tbuckley/cabot-search huggingface dataset:
The value of endoscopic ultrasound after bronchoscopy to diagnose thoracic sarcoidosis
Authors: K. G. Tournoy, A. Bolly, J. G. Aerts, P. Pierard, R. De Pauw, D. Leduc, A. Leloup, T. Pieters, H. Slabbynck, A. Janssens, K. Carron, L. Schrevens, K. Pat, T. De Keukeleire, C. Dooms
Journal: European Respiratory Journal (2009)

A clinicoradiological presentation of thoracic sarcoidosis requires histopathology in order to establish the diagnosis. Flexible bronchoscopy has a reasonable diagnostic yield and is the procedure of first choice for diagnosis. Endoscopic ultrasound (endoscopic ultrasound-guided fine needle aspiration/endobronchial ultrasound-guided transbronchial needle aspiration) can help in the diagnosis of sarcoidosis. An implementation strategy of endoscopic ultrasound for the diagnosis of sarcoidosis following negative flexible bronchoscopy results was examined prospectively in 15 clinics. A total of 137 patients (92 males; median age 43 yrs) were included, and sarcoidosis was found in 115 (84%). Alternative diagnoses were tuberculosis, lymphangitis carcinomatosa, pneumoconiosis and alveolitis. All patients were sent for flexible bronchoscopy, which was performed in 121 (88%), resulting in a definite diagnosis in 57 (42%). A total of 80 patients were sent for endoscopic ultrasound, which could be performed in 72 (90%), yielding a definite diagnosis in 47 (59%). Endoscopic ultrasound following negative flexible bronchoscopy avoided a surgical procedure in 47 out of 80 patients. The sensitivity of flexible bronchoscopy for sarcoidosis was 45% (95% confidence interval 35–54%), but 62% (50–72%) if biopsy specimens were taken. The sensitivity of endoscopic ultrasound following negative flexible bronchoscopy results was 71% (58–82%). With this strategy, 97 out of 115 (84% (76–90%)) of proven sarcoidosis was diagnosed using endoscopy. This large prospective implementation study (trial number NCT00888212 ; ClinicalTrials.gov) shows that endoscopic ultrasound is valuable for diagnosing sarcoidosis after negative flexible bronchoscopy results.
Human secondary lymphoid organs typically contain polyclonally-activated proliferating regulatory T cells
Authors: Jorieke H. Peters, Hans J. P. M. Koenen, Esther Fasse, Henk J. Tijssen, Jan N. M. IJzermans, Patricia J. T. A. Groenen, Nicolaas P. M. Schaap, Jaap Kwekkeboom, Irma Joosten
Journal: Blood (2013)
Differential Effects of HOXB4 on Nonhuman Primate Short- and Long-Term Repopulating Cells
Authors: Xiao-Bing Zhang, Brian C Beard, Katherine Beebe, Barry Storer, R. Keith Humphries, Hans-Peter Kiem
Journal: PLoS Medicine (2006)

Hematopoietic stem cells (HSCs) or repopulating cells are able to self-renew and differentiate into cells of all hematopoietic lineages, and they can be enriched using the CD34 cell surface marker. Because of this unique property, HSCs have been used for HSC transplantation and gene therapy applications. However, the inability to expand HSCs has been a significant limitation for clinical applications. Here we examine, in a clinically relevant nonhuman primate model, the ability of HOXB4 to expand HSCs to potentially overcome this limitation.Using a competitive repopulation assay, we directly compared in six animals engraftment of HOXB4GFP (HOXB4 green fluorescent protein) and control (yellow fluorescent protein [YFP])-transduced and expanded CD34+ cells. In three animals, cells were infused after a 3-d transduction culture, while in three other animals cells were infused after an additional 6-9 d of ex vivo expansion. We demonstrate that HOXB4 overexpression resulted in superior engraftment in all animals. The most dramatic effect of HOXB4 was observed early after transplantation, resulting in an up to 56-fold higher engraftment compared to the control cells. At 6 mo after transplantation, the proportion of marker gene-expressing cells in peripheral blood was still up to 5-fold higher for HOXB4GFP compared to YFP-transduced cells.These data demonstrate that HOXB4 overexpression in CD34+ cells has a dramatic effect on expansion and engraftment of short-term repopulating cells and a significant, but less pronounced, effect on long-term repopulating cells. These data should have important implications for the expansion and transplantation of HSCs, in particular for cord blood transplantations where often only suboptimal numbers of HSCs are available.
Disrupted Reinforcement Signaling in the Orbitofrontal Cortex and Caudate in Youths With Conduct Disorder or Oppositional Defiant Disorder and a High Level of Psychopathic Traits
Authors: Elizabeth C. Finger, Abigail A. Marsh, Karina S. Blair, Marguerite E. Reid, Courtney Sims, Pamela Ng, Daniel S. Pine, R. James R. Blair
Journal: American Journal of Psychiatry (2010)

