tbuckley/cabot-search huggingface dataset:
Molecular phylogeny of annexins and identification of a primitive homologue in Giardia lamblia.
Authors: R O Morgan, M P Fernández
Journal: Molecular Biology and Evolution (1995)

The homologous repeats of annexin tetrads are believed to have originated by successive duplication and fusion from a putative monomeric precursor, but neither the nature of their ancestor nor the events leading to the formation of different subfamilies have been elucidated. We have performed molecular phylogenetic analysis of aligned annexin nucleotide and amino acids sequences to characterize subfamily branching, to delineate the temporal order of appearance of individual repeat units, and to gain insight into the origin and nature of the primordial unit. All extant annexins appear to have a common tetrad precursor that may have originated from a progenitor unit resembling repeat 3, followed by the generation of repeats 4, 1, and 2 from a more evolved progenitor with subsequent fusion. Repeat sequences of the earliest human annexins VII and XIII were used to identify alpha-giardin genes as primitive homologues from the unicellular protozoan Giardia lamblia, which diverged from eukaryote lineage 1-1.5 billion yr ago. The significant homology between alpha-giardins and annexins suggested that the cell membrane adhesive role of these proteins may be a common, fundamental property of the annexin C-terminal core region. Purported annexin VII of Dictyostelium discoideum was reclassified as new annexin XIV, three Caenorhabditis elegans genes were assigned to new subfamilies XV, XVI, and XVII, and plant annexin XVIII from Medicago sativa was among the earliest diverging subfamilies. Annexins I and II were found to be closely related, but analysis of protein mutation rates confirmed that the former is evolving up to three times more rapidly. The inclusion of early phyla in annexin taxonomy provides a useful basis for assessing the structural and functional changes associated with annexin evolution.
The association between quality of life and overall survival in ovarian cancer patients during adjuvant chemotherapy: A Gynecologic Oncology Group study.
Authors: V. E. Von Gruenigen, H. Q. Huang, K. M. Gil, H. E. Frasure, D. K. Armstrong, L. B. Wenzel
Journal: Journal of Clinical Oncology (2010)

5075 Background: To explore the association between baseline quality-of-life (QOL) domain scores and overall survival (OS) in ovarian cancer patients receiving adjuvant chemotherapy. Methods: Patients with optimal stage III ovarian cancer on Gynecologic Oncology Group protocol #172 completed the Functional Assessment of Cancer Therapy-Generic (FACT-G) and were then randomly assigned to either intravenous (IV) or intraperitoneal (IP) chemotherapy. The FACT scale includes physical, functional, social, and emotional well- being domains (PWB, FWB, SWB, EWB). Patients who rated their lack of energy as ‘
Subpopulations of Cytogenetically Abnormal Cells in Fibroblast Cultures Derived From Workers Exposed to Mineral Oil 2
Authors: P. A. Benn, D. G. Harnden, E. A. Fairburn
Journal: JNCI Journal of the National Cancer Institute (1978)

Fibroblast cultures were grown from skin biopsy specimens from individuals with a high risk of cancer due to occupational exposure to mineral oil. A high frequency of chromosomally abnormal fibroblast subpopulations was found in cultures derived from tissue that had been exposed to the carcinogen, but these aberrant clonal populations were also present in control lines from the same individuals. Abnormal clones formed a greater proportion of the total cell population in the lines derived from the oil-exposed tissue compared with the control lines after a comparable time in culture. This difference in clone size may be a consequence of the in vivo exposure to mineral oil or other environmental agents.
Cytogenetic Study of a European Burkitt’s Lymphoma Cell Line
Authors: R Berger, A Bernheim, M Fellous, J C Brouet
Journal: JNCI Journal of the National Cancer Institute (1979)

