tbuckley/cabot-search huggingface dataset:
Single bolus administration of recombinant tissue plasminogen activator: effects on infarct related vessel patency, microvascular perfusion, and microvascular reocclusion in a canine model of thrombotic occlusion/reperfusion
Authors: D. J Longridge, M. J Follenfant, A. J Ford
Journal: Cardiovascular Research (1991)

Study objective – The aim was to evaluate the thrombolytic efficacy of recombinant double chain tissue plasminogen activator (Duteplase, t-PA) given as a single intravenous bolus versus an infusion in a canine model of coronary arterial occlusion/reperfusion. Design – Coronary arterial thrombi were induced by a copper coil (placed under fluoroscopic control) in the left anterior descending coronary artery of anaesthetised dogs. Following 90 min thrombotic occlusion, animals were randomly assigned to one of two treatment groups: group 1 = t-PA infused intravenously at 0.6 × 106 IU·kg−1·h−1, or group 2 = t-PA (0.6 × 106 IU·kg−1) by intravenous bolus over 6 min. Both groups received concurrent heparin (six 1000 IU boluses, + 100 IU·kg−1 h−1) throughout t-PA administration and the 2 h reperfusion period. Subjects – 16 beagle dogs of either sex were used, weight 9.2-20.3 kg. Measurements and main results – Radiolabelled microspheres were injected to assess microvascular coronary flow at various time points throughout the experimental period. Infarct related vessel patency (IRVP) was assessed arteriographically every 5 min. Infarct size was assessed histochemically at the end of the reperfusion period, IRVP was achieved within 42.9 (SEM 7.4) min and 43.1(7.0) min for infusion and bolus groups respectively; 60 min patency rates were 88% for both groups. t-PA restored full microvascular flow to ischaemie subendocardial and subepicardial regions in both groups compared to initial preocclusion regional blood flow. Extent of reactive hyperaemia was greater in infusion than bolus treatment animals: infusion group 1.18(0.15) v bolus group 0.72(0.14) ml·min−1·g−1 (subepicardial). Degree of microvascular reocclusion at 120 min reperfusion was similar for both groups despite aggressive anticoagulation throughout: infusion group 0.33(0.08) v bolus group 0.42(0.11) ml·min−1·g−1(subendocardial). Areas of the myocardium at risk (R), absolute infarct size (I), and infarct risk ratio (I/R) were similar for both groups: R = 33.9(1.5) v 30.9(1.9)%; I = 15.9(3.1) v 13.3(3.1)%; I/R = 46.3(8.4) v 42.1(9.2)%. Degree of systemic flbrinogenolysis was similar for both groups: infusion 1.65(0.40) to 0.67(0.07) g·litre−1v bolus 1.68(0.15) to 0.96(0.12) g·litre−1. Conclusions – Single bolus administration of t-PA showed equivalent efficacy to infusion dosing in respect of IRVP, microvascular reperfusion, and microvascular reocclusion. As a result the degree of tissue necrosis (I/R ratio) was no different when comparing the two dosing regimens. Similar degrees of systemic flbrinogenolysis were observed for both treatment groups.
Genotype and phenotype in susceptibility to coal workers' pneumoconiosis. The use of cytokines in perspective
Authors: P J Borm, R P Schins
Journal: European Respiratory Journal (2001)

The readily available technique of screening for gene polymorphisms could be used to explain inter-individual variability in a classic occupational interstitial lung disease, such as coal workers' pneumoconiosis (CWP). The objective of this paper is to describe candidate genes selected from the wide pool of cytokines and growth factors, and to discuss the applications and pitfalls when using them as biomarkers for susceptibility to CWP. The selection of candidate genes is mainly based on observed phenotypic changes in bronchoalveolar lavage (BAL) fluid or BAL cells of patients with CWP, or on animal experiments that use quartz as the fibrogenic agent. This paper also reviews the studies that have been performed to validate tumour necrosis factor genotype and phenotype with respect to CWP. Finally, it is proposed that a multiple marker approach to susceptibility to CWP should be used. This involves the measurement of two cytokines (tumour necrosis factor and transforming growth factor-beta) to improve denomination of high- and low-risk groups.
Early detection of asthma exacerbations by using action points in self-management plans
Authors: Persijn J. Honkoop, D. Robin Taylor, Andrew D. Smith, Jiska B. Snoeck-Stroband, Jacob K. Sont
Journal: European Respiratory Journal (2012)

