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1
Glöckner, Andreas. "Zur Echtheit und Datierung der Kantate BWV 150 "Nach dir, Herr, verlanget mich"." Bach-Jahrbuch 74 (January 1, 1988): 195–203. http://dx.doi.org/10.13141/bjb.v19882587.
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Vergleiche auch: Arnold Schering: Die Kantate Nr. 150 "Nach dir, Herr verlanget mich". BJ 1913, S. 39-52
 Hans-Joachim Schulze: Rätselhafte Auftragswerke Johann Sebastian Bachs. Anmerkungen zu einigen Kantatentexten. BJ 2010, S. 69-93
 Hans-Joachim Schulze: Die Bach-Kantate "Nach dir, Herr verlanget mich" und ihr Meckbach-Akrostichon. BJ 2011, S. 255-257
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Schulze, Hans-Joachim. "Die Bach-Kantate "Nach dir, Herr, verlanget mich" und ihr Meckbach-Akrostichon." Bach-Jahrbuch 97 (January 1, 2011): 255–57. http://dx.doi.org/10.13141/bjb.v20111235.
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Der Autor liefert einige Ergänzungen und Berichtigungen zu seinem im Vorjahr im BJ veröffentlichten Artikel (Link s.u.), speziell das im Titel genannte Akrostichon betreffend. Dabei geht es um Fragen der Schreibweise, eines möglichen, verschollenen Textdrucks, den Entstehungsanlass des Werks und zuletzt die Interpretationsmöglichkeiten, die diese Namensnennung im Kontext des Werkes bietet.
 
 Vergleiche auch: Andreas Glöckner: Zur Echtheit und Datierung der Kantate BWV 150 "Nach dir, Herr, verlanget mich". BJ 1988, S. 195-203
 Hans-Joachim Schulze: Rätselhafte Auftragswerke Johann Sebastian Bachs. Anmerkungen zu einigen Kantatentexten. BJ 2010, S. 69-93
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Hofmann, Klaus. "Alte und neue Überlegungen zur Kantate "Non sa che sia dolore" BWV 209." Bach-Jahrbuch 76 (May 11, 2018): 7–25. http://dx.doi.org/10.13141/bjb.v19902711.
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Der Beitrag knüpft an bestehende Überlegungen zu dieser aufgrund von Stileigentümlichkeiten, Fragen der Überlieferung, des unklaren Anlasses und der bei Bach singulären Verwendung eines italienischsprachigen Librettos rätselhaften Komposition an. Lösungsvorschlag. Zunächst wird die Echtheitsdiskussion umrissen und Stellung zugunsten der Zuschreibung an Johann Sebastian Bach bezogen. Die Erörterung der Frage nach dem Textdichter bleibt unentschieden, schränkt aber anhand textlicher Indizien das Entstehungsdatum auf nicht vor 1729 ein. Aufgrund des Abschiedscharakters der Kantate und dieser Jahreszahl wird nach Darstellung möglicher Anlässe und Widmungsträger der Blick auf Lorenz Christoph Mizler gerichtet, was nach Ansicht des Autors einen plausiblen, wenn auch weiterer Untermauerung bedürfenden neuen Lösungsansatz darstellt.
 
 Bezugnehmend auf: Arnold Schering: Beiträge zur Bachkritik. BJ 1912, S. 124-133 [=Rezension zu: Johannes Schreyer, Beiträge zur Bach-Kritik, Leipzig 1910
 Vergleiche auch: Hans-Joachim Schulze: Rätselhafte Auftragswerke Johann Sebastian Bachs. Anmerkungen zu einigen Kantatentexten. BJ 2010, S. 69-93
4
Maul, Michael. ""Die große catholische Messe". Bach, Graf Questenberg und die "Musicalische Congregation" in Wien." Bach-Jahrbuch 95 (March 13, 2018): 153–75. http://dx.doi.org/10.13141/bjb.v20091864.
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Unter Berücksichtigung neuerer Widersprüche gegen das Verständnis der h-moll-Messe BWV 232 als Vermächtniswerk ohne eigentlichen Anlass wird im vorliegenden Artikel, der im Wesentlichen ein Referat des Autors auf dem Symposium „Understanding Bach’s B-minor Mass 2007 in Belfast wiedergibt, eine weitere neue Erklärungsgrundlage für die Vervollständigung der Messe eingeführt. Dazu wird die Person Graf Johann Adam von Questenbergs mit seiner Hofhaltung im mährischen Jarmeritz und ihren Beziehungen zum kaiserlichen Hof in Wien in den Mittelpunkt gestellt. Über die Frage eines möglichen Kontakts zu Johann Sebastian Bach wird die Möglichkeit eröffnet, die Messe könnte durch Vermittlung Graf Questenbergs für Wien entstanden sein.
 
 Erwähnte Artikel: Friedrich Wilhelm Riedel: Aloys Fuchs als Sammler Bachscher Werke. BJ 1960, S. 83-99
 Alois Plichta: Johann Sebastian Bach und Johann Adam Graf von Questenberg. BJ 1981, S. 23-30
 Peter Wollny: Neue Bach-Funde. BJ 1997, S. 7-50
 Maria Hübner: Neues zu Johann Sebastian Bachs Reisen nach Karlsbad. BJ 2006, S. 93-108
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Krummacher, Friedhelm. "Textauslegung und Satzstruktur in J. S. Bachs Motetten." Bach-Jahrbuch 60 (March 15, 2018): 5–43. http://dx.doi.org/10.13141/bjb.v19741980.
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Obwohl Bachs Vokalwerk unbestreitbar durch seine konstruktiven Eigenschaften und seine expressiven Qualitäten gekennzeichnet ist, ist das wechselseitige Verhältnis dieser beiden Elemente keineswegs selbstverständlich. Angesichts der Tendenzen zur Trennung beider Aspekte ist es gerade ihre spezifische Korrelation, die geklärt werden muss. Für diese Frage können Bachs Motetten, ungeachtet ihrer Sonderstellung, als Beispiel dienen. Definiert durch die vokale Konzeption aller Stimmen, zeigen sie einen deutlichen Bruch mit der traditionellen Abfolge von Textelementen und entwickeln eigenständige zyklische Formstrukturen. Entsprechungen und Kontraste, Analogien und Varianten sowohl in Bezug auf deklamatorische, rhythmische, motivische und polyphone Verfahren sind die Grundvoraussetzungen für die Entwicklung einer komplexen formalen Struktur, die trotz textlicher Veränderungen und kraftvoller Interpretation einzelner Wörter unbestreitbar integer ist. Von daher werden Argumente für die Authentizität von BWV 230 sowie Schlussfolgerungen für weitere Vokalwerke entwickelt. (Übertragung des englischen Resümees am Ende des Bandes)
 
 Erwähnte Artikel: Bernhard Friedrich Richter: Über die Motetten Seb. Bachs. BJ 1912, S. 1-32
 Arnold Schering: Bach und das Symbol, insbesondere die Symbolik seines Kanons. BJ 1925, S. 40-63
 Arnold Schering: Bach und das Symbol (2. Studie). BJ 1928, S. 119-137
 Joseph Bachmair: "Komm, Jesu, komm" (Der Textdichter. Ein unbekanntes Werk von Johann Schelle) BJ 1932, S. 142-145
 Arnold Schering: Bach und das Symbol. 3. Studie: Psychologische Grundlegung des Symbolbegriffs aus Christian Wolffs "Psychologia empirica". BJ 1937, S. 83-95
 Alfred Dürr: Zur Echtheit einiger Bach zugeschriebener Kantaten. BJ 1951-52, S. 30-46
 Peter Benary: Zum periodischen Prinzip bei J. S. Bach. BJ 1958, S. 84-93
 Ulrich Siegele: Bemerkungen zu Bachs Motetten. BJ 1962, S. 33-57
 Roger Bullivant: Zum Problem der Begleitung der Bachschen Motetten. BJ 1966, S. 59-68
 Martin Geck: Zur Echtheit der Bach-Motette "Lobet den Herrn, alle Heiden". BJ 1967, S. 57-69
 Hans-Joachim Schulze: Der Schreiber "Anonymus 400" - ein Schüler Johann Sebastian Bachs. BJ 1972, S. 104-117
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Aalaei-Andabili, Seyed Hossein, Thomas M. Beaver, Tomas D. Martin, Philip J. Hess, and George J. Arnaoutakis. "Outcomes of Florida Sleeve Procedure in Patients with Bicuspid Versus Tricuspid Aortic Valve." Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery 15, no. 4 (2020): 361–68. http://dx.doi.org/10.1177/1556984520938470.
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Objective Outcomes of the Florida Sleeve (FS) procedure in patients with bicuspid aortic valve (BAV) have not been reported before. We compared outcomes of the FS procedure between patients with BAV and those with tricuspid aortic valve (TAV). Methods From May 1, 2002 to January 1, 2016, 177 patients including 18 BAV and 159 TAV underwent the FS procedure. Baseline characteristics, perioperative outcomes, and echocardiographic measurements were compared between the 2 groups. Kaplan–Meier and life-table analyses were used to evaluate survival and freedom from reintervention rates. Results Mean ± standard deviation age and aortic root diameter were comparable in BAV and TAV groups, 47.83 ± 11.19 versus 49.59 ± 15.79 years ( P = 0.55) and 56.57 ± 6.18 versus 55.17 ± 8.84 mm ( P = 0.46), respectively. The 30-day mortality and stroke rates were zero in the BAV group and 1.88% ( n = 3) in the TAV group ( P = 1.00). One patient (5.55%) in the BAV group and 8 (5.03%) patients in the TAV group needed permanent pacemaker implantation ( P = 0.62). Freedom from reoperation was 93% in the BAV group and 99% in the TAV group at 8 years ( P = 0.041). Patient survival rate was 100% in the BAV group and 91% in the TAV group at 8 years ( P = 0.42). Freedom from aortic insufficiency greater than mild was 93% in the BAV group and 96.5% in the TAV group at 5 years ( P = 0.61). Conclusions This is the first study reporting outcomes of the FS procedure in patients with BAV. This technique is feasible, and the results appear to be durable when compared to patients with TAV.
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Karalic, Danijela, Ivana Lazarevic, Maja Cupic, Dj Jevtovic, and Tanja Jovanovic. "Prevalence of JC and BK polyomavirus excretion in the urine of HIV-infected patients from Serbia." Archives of Biological Sciences 66, no. 2 (2014): 609–14. http://dx.doi.org/10.2298/abs1402609k.
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BK virus (BKV) and JC virus (JCV) persist as latent infection in the kidneys. Reactivation of both viruses may be linked to immunodeficiency. The aims of this study were to determine the prevalence of BKV and JCV viruria and to evaluate the relationship between immunodeficiency and viruria in a cohort of HIV-infected patients. Urine samples from 93 HIV-infected patients were collected and tested for the presence of BKV and JCV DNA by PCR. The overall prevalence of polyomavirus DNA in urine was 74.2%. BKV DNA was detected in 30.1% urine samples and JCV DNA in 23.7% samples. Both BKV and JCV DNA were detected in 20.4% samples. There was no association between BKV/JCV urinary shedding and the degree of immunosuppression measured by CD4+ cell count. However, taking into account the severity of disease resulting from reactivation of BKV and JCV, patients with HIV/polyomavirus co-infection should be kept under frequent and regular supervision.
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Špak, Josef, Darina Kubelková, Jaroslava Přibylová, Vlastimila Špaková, and Karel Petrzik. "Elucidation of the Roles of Blackcurrant reversion virus and Phytoplasma in the Etiology of Full Blossom Disease in Currants." Plant Disease 93, no. 8 (2009): 832–38. http://dx.doi.org/10.1094/pdis-93-8-0832.