Objective: Dysfunction in the amygdala and orbitofrontal cortex has been reported in youths and adults with psychopathic traits. The specific nature of the functional irregularities within these structures remains poorly understood. The authors used a passive avoidance task to examine the responsiveness of these systems to early stimulus-reinforcement exposure, when prediction errors are greatest and learning maximized, and to reward in youths with psychopathic traits and comparison youths. Method: While performing the passive avoidance learning task, 15 youths with conduct disorder or oppositional defiant disorder plus a high level of psychopathic traits and 15 healthy subjects completed a 3.0-T fMRI scan. Results: Relative to the comparison youths, the youths with a disruptive behavior disorder plus psychopathic traits showed less orbitofrontal responsiveness both to early stimulus-reinforcement exposure and to rewards, as well as less caudate response to early stimulus-reinforcement exposure. There were no group differences in amygdala responsiveness to these two task measures, but amygdala responsiveness throughout the task was lower in the youths with psychopathic traits. Conclusions: Compromised sensitivity to early reinforcement information in the orbitofrontal cortex and caudate and to reward outcome information in the orbitofrontal cortex of youths with conduct disorder or oppositional defiant disorder plus psychopathic traits suggests that the integrated functioning of the amygdala, caudate, and orbitofrontal cortex may be disrupted. This provides a functional neural basis for why such youths are more likely to repeat disadvantageous decisions. New treatment possibilities are raised, as pharmacologic modulations of serotonin and dopamine can affect this form of learning.
The Supreme Court Decision in the Hobby Lobby Case
Authors: R. Alta Charo
Journal: JAMA Internal Medicine (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Enhanced susceptibility of blood monocytes from patients with pulmonary tuberculosis to productive infection with human immunodeficiency virus type 1.
Authors: Z Toossi, J G Sierra-Madero, R A Blinkhorn, M A Mettler, E A Rich
Journal: The Journal of Experimental Medicine (1993)

Blood monocytes from patients with active pulmonary tuberculosis and age-matched healthy purified protein derivative-reactive donors were infected with human immunodeficiency virus type 1 (HIV-1)JR-FL in vitro to assess their susceptibility to productive infection by HIV-1. HIV-1 p24 levels (enzyme-linked immunosorbent assay) in supernatants of infected cells from patients with tuberculosis, albeit variable, were significantly higher at days 10-20 of culture; the maximum levels of p24 antigen were greater in supernatants of HIV-1-infected monocytes from patients than maximum levels for controls (p &amp;lt; 0.05). The maximum increment in p24 levels for patients also exceeded that for controls (p &amp;lt; 0.05). Entry of HIV-1 and/or initiation of reverse transcription, measured by polymerase chain reaction using HIV-1 R/U5 primer pairs, was variable and low in infected monocytes from both patients and controls, and did not correlate with HIV-1 p24 levels. The frequency of infected cells as assessed by endpoint dilution viral cultures was similar for both groups. Therefore, blood monocytes from patients with active tuberculosis can develop a highly productive infection with HIV-1 that does not appear to be due to enhanced HIV entry or higher frequency of infected cells. The enhanced susceptibility may result directly from activation of monocytes by exposure to Mycobacterium tuberculosis and its products in situ.
Role of Synaptojanin 2 in Glioma Cell Migration and Invasion
Authors: Ya-yu Chuang, Nhan L. Tran, Nicole Rusk, Mitsutoshi Nakada, Michael E. Berens, Marc Symons
Journal: Cancer Research (2004)

