tbuckley/cabot-search huggingface dataset:
Pseudo-Myocardial Infarction Versus Pseudo-Pseudo-Myocardial Infarction
Authors: Kenneth M. Kessler
Journal: Circulation (2001)

To the Editor:Hung and colleagues 1 present a very important example of a pseudo-infarction pattern presumably related to pancreatitis, one of several clinical situations in which thrombolytic therapy is either not indicated or contraindicated.I am intrigued by the pattern of the bizarre T waves in the limb leads and wonder if part or all of this phenomenon is artifact.The T waves are of unusually abrupt onset and offset.They are of greatest magnitude in leads I, II, and aVR.Lead III, however, appears to be isoelectric to this postulated artifact but not to the T wave that is 1 to 2 mm in height and gently (ie, normally) inscribed.The artifact is of about half the magnitude and is approximately equal in leads aVL and aVF.The precordial leads reflect the artifact, which is increasing the apparent height of the actual T waves, which appear inscribed on top of the artifactual elevation.The initial j-point or ST elevation in the precordial leads appears real, in that the onset is before that of the artifact in the limb leads but difficult to interpret in the presence of the artifact.Because the artifact is of greatest magnitude in the 3 leads that have a right arm electrode attachment in common, could there have been motion of the electrode or its connections leading to this artifact?For instance, the timing of onset, duration, and contour of the artifact seem compatible with an arterial pulse wave altering skin contact with each heart beat.It would be important to know whether the bizarre T waves in the limb leads and the terminal T wave elevation in the precordial leads all resolved slowly or whether there was an abrupt change that would favor artifact.The follow up electrocardiograms are essential to resolving this issue.Finally, whenever an unusual, bizarre, or unexplainable electrocardiographic finding is detected, it is most helpful to repeat the electrocardiogram personally, with a machine that is known to be trustworthy, to confirm that the findings are indeed real.
Interleukin 2 regulates the expression of Tac antigen on peripheral blood T lymphocytes.
Authors: K Welte, M Andreeff, E Platzer, K Holloway, B Y Rubin, M A Moore, R Mertelsmann
Journal: The Journal of Experimental Medicine (1984)

We investigated the effect of OKT3 antibody and interleukin 2 (IL-2) on Tac antigen expression and the proliferation of human peripheral blood mononuclear leukocytes. OKT3 monoclonal antibody at low, nonmitogenic concentrations (25 pg/ml) or IL-2 alone at optimal concentrations (20 U/ml) did not induce IL-2 receptor expression, as measured by Tac antibody or by T cell proliferation. However, costimulation with these concentrations of OKT3 antibody and IL-2 led to Tac antigen expression and T cell proliferation. These data suggest that the T cells are activated in two steps: OKT3 antibody at 25 pg/ml does not induce Tac antigen expression, but preactivates T cells to become responsive to IL-2. The addition of exogenous IL-2 then leads to expression of the IL-2 receptor, as recognized by Tac antibody, and to subsequent proliferation.
Who Benefits From Intensive Therapy in Type 1 Diabetes?
Authors: Barbara J. Anderson
Journal: Diabetes Care (2003)

Our assumptions about what kinds of patients benefit most from intensive therapy (IT) are rarely questioned. Thanks to the empirical evidence provided by Wysocki et al. (1) in this issue of Diabetes Care , we now have a fresh perspective on the critical question of who benefits from IT. In the landmark study that established the benefits of IT for people with type 1 diabetes, the Diabetes Control and Complications Trial (DCCT) employed strict eligibility criteria and screened out patients who were assessed as too unstable or unmotivated to follow through on the rigorous demands of IT. Each DCCT participant had to complete a series of demanding behavioral tasks during the run-in period before randomization. Thus, the DCCT study population was a “young, generally healthy, and highly motivated” sample (2) that was also steadily employed and lived in a stable home environment. The assumption that IT was best suited for the highly adherent and informed patient, which guided the DCCT screening procedure and subsequent decisions about who would adhere to and benefit from it, has become dogma (2).