Our aim was to validate optimal action points in written action plans for early detection of asthma exacerbations. We analysed daily symptoms and morning peak expiratory flows (PEFs) from two previous studies. Potential action points were based on analysis of symptom scores (standard deviations) percentage of personal best PEF, PEF variability in relation to a run-in period or combinations of these measures. Sensitivity and specificity for predicting exacerbations were obtained for each action point. The numbers needed to treat to prevent one exacerbation and the time interval between reaching action point criteria and the start of the exacerbation were calculated. Based on these parameters, the optimal action points for symptoms, PEF and PEF plus symptoms were determined, and their performance compared with published guidelines’ action points. The optimal action points were, for symptoms, statistical variability (standard deviations) and, for PEF, &lt;70% of personal best. The combination of PEF plus symptoms performed best, with improved specificity and earlier detection. The main benefits associated with using these action points was to reduce false positive rates for detecting exacerbations. Early detection of asthma exacerbations can be improved using a composite action point comprising symptoms and PEF measurements over 1 week.
Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy Improves Survival in Older Patients With Acute Myeloid Leukemia
Authors: Alan K. Burnett, Nigel H. Russell, Robert K. Hills, Jonathan Kell, Sylvie Freeman, Lars Kjeldsen, Ann E. Hunter, John Yin, Charles F. Craddock, Inge Hoegh Dufva, Keith Wheatley, Donald Milligan
Journal: Journal of Clinical Oncology (2012)

There has been little survival improvement in older patients with acute myeloid leukemia (AML) in the last two decades. Improving induction treatment may improve the rate and quality of remission and consequently survival. In our previous trial, in younger patients, we showed improved survival for the majority of patients when adding gemtuzumab ozogamicin (GO) to induction chemotherapy.Untreated patients with AML or high-risk myelodysplastic syndrome (median age, 67 years; range, 51 to 84 years) were randomly assigned to receive induction chemotherapy with either daunorubicin/ara-C or daunorubicin/clofarabine, with (n = 559) or without (n = 556) GO 3 mg/m(2) on day 1 of course one of therapy. The primary end point was overall survival (OS).The overall response rate was 69% (complete remission [CR], 60%; CR with incomplete recovery [CRi], 9%), with no difference between GO (70%) and no GO (68%) arms. There was no difference in 30- or 60-day mortality and no major increase in toxicity with GO. With median follow-up of 30 months (range, 5.5 to 54.6 months), 3-year cumulative incidence of relapse was significantly lower with GO (68% v 76%; hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .007), and 3-year survival was significantly better (25% v 20%; HR, 0.87; 95% CI, 0.76 to 1.00; P = .05). The benefit was apparent across subgroups. There was no interaction with other treatment interventions. A meta-analysis of 2,228 patients in two United Kingdom National Cancer Research Institute trials showed significant improvements in relapse (HR, 0.82; 95% CI, 0.72 to 0.93; P = .002) and OS (HR, 0.88; 95% CI, 0.79 to 0.98; P = .02).Adding GO (3 mg/m(2)) to induction chemotherapy reduces relapse risk and improves survival with little increase in toxicity.
Detection of replication-competent adenoviruses spiked into recombinant adenovirus vector products by infectivity PCR
Authors: Akiko Ishii-Watabe, Eriko Uchida, Akiko Iwata, Ryuji Nagata, Kouei Satoh, Kejun Fan, Mitsuhiro Murata, Hiroyuki Mizuguchi, Nana Kawasaki, Toru Kawanishi, Teruhide Yamaguchi, Takao Hayakawa
Journal: Molecular Therapy (2003)

The presence of replication-competent adenovirus (RCA) in clinical lots of adenovirus vectors raises a variety of safety concerns. To detect RCA in adenovirus vector products, the cell culture/cytopathic effect (CPE) method has generally been preferred. However, it is difficult to evaluate the amount of RCA clearly and quantitatively by this method. In addition, the cell culture/CPE method requires large-scale cell culturing and a substantial amount of time. For the purpose of establishing a method to detect RCA more sensitively and rapidly, we developed the infectivity PCR, a hybrid method that combines the infectivity assay and quantitative PCR. This method allows RCA to be quantified by real-time quantitative PCR using primers and a probe designed for E1 DNA. By infectivity PCR, 1 pfu of RCA spiked into 10(9) particles of adenovirus vectors could be detected. In contrast, CPE was observed in the cells infected with 10(4) pfu of RCA spiked into 10(9) particles of adenovirus vectors. The glass-beads method was suitable for extracting DNA rapidly from the RCA-infected cells. These results showed that infectivity PCR combined with the glass-beads-based DNA extraction method was useful for the detection of RCA in adenovirus vector products.
Understanding Adherence to HIV Medication
Authors: Jason M. Leider, Gary Kalkut
Journal: Annals of Internal Medicine (2000)

