tbuckley/cabot-search huggingface dataset:
Restoration of Promyelocytic Leukemia Protein-Nuclear Bodies in Neuroblastoma Cells Enhances Retinoic Acid Responsiveness
Authors: Jiang Hong Yu, Ayako Nakajima, Hiroshi Nakajima, Lisa R. Diller, Kenneth D. Bloch, Donald B. Bloch
Journal: Cancer Research (2004)

Abstract Neuroblastoma is the most common solid tumor of infancy and is believed to result from impaired differentiation of neuronal crest embryonal cells. The promyelocytic leukemia protein (PML)-nuclear body is a cellular structure that is disrupted during the pathogenesis of acute promyelocytic leukemia, a disease characterized by impaired myeloid cell differentiation. During the course of studies to examine the composition and function of PML-nuclear bodies, we observed that the human neuroblastoma cell line SH-SY5Y lacked these structures and that the absence of PML-nuclear bodies was a feature of N- and I-type, but not S-type, neuroblastoma cell lines. Induction of neuroblastoma cell differentiation with 5-bromo-2′deoxyuridine, all-trans-retinoic acid, or IFN-γ induced PML-nuclear body formation. PML-nuclear bodies were not detected in tissue sections prepared from undifferentiated neuroblastomas but were present in neuroblasts in differentiating tumors. Expression of PML in neuroblastoma cells restored PML-nuclear bodies, enhanced responsiveness to all-trans-retinoic acid, and induced cellular differentiation. Pharmacological therapies that increase PML expression may prove to be important components of combined modalities for the treatment of neuroblastoma.
The origin of intimal smooth muscle cells: are we on a steady road back to the past?
Authors: B. De Geest
Journal: Cardiovascular Research (2008)

The origin of intimal smooth muscle cells in native atherosclerosis, post-injury neointima formation, allograft vasculopathy, and vein graft atherosclerosis has been the subject of a confusing literature in the past decade. Rodriguez-Menocal et al. 1 show in an elegant series of experiments that neointimal cells in a rat balloon injury model originate from pre-existing vascular cells and only rarely come from circulating progenitor cells derived from the bone marrow or from other sources. Two different experimental approaches in an inbred strain of rats lead to essentially the same conclusions. First, the authors performed balloon angioplasty experiments in the right iliac artery of chimeric rats rescued following lethal irradiation with bone marrow from syngeneic transgenic rats expressing green fluorescent protein (GFP) under the control of a ubiquitously active promoter. Second, injured arteries were transplanted between syngeneic wild-type and GFP transgenic rats. This latter approach may identify smooth muscle cells derived from circulating progenitor cells irrespective whether these originate from the bone marrow or from other tissues. In light of the existing controversy on the contribution of circulating progenitor cells to vascular lesion formation,2–7 it is indicated to look at methodological issues that may explain the apparent contradictory results in the literature.

Before addressing these methodological issues, an important secondary observation of the study should be highlighted. The authors clearly show that both bone-marrow transplantation and syngeneic artery transplantation affect the neointima/media ratio post-balloon injury. Using the neointima/media ratio in non-irradiated and non-transplanted arteries as a reference, this ratio is roughly 1.8-fold lower in the injured arteries … 

*Corresponding author. Tel: +32 16 33 0578; fax: +32 16 34 5990. E-mail address : bart.degeest{at}med.kuleuven.be
We could eschew "UK style" rationing here too
Authors: Calum Paton
Journal: BMJ (2010)

In 2010 most Republicans in the United States, with the recent vice presidential candidate Sarah Palin promoted to chief Cassandra, became garment rending soothsayers, predicting doom when President Obama’s health reform became law. This is principally because they claim that the spectre of “rationing”’ stalks the land, threatening the ability to purchase expensive health care in the land of the free.

Attacks on rationing are familiar in the United Kingdom but from the other end of the political spectrum—from those who see it as a betrayal of the NHS, which should be not only free at the point of use and universal but also fully comprehensive. 