This legacy is turned upside down by the empirical data of Wysocki et al. Their data suggest that patients/parents with the lowest levels of diabetes knowledge and adherence had the greatest glycemic benefits from IT. As one part of a larger pediatric randomized trial of IT versus usual care (UC), the authors sought to identify and objectively characterize the subgroup of youth (and their families) that experienced the most significant glycemic benefits from participation in IT. As in the DCCT, very different levels of support and services were available to families in the IT condition as compared with UC. Families randomized to UC received quarterly clinical visits with the nurse and physician, one annual clinical visit with a dietitian and a …
Sports nutrition (handbook of sports medicine and science)
Authors: C Williams
Journal: British Journal of Sports Medicine (2005)

Edited by R J Maughan, L M Burke. London: Published by Blackwell Publishing, 2002, £25.95, softcover, pp 187. ISBN 063205814

At first glance, this book could be mistaken as the abridged version of Nutrition in sport , which is the latest publication in the IOC Medical Commission’s Encyclopaedia in sports medicine and science series. Nutrition in sport is the definitive text on sports nutrition because all the relevant topics are covered by internationally recognised experts in the field. It is a delight for researchers and teachers because it provides authoritative, well written comprehensive reviews of the current literature on all the relevant topics in sports nutrition. So why bring out another text so quickly after the publication of Nutrition in sport ? The answer is to help bridge the gap between principles and practice. This Handbook succeeds because it not only provides the reader with the essential background on the nutritional preparation for, the participation …
Tribbles-1 as a Novel Biomarker of Chronic Antibody-Mediated Rejection
Authors: Joanna Ashton-Chess, Magali Giral, Michael Mengel, Karine Renaudin, Yohann Foucher, Wilfried Gwinner, Christophe Braud, Emilie Dugast, Thibaut Quillard, Pamela Thebault, Elise Chiffoleau, Cécile Braudeau, Béatrice Charreau, Jean-Paul Soulillou, Sophie Brouard
Journal: Journal of the American Society of Nephrology (2008)

Diagnosis of the specific cause of late allograft injury is necessary if more personalized and efficient immunosuppressive regimens are to be introduced. This study sought previously unrecognized biomarkers for specific histologic diagnoses of late graft scarring by comparison of gene sets from published microarray studies. Tribbles-1 (TRIB1), a human homolog of Drosophila tribbles, was identified to be a potentially informative biomarker. For testing this, mRNA expression in 76 graft biopsies, 71 blood samples, and 11 urine samples were profiled from independent cohorts of renal transplant patients with different histologic diagnoses recruited at two European centers. TRIB1 but not TRIB2 or TRIB3 was found to be a potential blood and tissue biomarker of chronic antibody-mediated rejection, an active immune-mediated form of chronic allograft failure associated with a poor prognosis. TRIB1 mRNA levels in peripheral blood mononuclear cells discriminated patients with chronic antibody-mediated rejection from those with other types of late allograft injury with high sensitivity and specificity. TRIB1 was also upregulated in a rodent model of chronic cardiac vasculopathy, suggesting that this biomarker may be useful in other solid-organ transplants and across species. It was determined that TRIB1 is expressed primarily by antigen-presenting cells and activated endothelial cells. Overall, these data support the potential use of TRIB1 as a biomarker of chronic antibody-mediated allograft failure.
2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention
Authors: Glenn N. Levine, Eric R. Bates, James C. Blankenship, Steven R. Bailey, John A. Bittl, Bojan Cercek, Charles E. Chambers, Stephen G. Ellis, Robert A. Guyton, Steven M. Hollenberg, Umesh N. Khot, Richard A. Lange, Laura Mauri, Roxana Mehran, Issam D. Moussa, Debabrata Mukherjee, Brahmajee K. Nallamothu, Henry H. Ting
Journal: Circulation (2011)
Detection and correction of false segmental duplications caused by genome mis-assembly
Authors: David R Kelley, Steven L Salzberg
Journal: Genome biology (2010)

Abstract Diploid genomes with divergent chromosomes present special problems for assembly software as two copies of especially polymorphic regions may be mistakenly constructed, creating the appearance of a recent segmental duplication. We developed a method for identifying such false duplications and applied it to four vertebrate genomes. For each genome, we corrected mis-assemblies, improved estimates of the amount of duplicated sequence, and recovered polymorphisms between the sequenced chromosomes.
Reorganization of Adjacent Gene Relationships in Yeast Genomes by Whole-Genome Duplication and Gene Deletion
Authors: J. K. Byrnes
Journal: Molecular Biology and Evolution (2006)