Letters7 March 2000Understanding Adherence to HIV MedicationJason M. Leider, MD, PhD and Gary Kalkut, MD, MPHJason M. Leider, MD, PhDSt. Luke's-Roosevelt Hospital Center; New York, NY 10019 (Leider)Montefiore Medical Center; Bronx, NY 10467 (Kalkut)Search for more papers by this author and Gary Kalkut, MD, MPHSt. Luke's-Roosevelt Hospital Center; New York, NY 10019 (Leider)Montefiore Medical Center; Bronx, NY 10467 (Kalkut)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-5-200003070-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Highly active antiretroviral therapy (HAART) has been associated with reduced mortality and morbidity in HIV-infected patients (1). Successful management of HIV relies on near-perfect adherence to complex treatment regimens. To better understand this dilemma, 35 members (including 6 physicians) of our AIDS center participated in a 2-week simulation of common antiretroviral regimens.The study involved communicating a clinical scenario to the participants, random assignment to a mock antiretroviral regimen (stavudine, lamivudine, and indinavir; lamivudine, ritonavir, and invirase; or didanosine, stavudine, and nelfinavir), and diaries for recording daily behaviors and medication intake. After 1 week of “therapy,” volunteers ...References1. Friedland GH. Adherence: the Achilles' heel of highly active antiretroviral therapy. Improving the Management of HIV Disease. 1997;5:13-5. Google Scholar2. Crespo-Fierro M. Compliance/adherence and care management in HIV disease. J Assoc Nurses AIDS Care. 1997;8:43-54. CrossrefMedlineGoogle Scholar3. Ungvarski P. Adherence to prescribed HIV-1 protease inhibitors in the home setting. J Assoc Nurses AIDS Care. 1997;8 Suppl 37-45. CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: St. Luke's-Roosevelt Hospital Center; New York, NY 10019 (Leider)Montefiore Medical Center; Bronx, NY 10467 (Kalkut) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAn information-motivation-behavioral skills model of adherence to antiretroviral therapy.A prospective study of predictors of adherence to combination antiretroviral medicationSelf-Reported Nonadherence with Antiretroviral Drugs Predicts Persistent Condition 7 March 2000Volume 132, Issue 5Page: 418KeywordsAntiretroviralsCalciumCarbonatesHIVMortalityProtease inhibitorsSwallowingTreatment guidelinesVitamin CVitamin E ePublished: 15 August 2000 Issue Published: 7 March 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Extramedullary blast transformation in the central nervous system in idiopathic myelofibrosis
Authors: Harry M. Barnes, Josef T. Prchal, C. W. Scott
Journal: American Journal of Hematology (1981)

Abstract Idiopathic myelofibrosis (IM) is a myeloproliferative syndrome characterized by anemia, fibrosis of the bone marrow, variable proliferation of megakaryocytes, myelocytic and erythrocytic precursors, and splenomegaly. Extramedullary hematopoiesis can develop in diverse areas. Unlike in chronic granulocytic leukemia, transformation to acute leukemia is uncommon in IM. Transformation to acute leukemia is usually accompanied by the findings of progressive increase in blasts in peripheral blood or bone marrow [1]. We have recently treated a patient with an unusual transition from IM to acute leukemia in whom leukemic transformation began in the central nervous system.
The microbial selenoproteome of the Sargasso Sea.
Authors: Yan Zhang, Dmitri E Fomenko, Vadim N Gladyshev
Journal: Genome biology (2005)

Selenocysteine (Sec) is a rare amino acid which occurs in proteins in major domains of life. It is encoded by TGA, which also serves as the signal for termination of translation, precluding identification of selenoprotein genes by available annotation tools. Information on full sets of selenoproteins (selenoproteomes) is essential for understanding the biology of selenium. Herein, we characterized the selenoproteome of the largest microbial sequence dataset, the Sargasso Sea environmental genome project.We identified 310 selenoprotein genes that clustered into 25 families, including 101 new selenoprotein genes that belonged to 15 families. Most of these proteins were predicted redox proteins containing catalytic selenocysteines. Several bacterial selenoproteins previously thought to be restricted to eukaryotes were detected by analyzing eukaryotic and bacterial SECIS elements, suggesting that eukaryotic and bacterial selenoprotein sets partially overlapped. The Sargasso Sea microbial selenoproteome was rich in selenoproteins and its composition was different from that observed in the combined set of completely sequenced genomes, suggesting that these genomes do not accurately represent the microbial selenoproteome. Most detected selenoproteins occurred sporadically compared to the widespread presence of their cysteine homologs, suggesting that many selenoproteins recently evolved from cysteine-containing homologs.This study yielded the largest selenoprotein dataset to date, doubled the number of prokaryotic selenoprotein families and provided insights into forces that drive selenocysteine evolution.
Prolonged intracerebral convection-enhanced delivery of topotecan with a subcutaneously implantable infusion pump
Authors: A. M. Sonabend, R. M. Stuart, J. Yun, T. Yanagihara, H. Mohajed, S. Dashnaw, S. S. Bruce, T. Brown, A. Romanov, M. Sebastian, F. Arias-Mendoza, E. Bagiella, P. Canoll, J. N. Bruce
Journal: Neuro-Oncology (2011)