The chromosomes of an Epstein-Barr virus-negative European Burkitt's lymphoma cell line were studied. All the cells carried the t(8;14) translocation. One clone had 51 chromosomes and was (+1,+7,+16,+15,+21), whereas another clone also had 51 chromosomes but was (+1q+,+7,+16,+15,+21). A third clone had 46 chromosomes (4q+/-).
Farewell, king coal!
Authors: Anthony Seaton
Journal: Thorax (2016)

Coal mining provided the power for the industrial development of the West, at great cost to the health of the workforce and, from industrial pollution, of the population. Medical appreciation of the diseases of miners was slow to develop and has been marked by controversy relating to the roles of coal and quartz and the causation of emphysema. Research by the MRC and the British coal industry resolved these issues as the industry itself declined. However, from the research has come an understanding of the influence of inhalation of different inhaled pollutants on human health that has been applied to predicting and preventing possible hazards of developing nanotechnologies.
The cognitive-emotional brain: Opportunities and challenges for understanding neuropsychiatric disorders – ERRATUM
Authors: Alexander J. Shackman, Andrew S. Fox, David A. Seminowicz
Journal: Behavioral and Brain Sciences (2015)

An abstract is not available for this content. As you have access to this content, full HTML content is provided on this page. A PDF of this content is also available in through the ‘Save PDF’ action button.
Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer: CALGB 9741 (Alliance)
Authors: Jennifer A Ligibel, Constance T Cirrincione, Minetta Liu, Marc Citron, James N Ingle, William Gradishar, Silvana Martino, William Sikov, Richard Michaelson, Elaine Mardis, Charles M Perou, Matthew Ellis, Eric Winer, Clifford A Hudis, Donald Berry, William T Barry
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Obesity at diagnosis is associated with poor prognosis in women with breast cancer, but few reports have been adjusted for treatment factors.
Abstract 14583: Sleep Apnea is Associated with Elevated High Sensitivity Troponin T in an Asymptomatic Community Dwelling Cohort: Data from the NHLBI ARIC-SHHS Study
Authors: Gabriela M Querejeta Roca, Susan Redline, Naresh M Punjabi, Christie Ballantyne, Scott D Solomon, Amil M Shah
Journal: Circulation (2012)

Background: Obstructive sleep apnea (OSA) is associated with heart failure (HF) and death. We hypothesized that among asymptomatic persons, severity of OSA measured by the respiratory disturbance index (RDI) is associated with higher levels of high sensitivity troponin T (hsTnT), reflecting cardiac stress and subclinical injury. Methods: Overnight polysomnography and hsTnT were measured in 1,655 persons without prevalent cardiovascular disease participating in both the Sleep Heart Health and Atherosclerosis Risk in Communities studies. OSA severity was defined using established clinical categories -none (RDI≤5), mild (RDI 5-15), moderate (RDI 15-30), and severe (RDI>30). HsTnT was divided into five categories. The association between RDI and hsTnT was assessed using multivariable ordered logistic regression. Median follow-up was 12.3 years. The association of hsTnT and OSA with the composite HF or cardiovascular death (death/HF) was assessed by Cox proportional hazard regression. Results: Average age was ...
Outcome analysis of “do not resuscitate” versus “full resuscitation” patients with an acute exacerbation of COPD treated with noninvasive ventilation in a pulmonary unit
Authors: Ruben van der Wekken, Aik Bossink, Folkert Brijker
Journal: European Respiratory Journal (2011)