So how come both left and right oppose rationing? One view would say it is self interest. Those in the US who have good access to health care don’t want to lose it; …
Fibrinolytic activity in pregnancy.
Authors: I S Menon
Journal: BMJ (1970)

demonstrated in small amounts.Liver func- tion tests on that day were as follows:Total bilirubin 1.1 mg./100 ml.; conjugated bilirubin 0-6 mg./ 100 ml.; alanine transaminase 60 I.U.; alkaline phosphatase 10 K.A. units; thymol turbidity 1; thymol flocculation 0; col- loidal gold 0.
Disturbed hepatic carbohydrate management during high metabolic demand in medium-chain acyl–CoA dehydrogenase (MCAD)–deficient mice
Authors: Hilde Herrema, Terry G. J. Derks, Theo H. van Dijk, Vincent W. Bloks, Albert Gerding, Rick Havinga, Uwe J. F. Tietge, Michael Müller, Peter G. A. Smit, Folkert Kuipers, Dirk-Jan Reijngoud
Journal: Hepatology (2008)

Medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) catalyzes crucial steps in mitochondrial fatty acid oxidation, a process that is of key relevance for maintenance of energy homeostasis, especially during high metabolic demand. To gain insight into the metabolic consequences of MCAD deficiency under these conditions, we compared hepatic carbohydrate metabolism in vivo in wild-type and MCAD(-/-) mice during fasting and during a lipopolysaccharide (LPS)-induced acute phase response (APR). MCAD(-/-) mice did not become more hypoglycemic on fasting or during the APR than wild-type mice did. Nevertheless, microarray analyses revealed increased hepatic peroxisome proliferator-activated receptor gamma coactivator-1alpha (Pgc-1alpha) and decreased peroxisome proliferator-activated receptor alpha (Ppar alpha) and pyruvate dehydrogenase kinase 4 (Pdk4) expression in MCAD(-/-) mice in both conditions, suggesting altered control of hepatic glucose metabolism. Quantitative flux measurements revealed that the de novo synthesis of glucose-6-phosphate (G6P) was not affected on fasting in MCAD(-/-) mice. During the APR, however, this flux was significantly decreased (-20%) in MCAD(-/-) mice compared with wild-type mice. Remarkably, newly formed G6P was preferentially directed toward glycogen in MCAD(-/-) mice under both conditions. Together with diminished de novo synthesis of G6P, this led to a decreased hepatic glucose output during the APR in MCAD(-/-) mice; de novo synthesis of G6P and hepatic glucose output were maintained in wild-type mice under both conditions. APR-associated hypoglycemia, which was observed in wild-type mice as well as MCAD(-/-) mice, was mainly due to enhanced peripheral glucose uptake.Our data demonstrate that MCAD deficiency in mice leads to specific changes in hepatic carbohydrate management on exposure to metabolic stress. This deficiency, however, does not lead to reduced de novo synthesis of G6P during fasting alone, which may be due to the existence of compensatory mechanisms or limited rate control of MCAD in murine mitochondrial fatty acid oxidation.
Prospective randomised phase II study of docetaxel versus paclitaxel administered weekly in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy
Authors: E. Esteban, L. González de Sande, Y. Fernández, N. Corral, J Fra, I. Muñiz, J.M. Vieitez, I. Palacio, J.L. Fernández, E. Estrada, A.J. Lacave
Journal: Annals of Oncology (2003)
Activated tumor-infiltrating CD4+ regulatory T cells restrain antitumor immunity in patients with primary or metastatic liver cancer
Authors: Alexander Pedroza-Gonzalez, Cornelis Verhoef, Jan N. M. Ijzermans, Maikel P. Peppelenbosch, Jaap Kwekkeboom, Joanne Verheij, Harry L. A. Janssen, Dave Sprengers
Journal: Hepatology (2012)

Abstract The mechanisms that enable liver cancer to escape elimination by the immune system remain unclear, but their elucidation may provide novel therapeutic interventions. We investigated the influence of tumor-infiltrating regulatory T cells on tumor-specific T cell responses in patients with liver cancer, using ex vivo isolated cells from individuals with hepatocellular carcinoma (HCC) or liver metastases from colorectal cancer (LM-CRC). Here we report that in both HCC and LM-CRC, CD4+CD25+Foxp3+ regulatory T cells (Tregs) accumulate in the tumor milieu and are potent suppressors of autologous tumor-specific T cell responses. Especially in LM-CRC, where Treg accumulation is more prominent, there is good evidence for local proliferation of Tregs at the cancer site. We show that tumor Tregs up-regulate the expression of glucocorticoid-induced tumor necrosis factor receptor (GITR) compared with Tregs in tumor-free liver tissue and blood. Importantly, treatment with soluble GITR ligand (GITRL) induces a decrease in the suppression mediated by the activated tumor-infiltrating Tregs and restores the proliferative capacity and cytokine production of CD4+CD25− T cells. Conclusion : Our results show that tumor-associated Tregs are critical for immune evasion in liver cancer, and we propose that GITRL constitutes a rational treatment for this disease. (Hepatology 2013)
Use of whole blood platelet lumi‐aggregometry to optimize anti‐platelet therapy in patients with chronic myeloproliferative disorders
Authors: A. Manoharan, R. Gemmell, T. Hartwell
Journal: American Journal of Hematology (2006)

