella Riemekasten, Paolo Airo, Inga Melchers, Eric Hachulla, Daniele Cusi, H- Erich Wichmann, Nicolas Hunzelmann, Kiet Tiev, Paola Caramaschi, Elisabeth Diot, Otylia Kowal-Bielecka, Giovanna Cuomo, Ulrich Walker, László Czirják, Nemanja Damjanov, Sara Lupoli, Costanza Conti, Martina Müller-Nurasyid, Ulf Müller-Ladner, Valeria Riccieri, Jean-Luc Cracowski, Franco Cozzi, Vasiliki Kalliopi Bournia, P Vlachoyiannopoulos, Gilles Chiocchia, Catherine Boileau, Yannick Allanore
Journal: Annals of the Rheumatic Diseases (2012)

Introduction Systemic sclerosis (SSc)-related pulmonary arterial hypertension (PAH) has emerged as a major mortality prognostic factor. Mutations of transforming growth factor beta (TGFβ) receptor genes strongly contribute to idiopathic and familial PAH. Objective To explore the genetic bases of SSc–PAH, we combined direct sequencing and genotyping of candidate genes encoding TGFβ receptor family members. Materials and methods TGFβ receptor genes, BMPR2, ALK1 , TGFR2 and ENG , were sequenced in 10 SSc–PAH patients, nine SSc and seven controls. In addition, 22 single-nucleotide polymorphisms (SNP) of these four candidate genes were tested for association in a first set of 824 French Caucasian SSc patients (including 54 SSc–PAH) and 939 controls. The replication set consisted of 1516 European SSc (including 219 SSc–PAH) and 3129 controls from the European League Against Rheumatism Scleroderma Trials and Research group network. Results No mutation was identified by direct sequencing. However, two repertoried SNP, ENG rs35400405 and ALK1 rs2277382, were found in SSc–PAH patients only. The genotyping of 22 SNP including the latter showed that only rs2277382 was associated with SSc–PAH (p=0.0066, OR 2.13, 95% CI 1.24 to 3.65). Nevertheless, this was not replicated with the following result in combined analysis: p=0.123, OR 0.79, 95% CI 0.59 to 1.07. Conclusions This study demonstrates the lack of association between these TGFβ receptor gene polymorphisms and SSc–PAH using both sequencing and genotyping methods.