tbuckley/cabot-search huggingface dataset:
Influence of ventricular ejection on the relationship between central aortic and brachial pressure pulse in man
Authors: M. F. O'Rourke
Journal: Cardiovascular Research (1970)

Journal Article Influence of ventricular ejection on the relationship between central aortic and brachial pressure pulse in man Get access Michael F. O'Rourke Michael F. O'Rourke 1 From the Cardiology Division, Department of Medicine, University of Sydney, and the Hallstrom Institute of Cardiology, Royal Prince Alfred Hospital, Sydney, N.S. W., Australia 1Research Fellow for the National Heart Foundation of Australia. Present address: Physiology Dept., University of N.S.W., Box 1, P.O Kensington N.S.W. 2033. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 4, Issue 3, July 1970, Pages 291–300, https://doi.org/10.1093/cvr/4.3.291 Published: 01 July 1970 Article history Accepted: 16 January 1970 Published: 01 July 1970
Immunologic studies on the influenza A virus nonstructural protein NS1.
Authors: M W Shaw, E W Lamon, R W Compans
Journal: The Journal of Experimental Medicine (1982)

We purified the major influenza virus nonstructural protein, designated NS1, from cytoplasmic inclusions that were solubilized and used to raise antisera in rabbits. One of the antisera was found to be specific for NS1 by complement fixation tests and analyses of immune precipitates. Antiserum to NS1 isolated from cells infected with A/WSN/33 virus specifically precipitated NS1 from extracts of cells infected with seven distinct isolates of influenza A virus representing five different antigenic subtypes. These included A/WSN/33, A/PR/8/34, A/FW/5/50, A/USSR/90/77, A/RI/5+/57, A/Victoria/3/75, and A/Swine /1977/31; however, NS1 from cells infected with B/Lee/40 virus was not precipitated. Radioimmunoassays using radioiodinated NS1 protein from A/WSN virus-infected cells and unlabeled cytoplasmic extracts of cells infected with various strains of influenza virus as competitors indicated significant antigenic cross-reactivities for the NS1 proteins of all influenza A viruses tested. The results suggest a gradual antigenic drift over the 45 yr separating the earliest and most recent virus isolates examined. Thus, compared with the virion neuraminidase and hemagglutinin antigens, NS1 appears to be highly conserved in different influenza A virus isolates.
The Contemporary Role of Chemotherapy for Advanced Testis Cancer: A Systematic Review of the Literature
Authors: Fabio Calabrò, Peter Albers, Carsten Bokemeyer, Chris Martin, Lawrence H. Einhorn, Alan Horwich, Susanne Krege, Hans Joachim Schmoll, Cora N. Sternberg, Gedske Daugaard
Journal: European Urology (2012)
Optimization of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of leucovorin, 5-FU and cisplatin (LV5FU2-P regimen) in patients with biliary tract carcinoma
Authors: J. Taïeb, E. Mitry, V. Boige, P. Artru, J. Ezenfis, T. Lecomte, M.C. Clavero-Fabri, J.N. Vaillant, P. Rougier, M. Ducreux
Journal: Annals of Oncology (2002)
Randomized Comparison of Low-Dose Involved-Field Radiotherapy and No Radiotherapy for Children With Hodgkin’s Disease Who Achieve a Complete Response to Chemotherapy
Authors: James B. Nachman, Richard Sposto, Philip Herzog, Gerald S. Gilchrist, Suzanne L. Wolden, John Thomson, Marshall E. Kadin, Paul Pattengale, P. Charlton Davis, Raymond J. Hutchinson, Keith White
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Current standard therapy for children and adolescents with Hodgkin’s disease includes combination chemotherapy and low-dose involved-field radiation (LD-IFRT). Because radiation may be associated with adverse late effects, the Children’s Cancer Group (CCG) investigated whether radiation could be omitted in patients achieving a complete response to initial chemotherapy without jeopardizing the excellent outcome obtained with combined-modality therapy. PATIENTS AND METHODS: Between January 1995 and December 1998, 829 eligible patients were enrolled onto CCG 5942. A total of 501 patients who achieved an initial complete response after risk-adapted combination chemotherapy were randomized to receive LD-IFRT or no further treatment. Event-free survival (EFS) and overall survival were assessed from the date of study entry or the date of randomization, as appropriate. RESULTS: The projected 3-year EFS from study entry for the entire cohort was 87% ± 1.2%. Among patients who achieved a complete response to initial chemotherapy, 92% ± 1.9% of those randomized to receive LD-IFRT were alive and disease free 3 years after randomization, versus 87% ± 2.2% for patients randomized to receive no further therapy (stratified log-rank test; P = .057). With an “as-treated” analysis, 3-year EFS after randomization for the radiation cohort was 93% ± 1.7% versus 85% ± 2.3% for patients receiving no further therapy (stratified log-rank test; P = .0024). Three-year survival estimates for patients treated with and without LD-IFRT were 98% ± 1.1% for patients who received radiation and 99% ± 0.5% for patients who did not receive radiation. CONCLUSION: LD-IFRT after an initial complete response to risk-adapted chemotherapy improved EFS. At this time, there is no survival advantage for LD-IFRT, but follow-up remains short.
Prodeath Signaling of G Protein–Coupled Receptor Kinase 2 in Cardiac Myocytes After Ischemic Stress Occurs Via Extracellular Signal–Regulated Kinase-Dependent Heat Shock Protein 90–Mediated Mitochondrial Targeting
Authors: Mai Chen, Priscila Y. Sato, J. Kurt Chuprun, Raymond J. Peroutka, Nicholas J. Otis, Jessica Ibetti, Shi Pan, Shey-Shing Sheu, Erhe Gao, Walter J. Koch
Journal: Circulation Research (2013)