Twenty-seven patients with chronic myeloproliferative disorders and in vitro evidence of platelet hyperactivity on whole blood platelet lumi-aggregometry were commenced on anti-platelet therapy comprising aspirin, clopidogrel, and/or odorless garlic and the studies were repeated to assess the efficacy of the therapeutic agent(s). Only 8 patients showed clear evidence of anti-platelet effect while receiving the standard low-dose (100 mg/day) aspirin therapy. Thirteen patients required a higher dosage of aspirin and/or an additional anti-platelet agent to achieve therapeutic adequacy. Lumi-aggregometry also proved useful to optimize therapy in the 6 patients who received clopidogrel or odorless garlic because of aspirin intolerance.
Evaluation of Wellness Determinants and Interventions by Citizen Scientists
Authors: Huseyin Naci, John P. A. Ioannidis
Journal: JAMA (2015)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Major histocompatibility complex class II-associated p41 invariant chain fragment is a strong inhibitor of lysosomal cathepsin L.
Authors: T Bevec, V Stoka, G Pungercic, I Dolenc, V Turk
Journal: The Journal of Experimental Medicine (1996)

The invariant chain (Ii) is associated with major histocompatibility complex class II molecules during early stages of their intracellular transport. In an acidic endosomal/lysosomal compartment, it is proteolytically cleaved and removed from class II heterodimers. Participation of aspartic and cysteine proteases has been observed in in vitro degradation of Ii, but the specific enzymes responsible for its in vivo processing are as yet undefined. We have previously isolated a noncovalent complex of the lysosomal cysteine protease cathepsin L with a peptide fragment derived from the p41 form of Ii from human kidney. Here we show that this Ii fragment, which is identical to the alternatively spliced segment of p41, is a very potent competitive inhibitor of cathepsin L (equilibrium inhibition constant Ki = 1.7 X 10(-12) M). It inhibits two other cysteine proteases, cathepsin H and papain, but to much lesser extent. Cysteine proteases cathepsins B, C, and S, as well as representatives of serine, aspartic, and metalloproteases, are not inhibited at all. These findings suggest a novel role for p41 in the regulation of various proteolytic activities during antigen processing and presentation. The Ii inhibitory fragment shows no sequence homology with the known cysteine protease inhibitors, and may, therefore, represent a new class.
Data Sharing, Year 1 — Access to Data from Industry-Sponsored Clinical Trials
Authors: Brian L. Strom, Marc Buyse, John Hughes, Bartha M. Knoppers
Journal: New England Journal of Medicine (2014)