In Saccharomyces, an ancient whole-genome duplication (WGD) and widespread duplicate gene deletion resulted in extensive reorganization of adjacent gene relationships. We have studied the evolution of adjacent gene pairs' identity, orientation, and spacing following whole-genome duplication and deletion (WGD-D) using comparative genomic analyses and simulations. Surveying adjacent gene organization across the Saccharomyces species complex, we find a genome-wide bias toward divergently and convergently transcribed gene pairs in all species but a reduction in this bias in the species that underwent WGD-D. Among neutral models of WGD-D, only single-gene deletion can produce the appropriate reduction in orientation bias and recapitulate the pattern of short, highly dispersed deletions we observe in Saccharomyces cerevisiae. To characterize the dynamics of WGD-D, we trace the conservation and creation of adjacent gene pairs along the S. cerevisiae lineage. We find that newly created adjacencies have a tandem orientation bias, while adjacencies conserved from prior to WGD-D have the same divergent-convergent bias as found in the species that diverged before WGD. We also find that adjacent gene pairs produced by WGD-D gained greater intergenic spacing but that this is reduced in the older adjacencies. Given this, and the preponderance of short deleted blocks, we argue that the deletion phase of WGD-D occurred primarily by small inactivating mutations followed by numerous small deletions. Newly created adjacent gene pairs also have an initial increase in mean log2 expression ratios and maximal expression levels, suggesting that increased intergenic spacing caused a genome-wide reduction in transcriptional interference.
Recovery of Mycobacterium tuberculosis DNA in biopsies of erythema induratum-results in a series of patients using an improved polymerase chain reaction technique
Authors: B. Vieites, J.M. Suarez-Penaranda, M.L. Perez del Molino, H. Vazquez-Veiga, F. Pardo, E. Del Rio, D. Sanchez-Aguilar, J. Forteza
Journal: British Journal of Dermatology (2005)
Risk disclosure prior to bronchoscopy
Authors: C Echevarria, G A Anwar, S Parker, R M Rutherford
Journal: Thorax (2010)

We read with great interest the recent article by Uzbeck et al 1 demonstrating increased anxiety in patients following detailed risk disclosure prior to bronchoscopy. This timely well-conducted study engages with the challenging area of informed consent, and the authors eloquently outline the difficulties in balancing patient autonomy and physician desire to minimise patient anxiety but also to avoid litigation. We agree that the small increase in patient anxiety following explicit consent “seems a price worth paying for most patients”. We wish to comment, however, on a couple of …
Therapy of experimental type 1 diabetes by isolated Sertoli cell xenografts alone
Authors: Francesca Fallarino, Giovanni Luca, Mario Calvitti, Francesca Mancuso, Claudio Nastruzzi, Maria C. Fioretti, Ursula Grohmann, Ennio Becchetti, Anne Burgevin, Roland Kratzer, Peter van Endert, Louis Boon, Paolo Puccetti, Riccardo Calafiore
Journal: The Journal of Experimental Medicine (2009)

Type I diabetes mellitus is caused by autoimmune destruction of pancreatic β cells, and effective treatment of the disease might require rescuing β cell function in a context of reinstalled immune tolerance. Sertoli cells (SCs) are found in the testes, where their main task is to provide local immunological protection and nourishment to developing germ cells. SCs engraft, self-protect, and coprotect allogeneic and xenogeneic grafts from immune destruction in different experimental settings. SCs have also been successfully implanted into the central nervous system to create a regulatory environment to the surrounding tissue which is trophic and counter-inflammatory. We report that isolated neonatal porcine SC, administered alone in highly biocompatible microcapsules, led to diabetes prevention and reversion in the respective 88 and 81% of overtly diabetic (nonobese diabetic [NOD]) mice, with no need for additional β cell or insulin therapy. The effect was associated with restoration of systemic immune tolerance and detection of functional pancreatic islets that consisted of glucose-responsive and insulin-secreting cells. Curative effects by SC were strictly dependent on efficient tryptophan metabolism in the xenografts, leading to TGF-β–dependent emergence of autoantigen-specific regulatory T cells and recovery of β cell function in the diabetic recipients.
Differential Suppression of Thromboxane Biosynthesis by Indobufen and Aspirin in Patients With Unstable Angina
Authors: Francesco Cipollone, Paola Patrignani, Anita Greco, Maria Rosaria Panara, Roberto Padovano, Franco Cuccurullo, Carlo Patrono, Antonio G. Rebuzzi, Giovanna Liuzzo, Gaetano Quaranta, Attilio Maseri
Journal: Circulation (1997)