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To determine the roles of phytoplasmas and Blackcurrant reversion virus (BRV) in the etiology of full blossom disease (FBD), we conducted graft and dodder transmission experiments. Scions from FBD-affected Ribes rubrum were grafted onto red currants, white currants, and black currants. Red and white cultivars revealed symptoms of FBD, whereas blackcurrant displayed symptoms of BRV. No differences in symptoms were observed between plants infected with BRV only and those infected with BRV and phytoplasma. Aster yellows phytoplasma subgroup 16SrI-C was transferred from FBD-infected red currants to periwinkle, where symptoms of green and yellow petal were observed. Back-transmission of phytoplasma to currant seedlings of red and black currant was not successful. Scions of periwinkle infected with aster yellows phytoplasmas of subgroup 16SrI-C and 16SrI-B, which were bottle-, bark-, and approach-grafted onto seedlings of red and black currant, resulted in positive but symptomless transmission of phytoplasma to red currant. We conclude that FBD symptoms are induced by BRV rather than by phytoplasma, which was originally described as the causal agent of FBD.
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Abraheem, Hatim H., Amira M. Elhassan, Mohammed O. Hussien, Khalid A. Enan, Azza B. Musa, and Abdel Rahim M. El Hussein. "A Survey of Bluetongue Infection and Associated Risk Factors among the One-Humped Camel (Camelus dromedaries) in Gadarif State, Eastern Sudan." Veterinary Medicine International 2021 (March 24, 2021): 1–5. http://dx.doi.org/10.1155/2021/6613217.
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Bluetongue (BT) is an infectious, noncontagious, vector-borne viral disease that affects wild and domestic ruminants transmitted by Culicoides spp. A cross-sectional study was carried out during the period 2016-2017 in Gadarif state. A total of 276 sera samples were collected from camels in six localities of Gadarif state, eastern Sudan, to investigate bluetongue virus (BTV) seroprevalence and associated risk factors of BTV infection including age, sex, breed, locality, and ecology of the region. Enzyme-linked immunosorbent assay (ELISA) was used for estimation of BTV seroprevalence rate. The overall BTV seroprevalence rate was 96.7% in the study area ranging from 93.5% to 100% in six screened localities with no significant differences. The findings revealed similar BTV seroprevalence rates in both males and females, but high rates were found in age group of less than one year and two to three years with estimated 100%. However, the lowest seroprevalence was found in the age group of five to four years with estimated BTV to be 92.3%. BTV seropositivity was not found to be statistically associated with examined different camel breeds which revealed 93%, 94.4%, 97.6%, and 97.8% seroprevalence in Bushari, Rashide, Arabi, and Anafi, breeds, respectively. Epidemiology of BTV assessment according to the ecology of the area showed high BTV seroprevalence in desert and savanna with estimated 100% and lower BTV seroprevalence in arid and rich savanna with estimated 94.8% and 95.7%, respectively. There was no significant association between BTV ELISA positivity and sex, breed, and ecology of the area.
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Irtyuga, O. B., E. V. Zhiduleva, E. E. Kazakova, and O. M. Moiseeva. "PATHOGENESIS OF AORTIC STENOSIS IN HYPERTENSIVE PATIENTS." "Arterial’naya Gipertenziya" ("Arterial Hypertension") 19, no. 6 (2013): 495–501. http://dx.doi.org/10.18705/1607-419x-2013-19-6-495-501.
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Objective. To assess osteoprotegerin (OPG) and soluble ligand receptor activator of transcription factor kappa-B (RANKL) levels in patients with aortic stenosis and systemic hypertension.Design and methods. Sixty-one patients with aortic valve stenosis (AVS) [31 patients with bicuspid aortic valve (BAV) and 30 patients with tricuspid aortic valve (TAV)] were examined. Thirty-two patients without heart diseases formed the control group. Serum levels of C-reactive protein, ОPG, sRANKL and lipid profile were assessed in all patients.Results. Elevated blood pressure (BP) was found in 93 % patients with TAV and in 71 % patients with BAV. Serum concentration of OPG was increased in patients with TAV and BAV vs control group. OPG concentration was negatively correlated with BP level only in patients with TAV. sRANKL level was increased only in patients with BAV. At the same time sRANKL level positively correlated with BP in patients with TAV. Conclusion. Systemic hypertension is the key risk factor for OPG/RANKL/RANK system activation in patients without congenital heart disease.
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Altarabsheh, Salah Eldien, Kevin L. Greason, Hartzell V. Schaff, et al. "Staged Balloon Aortic Valvuloplasty before Standard Aortic Valve Replacement in Selected Patients with Severe Aortic Valve Stenosis." Texas Heart Institute Journal 41, no. 2 (2014): 152–58. http://dx.doi.org/10.14503/thij-13-3298.
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This study evaluated preoperative balloon aortic valvuloplasty (BAV) as a technique to decrease aortic valve replacement (AVR) risk in patients who have severe symptomatic aortic valve stenosis with substantial comorbidity. We report the outcomes of 18 high-risk patients who received BAV within 180 days before AVR from November 1993 through December 2011. Their median age was 78 years (range, 51–93 yr), and there were 11 men (61%). The pre-BAV median calculated Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) was 18.3% (range, 9.4%–50.7%). Preoperative left ventricular ejection fraction measured a median of 0.23 (range, 0.05–0.68), and the median aortic valve area index was 0.4 cm2/m2 (range, 0.2–0.7 cm2/m2). The median interval from BAV to AVR was 28 days (range, 1–155 d). There were no strokes or deaths after BAV; however, 4 patients (22%) required mechanical circulatory support, 3 (17%) required femoral artery operation, and 1 (6%) developed severe aortic valve regurgitation. After BAV, the median STS PROM fell to 9.1% (range, 2.6%–25.7%) (compared with pre-BAV, P <0.001). Echocardiography before AVR showed that the median left ventricular ejection fraction had improved to 0.35 (range, 0.15–0.66), and the aortic valve area index to 0.5 cm2/m2 (range, 0.3–0.7 cm2/m2) (compared with pre-BAV, both P <0.05). All patients received AVR. Operative death occurred in 2 patients (11%), and combined operative death and morbidity in 7 patients (39%). Staged BAV substantially reduces the operative risk associated with AVR in selected patients.
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Sui, C., J. H. Wei, Q. Q. Zhan, and J. Zhang. "First Report of Broad bean wilt virus 2 Infecting Bupleurum chinense in China." Plant Disease 93, no. 8 (2009): 844. http://dx.doi.org/10.1094/pdis-93-8-0844b.
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Samples of the medicinal plant, Bupleurum chinense DC., were collected in October 2007 from the garden of the Institute of Medicinal Plant Development in Beijing. Partial fragments of the genomic RNA1 and RNA2 of Broad bean wilt virus 2 (BBWV-2) were obtained from the root cDNA library of these plants. Sequence analyses showed the 1,896-nt RNA1 fragment (GenBank No. FJ485684) encoding a portion of the RNA-dependent RNA polymerase (RdRp) and the 2,017-nt RNA2 fragment (No. FJ485685) encoding 612 amino acids of the complete large (LCP) and small coat protein (SCP), respectively. The amino acid identities of LCP and SCP were 90.8 to 96.7% compared with sequences of other BBWV-2 isolates deposited in the GenBank with the highest homology to Japanese IP (No. AB018698) and the lowest to Japanese 1-2 (No. AB018701). This strongly suggests that the B. chinense plants utilized for cDNA library construction were infected by what appears to be an isolate of BBWV-2. Seeds from the same batch were sown again in the same garden in May 2008. In August 2008, approximately 30% of these plants showed mosaic, distortion, and stunting. Reverse transcription (RT)-PCR amplicons were obtained from eight symptomatic plants using a pair of conserved primers for specific detection of viruses within the Fabavirus genus (2). A symptomless plant tested negative by RT-PCR. The same single 391-bp amplicon of RNA1 (No. FJ485686) obtained from five of those eight symptomatic plants were cloned and sequenced. Sequence comparison with the corresponding sequences of other BBWV-2 isolates showed that the sequenced isolate was most closely related to B935-a Chinese faba bean isolate (No. AF149425). Crude sap of one diseased B. chinense plant was used for mechanical inoculation to Chenopodium amaranticolor Coste & Reyn. Chlorotic local lesions were observed on inoculated leaves 5 days after inoculation, and subsequently, systemic mottle and malformed symptoms appeared on the upper leaves. Twelve plants were inoculated and all plants showed symptoms of virus infection. RT-PCR tests of inoculated indicator plants showing local lesions confirmed the presence of BBWV-2. To date, Clover yellow vein virus and Lettuce mosaic virus have been isolated from the genus Bupleurum (B. griffithii hort. and B. falcatum L. sensu lato) in Japan and Israel, respectively (1,3). Furthermore, to our knowledge, no genomic sequence of BBWV-2 naturally infecting plants in the family Umbelliferae/Apiaceae has been reported. Therefore, this is the first report of BBWV-2 on B. chinense (Umbelliferae/Apiaceae), which was designated as a BC isolate of BBWV-2. In China, BBWV-2 was reported to be infecting and causing heavy losses to many plant species mostly belonging to the family Leguminosae (4). B. chinense is a commonly used bulk medicinal plant mainly cultivated in Hebei, Sichuan, Gansu, and Shanxi provinces in China for decoction pieces and extracts of its dried roots, which are also exported to Japan, Korea, and Southeast Asia. These results demonstrate the need for further assessment of BBWV-2 incidence and the losses it may cause. References: (1) J. Cohen et al. Phytoparasitica 30:88, 2002. (2) R. M. Ferrer et al. J. Virol. Methods 144:156, 2007. (3) H. Yamamoto. Jpn. J. Phytopathol. 69:420, 2003. (4) X. P. Zhou et al. Acta Phytopathol. Sin. 26:347, 1996.
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Braun, Eduardo, Mary J. Fidler, Sanjib Basu, et al. "Panel of serum biomarkers to predict benefit from bevacizumab (BEV) in advanced NSCLC patients." Journal of Clinical Oncology 30, no. 15_suppl (2012): e21069-e21069. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e21069.
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e21069 Background: BEV has produced modest benefits in patients (PTS) with advanced NSCLC. Identification of positive predictors for BEV would have important implications for individual PTS and health care costs. Methods: We performed a prospective exploratory analysis to identify serum biomarkers as predictors of improved outcomes with BEV. Pre treatment sera were collected from 93 pts prior to initiation of first line treatment for advanced NSCLC. Treatment drugs, including BEV, were prescribed according to treating physician’s discretion. Seventy two serum biomarkers, relevant to angiogenesis and tumor progression, were recorded using Luminex immunobead platform. Serum levels were correlated with progression free survival (PFS) and overall survival (OS) and compared between patient treated with or without BEV containing regimens, BEV + and BEV- groups respectively. Log-rank and interaction p value tests were used to identify markers associated with longer PFS and OS in the BEV+ group but not in BEV- group. Results: Characteristics for each group were: BEV+ (n=43, median age 65 y/o, 72% smokers, 60% females, 100% non-squamous). BEV– (n=50, median age 64 y/o, 84% smokers, 50% female, 70 % non-squamous). The BEV+ group had longer PFS (5.8 vs. 3.0 mos, log-rank p= 0.039) and OS (13.1 vs. 8.5 mos, log-rank p =0.11) when compared to the BEV- group. High serum levels of these markers resulted in a differential decreased hazard in the BEV+ group: PDGF-AB/BB (interaction p <0.01 for PFS, p=0.04 for OS), FGF (interaction p=0.15 for PFS, p<0.04 for OS), tenascin-c (interaction p=0.18 for PFS, p=0.04 for OS), RANTES (interaction p=0.04 for PFS, p=0.6 for OS), epiregulin (interaction p=0.31 for PFS, p=0.04 for OS) and anti-HGF (interaction p=0.18 for PFS, p=0.03 for OS). In the BEV+ group higher levels of PDGF-AB/BB were associated with a better outcome (log-rank p=0.05 and p=0.01 for PFS and OS respectively). We did not find significant correlations between serum levels of VEGF, anti-VEGF or VEGFR and benefit from BEV. Conclusions: This exploratory analysis suggests that these biomarkers may have predictive value for BEV in NSCLC PTS and should be considered for further studies.
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Kim, Jae-Hyun, Young-Soo Kim, and Yong-Ho Jeon. "Complete Nucleotide Sequence Analysis of RNA2 and Phylogenetic Analyses of a Paprika Isolate of Broad Bean Wilt Virus in Korea." International Journal of Phytopathology 3, no. 1 (2014): 11–20. http://dx.doi.org/10.33687/phytopath.003.01.0377.