Since May 2013, researchers have been able to request access to deidentified patient-level data from GlaxoSmithKline–sponsored clinical trials, subject to oversight by an independent review panel. The initiative has been a productive first step in transparency.
Safety and Efficacy of Bronchial Thermoplasty in Symptomatic, Severe Asthma
Authors: Ian D Pavord, Gerard Cox, Neil C Thomson, Adalberto S Rubin, Paul A Corris, Robert M Niven, Kian F Chung, Michel Laviolette
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Bronchial thermoplasty (BT) is designed to reduce airway smooth muscle and improve asthma control.This study was conducted to determine the safety and efficacy of this procedure in subjects with symptomatic, severe asthma.Adults who were symptomatic despite treatment with fluticasone or equivalent at more than 750 mug/day, a long-acting beta(2)-agonist, and other medications, which could include 30 mg or less of oral prednisolone/day, were randomized to BT or to a control group. After treatment, subjects entered a 16-week steroid stable phase (Weeks 6-22), a 14-week steroid wean phase (Weeks 22-36), and a 16-week reduced steroid phase (Weeks 36-52).BT resulted in a transient worsening of asthma symptoms. Seven hospitalizations for respiratory symptoms occurred in 4 of 15 BT subjects during the treatment period. Five hospitalizations were within 3 days of treatment. Two subjects had segmental collapse involving the most recently treated lobe; one required bronchoscopy and aspiration of a mucus plug. There were no hospitalizations during this period in the 17 control subjects. The rate of hospitalizations was similar in both groups in the post-treatment period. At 22 weeks, BT subjects had significant improvements versus control subjects in rescue medication use (-26.6 +/- 40.1 vs. -1.5 +/- 11.7 puffs/7 d, P < 0.05), prebronchodilator FEV(1)% predicted (14.9 +/- 17.4 vs. -0.94 +/- 22.3%, P = 0.04), and Asthma Control Questionnaire scores (-1.04 +/- 1.03 vs. -0.13 +/- 1.00, P = 0.02). Improvements in rescue medication use and Asthma Control Questionnaire scores remained significantly different from those of controls at 52 weeks.BT is associated with a short-term increase in asthma-related morbidity. However, there is preliminary evidence of long-lasting improvement in asthma control. Clinical trial registered with www.clinicaltrials.gov (NCT 00214539).
Can the prognosis of individual patients with glioblastoma be predicted using an online calculator?
Authors: C. Parks, J. Heald, G. Hall, I. Kamaly-Asl
Journal: Neuro-Oncology (2013)

In an exploratory subanalysis of the European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada (EORTC/NCIC) trial data, Gorlia et al. identified a variety of factors that were predictive of overall survival, including therapy administered, age, extent of surgery, mini-mental score, administration of corticosteroids, World Health Organization (WHO) performance status, and O-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Gorlia et al. developed 3 nomograms, each intended to predict the survival times of patients with newly diagnosed glioblastoma on the basis of individual-specific combinations of prognostic factors. These are available online as a "GBM Calculator" and are intended for use in patient counseling. This study is an external validation of this calculator. One hundred eighty-seven patients from 2 UK neurosurgical units who had histologically confirmed glioblastoma (WHO grade IV) had their information at diagnosis entered into the GBM calculator. A record was made of the actual and predicted median survival time for each patient. Statistical analysis was performed to assess the accuracy, precision, correlation, and discrimination of the calculator. The calculator gives both inaccurate and imprecise predictions. Only 23% of predictions were within 25% of the actual survival, and the percentage bias is 140% in our series. The coefficient of variance is 76%, where a smaller percentage would indicate greater precision. There is only a weak positive correlation between the predicted and actual survival among patients (R2 of 0.07). Discrimination is inadequate as measured by a C-index of 0.62. The authors would not recommend the use of this tool in patient counseling. If departments were considering its use, we would advise that a similar validating exercise be undertaken.
CXCR3 and E 7 integrin identify a subset of CD8+ mature thymocytes that share phenotypic and functional properties with CD8+ gut intraepithelial lymphocytes
Authors: F Annunziato
Journal: Gut (2005)

We previously demonstrated the existence of two distinct subsets of T cell receptor (TCR)alphabeta+CD8alphabeta+ single positive (SP) cells in human postnatal thymus which express the chemokine receptor CCR7 or CXCR3 and migrate in vitro in response to their specific ligands.To investigate whether these two CD8+ thymocyte subsets had distinct peripheral colonisation.TCRalphabeta+CD8+ SP cells were obtained from normal postnatal thymus, mesenteric lymph node (LNs), small bowel, and peripheral blood (PB) specimens. Cells were then evaluated for expression of surface molecules, cytolytic potential, telomere length, and profile of cytokine production.CD8+CCR7+CXCR3- thymocytes exhibited CD62L, in common with those which localise to LNs. In contrast, CD8+CCR7-CXCR3+ thymocytes lacked CD62L but exhibited CD103, similar to intraepithelial lymphocytes (IELs) present in the gut mucosa where the CXCR3 ligand, CXCL10, and the CD103 ligand, E-cadherin, are highly and consistently expressed. In addition, thymocytes and gut CD8+CXCR3+CD103+ cells showed comparable telomere length, which was higher than that of PB CXCR3+CD8+ T cells. However, both of these populations contained perforin and granzyme A, and displayed the ability to produce interferon gamma and interleukin 2. Of note, CXCR3 deficient, in comparison with wild-type C57Black/6, mice showed decreased proportions of CD3+CD8alphabeta+ and increased proportions of CD3+CD8alphaalpha+ lymphocytes at gut level. Moreover, adoptive transfer of CD3+CD8alphabeta+ thymocytes from wild-type into CXCR3 deficient mice resulted in a significant increase in CD3+CD8alphabeta+ T cells in the gut mucosa but not in other tissues.The results of this study demonstrate the existence of a previously unrecognised subset of TCRalphabeta+CD8alphabeta+ SP CXCR3+CD103+ thymocytes which share phenotypic and functional features with CD8+ IELs, thus suggesting the possibility of their direct colonisation of the gut mucosa.
The important role of the arthroscopic hip surgery in the athletes with hip injuries. our experience. a retrospective study
Authors: G Tsikouris, I Tsolos, Ch Gosis, S Plessas, S Moschonas, D Tsikouris
Journal: British Journal of Sports Medicine (2011)