Rationale: G protein–coupled receptor kinase 2 (GRK2) is abundantly expressed in the heart, and its expression and activity are increased in injured or stressed myocardium. This upregulation has been shown to be pathological. GRK2 can promote cell death in ischemic myocytes, and its inhibition by a peptide comprising the last 194 amino acids of GRK2 (known as carboxyl-terminus of β-adrenergic receptor kinase [bARKct]) is cardioprotective. Objective: The aim of this study was to elucidate the signaling mechanism that accounts for the prodeath signaling seen in the presence of elevated GRK2 and the cardioprotection afforded by the carboxyl-terminus of β-adrenergic receptor kinase. Methods and Results: Using in vivo mouse models of ischemic injury and also cultured myocytes, we found that GRK2 localizes to mitochondria, providing novel insight into GRK2-dependent pathophysiological signaling mechanisms. Mitochondrial localization of GRK2 in cardiomyocytes was enhanced after ischemic and oxidative stress, events that induced prodeath signaling. Localization of GRK2 to mitochondria was dependent on phosphorylation at residue Ser670 within its extreme carboxyl-terminus by extracellular signal–regulated kinases, resulting in enhanced GRK2 binding to heat shock protein 90, which chaperoned GRK2 to mitochondria. Mechanistic studies in vivo and in vitro showed that extracellular signal–regulated kinase regulation of the C-tail of GRK2 was an absolute requirement for stress-induced, mitochondrial-dependent prodeath signaling, and blocking this led to cardioprotection. Elevated mitochondrial GRK2 also caused increased Ca 2+ -induced opening of the mitochondrial permeability transition pore, a key step in cellular injury. Conclusions: We identify GRK2 as a prodeath kinase in the heart, acting in a novel manner through mitochondrial localization via extracellular signal–regulated kinase regulation.
Alcohol drinking and colorectal cancer risk: an overall and dose–response meta-analysis of published studies
Authors: V. Fedirko, I. Tramacere, V. Bagnardi, M. Rota, L. Scotti, F. Islami, E. Negri, K. Straif, I. Romieu, C. La Vecchia, P. Boffetta, M. Jenab
Journal: Annals of Oncology (2011)
Quantitative assessment of serum IgM anti-HBc in the natural course and during interferon treatment of chronic hepatitis B virus infection
Authors: George Marinos, Heather M. Smith, Nikolai V. Naoumov, Roger Williams
Journal: Hepatology (1994)