Abstract The small GTPase Rac1 is thought to play an important role in cell migration and invasion. We have previously identified synaptojanin 2, a phosphoinositide phosphatase, as an effector of Rac1. Here, we show that small interfering RNA-mediated depletion of either Rac1 or synaptojanin 2 inhibits invasion of SNB19 and U87MG glioblastoma cells through Matrigel and rat brain slices. Depletion of Rac1 or synaptojanin 2 also inhibits migration of SNB19 and U87MG cells on glioma-derived extracellular matrix. In addition, we found that depletion of Rac1 or synaptojanin 2 inhibits the formation of lamellipodia and invadopodia, specialized membrane structures that are thought to be involved in extracellular matrix degradation. These results suggest that synaptojanin 2 contributes to the role of Rac1 in cell invasion and migration by regulating the formation of invadopodia and lamellipodia. This study also identifies synaptojanin 2 as a novel potential target for therapeutic intervention in malignant tumors.
Surgeon-Captain Peter de Bec Turtle
Authors: T. Hoskins
Journal: British Journal of Sports Medicine (1984)

Peter Turtle, who died suddenly in August 1983, did a great deal to foster friendly relations between the BASM and the Medical Officers of Schools Association, of which he was the dynamic Hon.Secretary from 1961 until 1974.He was a member of BASM from 1961 until he resigned on his retirement in 1978.After service in the Royal Navy and private practice in London he was appointed Medical Officer to Haileybury in 1954, and this led to his passionate interest in MOSA which lasted for the rest of his life.In 1975, during his term of office as President of the Association he was awarded the OBE "for services to MOSA".He strove constantly to inculcate high standards of medical care in schools, and sports medicine had a central place in his work.He attended most of the meetings of the International Union of School Health and Medicine, of which he was an officer, and presented a survey of 20 years' sports injuries at Haileybury at its meeting in Mexico City in 1975.An extremely friendly and hospitable man, his cheerful presence at gather- ings of school doctors is greatly missed.
REV3L confers chemoresistance to cisplatin in human gliomas: The potential of its RNAi for synergistic therapy
Authors: Huibo Wang, Shu-Yu Zhang, Shuai Wang, Juan Lu, Wenting Wu, Lin Weng, Dan Chen, Yu Zhang, Zhipeng Lu, Jingmin Yang, Yuanyuan Chen, Xu Zhang, Xiaofeng Chen, Caihua Xi, Daru Lu, Shiguang Zhao
Journal: Neuro-Oncology (2009)