Introduction:  Noninvasive ventilation (NIV) is common practice in acute respiratory failure due to acute exacerbation of COPD (AECOPD). NIV is administered to patients with both “Do Not Resuscitate” (DNR) and Full Resuscitation (FR) order. Little is known about the outcome of DNR-patients treated with NIV in a pulmonary unit, compared to patients with a FR order.   Methods:  In a single centre study, during a period of three years, we followed all patients with AECOPD who underwent NIV in a pulmonary unit (n= 67). NIV was initiated in case of respiratory acidosis with pH   Results:  In the DNR-group 9 patients died in the hospital and another 3 died within three months after discharge (total failure: 55%). In the FR-group 1 patient died in the hospital, no extra mortality was observed within three months after discharge and 11 patients were transferred to the ICU (total failure: 27%) (Fisher exact p    Conclusion:  There was more failure of treatment in the DNR-group than in the FR-group. However, still a substantial number in the DNR-group benefited from NIV. To clarify in which DNR-patients NIV should be performed, further research is warranted to identify parameters predicting outcome.
Abstract 18832: High-Resolution, Whole Heart T1 Mapping in a Chronic Atrial Fibrillation Model
Authors: Eugene G Kholmovski, Daniel Kim, Sathya Vijayakumar, Ravi Ranjan, Derek Dosdall, Koji Higuchi, Rob MacLeod, Nassir F Marrouche
Journal: Circulation (2013)

Introduction: Cardiac fibrosis is a marker of adverse remodeling of the heart. Cardiac T1 mapping is the only non-invasive method to assess diffuse myocardial fibrosis. However, existing T1 mapping techniques are not applicable for whole heart mapping with adequate spatial resolution to accurately evaluate the thin atrial wall. We have developed a novel, high-resolution, whole heart T1 mapping technique which can be used to characterize fibrosis in all cardiac chambers simultaneously. Methods: We applied the whole heart T1 mapping technique to study fibrosis progression in a canine, chronic atrial fibrillation (AF) model. Dogs (n=8) were subjected to rapid atrial pacing (RAP) and underwent baseline (n=8) and 8-month RAP MRIs (n=4) to evaluate myocardial fibrosis. Whole heart T1 mapping was performed on a 3 Tesla MRI scanner during slow contrast infusion (0.05 micromol/kg/sec of Gd-BOPTA). Spatial resolution of T1 mapping scans was 1.25x1.25x2.5 mm. T1 mapping was performed at least 30 minutes after start of slow contrast infusion to achieve steady-state for contrast distribution. Results: Figure 1a shows representative image of cardiac T1 maps that visualize the myocardium of all cardiac chambers clearly. Myocardium of LV and LA has similar T1 values in baseline scans (p=NS), which decreased significantly in the LV and LA 8 months after initialization of RAP (p&lt;0.05, Fig. 1b). This change in T1 indicates increased fibrosis of left ventricle and atrium after 8 months of AF. Conclusions: High-resolution, whole heart T1 mapping technique can be used to non-invasively assess diffuse myocardial fibrosis in all cardiac chambers. T1 mapping indicates that 8-months RAP results in increased LV and LA fibrosis.
Revertant and potentiating activity of lonidamine in patients with ovarian cancer previously treated with platinum.
Authors: M De Lena, V Lorusso, C Bottalico, M Brandi, A De Mitrio, A Catino, M Guida, A Latorre, B Leone, C Vallejo, G Gargano
Journal: Journal of Clinical Oncology (1997)