Serum IgM anti-HBc was determined in 135 chronic HBsAg carriers with various categories of histological activity on liver biopsy and hepatitis B serological profile. Thirty-three patients were treated with interferon-alpha to investigate the correlation between serum IgM anti-HBc with histological activity and viral replication, to evaluate the usefulness of pretreatment IgM anti-HBc as a predictor of a successful response to interferon-alpha and to examine the IgM anti-HBc response during this treatment. All 53 patients with chronic active hepatitis with either wild-type (n = 42) or precore mutant variant HBV infection (n = 11) had an IgM anti-HBc index greater than 0.300 compared with 7.4% (2 of 27) of the chronic HBsAg/HBeAg-positive carriers with chronic persistent hepatitis, 10% (3 of 30) of the anti-HBe-positive asymptomatic carriers and none of the 25 patients with hepatitis D virus-positive chronic active hepatitis (p < 0.0001). Pretreatment IgM anti-HBc index was greater than 0.300 in 82.4% (14 of 17) of HBeAg/HBV DNA-positive patients who seroconverted after interferon-alpha treatment compared with 25% (4 of 16) of the patients who did not seroconvert (p = 0.0013), whereas an elevated pretreatment AST was present in only 52.9% (9 of 17) of responders and in 37.5% (6 of 16) of nonresponders (p = 0.42). Serial testing of IgM anti-HBc in these 33 patients during interferon-alpha treatment showed a significant rise in IgM anti-HBc in all responders, which followed the AST flare-up but preceded the time of the HBeAg to anti-HBe seroconversion.(ABSTRACT TRUNCATED AT 250 WORDS)
MicroRNA-126 modulates endothelial SDF-1 expression and mobilization of Sca-1+/Lin− progenitor cells in ischaemia
Authors: Coen van Solingen, Hetty C. de Boer, Roel Bijkerk, Matthieu Monge, Annemarie M. van Oeveren-Rietdijk, Leonard Seghers, Margreet R. de Vries, Eric P. van der Veer, Paul H.A. Quax, Ton J. Rabelink, Anton Jan van Zonneveld
Journal: Cardiovascular Research (2011)

MicroRNA-126 (miR-126), which is enriched in endothelial cells, plays a role in angiogenesis. Based on the seed sequence, miR-126 can also be predicted to regulate vasculogenesis by modulating the endothelial expression of stromal cell-derived factor-1 (SDF-1). Using miR-reporter constructs, we first validated that miR-126 inhibits SDF-1 expression in endothelial cells in vitro. Next, we investigated the potential relevance of this observation with respect to the mobilization of progenitor cells. For this, we studied the migration of human CD34+ progenitor cells towards chemotactic factors present in endothelial cell-conditioned medium. Antagomir-induced silencing of miR-126 elevated SDF-1 expression by human umbilical vein endothelial cells and enhanced migration of the CD34+ cells. In a murine model of hind limb ischaemia, a striking increase in the number of circulating Sca-1+/Lin− progenitor cells in antagomir-126-treated mice was observed when compared with scramblemir-treated controls. Immunohistochemical staining of capillaries in the post-ischaemic gastrocnemius muscle of miR-126-silenced mice revealed elevated SDF-1 expressing CD31-positive capillaries, whereas a mobilizing effect of miR-126 inhibition was not detected in healthy control animals. miR-126 can regulate the expression of SDF-1 in endothelial cells. In the context of an ischaemic event, systemic silencing of miR-126 leads to the mobilization of Sca-1+/Lin− progenitor cells into the peripheral circulation, potentially in response to elevated SDF-1 expression by endothelial cells present in the ischaemic tissue.
Preserving today's scientific record for tomorrow
Authors: V. Reich
Journal: BMJ (2004)

LOCKSS marries age old concepts of librarianship with modern technology 

Let us save what remains: not by vaults and locks which fence them from the public eye and use in consigning them to the waste of time, but by such a multiplication of copies, as shall place them beyond the reach of accident. 

Thomas Jefferson1

Information stored on paper can survive for millennia; information stored digitally today may not be recoverable this time next week. With seven million pages of new information added to the world wide web each day, the volatility of websites has emerged as an urgent problem, especially as websites are becoming the version of record for scientific journals. Three studies of links in peer reviewed journals all found their useful life to be a few …
Hepatitis C viral quasispecies and liver damage in patients with chronic hepatitis C virus infection
Authors: J Hayashi, Y Kishihara, K Yamaji, N Furusyo, T Yamamoto, Y Pae, Y Etoh, H Ikematsu, S Kashiwagi
Journal: Hepatology (1997)