The REV3L gene, encoding the catalytic subunit of human polymerase zeta, plays a significant role in the cytotoxicity, mutagenicity, and chemoresistance of certain tumors. However, the role of REV3L in regulating the sensitivity of glioma cells to chemotherapy remains unknown. In this study, we investigated the expression of the REV3L gene in 10 normal brain specimens and 30 human glioma specimens and examined the value of REV3L as a potential modulator of cellular response to various DNA-damaging agents. Reverse transcriptase PCR/real-time PCR analysis revealed that REV3L was overexpressed in human gliomas compared with normal brain tissues. A glioma cell model with stable overexpression of REV3L was used to probe the role of REV3L in cisplatin treatment; upregulation of REV3L markedly attenuated cisplatin-induced apoptosis of the mitochondrial apoptotic pathway. We therefore assessed the REV3L-targeted treatment modality that combines suppression of REV3L expression using RNA interference (RNAi) with the cytotoxic effects of DNA-damaging agents. Downregulation of REV3L expression significantly enhanced the sensitivity of glioma cells to cisplatin, as evidenced by the increased apoptosis rate and marked alterations in the anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl) and proapoptotic Bcl-2-associated x protein (Bax) expression levels, and reduced mutation frequencies in surviving glioma cells. These results suggest that REV3L may potentially contribute to gliomagenesis and play a crucial role in regulating cellular response to the DNA cross-linking agent cisplatin. Our findings indicate that RNAi targeting REV3L combined with chemotherapy has synergistic therapeutic effects on glioma cells, which warrants further investigation as an effective novel therapeutic regimen for patients with this malignancy.
901-7 The Survival Advantage of Early Grade 3 Patency After Thrombolysis for Infarction Increases Over Time
Authors: Allan M. Ross, Shyuan Cho, Conor Lundergan, Jonathan Reiner, Maarten Simoons, Frans Van de Wert, Karin Coyne, Robert Califf, Eric Topol
Journal: Journal of the American College of Cardiology (1995)
Differential Up-Regulation of Cytosolic and Membrane-Bound Heat Shock Protein 70 in Tumor Cells by Anti-Inflammatory Drugs
Authors: Mathias Gehrmann, Marion Brunner, Karin Pfister, Albrecht Reichle, Elisabeth Kremmer, Gabriele Multhoff
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Modulation of the heat shock protein (HSP) response affects sensitivity to therapeutic agents in cancer. Here, drugs with anti-inflammatory potential (cyclooxygenase 1/2 inhibitors) and peroxidase proliferator-activated receptor-γ agonists were analyzed for their capacity to affect Hsp70 expression in human cancer cells with a divergent Hsp70 membrane expression pattern. Experimental Design: In dose kinetics, the nonlethal concentration of acetyl-salicyl acid, celecoxib, rofecoxib, and the insulin-sensitizer pioglitazone was identified for the human adenocarcinoma cell line CX−. With the exception of CLX, which was diluted in DMSO, all reagents were dissolved in water. After treatment with the different compounds at nontoxic concentrations for 6 h, followed by a 1-h recovery period, the cytosolic Hsp70 levels were measured in CX-2 and CX− tumor cells by Western blot analysis. Fold increase was calculated in relation to the housekeeping protein tubulin. Membrane-bound Hsp70 was analyzed by flow cytometry using a FITC-labeled Hsp70-specific monoclonal antibody. Untreated cells and cells incubated with equivalent amounts of the diluting agents served as controls. The immunological function was tested in granzyme B apoptosis assays, standard 51Cr release assays, and antibody blocking studies. Results: Compared with aqua dest, the cytoplasmic amount of Hsp70 was equally enhanced in CX-2 and CX− cells by all compounds. An increase in membrane-bound Hsp70, detected selectively in CX− cells, corresponded to an enhanced sensitivity to granzyme B- and natural killer cell-mediated kill that was blockable by using a Hsp70-specific antibody. Conclusions: Although increase in cytosolic Hsp70 levels conferred resistance to further stress, membrane-bound Hsp70 rendered tumor cells more sensitive to the immunological attack mediated by granzyme B and natural killer cells. Our data provide a biological rational for combining anti-inflammatory drugs with immunotherapy in cancer therapy.
Structure and dynamics of the fenestrae-associated cytoskeleton of rat liver sinusoidal endothelial cells
Authors: Filip Braet, Ronald De Zanger, Marijke Baekeland, Evelyne Crabbé, Patrick Van Der Smissen, Eddie Wisse
Journal: Hepatology (1995)

This article describes the cytoskeleton associated with fenestrae and sieve plates of rat liver sinusoidal endothelial cells. Fenestrae control the exchange between the blood and parenchymal cells. We present evidence indicating that several agents that change the fenestrae and sieve plates also cause changes in the cytoskeleton. Cultured liver endothelial cells (LECs) were slightly fixed and treated with cytoskeleton extraction buffer. Detergent-extracted whole mounts of cultured cells were prepared for either scanning electron microscopy (SEM) or transmission electron microscopy (TEM). Extracted cells show an integral intricate cytoskeleton; sieve plates and fenestrae are delineated by cytoskeleton elements. Fenestrae are surrounded by a filamentous, fenestrae-associated cytoskeleton with a mean filament thickness of 16 nm. Sieve plates are surrounded and delineated by microtubuli, which form a network together with additional branching cytoskeletal elements. The addition of ethanol to cultured cells enlarged the diameter for these fenestrae-associated cytoskeleton rings by 5%, whereas serotonin treatment reduced the diameter by 20%. These observations indicate that the fenestrae-associated cytoskeleton probably changes the size of fenestrae after different treatments. After treatment with cytochalasin B the number of fenestrae increased. However, cytochalasin B did not change the structure of the fenestrae-associated cytoskeleton ring, but disperses the microtubuli. In conclusion, LECs have a cytoskeleton that defines and supports sieve plates and fenestrae. Fenestrae-associated cytoskeleton is a dynamic structure and plays a role in maintaining and regulating the size of fenestrae after different treatments. Therefore, the fenestrae-associated cytoskeleton controls the important hepatic function of endothelial filtration. (Hepatology 1995;21:180–189).
Molecular mechanisms of remodeling in human atrial fibrillation
Authors: B Brundel
Journal: Cardiovascular Research (2002)