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An isolate of Broad bean wilt virus 2 (BBWV 2), which was isolated from paprika showed spotty fruits. Host range of BBWV 2 was nine species including Chenopodium amaranticolor, and could be characterized by the symptoms include chlorotic local and distortion on upper leaves of C. amaranticolor. Datura stramonium induced chlorotic spot on uninoculated upper leaves. The purified virus particles were isometric about 25 nm in diameter. The genomic RNA of this virus consisted of two components of about 6.3 kb and 4.5 kb molecules and coat protein contained two polypeptide species which calculated with about 42 kDa and 22 kDa. We determined the complete sequence of RNA2 from Broad bean wilt virus 2 isolate Pa. The complete nucleotide (nt) sequence of RNA 2 for BBWV 2-Pa was 3,597 nt in length. encoding a pupative movement protein (MP) and coat protein (CP). Between BBWV 2-Pa and other serotype II favaviruses, the overall amino acid similarities in the polyprotein coding regions was and 84%-93% for RNA2. In the 5′UTR, the nucleotide similarity was 65%-92%. For the 3′UTRs, they are 38%-60%, respectively. For the Genome organization of BBWV 2-Pa was similar to other comoviruses in the Comoviridae.
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Cha, Yongjun, Yu Jung Kim, Tae Min Kim, et al. "Post-bevacizumab treatment and clinical outcomes in recurrent malignant glioma." Journal of Clinical Oncology 31, no. 15_suppl (2013): 2098. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.2098.
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2098 Background: Bevacizumab (Bev) and irinotecan combination therapy is effective against recurrent malignant glioma. However, post-Bev treatment and its clinical outcomes are not well investigated. Methods: We identified 103 consecutive recurrent malignant glioma patients who received Bev plus irinotecan at our institutions.Clinical records and magnetic resonance images were reviewed. Response and progression were assessed by RANO criteria. Results: Bev and irinotecan treatment produced response rate of 37.9% (95% CI, 29.1-47.5%). At a median follow-up time of 41 weeks, the median progression-free survival (PFS) was 17.1 weeks (95% CI, 14.3-20.0), and 6-month PFS (6M-PFS) was 27.8% (95% CI, 18.4-37.2). The median overall survival (OS) was 33.4 weeks (95% CI, 27.8-39.1). Response predicted for superior PFS (25.0 weeks vs. 11.0 weeks, p < .001) and OS (45.9 weeks vs. 26.7 weeks, p < .001). A total of 93 patients discontinued Bev treatment and the reasons for discontinuation were: disease progression in 59 (63.4%), toxicities in 4 (4.3%), physician’s decision in 5 (5.4%), patient’s refusal to further treatment in 25 (26.9%). The median OS was 26.7 weeks in 59 patients who discontinued Bev due to disease progression, and 45.7 weeks in 34 patients who discontinued Bev for reasons other than disease progression (p < .001). Among 85 patients who progressed after Bev, 42 (49.4%) received further therapy: chemotherapy in 32 (37.6%), radiotherapy in 9 (10.6%), and surgery in 1 (1.2%). Further chemotherapy regimens included temozolomide (31.2%), ACNU/CDDP (25.0%), Bev reintroduction (18.8%), erlotinib (12.5%), PCV (9.4%), and intrathecal methotrexate (3.1%). The median survival time after Bev failure was 15.6 weeks (95% CI, 13.3-17.8). Patients who received further therapy showed longer median OS (18.6 weeks vs. 12.9 weeks, p < .001). In patients who received chemotherapy, the median PFS and OS was 6.6 weeks and 20.6 weeks, respectively. Conclusions: Prognosis after Bev failure was poor. Proper selection of patients who may benefit from further treatment is warranted.
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Kelsen, D., M. Jhawer, D. Ilson, et al. "Analysis of survival with modified docetaxel, cisplatin, fluorouracil (mDCF), and bevacizumab (BEV) in patients with metastatic gastroesophageal (GE) adenocarcinoma: Results of a phase II clinical trial." Journal of Clinical Oncology 27, no. 15_suppl (2009): 4512. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.4512.
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4512 Background: Metastatic GE cancer is an aggressive disease with poor patient (pt) outcomes. Despite response rates of 30–60% to combination chemotherapy, response duration is usually 4–6 mo and 24-mo survival is 5–10%. The addition of BEV to chemotherapy has improved survival in several solid tumors, and has demonstrated encouraging activity in GE cancer (Shah et al, JCO 2006). We report mature tolerability and efficacy results of mDCF+BEV in GE cancer, with an emphasis on prolonged pt survival. Methods: Previously untreated metastatic GE pts with adequate end organ function received BEV 10mg/kg, Docetaxel 40mg/m2, FU 400mg/m2, Leucovorin 400mg/m2 on day 1, FU 1000 mg/m2/day x 2 days IVCI, and Cisplatin 40mg/m2 on day 3. Treatment is repeated every 14 days without prophylactic growth factor support. The primary objective is to improve 6-month progression free survival (PFS) from 43% (historical DCF control) to 63% with the addition of BEV. Target accrual is 44 evaluable pts, with 10% type I & II error. Secondary objectives include tolerability, response rates (RECIST), median PFS, 12-mo survival, and overall survival (OS). Results: Pt enrollment has completed: median age 57(range 29–74), median KPS 80% (70–100), M:F 32:12, gastric/GEJ/esophagus 22:17:5. In 39 patients with measurable disease we observed 26 confirmed partial responses (67%, 95% CI 50%- 81%), and 12 (31%) stable disease. Six-month PFS is 79% (95% CI 68%-93%), the median PFS is 12 mo (95% CI: 8.8–16). At median follow up of 12.3 mo, median OS is 16.2 mo (95%CI 11.4-infinitiy). 12- and 18-mo OS is 63% (95%CI 44–77%) and 46% (95%CI 27–63%), respectively. Minimal chemotherapy related grade 3–4 adverse events were observed: fatigue (20%), dehydration (13%), mucositis (9%), nausea/vomiting (7%), febrile neutropenia (4%). BEV related adverse event was perforation (n=1) and bleeding (n=1). 31% developed grade 3–4 venous thromboembolism, of which 93% were asymptomatic. No grade 3–4 hypertension, proteinuria or arterial thrombosis was observed. Conclusions: mDCF+BEV appears tolerable and has notable long term pt outcomes: 6-mo PFS is 79% (surpassing our efficacy endpoint), median OS 16.2 mo, and 18-mo OS 46%. No significant financial relationships to disclose.
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Markus, Richard, Primal Kaur, Vincent Chow, et al. "Results of functional testing and pharmacokinetics comparing ABP 215 to bevacizumab." Journal of Clinical Oncology 33, no. 3_suppl (2015): 711. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.711.
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711 Background: ABP 215 is a biosimilar candidate to bevacizumab (BEV), a monoclonal antibody (mAb) that binds and inhibits vascular endothelial growth factor (VEGF). Biosimilar mAbs are likely to have differences in product quality attributes due to different expression systems, bioprocess and purification, so demonstration of functional similarity and pharmacokinetic (PK) equivalence is the foundation for biosimilarity. Objectives: To assess functional similarity and PK equivalence of ABP 215 and BEV sourced from EU and US. Methods: Functional similarity testing included binding to VEGF and VEGF isoforms by surface plasmon resonance and to FcRn and FcγRIIIa. Inhibition of proliferation and VEGFR2 autophosphorylation was compared in endothelial cells. PK equivalence was evaluated in a randomized, single-dose, 3-arm study in healthy adult male subjects. Primary endpoints were area under the serum concentration-time curve from time 0 to infinity (AUCinf) and maximum observed serum concentration (Cmax). Secondary endpoints were safety, tolerability, and immunogenicity. Results: ABP 215 and BEV (EU) are functionally similar as previously presented. Binding affinity to VEGF was similar between ABP 215 (117 pM) and BEV (US) (126 pM) as was binding to VEGF165 and VEGF121. Binding to FcRn was similar between ABP 215 (95-102%) and BEV (96-111%). Binding to FcγRIIIa was also similar; ABP 215 (108-115%) and BEV (85-93%). Potency in proliferation inhibition was similar between ABP 215 (91-97%) and BEV (91-96%), as was inhibition of autophosphorylation. After a single dose, geometric mean (GM) of Cmax and AUCinf for ABP 215 were 87.2 µg/mL and 29,400 µg.h/mL, for BEV (US) were 89.1 µg/mL and 29,600 µg.h/mL, for BEV (EU) were 84.7 µg/mL and 30,600 µg.h/mL. The 90% CIs of GM ratio for Cmax and AUCinf were within pre-specified equivalence criterion of 0.80 to 1.25 confirming PK equivalence. There were no adverse events (AEs) or serious AEs leading to study discontinuation. Treatment-related AEs were reported for 22.1% in ABP 215, 16.4% in BEV (US) and 22.4% in BEV (EU) groups; no subjects developed anti-drug antibodies. Conclusions: ABP 215 is similar to BEV in sensitive functional tests and equivalent to BEV based on results of the phase 1 PK study.
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Clarke, Nathan. "NCMP-28. BEVACIZUMAB ASSOCIATED INTRACEREBRAL HEMORRHAGE IN PATIENTS WITH PRIMARY CNS MALIGNANCY." Neuro-Oncology 22, Supplement_2 (2020): ii128—ii129. http://dx.doi.org/10.1093/neuonc/noaa215.539.
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Abstract The risk of intracranial hemorrhage (ICH) associated with the use of bevacizumab (BEV) has been a topic of several reviews in the literature, and is considered to be a potential adverse effect of BEV when used in patients with malignant glioma. We performed a single-center retrospective chart-review identifying glioma patients treated with BEV at our institution. 595 unique patients who received BEV with documented follow up were identified. Of these patients, 23 (3.9%) developed ICH within 12 weeks (five half-lives) of a BEV infusion (median 9 days post infusion, 1-24 days IQR). There was a trend towards statistical significance between dose administered and the incidence of hemorrhage (P=0.06), with all 23 hemorrhages occurring in patients treated with 10 mg/kg (n=21/490) per infusion or 15 mg/kg per infusion (n=2/35) (n=525, 88.2% of cohort). No patient on dosing regimens of 7.5 mg/kg (n=72) or 5 mg/kg per infusion (n=16) (n=88, 14.7% of cohort) developed ICH. Therapeutic anticoagulation and concomitant BEV therapy was observed in 103 (17%) patients with 10 patients (10/93, 9.7%) developing an ICH (n=10), at a rate significantly higher than in patients treated with bevacizumab alone (13/479, 2.6%) (p=0.0025). When hemorrhages occurred (with or without concomitant anticoagulation) they were associated with high morbidity and mortality (ECOG 3.54 versus 1.26, p = &lt; 0.0001), with 12 patients (52%) suffering severe debility (n=2) or death (n=10). CONCLUSION: Bevacizumab associated intracerebral hemorrhages remain uncommon events, similar to the baseline rate of spontaneous hemorrhage associated with malignant glioma. We observed a trend towards significance with higher doses per infusion associated with an increased rate of intracerebral hemorrhage. The combination of anticoagulation and BEV appears to confer a greater risk of hemorrhage than BEV alone.
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Rouch, Laure, Philippe Cestac, Brigitte Sallerin, et al. "Visit-to-Visit Blood Pressure Variability Is Associated With Cognitive Decline and Incident Dementia." Hypertension 76, no. 4 (2020): 1280–88. http://dx.doi.org/10.1161/hypertensionaha.119.14553.