To clarify the virological differences in patients with chronic hepatitis C virus (HCV) infection with and without liver damage, we assessed HCV markers in 306 patients from a rural area of Japan. Genotypes of HCV RNA were determined by polymerase chain reaction, and levels of RNA were determined by branched DNA signal-amplification assay. All patients had undergone annual tests for alanine aminotransferase (ALT) levels from 1986 to 1995. Patients were categorized into three groups: group A, 121 patients (39.5%) with normal ALT levels on all occasions for 10 years; group B, 127 patients (41.5%) with intermittently abnormal ALT levels; and group C, 58 patients (19.0%) with consistently abnormal ALT levels. There were no significant differences in serum RNA levels or distribution of genotypes among the three groups. We selected 10 patients from group A with normal ALT levels and 10 from group C with abnormal levels for sequence analysis of the HCV core region (nt 169-378) of five clones from each patient. More mutations were found in the 50 clones from the 10 patients from group C than in the 10 patients from group A. In group A, all mutations were synonymous so that the deduced amino acid sequences were identical among clones from each patient, whereas in group C 16 of 57 mutations were nonsynonymous so that the deduced amino acid sequences showed differences in the five clones of eight of 10 patients. In conclusion, the HCV core region was highly conserved in patients with normal liver biochemical test results but not in those with abnormal results. Our results suggest that abnormal liver biochemical test results in patients with chronic HCV infection may be associated with high degrees of virus quasispecies diversity.
A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours
Authors: J.-L. Pico, G. Rosti, A. Kramar, H. Wandt, V. Koza, R. Salvioni, C. Theodore, G. Lelli, W. Siegert, A. Horwich, M. Marangolo, W. Linkesch, G. Pizzocaro, H.-J. Schmoll, J. Bouzy, J.-P. Droz, P. Biron
Journal: Annals of Oncology (2005)
Dominant Effect of Antiangiogenesis in Combination Therapy Involving Cyclophosphamide and Axitinib
Authors: Jie Ma, David J. Waxman
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Antiangiogenic drug treatment inhibits tumor growth by decreasing blood supply, which can also reduce the delivery of other therapeutic agents. Presently, we investigated the effect of the vascular endothelial growth factor receptor tyrosine kinase inhibitor axitinib (AG-013736) on tumor vascular patency and chemotherapeutic drug uptake. Furthermore, the effect of axitinib on the antitumor activity of combination treatments with cyclophosphamide was examined. Experimental Design: Prostate cancer PC-3 xenografts were used to evaluate the effect of axitinib treatment on tumor vascular morphology, fluorescent dye perfusion, hypoxia, and uptake of 4-hydroxycyclophosphamide, the active metabolite of the chemotherapeutic prodrug cyclophosphamide. Sequential or simultaneous schedules for axitinib and cyclophosphamide administration were evaluated in both PC-3 tumors and 9L gliosarcoma xenograft models. Results: Axitinib monotherapy induced sustained growth stasis in PC-3 tumors in association with extensive apoptotic cell death. A substantial decrease in tumor vascular patency was observed, exemplified by a near complete loss of Hoechst 33342 perfusion and the absence of pimonidazole staining in the increasingly hypoxic tumors. Antitumor activity was significantly enhanced in both PC-3 and 9L tumors treated using an optimized schedule of sequential, intermittent axitinib-cyclophosphamide combination therapy despite a 40% to 70% decrease in tumor tissue uptake of 4-hydroxycyclophosphamide. Conclusions: In axitinib-cyclophosphamide combination therapy, enhanced anticancer activity can be achieved when the reduced tumor cell exposure to the cancer chemotherapeutic agent is compensated by antiangiogenesis-induced tumor cell starvation. This intrinsic antitumor effect was particularly evident in PC-3 tumor xenografts, where tumor blood flow deprivation dominates the overall therapeutic response.
Deficiency of Fibroblast Growth Factor-Inducible 14 (Fn14) Preserves the Filtration Barrier and Ameliorates Lupus Nephritis
Authors: Yumin Xia, Leal C. Herlitz, Simona Gindea, Jing Wen, Rahul D. Pawar, Alexander Misharin, Harris Perlman, Lan Wu, Ping Wu, Jennifer S. Michaelson, Linda C. Burkly, Chaim Putterman
Journal: Journal of the American Society of Nephrology (2014)