An important acknowledgement of the last several years is that atrial fibrillation (AF) modifies the electrical properties of the atrium in a way that promotes its occurrence and maintenance. This arrhythmogenic electrophysiological remodeling is well established, but can not explain by itself that 'AF begets AF'. This review describes molecular changes involving rapid functional alterations and slower changes in protein expression that cause electrical remodeling and contractile dysfunction in AF. An important molecular feature of AF is the reduction in L-type Ca2+ channel function and protein expression. This reduction may serve to protect the cell against a potentially lethal Ca2+ overload resulting from the increased activation rate in AF. Further, the review discusses the possible role of proteolytic systems, notably the calpains, as a mechanism linking Ca2+ overload to reduced protein expression. Thus, it appears that the elaborate molecular changes in AF are directed primarily at protecting the myocyte from cellular stress. However, such early protection occurs at the expense of electrophysiological changes that promote the long-term maintenance of AF.
Mefloquine Compared with Doxycycline for the Prophylaxis of Malaria in Indonesian Soldiers
Authors: Colin Ohrt
Journal: Annals of Internal Medicine (1997)

Background: Mefloquine and doxycycline are the two drugs recommended for prophylaxis of malaria for visitors to areas where Plasmodium falciparum is resistant to chloroquine. Objective: To compare the efficacy and tolerability of mefloquine with those of doxycycline as prophylaxis for malaria. Design: Randomized, double-blind, placebo-controlled field trial of chemoprophylaxis of malaria. Setting: Northeastern Irian Jaya, Indonesia. Participants: 204 Indonesian soldiers. Intervention: After radical curative treatment, participants were randomly assigned to receive 100 mg of doxycycline per day and mefloquine placebo; 250 mg of mefloquine per week (preceded by a loading dose of 250 mg/d for 3 days) and doxycycline placebo; or placebos for both drugs. Prophylaxis lasted approximately 13 weeks. Measurements: The primary end point for efficacy was the first occurrence of malaria, as documented by a positive malaria smear. Malaria smears were obtained weekly and when patients had symptoms suggesting malaria. Reported symptoms were recorded daily, and an exit study questionnaire was conducted. Results: In the placebo group, 53 of 69 soldiers developed malaria (9.1 person-years), resulting in an attack rate of 5.8 cases per person-year (95% CI, 4.3 to 7.7 cases per person-year). Plasmodium falciparum accounted for 57% of cases, and P. vivax accounted for 43% of cases. No malaria occurred in the 68 soldiers (16.9 person-years) in the mefloquine group; thus, the protective efficacy of mefloquine was 100% (CI, 96% to 100%). In the doxycycline group, P. falciparum malaria occurred in 1 of 67 soldiers (16.0 person-years), yielding a protective efficacy of 99% (CI, 94% to 100%). Both drugs were very well tolerated. Conclusions: Mefloquine and doxycycline were both highly efficacious and well tolerated as prophylaxis of malaria in Indonesian soldiers.
Randomised placebo-controlled trial of rituximab (anti-CD20) in active ulcerative colitis
Authors: Shomron Ben-Horin
Journal: Gut (2011)

I read with interest the study by Leiper and colleagues,1 and the authors should be commended for initiating this investigator-driven study. However, I beg to differ with the conclusion that reads ‘Rituximab has no significant effect on inducing remission in moderately active UC [ulcerative colitis] not responding to oral steroids.’

The authors state that the sample-size calculations were based on 80% power for excluding, at p<0.05, an 80% remission rate with active treatment compared with a predicted 25% placebo remission rate …