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To investigate the impact of visit-to-visit systolic blood pressure variability (BPV), diastolic BPV, mean arterial pressure variability, and pulse pressure variability on cognitive decline and incident dementia in noninstitutionalized patients aged ≥65 years. A total of 3319 subjects from the S.AGES (Sujets AGÉS—Aged Subjects) cohort underwent clinical examinations every 6 months during 3 years. Variability was evaluated using standard deviation (SD), coefficient of variation, average real variability, successive variation, variation independent of mean, and residual SD. Cognition was assessed using the Mini-Mental State Examination and dementia with the Diagnostic Statistical Manual of Mental Disorders. Linear mixed models and Cox proportional hazards models were used. Higher systolic BPV was associated with poorer cognition independently of baseline SBP: adjusted 1-SD increase of coefficient of variation: β (SE)=−0.12 (0.06), P =0.04. Similar results were observed for diastolic BPV and mean arterial pressure variability: β (SE)=−0.20 (0.06), P <0.001 for both. Higher pulse pressure variability was no longer associated with cognitive function after adjustment for age, except with residual SD ( P =0.02). Among the 3319 subjects, 93 (2.8%) developed dementia. Higher systolic BPV was associated with greater dementia risk (adjusted 1-SD increase of coefficient of variation: hazard ratios=1.23 [95% CI, 1.01–1.50], P =0.04). Similar results were found for diastolic BPV and mean arterial pressure variability ( P <0.01). Pulse pressure variability was not associated with dementia risk. Beyond hypertension, higher BPV is a major clinical predictor of cognitive impairment and dementia. Further studies are needed to assess whether controlling BP instability could be a promising interventional target in preserving cognition among older adults.
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Christensen, Neil D., and John W. Kreider. "Monoclonal antibody neutralization of BPV-1." Virus Research 28, no. 2 (1993): 195–202. http://dx.doi.org/10.1016/0168-1702(93)90136-b.
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Al-Mubarak, A., Y. Zhou, and S. I. Chowdhury. "A Glycine-Rich Bovine Herpesvirus 5 (BHV-5) gE-Specific Epitope within the Ectodomain Is Important for BHV-5 Neurovirulence." Journal of Virology 78, no. 9 (2004): 4806–16. http://dx.doi.org/10.1128/jvi.78.9.4806-4816.2004.
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ABSTRACT The bovine herpesvirus 5 (BHV-5) gE ectodomain contains a glycine-rich epitope coding region (gE5 epitope), residues 204 to 218, that is significantly different from the corresponding gE region of BHV-1. Deletion of the gE epitope significantly reduced the neurovirulence of BHV-5 in rabbits. Pulse-chase analyses revealed that the epitope-deleted and wild-type gE were synthesized as N-glycosylated endoglycosidase H-sensitive precursors with approximate molecular masses of 85 kDa and 86 kDa, respectively. Like the wild-type gE, epitope-deleted gE complexed with gI and was readily transported from the endoplasmic reticulum. Concomitantly, the epitope-deleted and wild-type gE acquired posttranslational modifications in the Golgi leading to an increased apparent molecular mass of 93-kDa (epitope-deleted gE) and 94-kDa (wild-type gE). The kinetics of mutant and wild-type gE processing were similar, and both mature proteins were resistant to endoglycosidase H but sensitive to glycopeptidase F. The gE epitope-deleted BHV-5 formed wild-type-sized plaques in MDBK cells, and the epitope-deleted gE was expressed on the cell surface. However, rabbits infected intranasally with gE epitope-deleted BHV-5 did not develop seizures, and only 20% of the infected rabbits showed mild neurological signs. The epitope-deleted virus replicated efficiently in the olfactory epithelium. However, within the brains of these rabbits there was a 10- to 20-fold reduction in infected neurons compared with the number of infected neurons within the brains of rabbits infected with the gE5 epitope-reverted and wild-type BHV-5. In comparison, 70 to 80% of the rabbits exhibited severe neurological signs when infected with the gE5 epitope-reverted and wild-type BHV-5. These results indicated that anterograde transport of the gE epitope-deleted virus from the olfactory receptor neurons to the olfactory bulb is defective and that, within the central nervous system, the gE5 epitope-coding region was required for expression of the full virulence potential of BHV-5.
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Charafeddine, Fatme A., Haytham Bou Houssein, Nadine B. Kibbi, et al. "Balloon Valvuloplasty for Congenital Aortic Stenosis: Experience at a Tertiary Center in a Developing Country." Journal of Interventional Cardiology 2021 (January 12, 2021): 1–7. http://dx.doi.org/10.1155/2021/6681693.
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Background. Aortic valve stenosis accounts for 3–6% of congenital heart disease. Balloon aortic valvuloplasty (BAV) is the preferred therapeutic intervention in many centers. However, most of the reported data are from developed countries. Materials and Methods. We performed a retrospective single-center study involving consecutive eligible neonates and infants with congenital aortic stenosis admitted for percutaneous BAV between January 2005 and January 2016 to our tertiary center. We evaluated the short- and mid-term outcomes associated with the use of BAV as a treatment for congenital aortic stenosis (CAS) at a tertiary center in a developing country. Similarly, we compared these outcomes to those reported in developed countries. Results. During the study period, a total of thirty patients, newborns (n = 15) and infants/children (n = 15), underwent BAV. Left ventricular systolic dysfunction was present in 56% of the patients. Isolated AS was present in 19 patients (63%). Associated anomalies were present in 11 patients (37%): seven (21%) had coarctation of the aorta, two (6%) had restrictive ventricular septal defects, one had mild Ebstein anomaly, one had Shone’s syndrome, and one had cleft mitral valve. BAV was not associated with perioperative or immediate postoperative mortality. Immediately following the valvuloplasty, a more than mild aortic regurgitation was noted only in two patients (7%). A none-to-mild aortic regurgitation was noted in the remaining 93%. One patient died three months after the procedure. At a mean follow-up of 7 years, twenty patients (69%) had more than mild aortic regurgitation, and four patients (13%) required surgical intervention. Kaplan–Meier freedom from aortic valve reintervention was 97% at 1 year and 87% at 10 years of follow-up. Conclusion. Based on outcomes encountered at a tertiary center in a developing country, BAV is an effective and safe modality associated with low complication rates comparable to those reported in developed countries.
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Nogami, Naoyuki, Katsuyuki Hotta, Toshiyuki Kozuki, et al. "Survival analysis of induction cisplatin (CDDP)-docetaxel (DOC)-bevacizumab (BEV) chemotherapy followed by maintenance BEV-pemetrexed (PEM) therapy in advanced nonsquamous non-small cell lung cancer (NonSq NSCLC): A phase II trial from Okayama Lung Cancer Study Group 0903." Journal of Clinical Oncology 31, no. 15_suppl (2013): e19040-e19040. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e19040.
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e19040 Background: BEV maintenance therapy and PEM maintenance therapy in platinum-based chemotherapy yield a significant survival advantage in CALGB and PARAMUNT trials, respectively, but each agent gave only modest impact on survival. We conducted a phase II trial of CDDP-DOC-BEV therapy followed by maintenance BEV-PEM therapy inchemo-naïve advanced NonSq NSCLC. Methods: Forty-one patients (pts) participated in the induction phase, specified as four cycles of induction CDDP (80 mg/m2), DOC (60 mg/m2) and BEV (15 mg/kg) on day 1 of a 21-day cycle. Pts who had not progressed during CDDP-DOC-BEV received maintenance BEV (15 mg/kg) and PEM (500 mg/m2) on day 1 of a 21-day cycle until disease progression. The primary endpoint was PFS, and the secondary endpoints included OS, toxicity, and response. Survival time was calculated from the date of registration. Results: Pt characteristics were as follows: median age: 62 yrs; 76% male; 32% PS 0; 73% stage IV; 93% Ad; 5% EGFR-mutant and 2% ALK-mutant. At the time of this analysis, 34 pts (83%) discontinued the treatment, mainly due to progressive disease (53%). The principal toxicity was myelosuppression (gr. 4 hematological: 21 pts [51%]), and grs. 3/4 febrile neutropenia was observed in 10 (24%) despite no treatment-related deaths. The objective response rate and disease control rate (DCR, % pts with CR/PR/SD) was 82.9% and 97.6%, respectively. Median follow-up time was 15.6 months, and 1-yr PFS rate was 34.2% with 95% confidence interval (CI) of 20.3-48.5%, which met the primary endpoint. Also, 1-yr OS rate was 75.6% (95%CI: 59.4-86.1%). Exploratory analysis for pts with both EGFR- and ALK-wild-typed NonSq NSCLC (n = 16) demonstrated 1-yr PFS and OS rates of 50.0% (24.5-71.1%) and 87.5% (58.6-96.7%), respectively. Also, pts with maintenance therapy (n = 34) had 1-yr PFS and OS rates of 41.2% (24.8-56.9%) and 82.4% (64.9-91.7%), respectively. Conclusions: CDDP-DOC-BEV followed by BEV-PEM maintenance seems highly effective despite moderately toxic profiles in chemo-naïve pts with advanced NonSq NSCLC. Clinical trial information: UMIN000004127.
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Peach, Elizabeth, Shelley Cogger, Kat Byron, et al. "Blood-borne virus transmission in an urban, culturally diverse neighbourhood: results from a cross-sectional bio-behavioural survey using innovative outreach methods in a hard-to-reach population." Sexual Health 15, no. 1 (2018): 54. http://dx.doi.org/10.1071/sh16219.
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Background Following a HIV outbreak among Aboriginal people in a culturally diverse inner-city suburb of Melbourne, a blood-borne virus (BBV) screening program was conducted to inform public health interventions to prevent transmission and facilitate timely diagnosis and linkage to care. Methods: In August–September 2014, community health workers recruited people who inject drugs (PWID) from a local needle and syringe program. Participants were tested for hepatitis C virus (HCV), hepatitis B virus (HBV), HIV and syphilis and completed a bio-behavioural questionnaire. Results: In total, 128 PWID participated in the study. Serological evidence of exposure to HCV and HBV was detected among 118 (93%) and 57 participants (45%) respectively. Five participants were HIV positive. Independent risk factors for needle sharing were Aboriginality (AOR = 6.21, P < 0.001), attending health care for mental health problems (AOR = 2.79, P = 0.023) and inability to access drug treatment in the previous 6 months (AOR = 4.34, P = 0.023). Conclusions: BBV prevalence in this sample was much higher than reported in other recent Australian studies. This local population is at high risk of further BBV transmission, particularly Aboriginal PWID. Individual and service-related factors associated with risk in the context of a dynamic urban drug culture and HIV outbreak suggest an urgent need for tailored harm-reduction measures.
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Piyumanthi, Ranasingha A. P., Napagoda A. Y. Isuruni, Geekiyanage N. U. Abeyrathne, et al. "Are the future nurses geared to protect themselves from blood borne viruses? A descriptive cross-sectional study from Sri Lanka." International Journal Of Community Medicine And Public Health 7, no. 11 (2020): 4227. http://dx.doi.org/10.18203/2394-6040.ijcmph20204718.
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Background: Nurses have a high risk of being exposed to blood borne viruses (BBV) during their day to day practices and knowledge on transmission is important. The objective was to describe the knowledge in a selected Nursing Training School in Western Province, Sri Lanka and their associated factors of transmission of BBV, among nursing students in a selected Nursing Training School in Western Province and their associated factors in Sri Lanka.Methods: A descriptive cross-sectional study was carried out among 209 nursing students from a nursing school in Sri Lanka. Data collection was done using a self-administered questionnaire. Data was analysed using SPSS software version 15.0. Statistical significance was tested at p<0.05.Results: Majority (57%) had poor knowledge on transmission of BBV. Most gave correct answers for transmission of HIV and Hepatitis B virus 91%, 64% (HBV) by needle stick injury (82%, 87%), through blood transfusion (90%, 80%), mother to child at birth (90%, 64%), through organ and for transmission of HBV via tattooing/piercing, 58% gave correct answers transplant (80%, 66%), direct contact with blood (75%, 62%), through unprotected sexual intercourse (93%, 50%) and tattooing/ piercing (48%, 58%). Many had poor knowledge on transmission of HIV and HBV via sharing household equipment (50%, 84%), by kissing/hugging (57%, 75%), through mosquito bites (76%, 86%), by swimming in pools (80%, 87%), by eating contaminated food (81%, 88%) and through exposure to saliva/tears/stools and urine (89%, 92%). There was a statistically significant association between knowledge on transmission of BBV with higher academic year and older age (p<0.05).Conclusions: BBV transmission needs further emphasis on the curriculum for future nurses to deliver to their utmost capabilities in the future.