TNF ligand superfamily member 12, also known as TNF-related weak inducer of apoptosis (TWEAK), acts through its receptor, fibroblast growth factor-inducible 14 (Fn14), to mediate several key pathologic processes involved in tissue injury relating to lupus nephritis. To explore the potential for renal protection in lupus nephritis by targeting this pathway, we introduced the Fn14 null allele into the MRL-lpr/lpr lupus mouse strain. At 26–38 weeks of age, female Fn14-knockout MRL-lpr/lpr mice had significantly lower levels of proteinuria compared with female wild-type MRL-lpr/lpr mice. Furthermore, Fn14-knockout mice had significantly improved renal histopathology accompanied by attenuated glomerular and tubulointerstitial inflammation. There was a significant reduction in glomerular Ig deposition in Fn14-knockout mice, despite no detectable differences in either serum levels of antibodies or splenic immune cell subsets. Notably, we found that the Fn14-knockout mice displayed substantial preservation of podocytes in glomeruli and that TWEAK signaling directly damaged barrier function and increased filtration through podocyte and glomerular endothelial cell monolayers. Our results show that deficiency of the Fn14 receptor significantly improves renal disease in a spontaneous lupus nephritis model through prevention of the direct injurious effects of TWEAK on the filtration barrier and/or modulation of cytokine production by resident kidney cells. Thus, blocking the TWEAK/Fn14 axis may be a novel therapeutic intervention in immune-mediated proliferative GN.
Invasion of Distal Nephron Precursors Associates with Tubular Interconnection during Nephrogenesis
Authors: Robert M. Kao, Aleksandr Vasilyev, Atsushi Miyawaki, Iain A. Drummond, Andrew P. McMahon
Journal: Journal of the American Society of Nephrology (2012)

Formation of a functional renal network requires the interconnection of two epithelial tubes: the nephron, which arises from kidney mesenchyme, and the collecting system, which originates from the branching ureteric epithelium. How this connection occurs, however, is incompletely understood. Here, we used high-resolution image analysis in conjunction with genetic labeling of epithelia to visualize and characterize this process. Although the focal absence of basal lamina from renal vesicle stages ensures that both epithelial networks are closely apposed, we found that a patent luminal interconnection is not established until S-shaped body stages. Precursor cells of the distal nephron in the interconnection zone exhibit a characteristic morphology consisting of ill-defined epithelial junctional complexes but without expression of mesenchymal markers such as vimentin and Snai2. Live-cell imaging revealed that before luminal interconnection, distal cells break into the lumen of the collecting duct epithelium, suggesting that an invasive behavior is a key step in the interconnection process. Furthermore, loss of distal cell identity, which we induced by activating the Notch pathway, prevented luminal interconnection. Taken together, these data support a model in which establishing the distal identity of nephron precursor cells closest to the nascent collecting duct epithelium leads to an active cell invasion, which in turn contributes to a patent tubular interconnection between the nephron and collecting duct epithelia.
Screening of Cytotoxic Drugs for Residual Bone Marrow Damage 2
Authors: K. J. Trainor, A. A. Morley
Journal: JNCI Journal of the National Cancer Institute (1976)

Several cytotoxic drugs were tested for their ability to produce permanent residual damage to the bone marrow. A short course of the drug was given to BALB/c female mice, and the numbers of various types of bone marrow cells were determined at least two months later. Evidence of residual damage was found after administration of busulfan and 1,3-bis(chloroethyl)-1-nitrosourea, but not after administration of cyclophosphamide, 5-fluorouracil, 6-mercaptopurine, methotrexate, or vinblastine.
Natriuretic Peptides, Their Receptors, and Cyclic Guanosine Monophosphate-Dependent Signaling Functions
Authors: Lincoln R. Potter, Sarah Abbey-Hosch, Deborah M. Dickey
Journal: Endocrine Reviews (2005)

Natriuretic peptides are a family of structurally related but genetically distinct hormones/paracrine factors that regulate blood volume, blood pressure, ventricular hypertrophy, pulmonary hypertension, fat metabolism, and long bone growth. The mammalian members are atrial natriuretic peptide, B-type natriuretic peptide, C-type natriuretic peptide, and possibly osteocrin/musclin. Three single membrane-spanning natriuretic peptide receptors (NPRs) have been identified. Two, NPR-A/GC-A/NPR1 and NPR-B/GC-B/NPR2, are transmembrane guanylyl cyclases, enzymes that catalyze the synthesis of cGMP. One, NPR-C/NPR3, lacks intrinsic enzymatic activity and controls the local concentrations of natriuretic peptides through constitutive receptor-mediated internalization and degradation. Single allele-inactivating mutations in the promoter of human NPR-A are associated with hypertension and heart failure, whereas homozygous inactivating mutations in human NPR-B cause a form of short-limbed dwarfism known as acromesomelic dysplasia type Maroteaux. The physiological effects of natriuretic peptides are elicited through three classes of cGMP binding proteins: cGMP-dependent protein kinases, cGMP-regulated phosphodiesterases, and cyclic nucleotide-gated ion channels. In this comprehensive review, the structure, function, regulation, and biological consequences of natriuretic peptides and their associated signaling proteins are described.