PURPOSE Lonidamine (LND) is an energolytic derivative of indazol-carboxylic acid that has been shown to enhance cisplatin (CDDP) activity in both sensitive (A2780) and resistant (A2780/Cp8) ovarian cancer cell lines. The aim of this study was to confirm the potentiating or reverting activity of LND on CDDP activity obtained in experimental models in a phase II study of advanced ovarian cancer patients previously treated with platinum-based regimens. PATIENTS AND METHODS Twenty-seven consecutive women with histologically proven and measurable ovarian cancer previously treated with platinum compounds were treated with CDDP plus LND. CDDP was administered at 1 mg/kg intravenously (IV) once weekly for 6 weeks and every 3 weeks thereafter until disease progression or toxicity. LND was administered at 450 mg daily (1 tablet every 8 hours) for the entire period of therapy starting 3 days before the first CDDP administration. In addition, a higher LND dosage was provided on the day of CDDP administration in an attempt to maximize the synergy of this drug with CDDP. RESULTS Ten patients achieved a complete response (CR) or partial response (PR) for an overall response rate of 37% (95% confidence interval [CI], 19% to 55%). In particular, responses were observed in five of 18 (28%) refractory or early relapsed patients (one CR and four PRs) and in five of nine patients (55%) in the late-relapsed group (two CRs and three PRs). Grade 3 or 4 anemia, leukopenia, and thrombocytopenia were observed in 19%, 15%, and 11% of patients, respectively, whereas seven of 27 patients (26%) showed LND-related myalgia. Grade 3 renal toxicity was observed in two patients (8%). Neurotoxicity, often concealed by LND-related myalgia, was recorded as grade 1 or 2 in six patients (22%) and as grade 3 in one (4%). CONCLUSION The 37% response rate observed in this study (28% in refractory or early-relapsed patients), suggests that the synergism between CDDP and LND observed in vitro against ovarian cancer cell lines can be clinically confirmed. However, larger series and randomized studies are needed to assess definitely the revertant activity of LND on CDDP-refractory patients.
Short report: Phase II trials of fosquidone (GR63178A) in carcinoma of the breast, head and neck, ovary and melanoma
Authors: S.B. Kaye, J. Wanders, M. Clavel, J. Verweij, M.J. Piccart, J.F. Smyth, W.W. Ten Bokkel Huinink, D.J.T. Wagener, I.R. Judson, F. Cavalli
Journal: Annals of Oncology (1992)
A phase I/II study of CR011-vcMMAE, an antibody-drug conjugate (ADC) targeting glycoprotein NMB (GPNMB) in patients (pts) with advanced melanoma
Authors: P. Hwu, M. Sznol, A. Pavlick, H. Kluger, K. B. Kim, P. Boasberg, D. Sanders, R. Simantov, E. Crowley, O. Hamid
Journal: Journal of Clinical Oncology (2009)

9032 Background: GPNMB is expressed on melanoma cells and represents a potential target for ADCs. CR011-vcMMAE is a fully-human monoclonal antibody to GPNMB conjugated to the tubulin inhibitor monomethylauristatin E (MMAE). Dose limiting toxicity in Phase I (n=32) was rash; tumor shrinkage including one partial response (PR) was observed. We now report Phase II data at the maximum tolerated dose of 1.88 mg/kg iv q3w. Methods: Eligible pts had unresectable stage III or stage IV melanoma and had received no more than 1 prior cytotoxic regimen but any number of other therapies. Pts received CR011-vcMMAE until disease progression (PD) or intolerable toxicity. The primary endpoint was overall response (ORR) by RECIST using a minimax two-stage design (p 0 =0.5; p 1 =0.2, α=β=0.1) with 18 patients in the first stage and a total of 32 pts. Secondary endpoints included progression free survival (PFS) and duration of response. Results: 36 pts (median age 67 years [range 37–79]; 94% stage IV; 68% M1c) were treated for a median of 2.4 months (m)(range 0.5–7.5m). 18 pts discontinued (14 PD, 2 consent, 1 adverse event [AE], 1 stable disease [SD]) and 18 pts were ongoing. The study met the criteria for advancement to the second stage; 4 PRs (1 unconfirmed) and 19 SD (range 1.7–7.5 mo) have been observed; final ORR is pending. The unconfirmed PR was in a pt with 96% tumor reduction and PD 6 weeks later. Median PFS was 4m. The most common AEs were rash (81%), fatigue (72%), alopecia (63%) and pruritus (56%). The most common grade 3/4 AEs were neutropenia (22%) and rash (19%). Grade 2 or higher rash was associated with longer PFS. Conclusions: CR011-vcMMAE is active and well-tolerated in heavily pretreated pts with advanced melanoma. Rash may be a useful biomarker for activity. More frequent dosing is being explored. [Table: see text]
Loco-regional radioimmunotherapy of high grade malignant gliomas using the humanized monoclonal antibody, h-R3, labeled with 188-Re
Authors: A. Casaco, G. López, R. Fernandez, L. Diaz, A. Perera, J. Batista, R. Leyva, Y. Peña, J. A. Rodriguez, I. Garcia
Journal: Journal of Clinical Oncology (2004)