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Rabkin, Simon W. "Differential expression of MMP-2, MMP-9 and TIMP proteins in thoracic aortic aneurysm – comparison with and without bicuspid aortic valve: a meta-analysis." Vasa 43, no. 6 (2014): 433–42. http://dx.doi.org/10.1024/0301-1526/a000390.
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Background: It is believed that the balance of matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs), in the aorta, play a critical role in aneurysm formation. The objective of this study was to perform a meta-analysis of studies reporting protein expression of MMPs and TIMPs in the ascending aorta of thoracic aortic aneurysms (TAA) cases and to examine this expression in persons with TAA and bicuspid aortic valves (BAV). Methods: OvidSP Medline and EMbase were systematically searched for studies that were: human ascending TAA cases with measurement of MMP or TIMP protein expression in the aorta and a control group. A similar search was conducted for BAV compared to those with a normal or trileaflet aortic valve (TAV). Results: Eight studies fulfilled the inclusion criteria. There was a significant increase in MMP-9 and no change in MMP-2, in the aorta from persons with TAA (N = 106) compared to control (N = 30). There was also a highly significant reduction in TIMP-1 and TIMP-2 in TAA (N = 93) compared to control (N = 24) resulting in a MMP-9 to TIMP-1 or TIMP-2 ratio over 3.5 fold greater than controls. There was a highly significant increase in MMP-2 but not MMP-9 in TAA with BAV (N = 112) compared to TAV (N = 53). There was a significant reduction for TIMP-1 in BAV compared to TAV but no change in TIMP-2, TIMP-3 or TIMP-4. Conclusions: These data suggest that MMP may be implicated in the pathogenesis of TAA and there is a differential expression with MMP-9 increased and TIMP-1 and -2 reduced in the most common forms of TAA. MMP-2 is increased and only TIMP-1 decreased in TAA with BAV compared to TAV.
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Martinez Villacampa, Mercedes, Jaume Capdevila, Jose Luis Manzano, et al. "A randomized phase II study of capecitabine-based chemoradiation with or without bevacizumab in resectable locally advanced rectal cancer." Journal of Clinical Oncology 30, no. 15_suppl (2012): 3571. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.3571.
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3571 Background: The addition of bevacizumab (BEV) to capecitabine (CAP)-based chemoradiation (CRT) has shown encouraging efficacy in locally advanced rectal cancer (LARC), in nonrandomized studies. This randomized phase II study investigated the effect of adding BEV to preoperative CAP-based CRT in patients (pts), with LARC. Methods: The primary end point was pathologic complete response (pCR). A two-stage design was used. Assuming a minimum pCR rate of at least 15% in one of the arms, a difference between the two arms of 10%, and accepting a probability of correct selection of 87%, 41 pts per arm were needed. Patients with LARC (Stages II-III assessed by MRI) and ECOG PS <2 were randomized to concurrent radiotherapy 45Gy/25f/5 weeks + CAP (825mg/m²/bid) + BEV every 2 weeks (5 mg/kg for 3 doses) (arm A) or the same schedule without BEV (arm B). Surgery was scheduled 6-8 weeks after completing CRT. Results: 90 pts were randomized (arm A/B: 44/46). Patient’s characteristics were well balanced between both arms: male 61%, median age 62 years, median distance from anal verge 7 cm, T3 79%, N+ 87%. 40 (91%)/43 (93%) of pts (arm A/B) finalized the planned CRT + surgery treatment. Overall grade 3-4 toxicity rates were 18 % and 13% (arm A/B, p=0.50); no grade 3-4 hematological toxicity was reported. Postoperative complications were 19(43%)/17(37%)(arm A/B). Efficacy data on patients who actually underwent surgery are reported in the table. Conclusions: The addition of BEV to CAP-based preoperative CRT has shown to be feasible and safe in the local control of LARC. No differences in pCR were observed and longer follow-up is needed to assess the impact on survival endpoints. [Table: see text]
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Vincent, Cécile, Bernie J. McConnell, Stéphanie Delayat, Jean-François Elder, Gérard Gautier, and Vincent Ridoux. "Winter habitat use of harbour seals (Phoca vitulina) fitted with Fastloc™GPS/GSM tags in two tidal bays in France." NAMMCO Scientific Publications 8 (September 1, 2010): 285. http://dx.doi.org/10.7557/3.2691.
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Winter movements and habitat use of harbour seals (Phoca vitulina) were investigated in two tidal bays in France, at the southern limit of their species range in the Northeast Atlantic. We fitted 15 seals with Fastloc™GPS/GSMtags in the Baie du Mont-Saint-Michel (BMSM) and the Baie des Veys (BDV). Tags relayed 20.6±7.1 GPS locations per seal-day, 81% of all dives performed by the seals and 87% of haulouts, during an average tracking duration of 108±56 days. One seal travelled 380 km away from the BMSM but the other seals remained stationary, with 95% and 55% of at-sea locations ≤ 5 km from the haulout sites in BMSM and BDV respectively. Home range sizes were 137 and 161 km² in BMSM and BDV, and core areas’ sizes, 35 and 22 km² respectively. The seals remained very coastally in both sites with 93% and 71% of at-sea locations located in the intertidal zone of BMSM and BDV respectively. Accordingly, dives were shallow with 63% and 61% of dive maximum depths <4 m and 94% and 88% <10 m (in BMSM and BDV respectively). Preferred foraging areas were located in tidal channels in BMSM, sometimes in the vicinity of rocks or mussel farms. In BDV one seal made foraging trips 10-15 km offshore but all other seals repeatedly used coastal areas, often foraging around mussel farms, shipwrecks or intertidal rocks in tidal currents. We suggest that the importance of the tides combined with local features of the topography allow seals to predict prey availability, driving their foraging strategies towards a number of specific coastal areas. These results further illustrate the behavioural plasticity of the species according to habitat and environmental conditions. Fastloc™ GPS/GSM telemetry is particularly well adapted for the study of seals’ habitat use at a fine geographical and temporal scale, as long as they occasionally come close to shore within GSM coverage.
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Maniatis, G., N. Demiris, A. Kranis, G. Banos, and A. Kominakis. "Model comparison and estimation of genetic parameters for body weight in commercial broilers." Canadian Journal of Animal Science 93, no. 1 (2013): 67–77. http://dx.doi.org/10.4141/cjas2012-070.
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Maniatis, G., Demiris, N., Kranis, A., Banos, G. and Kominakis, A. 2013. Model comparison and estimation of genetic parameters for body weight in commercial broilers. Can. J. Anim. Sci. 93: 67–77. The availability of powerful computing and advances in algorithmic efficiency allow for the consideration of increasingly complex models. Consequently, the development and application of appropriate statistical procedures for model evaluation is becoming increasingly important. This paper is concerned with the application of an alternative model determination criterion (conditional Akaike Information Criterion, cAIC) in a large dataset comprising 203 323 body weights of broilers, pertaining to 7 (BW7) and 35 (BW35) days of age. Seven univariate and seven bivariate models were applied. Direct genetic, maternal genetic and maternal environmental (c2) effects were estimated via REML. The model evaluation criteria included conditional Akaike Information Criterion (cAIC), Bayesian Information Criterion (BIC) and the standard Akaike Information Criterion (henceforth marginal; mAIC). According to cAIC the best-fitting model included direct genetic, maternal genetic and c2 effects. Maternal heritabilities were low (0.10 and 0.03) compared to the direct heritabilities (0.17 and 0.21), while c2 was 0.05 and 0.04 for BW7 and BW35, respectively. BIC and mAIC favoured a model that additionally included a direct-maternal genetic covariance, resulting in highly negative direct-maternal genetic correlations (−0.47 and −0.64 for BW7 and BW35, respectively) and higher direct heritabilities (0.25 and 0.28 for BW7 and BW35, respectively). Results suggest that cAIC can select different animal models than mAIC and BIC with different biological properties.
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Holzhey, Tanja, Wolfram Pönisch, Song-Yau Wang, et al. "Prognostic impact of rapid reduction of involved free light chains in multiple myeloma patients under first-line treatment with Bendamustine, Prednisone, and Bortezomib (BPV)." Journal of Cancer Research and Clinical Oncology 147, no. 8 (2021): 2349–59. http://dx.doi.org/10.1007/s00432-020-03504-3.
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Abstract Introduction Light chain involvement is observed in almost every patient (pt) with newly diagnosed multiple myeloma (MM). Owing to a relatively short half-life, rapid reduction in the involved free light chain (iFLC) is of potential prognostic value. Methods This retrospective analysis included 92 pts with newly diagnosed MM treated with bendamustine, prednisone, and bortezomib (BPV). Results After a median number of two (range 1–5) BPV cycles, the majority of pts (n = 86; 93%) responded with either sCR (n = 21), CR (n = 1), nCR (n = 25), VGPR (n = 20), or PR (n = 19). PFS and OS at 48 months were 39% and 67%, respectively. At baseline, 79 out of 92 pts (86%) had iFLC levels above the upper standard level and an abnormal ratio of involved to uninvolved free light chain ≥ 8. In a subgroup analysis of these pts, we evaluated the prognostic importance of an early reduction of the iFLC during the first two BPV cycles. A reduction ≥ 50% of the iFLC on day 8 of the first cycle was observed in 31 of 69 pts. These pts had a significantly better median PFS of 49 months as compared to 20 months in 38 pts with a lower iFLC reduction (p = 0.002). In contrast, OS did not differ significantly with a 48 months survival of 77% vs 69% (p > 0.05). Conclusion These results indicate that a rapid decrease in the iFLC on day 8 is an early prognostic marker for newly diagnosed MM pts undergoing BPV treatment.
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Innocenti, Federico, Fang-Shu Ou, Tyler Zemla, et al. "Somatic DNA mutations, MSI status, mutational load (ML): Association with overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC) of CALGB/SWOG 80405 (Alliance)." Journal of Clinical Oncology 35, no. 15_suppl (2017): 3504. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.3504.
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3504 Background: CALGB 80405 was a randomized phase III trial that found no difference in OS in first-line mCRC pts treated with either bevacizumab (Bev) or cetuximab (Cet). Primary tumor DNA from 361 pts, including KRAS mutant (mut) pts, has been profiled for somatic gene mutations/ML/MSI to discover molecular markers of OS. Methods: Mutations in 11 genes were determined by PCR, MSI by microsatellite analysis, and ML by next-generation sequencing (FoundationOne). Cox proportional hazard models are used, stratified by prior XRT and +/- adjuvant chemotherapy; adjusted by age, race, gender, synchronous vs. metachronous, liver metastases, sidedness, all RAS. Results: BRAF: Mut pts had shorter OS than wild-type (wt) pts (HR 1.92, 95% CI 1.34,2.75; p<0.001); HR 1.65 (1.09,2.50) after adjusting for sidedness (p 0.022). In mut pts longer OS is observed in Bev arm vs. Cet arm (p 0.041); in wt pts no arm difference is observed (p 0.291, table). MSI: OS does not differ between MSI-H and MSI-S pts (HR 0.78 [0.40, 1.52], p 0.450). In MSI-H pts longer OS is observed in Bev arm vs. Cet arm (p 0.002); in MSI-S pts no difference is observed (p 0.305, table). ML: Hypermutated MSI-H pts are excluded. In a subset of 205 pts, pts with ML>5 (N=93) have longer OS than pts with ML≤5 (N=112) (HR 0.65 [0.42,1.00], p 0.048). In Bev arm higher ML confers longer OS than lower ML (HR 0.85 [0.80,0.96], p 0.004); in Cet arm no difference is observed (HR 0.99 [0.90,1.09], p 0.862). Conclusions: BRAF is a strong negative prognostic factor in mCRC, even when sidedness is taken into account. ML is a novel marker for further evaluation. The effect of Bev and Cet in either BRAF mut or MSI-H pts should be tested in larger datasets. Updated results from more screened samples will be presented. [Table: see text]
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Sugimoto, Masanobu, Kazuo Ohishi, and Yoji Ikawa. "Cell-mediated immunity to BLV replication: analogous to HIV immunopathogenesis?" Immunology Today 14, no. 4 (1993): 190. http://dx.doi.org/10.1016/0167-5699(93)90287-u.