Intracerebral convection-enhanced delivery (CED) of chemotherapeutic agents currently requires an externalized catheter and infusion system, which limits its duration because of the need for hospitalization and the risk of infection. To evaluate the feasibility of prolonged topotecan administration by CED in a large animal brain with the use of a subcutaneous implantable pump. Medtronic Synchromed-II pumps were implanted subcutaneously for intracerebral CED in pigs. Gadodiamide (28.7 mg/mL), with or without topotecan (136 μM), was infused at 0.7 mL/24 h for 3 or 10 days. Pigs underwent magnetic resonance imaging before and at 6 times points after surgery. Enhancement and FLAIR+ volumes were calculated in a semi-automated fashion. Magnetic resonance spectroscopy-based topotecan signature was also investigated. Brain histology was analyzed by hematoxylin and eosin staining and with immunoperoxidase for a microglial antigen. CED of topotecan/gadolinium was well tolerated in all cases (n = 6). Maximum enhancement volume was reached at day 3 and remained stable if CED was continued for 10 days, but it decreased if CED was stopped at day 3. Magnetic resonance spectroscopy revealed a decrease in parenchymal metabolites in the presence of topotecan. Similarly, the combination of topotecan and gadolinium infusion led to a FLAIR+ volume that tended to be larger than that seen after the infusion of gadolinium alone. Histological analysis of the brains showed an area of macrophage infiltrate in the ipsilateral white matter upon infusion with topotecan/gadolinium. Intracerebral topotecan CED is well tolerated in a large animal brain for up to 10 days. Intracerebral long-term CED can be achieved with a subcutaneously implanted pump and provides a stable volume of distribution. This work constitutes a proof of principle for the safety and feasibility for prolonged CED, providing a means of continuous local drug delivery that is accessible to the practicing neuro-oncologist.
Flt-1 Signaling in Macrophages Promotes Glioma Growth <i>In vivo</i>
Authors: Mark Kerber, Yvonne Reiss, Anke Wickersheim, Manfred Jugold, Fabian Kiessling, Matthias Heil, Vadim Tchaikovski, Johannes Waltenberger, Masabumi Shibuya, Karl H. Plate, Marcia Regina Machein
Journal: Cancer Research (2008)

Abstract Several lines of evidence indicate that Flt-1, a fms-like tyrosine kinase receptor, which binds to vascular endothelial growth factor (VEGF)-A, VEGF-B, and PlGF, is a positive regulator of angiogenesis in the context of tumor growth and metastasis. However, the molecular basis of its action is still not clear. Besides endothelial cells, Flt-1 is also expressed by other different cell types, including myeloid hematopoeitic cells (monocytes and macrophages). To examine the functions of Flt-1 expressed by bone marrow–derived myeloid cells in supporting tumor growth and angiogenesis, Flt-1 tyrosine kinase–deficient (Flt-1 TK−/−) bone marrow cells were transplanted into lethally irradiated syngeneic recipients. After hematopoietic reconstitution, we orthotopically implanted syngeneic wild-type glioma cells or glioma cells overexpressing either VEGF164 or PlGF-2. Loss of Flt-1 signaling in bone marrow–derived myeloid cells led to a significant decrease in tumor volume and vascularization in gliomas. VEGF but not PlGF overexpressed by glioma cells restored the tumor growth rate in Flt-1 TK−/− bone marrow chimera. VEGF and PlGF overexpression by tumor cells induced an accumulation of bone marrow–derived myeloid cells into tumor tissue. This infiltration was decreased in tumors grown in Flt-1 TK−/− bone marrow chimeras. When investigating chemokines and growth factors involved in myeloid cell recruitment, we determined elevated SDF-1/CXCL12 levels in VEGF- and PlGF-overexpressing tumors. Collectively, these results suggest that Flt-1 signaling in myeloid cells is essential to amplify the angiogenic response and to promote glioma growth. [Cancer Res 2008;68(18):7342–51]
Further statistical considerations for amino acid replacement data in protein sequences.
Authors: S R Wilson
Journal: Molecular Biology and Evolution (1987)