Hip arthroscopy has gradually evolved over the past two decades.Recently hip arthroscopy has increase its role in diagnosis and treatment for specific intraarticular and extraarticular hip injuries and especially for soft tissue injuries. Material and methods February 2004–March 2010, 48 athletes, football players, basketball players, weight lifters, gymnasts, three water polo players. Mean age: 32 years. (19–39 year old) Instrumentation and equipment 70°, 4.5 mm arthroscope, High flow rate mechanical pump, 15 gauge 6″ cardiac needle, Convex full radius chondroplasty blades, special electrocautery. Distraction apparatus, DVD unit, mechanical water pump unit, mage intensifier Indications Undiagnosed hip pain, early osteoarthritic signs, labral pathology, loose bodies, osteochondral defects, sepsis, ligamentum teres, trauma, synovitis, femoral acetabular impingment (FAI), ‘frozen hip’, chondrocalcinosis. Symptoms Deep dull ache pain during hip flexion and external or internal rotation, decrease range of motion, decreased hip flexion. Clinical findings 30/48 Cam sign: positive, 12/48 Pincher sign: positive, impingement syndrome in hip flexion and internal and rotation and occasionally in external rotation, snapping hip, iliopsoas tendinitis. Surgery Standard orthopaedic traction table, supine position, hip is extended and abducted 25° Portals Anterolateral, posterolateral, modified anterolateral Intraoperative findings Detachment of the labrum, 10/48 erosion of the articular cartilage of the acetabulum and drilling of the bare area, 30/48 Cam sign excision, 12/48 pincer sign excision, 8/48 superior medial and superior lateral labrum repair with anchors. (intra-articularly) Results The modified Harris Hip Score was used for their classification of their symptoms. Two of the athletes had a residual pain due to an iliopsoas tendinitis. 45/48 had relief from their arm symptoms, 1/48 will need to be reoperated shortly (after he developed FAI), 2/48 are treated for the iliopsoas tendinitis. Conclusion The athletes with symptoms of an internal hip pain and FAI signs after a detailed clinical exam of their hip and after failure of their conservative treatment, will certainly get a benefit from an arthroscopic procedure (which is technically demanding).
Maeve O'Connor "Editing scientific books and journals"
Authors: H. E. Robson
Journal: British Journal of Sports Medicine (1978)

The only fault I could find with this book is that it has been written some twelve years too late to prevent me making many of the errors it warns against, and that I have tried to eliminate slowly on a trial-and-error basis since taking over responsibility for this Journal in 1967.Much of the advice given in this book will go towards further improvements in the future.The early chapters describe the duties of the editor, how he should be selected, what help he needs, how to appoint referees and an editorial board, and how to persuade these often very senior scientists and clinicians to keep papers moving.The various processes of handling manuscripts at all stages, and the technical processes of preparing them for the printer, are all described in great detail.There are interesting chapters on the printer's and block-maker's techniques, on the financial aspects of publishing books and journals, and a look into possible future developments.The ten appendices show draft contracts with publishers, assignments of copyright, guidelines for authors, referees and reviewers, methods of laying out references (and we already seem to have found the recommended way ourselves, though we could simplify the lay-out and save the printer changes of fount without losing clarity).Maeve O'Connor is the senior editor of the Ciba Foundation, whose symposia proceedings set the standard for all scientific proceedings, with the possible exception of the Royal Society, which has had some three centuries longer in which to develop.