Background We have previously reported aspirin failure in suppressing enhanced thromboxane (TX) biosynthesis in a subset of episodes of platelet activation during the acute phase of unstable angina. The recent discovery of a second prostaglandin H synthase (PGHS-2), inducible in response to inflammatory or mitogenic stimuli, prompted us to reexamine TXA 2 biosynthesis in unstable angina as modified by two cyclooxygenase inhibitors differentially affecting PGHS-2 despite a comparable impact on platelet PGHS-1. Methods and Results We randomized 20 patients (15 men and 5 women aged 59±10 years) with unstable angina to short-term treatment with aspirin (320 mg/d) or indobufen (200 mg BID) and collected 6 to 18 consecutive urine samples. Urinary 11-dehydro-TXB 2 was extracted and measured by a previously validated radioimmunoassay as a reflection of in vivo TXA 2 biosynthesis. Metabolite excretion averaged 102 pg/mg creatinine (median value; n=76) in the aspirin group and 55 pg/mg creatinine (median value; n=99) in the indobufen group ( P &lt;.001). There were 16 samples (21%) with 11-dehydro-TXB 2 excretion &gt;200 pg/mg creatinine among patients treated with aspirin versus 6 such samples (6%) among those treated with indobufen ( P &lt;.001). In vitro and ex vivo studies in healthy subjects demonstrated the capacity of indobufen to largely suppress monocyte PGHS-2 activity at therapeutic plasma concentrations. In contrast, aspirin could only inhibit monocyte PGHS-2 transiently at very high concentrations. Conclusions We conclude that in unstable angina, episodes of aspirin-insensitive TXA 2 biosynthesis may reflect extraplatelet sources, possibly expressing the inducible PGHS in response to a local inflammatory milieu, and a selective PGHS-2 inhibitor would be an ideal tool to test the clinical relevance of this novel pathway of arachidonic acid metabolism in this setting.
Anti-CD26 Monoclonal Antibody–Mediated G1-S Arrest of Human Renal Clear Cell Carcinoma Caki-2 Is Associated with Retinoblastoma Substrate Dephosphorylation, Cyclin-Dependent Kinase 2 Reduction, p27kip1 Enhancement, and Disruption of Binding to the Extracellular Matrix
Authors: Teruo Inamoto, Tadanori Yamochi, Kei Ohnuma, Satoshi Iwata, Shinichiro Kina, Sakiko Inamoto, Masaaki Tachibana, Yoji Katsuoka, Nam H. Dang, Chikao Morimoto
Journal: Clinical Cancer Research (2006)

Abstract Purpose: CD26 is a 110-kDa cell surface glycoprotein with a role in tumor development through its association with key intracellular proteins. In this report, we show that binding of soluble anti-CD26 monoclonal antibody (mAb) inhibits the growth of the human renal carcinoma cells in both in vitro and in vivo experiments. Experimental Design: Growth inhibition by anti-CD26 mAb was assessed using proliferation assay and cell cycle analysis. Anti-CD26 mAb, chemical inhibitors, dominant-negative, or constitutively active forms of specific signaling molecules were used to evaluate CD26-associated pathways. The in vivo growth-inhibitory effect of anti-CD26 mAb was also assessed in a human renal carcinoma mouse xenograft model. Results: In vitro experiments show that anti-CD26 mAb induces G1-S cell cycle arrest associated with enhanced p27kip1 expression, down-regulation of cyclin-dependent kinase 2, and dephosphorylation of retinoblastoma substrate. Moreover, our data show that enhanced p27kip1 expression is dependent on the attenuation of Akt activity. Anti-CD26 mAb also internalizes cell surface CD26, leading to decreased binding to collagen and fibronectin. Experiments with a mouse xenograft model involving human renal carcinoma cells show that anti-CD26 mAb treatment drastically inhibits tumor growth in tumor-bearing mice, resulting in enhanced survival. Conclusions: Taken together, our data strongly suggest that anti-CD26 mAb treatment may have potential clinical use for CD26-positive renal cell carcinomas.
Toxicity and Costs of Toxicity Associated With New Cancer Drugs: International Implications
Authors: Terhi Hermanson, LeAnn B. Norris, John Bian, Oliver Sartor, Charles L. Bennett
Journal: Journal of Clinical Oncology (2014)