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Rossini, Daniele, Roberto Moretto, Chiara Cremolini, et al. "Treatments (tx) after progression to first-line FOLFOXIRI plus bevacizumab (bev) in metastatic colorectal cancer (mCRC) patients (pts): A pooled analysis of TRIBE and MOMA studies by GONO group." Journal of Clinical Oncology 35, no. 15_suppl (2017): 3542. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.3542.
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3542 Background: FOLFOXIRI plus bev is regarded by international guidelines as a valuable option in the first-line tx of mCRC pts. One of the major concerns for the adoption of this regimen is the potential limitation of subsequent therapeutic options. The aim of the present analysis was to focus on treatments received after progression in TRIBE (NCT00719797) and MOMA (NCTNCT02271464) studies. Methods: We collected data of tx received after progression and their outcome in terms of 2ndPFS (time from 2nd line tx start to disease progression or death) and OS II (time from 2nd line tx start to death). For pts in which the same drugs used in first-line were totally or partially reintroduced, the chemotherapy-free interval (CFI, time from the last administration of irinotecan or oxaliplatin during first-line to disease progression) was calculated. Results: Out of 482 pts treated with upfront FOLFOXIRI plus bev, 429 progressed. 303 (70.6%) pts received a 2nd line tx: 93 FOLFOXIRI +/- bev (Group A), 119 FOLFOX/XELOX or FOLFIRI +/- bev (Group B) and 91 other tx (Group C), including an anti-EGFR moAb in 60 cases. No difference was observed among the three groups in terms of 2ndPFS (median 2nd PFS Group A: 5.6 vs Group B: 4.4 vs Group C: 3.9 mos; p = 0.60) or OS II (median OS II Group A: 14.9 vs Group B: 13.8 vs Group C: 11.7 mos; p = 0.49). In the subgroup of pts with a CFI < 6 mos, Group A (n = 52) reported longer 2ndPFS compared to both Group B (n = 58) (median 2ndPFS 5.3 vs 3.0 mos; HR: 0.61,95%CI 0.41-0.89; p = 0.009) and Group C (n = 58) (5.3 vs 3.2 mos; HR: 0.71, 95%CI 0.48-1.05; p = 0.07). Consistent results were achieved in OS II (Group A vs Group B; median OS 13.6 vs 10.8 mos; HR: 0.65, 95%CI 0.42-1.00; p = 0.053; Group A vs Group C 13.6 vs 8.9 mos; HR: 0.60, 95%CI 0.39-0.93; p = 0.002). In the subgroup of pts with a CFI ≥ 6 mos, no significant difference was shown between Group A (n = 41) and Group B (n = 61) or C (n = 33). Conclusions: Tx after progression to first-line FOLFOXIRI plus bev are feasible and show expected efficacy results. The reintroduction of the triplet plus bev seems more effective than doublets plus bev or other tx when a more aggressive disease biology is suggested (CFI < 6 mos).
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Wang, Jingyuan, Joshua Millstein, Fotios Loupakis, et al. "Genetic variants involved in the lipid metabolism pathway to predict outcome in patients (pts) with metastatic colorectal cancer (mCRC): Data from FIRE-3 and MAVERICC trials." Journal of Clinical Oncology 39, no. 3_suppl (2021): 118. http://dx.doi.org/10.1200/jco.2021.39.3_suppl.118.
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118 Background: Antiangiogenic drug (AAD)-triggered oxygen and nutrient depletion through suppression of angiogenesis switches the glucose-dependent metabolism to lipid-dependent metabolism. Blocking fatty acid oxidation can enhance AAD-mediated anti-tumor effects in colorectal cancer. Previous reports suggested that polymorphisms of the lipid metabolism-related genes are associated with the increased risk of CRC and poor clinical outcome in CRC. Therefore, we hypothesized that genetic variants in the lipid metabolism pathway may predict first-line treatment outcome in mCRC pts. Methods: Genomic DNA from blood samples of pts enrolled in two independent randomized trials, FIRE-3 and MAVERICC, was genotyped through the OncoArray, a customized array manufactured by Illumina including approximately 530K SNP markers. The impact on outcome of 25 selected SNPs in 10 genes involved in the lipid metabolism pathway (CD36, FABP4, LPCAT1, LPCAT2, PPARG, CPT1A, ACSS2, SREBF1, FASN, ACACA) was analyzed. Those treated with FOLFIRI/ bevacizumab (bev) in FIRE-3 (n = 107) and MAVERICC (n = 163) served as discovery and validation cohorts respectively, while FIRE-3 FOLFIRI/ cetuximab (cet) (n = 129) arm was used as the control. Interaction between each SNP and treatment was evaluated in FIRE-3 (FOLFIRI/bev arm vs. FOLFIRI/cet arm). Results: In the discovery (FIRE-3 bev) cohort, pts with FASN rs4485435 any C allele (N = 21) showed significantly shorter progression-free survival (PFS) (8.69 vs 13.48 months) compared to carriers of G/G (N = 62) in both univariate (hazard ratio [HR] = 2.88; 95% confidence interval [CI]: 1.57-5.29; p = 0.00037) and multivariate (HR = 2.87; 95%CI 1.4-5.9; p = 0.00675) analyses. These data were validated in the MAVERICC bev cohort in multivariate analysis (11.17 vs 14.06 months; HR = 2.07; 95%CI: 1.15-3.74; p = 0.02). Pts carrying any T allele in PPARG rs3856806 (N = 36) showed significantly longer overall survival (OS) (Not reached vs 42 months) than carriers of C/C (n = 93) in the FIRE-3 cet cohort in both univariate (HR = 0.4; 95%CI 0.17-0.92; p = 0.03) and multivariate (HR = 0.37; 95%CI 0.15-0.93; p = 0.02) analyses, but the association was not observed in the bev cohort of MAVERICC and FIRE-3. In the comparison of bev arm vs cet arm in FIRE-3, interactions were shown with FASN rs4485435 (p = 0.017) on PFS and PPARG rs3856806 (p = 0.059) on OS. Conclusions: Our study demonstrates for the first time that FASN polymorphism could predict outcomes of bev-based treatment in mCRC patients; Meanwhile PPARG polymorphism could predict outcomes of cet-based treatment in mCRC patients. These findings support a possible role of the lipid metabolism pathway in contributing to resistance to anti-VEGF/EGFR treatment.
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Li, G. F., M. S. Wei, J. Ma, and S. F. Zhu. "First Report of Broad bean wilt virus 2 in Echinacea purpurea in China." Plant Disease 96, no. 8 (2012): 1232. http://dx.doi.org/10.1094/pdis-04-12-0409-pdn.
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Field-grown Echinacea purpurea plants showing necrosis, leaf roll, yellow mosaic, and mosaic symptoms in leaves were collected in June 2010 in Huairou, Beijing, China. ELISAs of extracts of four samples showed that one sample with mosaic symptoms had a positive reaction with Broad bean wilt virus 2 (BBWV-2) monoclonal antibody provided by Professor X. P. Zhou (1). The monoclonal antibody recognized the 44.7 kD coat protein subunit of BBWV-2. We used Chenopodium quinoa as an assay species to isolate the virus by sap transmissions and to maintain the virus strain. Sap from infected C. quinoa, when inoculated onto indicator plant species, induced the following symptoms: C. quinoa: local lesions in inoculated leaves, systemic chlorotic mottle in upper leaves, deformation, and apical necrosis; C. amaranticolor: chlorotic local lesions, systemic mosaic and leaf distortion; Nicotiana benthamiana: systemic mosaic; Gomphrena globosa: local purple spots in inoculated leaves and systemic infection in upper leaves; Tetragonia expansa: local lesions, but no symptoms of systemic infection; Physalis floridana: systemic mosaic. No symptoms were observed on Capsicum annuum, Datura stramonium, N. glutinosa, or N. tabacum cv. White Burley. To confirm BBWV-2 infection, total RNAs extracted from infected C. quinoa leaves were reverse transcripted to cDNA using oligo-dT primer (T17V). The primer pair Fab5′R1F (5′-AAATATTAAAACAAACAGCTTTCGTT-3′) and Fab5′R1R (5′-TTCAAAGCTCGTGCCATNTYATTKGC-3′) for specific detection of the Fabavirus genus (2) was used for PCR analysis. The amplified fragment is between the 5′-terminal non-translatable region (NTR) and the beginning of the coding region of RNA1. Amplicons of approximately the expected size (~391 bp) were produced from the virus-infected C. quinoa and a BBWV-2 positive control (ATCC PV131, PV0537). Amplicons of approximately the expected size (~350 bp) were produced from the BBWV-1 positive control (ATCC PV132). However, no such amplicons were observed from healthy C. quinoa plants and water control. The 391-bp amplicons of RNA1 obtained from the infected C. quinoa were cloned and sequenced. Comparison with sequences of other BBWV-2 isolates showed that the isolate we obtained (No. JX070674) had approximately 99% nt identity (98% amino acid identity) with Chinese BBWV-2 isolate BC (No. FJ485686.1) (3). As an ornamental and medicinal plant, E. purpurea is widely cultivated in northern China. Up until now, Tomato ring spot virus, Tobacco rattle virus, Cucumber mosaic virus, and Tomato spotted wilt virus have been detected or isolated from E. purpurea in the world (4). To our knowledge, this is the first report of BBWV-2 infecting E. purpurea in China. BBWV-2-infected E. purpurea may have less secondary metabolites, which could influence the quality and therapeutic efficacy of this herbal medicine. References: (1) L. Qing et al. Acta Microbiologica Sinica 40:166, 2000. (2) R. M. Ferrer et al. J. Virol. Methods 144:156, 2007. (3) C. Sui et al. Plant Dis. 93:844, 2009. (4) B. Dikova. Bulgarian J. Agric. Sci. 17:306, 2011.
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Glaser, Natalie, Veronica Jackson, Per Eriksson, Ulrik Sartipy, and Anders Franco-Cereceda. "Relative survival after aortic valve surgery in patients with bicuspid aortic valves." Heart 107, no. 14 (2021): 1167–72. http://dx.doi.org/10.1136/heartjnl-2020-318733.
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ObjectivesThe objective of this cohort study was to analyse long-term relative survival in patients with bicuspid aortic valve (BAV) who underwent aortic valve surgery.MethodsWe studied 865 patients with BAVs who participated in three prospective cohort studies of elective, open-heart, aortic valve surgery at the Karolinska University Hospital, Stockholm, Sweden, between 2007 and 2020. The expected survival for the age, sex and calendar year-matched general Swedish population was obtained from the Human Mortality Database. The Ederer II method was used to calculate relative survival, which was used as an estimate of cause-specific survival.ResultsNo differences were found in the observed versus expected survival at 1, 5, 10 or 12 years: 99%, 94%, 83% and 76% vs 99%, 93%, 84% and 80%, respectively. The relative survival at 1, 5, 10 and 12 years was 100% (95% CI 99% to 100%), 101% (95% CI 99% to 103%), 99% (95% CI 95% to 103%) and 95% (95% CI 87% to 102%), respectively. The relative survival at the end of follow-up tended to be lower for women than men (86% vs 95%). The mean follow-up was 6.3 years (maximum 13.3 years).ConclusionsThe survival of patients with BAV following aortic valve surgery was excellent and similar to that of the general population. Our results suggest that the timing of surgery according to current guidelines is correct and provide robust long-term survival rates, as well as important information about the natural history of BAV in patients following aortic valve surgery.
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Vilc̆ek, Štefan. "Detection of the bovine herpesvirus-1 (BHV-1) genome by PCR." Journal of Virological Methods 41, no. 2 (1993): 245–47. http://dx.doi.org/10.1016/0166-0934(93)90132-b.
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Raytseva, S. S., and S. L. Matusevich. "Assessment of efficiency of biorevitalization during work with skin component of aging at patients with different morphological types of involute changes of soft facial tissues." Medical alphabet 2, no. 26 (2019): 93–96. http://dx.doi.org/10.33667/2078-5631-2019-2-26(401)-93-96.