Gillespie (1986a) suggests a model of molecular evolution by natural selection. He has chosen this model to fit some statistical aspects of the sequence data that he examined. In the present letter I show that there may be more “wobble” in sequence data than the reader might suspect. The data for each protein sequence are taken to come from a star phylogeny and inference is for N,(t), the number of substitutions that occurred in the ith lineage of a radiation that occurred t years ago. Most of Gillespie’s discussion focuses on the estimation of the ratio R(t) = Var[Ni(t)]/E[Ni(t)]. The data available for estimation are the observed number of amino acids that differ between species i and j, Dw Gillespie (p. 140) writes: “As in other work, our results show that R(t) is always greater than one. The striking aspect of the estimates, however, is the narrow range of R(t) values: 1 .O < R(t) < 3.4.” However, the currently available data sets are sparse. First, it should be noted that the data on which Gillespie based his results are for just six protein sequences, four of which had counts of amino acid differences for six species and the other two of which had such counts for four species. The global number of species was 15, but only seven of these were considered in more than one sequence comparison. To demonstrate that even these data contain evidence that the range of R(t) may not be as narrow as Gillespie found, I consider the sequence comparison for the hemoglobin a-chain. The data are given in table 1, along with fictitious data for four
Desmosomal Dysfunction due to Mutations in Desmoplakin Causes Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Authors: Zhao Yang, Neil E. Bowles, Steven E. Scherer, Michael D. Taylor, Debra L. Kearney, Shuping Ge, Vyacheslav V. Nadvoretskiy, Gilberto DeFreitas, Blasé Carabello, Lois I. Brandon, Lisa M. Godsel, Kathleen J. Green, Jeffrey E. Saffitz, Hua Li, Gian Antonio Danieli, Hugh Calkins, Frank Marcus, Jeffrey A. Towbin
Journal: Circulation Research (2006)

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by progressive degeneration of the right ventricular myocardium, ventricular arrhythmias, fibrous-fatty replacement, and increased risk of sudden death. Mutations in 6 genes, including 4 encoding desmosomal proteins (Junctional plakoglobin (JUP), Desmoplakin (DSP), Plakophilin 2, and Desmoglein 2), have been identified in patients with ARVD/C. Mutation analysis of 66 probands identified 4 variants in DSP; V30M, Q90R, W233X, and R2834H. To establish a cause and effect relationship between those DSP missense mutations and ARVD/C, we performed in vitro and in vivo analyses of the mutated proteins. Unlike wild-type (WT) DSP, the N-terminal mutants (V30M and Q90R) failed to localize to the cell membrane in desomosome-forming cell line and failed to bind to and coimmunoprecipitate JUP. Multiple attempts to generate N-terminal DSP (V30M and Q90R) cardiac-specific transgenes have failed: analysis of embryos revealed evidence of profound ventricular dilation, which likely resulted in embryonic lethality. We were able to develop transgenic (Tg) mice with cardiac-restricted overexpression of the C-terminal mutant (R2834H) or WT DSP. Whereas mice overexpressing WT DSP had no detectable histologic, morphological, or functional cardiac changes, the R2834H-Tg mice had increased cardiomyocyte apoptosis, cardiac fibrosis, and lipid accumulation, along with ventricular enlargement and cardiac dysfunction in both ventricles. These mice also displayed interruption of DSP-desmin interaction at intercalated discs (IDs) and marked ultra-structural changes of IDs. These data suggest DSP expression in cardiomyocytes is crucial for maintaining cardiac tissue integrity, and DSP abnormalities result in ARVD/C by cardiomyocyte death, changes in lipid metabolism, and defects in cardiac development.
The influence of diabetes mellitus on acute and late clinical outcomes following coronary stent implantation
Authors: Alexandre Abizaid, Ran Kornowski, Gary S Mintz, Mun K Hong, Andrea S Abizaid, Roxana Mehran, Augusto D Pichard, Kenneth M Kent, Lowell F Satler, Hongsheng Wu, Jeffrey J Popma, Martin B Leon
Journal: Journal of the American College of Cardiology (1998)
P586 APPEARANCE OF COMBINED HEPATOCELLULAR CHOLANGIOCARCINOMA IN CIRRHOSIS AT CONTRAST ENHANCED IMAGING TECHNIQUES
Authors: E. Sagrini, M. Iavarone, S. Vavassori, F. Stefanini, M. Maggioni, I. Pettinari, A. Pecorelli, M. Colombo, L. Bolondi, F. Piscaglia
Journal: Journal of Hepatology (2014)