New cancer drugs provide hope for millions of individuals worldwide.These opportunities, often accompanied by expensive price tags, require discussions of the true clinical value of these agents.Although Amir et al 1 previously described the benefits and market costs of these new cancer agents, the current study by Niraula et al 2 addresses equally important but different questions.What are the adverse effects of new anticancer drugs?Are more targeted drugs distinctly different from other cancer therapies with respect to toxicities?What is the financial burden associated with these toxicities?These therapies bring new therapeutic possibilities.However, high expectations can be easily dampened by the occurrence of serious, frequent, or costly toxicities.As the authors opine, it is important to know in advance whether allocating resources to new anticancer drugs is reasonable in relation to other priorities and whether allocation of resources is efficient and appropriate.The authors 2 grouped cancer therapies approved by the US Food and Drug Administration between 2000 and 2011 into three categories: three new drugs directed against specific molecular targets on cancer cells, nine less specific targeted drugs, and seven new chemotherapeutic agents.The primary results of the study provide exciting news.New anticancer drugs associated with specific molecular targets on cancer cells (targeted drugs [TDs]) are less toxic than less specific targeted agents (LTD) or traditional chemotherapeutic agents (CT).Toxicity management leads to small increases in overall treatment costs.TDs are less expensive than LTDs although pricier than traditional chemotherapy.These higher costs are offset by less costly toxicity management.The prior study by these authors 1 showed that TDs also have the potential for remarkable efficacy.Given that TDs offer potentially great clinical benefit, it seems that they have the capacity to offer enhanced value compared with traditional anticancer treatments.These findings have international implications.Resources are limited in every country, and in the long run, it is unlikely that any country can afford to offer all available treatments without value assessments.
Normal Lymphocyte Development but Delayed Humoral Immune Response in CD81-null Mice
Authors: Holden T. Maecker, Shoshana Levy
Journal: The Journal of Experimental Medicine (1997)

CD81 is a cell surface molecule expressed on many cell types and associated with the CD19/ CD21/Leu13 signal-transducing complex on B cells. A recent report implies that CD81 expression on thymic stromal cells is important in the maturation of thymocytes from CD4− CD8− to CD4+CD8+. However, we have produced CD81-null mice by gene targeting, and find that they undergo normal development of thymocytes and express normal numbers of T cells. B cells are also found in normal numbers in the spleen, blood, and peritoneal cavity of CD81-null mice, but they express a lower level of CD19 compared to heterozygous littermates. Finally, early antibody responses to the protein antigen ovalbumin are weaker in CD81null mice compared to their heterozygous littermates. This is consistent with the proposed role of the CD19/CD21/CD81-signaling complex in lowering the threshold for B cell responses. These results show that CD81 is not required for maturation of T cells, but is important for optimal expression of CD19 on B cells and optimal stimulation of antibody production.
Signaling by lymphocyte function-associated antigen 1 (LFA-1) in B cells: enhanced antigen presentation after stimulation through LFA-1.
Authors: V T Moy, A A Brian
Journal: The Journal of Experimental Medicine (1992)

To examine the role of lymphocyte function-associated antigen 1 (LFA-1) expression on murine B cells as it pertains to their function in T cell activation, we carried out antigen-presentation assays in tissue culture wells coated with a purified, secreted form of the murine intercellular adhesion molecule 1 (ICAM-1). We observed a significant decrease in the concentration of antigen required to activate a T cell hybridoma and primary T cells in wells coated with ICAM-1. This effect was dependent on the amount of ICAM-1 used to coat the wells and was also observed in wells coated with anti-LFA-1-monoclonal antibodies and was blocked by soluble anti-LFA-1 antibodies. The effect on antigen dose was most pronounced in assays carried out with an ICAM-1-deficient mutant B lymphoma cell line, small resting primary B cells, and unfractionated primary B cells at low concentrations. No decrease in the antigen dose was observed if the B cells were chemically fixed or treated with ricin, or when antigen was presented by a HeLa cell line transfected with murine class II major histocompatibility complex (MHC) genes, indicating that the immobilized ICAM-1 was mediating its effect through B cell LFA-1, and that B cell protein synthesis was required. The enhancing effect was also observed if the B cells were prepulsed with antigen, indicating that improved uptake or processing of antigen, or increased class II MHC expression were unlikely mechanisms.