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Materials and methods. 38 patients aged 35 to 55 years old were under the surveillance. Depending on the aging morphotype, all patients were divided into three groups. All the participants of the study were subjected to a biorevitalization procedure (BRV) according to a single protocol prepared ex-temporarily by a mixture of multicomponent and prolonged biorevitalizers (BR).Results. After the course of BRV from three procedures it was reliably established that skin humidity increased from the initial level by 46.7 % at the absolute number (100.0 %) of patients regardless of morphotype (p < 0.01). Facial color improvement was recorded in 94.7 % of patients (p < 0.01). Length, width and depth of thin surface wrinkles on the face skin in patients with small and mixed morphotypes on average decreased by 41.1 %, 37.9 % and 50.0 %, respectively (p < 0.01). No convincing data have been obtained regarding the increase in skin elasticity, epidermis thickness and dermis. There is also no evident therapeutic effect on telangiectatic changes and non-tumor focal hyperpigmentation of facial skin. Clinical effects following the BRV course are most pronounced in patients with small-scale and mixed mofotypes. According to the patients themselves, the proposed program of injection therapy has high efficiency and safety.
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Randal, Michael, та Anthony A. Kossiakoff. "The 2.0 Å structure of bovine interferon-γ; assessment of the structural differences between species". Acta Crystallographica Section D Biological Crystallography 56, № 1 (2000): 14–24. http://dx.doi.org/10.1107/s0907444999014304.
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The structure of bovine interferon-γ (IFN-γ) was determined by multiple isomorphous replacement at 2.0 Å resolution. Bovine IFN-γ crystallizes in two related crystal forms. Crystal form 1 diffracts to 2.9 Å resolution and is reproducible and stable to derivatization. Crystal form 2 diffracts to 2.0 Å resolution, but shows significant non-isomorphism from crystal to crystal. The previously determined structures of several different species of INF-γ were either at too low a resolution [human, 1hig; Ealick et al. (1991), Science, 252, 698–702] or were too inaccurate [bovine, 1rfb; Samudzi & Rubin (1993), Acta Cryst. D49(6), 505–512; rabbit, 2rig; Samudzi et al. (1991), J. Biol. Chem. 266(32), 21791–21797] for the structure to be solved by molecular replacement. The structure was solved in crystal form 1 using two derivatives produced by chemically modifying two free cysteine residues that were introduced by site-directed mutagenesis (Ser30Cys, Asn59Cys). After model building and refinement, the final R value was 21.8% (R free = 30.9%) for all data in the resolution range 8.0–2.9 Å. The crystal form 1 structure was then used as a molecular-replacement model for crystal form 2 data collected from a flash-cooled crystal. Subsequent model building and refinement, using all data in the resolution range 15.0–2.0 Å, gave an R value of 19.7% and an R free of 27.5%. Pairwise comparison of Cα positions of bovine IFN-γ (BOV) and the previously determined 1rfb and 2rig structures indicated some significant differences in the models (r.m.s.d. values for BOV to 1rfb, 4.3 Å; BOV to 2rig, 4.0 Å). An assessment of the quality of the structures was made using the 3D–1D algorithm [Eisenberg et al. (1992), Faraday Discuss. 93, 25–34]. The resulting statistical scoring indicated that BOV was consistent with expected criteria for a 2.0 Å structure, whereas both 1rfb and 2rig fell below acceptable criteria.
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Grothey, Axel, Manish A. Shah, Takayuki Yoshino, et al. "CanStem303C trial: A phase III study of napabucasin (BBI-608) in combination with 5-fluorouracil (5-FU), leucovorin, irinotecan (FOLFIRI) in adult patients with previously treated metastatic colorectal cancer (mCRC)." Journal of Clinical Oncology 35, no. 15_suppl (2017): TPS3619. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.tps3619.
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TPS3619 Background: Cancer stem cells are considered to be fundamentally important for resistance to therapy, recurrence and metastasis. Napabucasin is a first-in-class cancer stemness inhibitor in development identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al, PNAS 112(6):1839, 2015). Preclinically, napabucasin sensitizes cancer cells to chemotherapeutics, including 5-FU and irinotecan. Encouraging anticancer activity in advanced CRC was observed in a phase Ib/II (Bendell et al, GI ASCO 2017) study of 63 pts with disease control rate (DCR) of 93% (28/30) and overall response rate (ORR) of 33% (10/30) in FOLFIRI-naïve pts who have had an on-study RECIST evaluation. On the basis of these data, a phase III trial is being conducted in North America, Europe, Australia, and Asia. Methods: This study (ClinicalTrials.gov NCT02753127) will assess the efficacy of napabucasin+FOLFIRI vs FOLFIRI in pts with mCRC (n = 1250). Addition of bevacizumab (bev) is permissible per investigator choice. Pts must have failed 1 prior line of therapy with oxaliplatin and a fluoropyrimidine +/- bev for metastatic disease. Pts are randomized 1:1 to receive napabucasin 240 mg PO BID plus FOLFIRI bi-weekly, or FOLFIRI bi-weekly (bev may be added to FOLFIRI by investigator choice) and stratified by geography, time to progression on 1st-line therapy, RAS mutation status, bev as part of study treatment and primary tumor location. Treatment will continue until disease progression, or another discontinuation criterion. Primary endpoint is overall survival (OS) in the general study population (ITT) (HR 0.80 for OS improvement from 12.54 to 15.68 months); secondary endpoints include OS in the biomarker positive (biomarker+) population, progression free survival (PFS) in the ITT population, PFS in biomarker+ population, ORR and DCR in the ITT and in biomarker+ populations, safety and quality of life. Also, blood and tumor archival tissue will be assessed for PK and biomarker analyses. Global enrollment is underway. Clinical trial information: NCT02753127.
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Folprecht, Gunnar, Marika Mende, Torsten Liersch, et al. "Cetuximab/irinotecan/5-FU +/-oxaliplatin or FOLFOXIRI +/- bevacizumab in patients with colorectal cancer and nonresectable liver metastases (AIO CELIM2-study)." Journal of Clinical Oncology 38, no. 15_suppl (2020): 4024. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.4024.
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4024 Background: EGFR based combinations and the triplet combination FOLFOXIRI are known to increase response rates compared to doublet combinations. Methods: Patients with colorectal cancer and non-resectable liver metastases were enrolled into the trial. RAS wild type patients were randomised to cetuximab/FOLFIRI or cetuximab/FOLFOXIRI, RAS/BRAF mutant patients were randomised to FOLFOXIRI with or without bevacizumab. The primary endpoint was response. Secondary endpoints included progression free and overall survival. The trial was closed early due to poor recruitment. Results: Between 2014 and 2018, ninety-two pts were enrolled into the study. 54 wild type pts were randomised into cetuximab based treatment with (28 pts) or without (26 pts) oxaliplatin, 38 RAS/BRAF mutant pts were randomised to receive FOLFOXIRI alone (18 pts) or plus bevacizumab (16 pts). Objective response was achieved in 21/26 pts (81 % [95 CI: 61 – 93 %]) with cet/FOLFIRI, 24/28 pts (86 % [95 CI: 67 – 96 %]) with cet / FOLFOXIRI, 13/1 8 pts (72 % [95 CI: 46 – 90 %]) with FOLFOXIRI and 14/20 pts (70 % [95 CI: 46 – 88 %]) with bev/FOLFOXIRI. Two pts with cet/FOLFOXIRI and one pat with FOLFOXIRI achieved CR according to imaging. The median PFS was 12.7 [95 % CI: 7.2 – 18.2], 15.0 [95 % CI: 11.3 – 18.7], 17.5 [95 % CI: 8.0 – 27.1] and 15.0 [95 % CI: 11.4 – 18.5] months with cet/FOLFIRI, cet/FOLFOXIRI, FOLFOXIRI and bev/FOLFOXIRI. The median overall survival was 42 mo. [95 % CI: 28 – 55], 55 [95 % CI:41 – 68], 28 [95 % CI: 22 – 36] and 44 [95 % CI: 0 – 94] months with cet/FOLFIRI, cet/FOLFOXIRI, FOLFOXIRI and bev/FOLFOXIRI. The frequency of grade ≥ 3 toxicity per arm (cet/FOLFIRI, cet/FOLFOXIRI, FOLFOXIRI and bev/FOLFOXIRI) was 29 %, 46 %, 56 %. 45 % for neutropenia/leukopenia, 11 %, 12 %, 28 %, 25 % for diarrhea and 29 %, 19 %, 6 % and 5 % for skin toxicities. Conclusions: High response rates were observed in patients with colorectal liver metastases with all regimens. The numerically highest response rate was observed in RAS wild type patients treated with cetuximab/FOLFOXIRI. Clinical trial information: NCT01802645 .
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Connolly, Florian, Stephan J. Schreiber, Christoph Leithner, Georg Bohner, Peter Vajkoczy, and José M. Valdueza. "Assessment of intracranial venous blood flow after subarachnoid hemorrhage: a new approach to diagnose vasospasm with transcranial color-coded duplex sonography." Journal of Neurosurgery 129, no. 5 (2018): 1136–42. http://dx.doi.org/10.3171/2017.5.jns17232.
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OBJECTIVETranscranial color-coded duplex sonography (TCCS) is a reliable tool that is used to assess vasospasm in the M1 segment of the middle cerebral artery (MCA) after subarachnoid hemorrhage (SAH). A distinct increase in blood flow velocity (BFV) is the principal criterion for vasospasm. The MCA/internal carotid artery (ICA) index (Lindegaard Index) is also widely used to distinguish between vasospasm and cerebral hyperperfusion. However, extracranial ultrasonography assessment of the neck vessels might be difficult in an intensive care unit. Therefore, the authors evaluated whether the relationship of intracranial arterial to venous BFV might indicate vasospasm with similar or even better accuracy.METHODSPatients who presented between 2008 and 2015 with aneurysmal SAH were prospectively enrolled in the study. Digital subtraction angiography (DSA) and TCCS were performed within 24 hours of each other to assess vasospasm 8–10 days after SAH. The following different TCCS parameters were analyzed to assess vasospasm in the MCA and were compared with the gold-standard DSA parameters: 1) mean time-averaged maximum BFV (Vmean) of the MCA, 2) peak systolic velocity (PSV) of the MCA, 3) the Lindegaard Index using Vmean as well as PSV, and 4) a new arteriovenous index (AVI) between the MCA and the basal vein of Rosenthal using Vmean and PSV. The best cutoff values for these parameters to distinguish vasospasm from normal perfusion or hyperperfusion were calculated using receiver operating characteristic curve analysis. Sensitivity, specificity, positive predictive value, and negative predictive value as well as the overall accuracy for each cutoff value were analyzed.RESULTSA total of 102 patients (mean age 52 ± 12 years) were evaluated. Bilateral MCA assessment by TCCS was successful in all patients. In 6 cases (3%), the BFV of the basal vein of Rosenthal could not be analyzed. The AVI could not be calculated in 50 of 204 cases (25%) because the insonation quality was very low in one of the ICAs. An AVI > 10 for Vmean and an AVI > 12 for systolic velocity provided the highest accuracies of 87% and 86%, respectively. Regarding the Lindegaard Index, the accuracy was highest using a threshold of > 3 for the mean BFV (84%) as well as systolic BFV (80%). BFVs in the MCA of ≥ 120 cm/sec (Vmean) and ≥ 200 cm/sec (PSV) predicted vasospasm with accuracies of 84% and 83%, respectively. A combined analysis of the MCA BFV and the AVI led to a slight increase in specificity (Vmean, 94%; PSV, 93%) and positive predictive value (Vmean, 88%; PSV 86%) without further improvement in accuracy (Vmean, 88%; PSV, 84%).CONCLUSIONSThe intracranial AVI is a reliable parameter that can be used to assess vasospasm after SAH. Its reliability for differentiating vasospasm and hyperperfusion is slightly higher than that for the established Lindegaard Index, and this method has the additional advantage of a remarkably lower failure rate.
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van Drunen Littel-van den Hurk, S., M. D. Parker, B. Massie, et al. "Protection of cattle from BHV-1 infection by immunization with recombinant glycoprotein gIV." Vaccine 11, no. 1 (1993): 25–35. http://dx.doi.org/10.1016/0264-410x(93)90336-v.
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Hubbard, Joleen Marie, Bert H. O'Neil, Derek J. Jonker, et al. "Phase Ib study of cancer stem cell (CSC) pathway inhibitor BBI-608 administered in combination with FOLFIRI with and without bevacizumab (Bev) in patients (pts) with advanced colorectal cancer (CRC)." Journal of Clinical Oncology 34, no. 4_suppl (2016): 569. http://dx.doi.org/10.1200/jco.2016.34.4_suppl.569.
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569 Background: BBI-608 is an oral first-in-class cancer stemness inhibitor that blocks STAT3-mediated transcription of cancer stemness genes. Potent anti-CSC activity was observed in vitro and in vivo,in mono and combination therapy. In phase I studies, BBI-608 was generally well tolerated with encouraging signs of anti-tumor activity. Methods: A phase Ib open label, multi-center study in pts with advanced CRC was undertaken to confirm the RP2D of BBI-608 in combination with FOLFIRI with or without BEV. BBI-608 was administered at 240 mg BID in combination with FOLFIRI (5-FU 400 mg/m2 bolus with 2400 mg/m2, irinotecan 180 mg/m2, and leucovorin 400 mg/m2infusion) with or without BEV 5 mg/kg, administered bi-weekly until progression of disease, unacceptable toxicity, or other discontinuation criterion was met. Results: 18 heavily pretreated pts with an average of > 3 prior lines of therapy of which 10 pts (56%) previously progressed on FOLFIRI were enrolled. Of the 17 pts evaluable for response, 8 pts received FOLFIRI and 9 pts received FOLFIRI with BEV in combination with BBI-608. Most common adverse events included grade 1 and 2 diarrhea, abdominal pain, nausea, vomiting and anorexia. No dose limiting toxicity or new adverse events were seen, and the safety profile was similar to that of each regimen as monotherapy. Grade 3 events related to protocol therapy included diarrhea occurring in 3 pts, fatigue in 2 pts and dehydration in 1 pt. All events resolved after dose reduction and/or start of anti-diarrheal medications. No significant pharmacokinetic interactions were observed. Disease control (PR+SD) was observed in 16 of 17 evaluable pts (94%) with 2 PR (per RECIST 1.1 criteria: 44% and 33% regression) and 14 SD (of which 13 (93%) had tumor regression < 25%). In the evaluable pts, median progression free survival was 5.54 months. Of 17 pts, 7 (41%) had prolonged SD of > 6 months. Conclusions: This phase Ib study confirmed that BBI-608 at 240 mg bid can be safely combined with FOLFIRI with and without BEV, and shows encouraging anti-tumor activity in heavily pretreated CRC pts, even in pts with prior progression on FOLFIRI-based therapy. Clinical trial information: NCT02024607.
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Comella, P., B. Massidda, D. Natale, et al. "Bevacizumab (Bev), irinotecan (IRI), folinic acid (FA), and 5-fluorouracil (FU) every 2 weeks (BIFF regimen) as first-line treatment for metastatic colorectal cancer (MCRC) patients (pts): The SICOG experience." Journal of Clinical Oncology 27, no. 15_suppl (2009): e15067-e15067. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e15067.
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e15067 Background: The IRIFAFU regimen produced in MCRC pts a consistent activity (RR, 33% [95% CI, 27–39%], PFS, 7.4 [95% CI, 6.5–8.3] mo.) in 2 consecutive randomized SICOG trials . Bev was proven to significantly improve the efficacy of IFL regimen. Here we report the safety and activity results of the BIFF regimen as first-line treatment of MCRC. Patients: From Feb 2007 to Jul 2008, 95 pts with MCRC were treated: so far, 85 pts were evaluated for safety: M/F were 47/38, median age (range) was 64 (35–78) yrs. Fifty-six pts had a colon, and 29 pts a rectal carcinoma. ECOG PS was 0 (63 pts, 74%), or 1 (22 pts, 26%). Thirty-four (40%) pts had 1 site, 33 (39%) 2 sites, and 18 (21%) pts ≥3 sites of disease. Liver was involved in 66 (78%), lung in 23 (24%) pts. Twenty-one (25%) pts had an unresected primary (colon 13, rectum 8). Bev 5 mg/kg (1-h), and IRI 180 mg/sqm (1-h) were given IV on day 1, 6S-FA 250 mg/sqm (2-h), and FU 850 mg/sqm (bolus) were given IV on day 2 biweekly for a maximum of 12 cycles. Bev was continued until progression, severe toxicity, or refusal. Results: A median of 9 (range, 1–12) cycles of BIFF were delivered. G4 hematologic toxicity was: neutropenia (21%), and febrile neutropenia (10%). G≥3 non-hematologic toxicity was: diarrhea 15%, vomiting 7%, stomatitis 4%, hypertension 1%. No severe episodes of bleeding were registered. Among 81 assessable pts, 5 CRs (3 in liver, 1 in liver & nodes, 1 in liver & lung), and 41 PRs were registered, giving a RR of 57% (95% CI, 45–68%). Overall, 71/81 (88%, 95% CI, 77–93%) pts obtained a disease control. Liver mets resection, or primary resection, was safely performed in 3 pts and in 2 pts, respectively. After a median follow- up of 12 (range, 6–24) mo., median FFS was 8.4 (95% CI, 6.8–10.0), and median PFS was 14.1 (95% CI, 9.6–18.6) mo. With only 14 deaths, OS results are still immature. Conclusions: Unexpected side effects of the BIFF regimen were not registered. Addition of Bev increased the activity without worsening the tolerability of IRIFAFU combination as compared with our previous experience. Efficacy of BIFF was comparable with that reported with other Bev plus IRI-based combinations. Updated follow-up will be presented. No significant financial relationships to disclose.
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Shaltout, Hossam A., James C. Rose, Jorge P. Figueroa, Mark C. Chappell, Debra I. Diz, and David B. Averill. "Acute AT1-receptor blockade reverses the hemodynamic and baroreflex impairment in adult sheep exposed to antenatal betamethasone." American Journal of Physiology-Heart and Circulatory Physiology 299, no. 2 (2010): H541—H547. http://dx.doi.org/10.1152/ajpheart.00100.2010.
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To accelerate lung development and protect neonates from other early developmental problems, synthetic steroids are administered maternally in the third trimester, exposing fetuses that are candidates for premature delivery to them. However, steroid exposure at this point of gestation may lead to elevated blood pressure [mean arterial pressure (MAP)] during adolescence. We hypothesize that fetal exposure to steroids activates the renin-angiotensin system, inducing an elevation in blood pressure and attenuation of baroreflex sensitivity (BRS) that is angiotensin II dependent in early adulthood. To test this hypothesis, fetal sheep were exposed to betamethasone (Beta) or vehicle (control) administered to ewes at day 80 of gestation and delivered at full term. At 1.8 yr of age, male offspring were instrumented for conscious recording of MAP, heart rate, and measurement of BRS [as low-frequency-α, high-frequency-α, sequence (seq) UP, seq DOWN, and seq TOTAL]. Beta-exposed sheep ( n = 6) had higher MAP than control sheep ( n = 5) (93 ± 2 vs. 84 ± 2 mmHg, P < 0.01). Acute blockade of angiotensin type 1 receptors with candesartan (0.3 mg/kg iv) normalized MAP in Beta-exposed sheep (85 ± 4 mmHg), with no effect in control sheep (82 ± 3 mmHg). Before angiotensin type 1 blockade, BRS maximum gain was significantly lower in Beta-exposed vs. control sheep (11 ± 3 vs. 26 ± 3 ms/mmHg, P < 0.0.01). However, 45 min after candesartan injection, BRS was increased in Beta-exposed (21 ± 5 ms/mmHg) and control (35 ± 4 ms/mmHg) sheep. Heart rate variability (HRV) and blood pressure variability (BPV) revealed lower HRV (SD of beat-to-beat interval and root mean square of successive beat-to-beat differences in R-R interval duration) and higher BPV (SD of MAP, systolic arterial pressure in low-frequency range) in Beta-exposed sheep. Candesartan partially restored HRV in Beta-exposed sheep and fully corrected BPV. Thus, in utero exposure to synthetic glucocorticoids causes long-lasting programming of the cardiovascular system via renin-angiotensin system-dependent mechanisms.
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Précigoux, G., S. Geoffre, R. Léonard, et al. "Modelling, synthesis and biological activity of a BLV proteinase, made of (only) 116 amino acids." FEBS Letters 326, no. 1-3 (1993): 237–40. http://dx.doi.org/10.1016/0014-5793(93)81798-5.
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Meirom, R., J. Brenner, and Z. Trainin. "BLV-infected lymphocytes exhibit two patterns of expression as determined by Ig and CD5 markers." Veterinary Immunology and Immunopathology 36, no. 2 (1993): 179–86. http://dx.doi.org/10.1016/0165-2427(93)90106-e.
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Agnew, T. A., and A. Silis. "Spring-season climate variability in the central Canadian Arctic Islands." Annals of Glaciology 21 (1995): 330–36. http://dx.doi.org/10.1017/s0260305500016025.
Full textAbstract:
The Resolute Bay area in the central Canadian Arctic Islands is in a region of maximum variability in 50 kPa heights in spring. This is the northern part of an oscillation in large-scale atmospheric circulation called the Baffin Island West Atlantic Oscillation (BWA). The historical record of temperature at Resolute Bay, Northwest Territories, over the 1948–93 period is compared with circulation patterns for extremely warm and cold spring seasons, using a composite technique and a simple index of the intensity of the BWA. The extremely cold spring of 1992, the second coldest of the 46a record, was probably caused by reduced solar radiational forcing due to the increased dust veil caused by Mount Pinatubo. Within each spring season, large-scale synoptic conditions provided an important control on the timing of critical stages leading to full snow melt on the sea-ice surface. The first stage is the change from dominance of the region by wintertime continental polar air to the frequent invasion of maritime polar air masses, resulting in increased cloud cover and reduced frequency of Arctic inversions. The second stage is the transition to full melt on the ice with a sharp drop in surface albedo. During the spring on 1993, the first stage was triggered by a major storm which moved through the area on 9–10 May 1993. The second snow-melt stage was triggered by a stationary upper ridge which remained over the area for a 2 week period from 15 May to early June and produced clear to scattered-cloud conditions and high downward solar radiation.
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Agnew, T. A., and A. Silis. "Spring-season climate variability in the central Canadian Arctic Islands." Annals of Glaciology 21 (1995): 330–36. http://dx.doi.org/10.3189/s0260305500016025.
Full textAbstract:
The Resolute Bay area in the central Canadian Arctic Islands is in a region of maximum variability in 50 kPa heights in spring. This is the northern part of an oscillation in large-scale atmospheric circulation called the Baffin Island West Atlantic Oscillation (BWA). The historical record of temperature at Resolute Bay, Northwest Territories, over the 1948–93 period is compared with circulation patterns for extremely warm and cold spring seasons, using a composite technique and a simple index of the intensity of the BWA. The extremely cold spring of 1992, the second coldest of the 46a record, was probably caused by reduced solar radiational forcing due to the increased dust veil caused by Mount Pinatubo.Within each spring season, large-scale synoptic conditions provided an important control on the timing of critical stages leading to full snow melt on the sea-ice surface. The first stage is the change from dominance of the region by wintertime continental polar air to the frequent invasion of maritime polar air masses, resulting in increased cloud cover and reduced frequency of Arctic inversions. The second stage is the transition to full melt on the ice with a sharp drop in surface albedo. During the spring on 1993, the first stage was triggered by a major storm which moved through the area on 9–10 May 1993. The second snow-melt stage was triggered by a stationary upper ridge which remained over the area for a 2 week period from 15 May to early June and produced clear to scattered-cloud conditions and high downward solar radiation.