2530 Background: Intralesional radioimmunotherapy (RIT) may improve the management of malignant gliomas. Current treatments modalities cannot prevent tumor recurrence. A clinical trial was performed to evaluate the toxicity, the maximal tolerated dose (MTD), dosimetry, biodistribution and any clinical effect after RIT using the humanized MAb, h-R3, labeled with188-Re. Methods: A Phase I dose escalation trial was performed by administrating into the post-operative cavity through an indwelling catheter a single dose of the h-R3 MAb directed against epidermal growth factor receptors (EGFR). The study was approved by the CIREN Ethics Committee. All patients had partial tumor resections and over-expressed the EGFR. One patient with anaplastic astrocytoma (AA) and 4 with glioblastoma multiforme (GBM) were treated with 3 mg of MAb labeled with 10 or 15 mCi of 188-Re. Patients signed a written informed consent. Results: Transitory acute side effects following treatment were headache, seizures, and worsening of pre-existing neurological symptoms. Two patients developed stable disease during 3 months, 2 GBM patients are practically asymptomatic and in complete remission after one year of treatment. The other GBM patient is not yet evaluable after one month of treatment. For the whole group, median survival time has not yet been reached. The average absorbed doses to organs and normal brain were minimal. Conclusions: MTD has not been reached. Although only 5 patients have been enrolled in the study, the fact that 1) mainly, only transitory side effects were detected, 2) 2 patients, one AA and one GBM, had a stable disease for more 3 months, and 3) 2 GBM patients are in complete remission after one year of a single dose treatment, strongly suggests that RIT using the h-R3 MAb labeled with 188-Re may be relatively safe and a promising therapeutic approach for treating high grade glioma patients. No significant financial relationships to disclose.
Abstract 16352: Temporal Trends in Mortality and Adverse Events in 24,890 Patients Undergoing Lead Extraction Over a Decade
Authors: David Kao, Paul Varosy, Duy T Nguyen, Wendy Tzou, David Katz, Joseph Schuller, Raphael Sung, David Steckman, William H Sauer, Ryan Aleong
Journal: Circulation (2013)

Background:  Despite the increasing number of pacemaker and defibrillator lead extractions, it is unclear whether lead extraction has become a safer procedure. We assessed the temporal trends in number of lead extractions performed and the associated rates of mortality and major adverse events (MAE) between the years of 2000 and 2011 in a large cohort of patients based on an administrative dataset.   Methods:  Hospital records were obtained from the California state agency for the years 2000-2011. Admissions including the ICD-9 CM procedure codes 37.75, 37.76 or 37.77 (lead extraction) were analyzed. MAE included cardiac tamponade, hemothorax and emergent cardiac surgery. The rates of in-hospital MAE and death were estimated using univariate and multivariate binomial mixed effects model with random effects terms for hospital, state and fixed effect terms for demographics and comorbid conditions.   Results:  24,890 hospital discharges included the diagnosis lead extraction (Age 43.2 ± 0.14, male 40.9%, white 53.3%). Between 2000 to 2011 there was an increase in the number of lead extractions (2000: n = 1661; 2011: n = 2106) with decrease in the number of hospitals performing lead extraction (2000: n= 255; 2011: n = 215). There was an increase in the rates of MAE and death associated with lead extraction increased between 2000 and 2011 (MAE p = 0.0005; death p = 0.037; Figure). By multivariate analysis, the MAE rate increased at high volume centers compared to low volume centers (p = 0.02).   Conclusions:  Despite the increasing number of lead extractions performed and a decreasing number of hospitals performing lead extraction, there was an increasing rate of associated adverse events and mortality.
Comparison of drug release from liquid crystalline monoolein dispersions and solid lipid nanoparticles using a flow cytometric technique
Authors: Mohamed Z. Dawoud, Mohamed Nasr
Journal: Acta Pharmaceutica Sinica B (2016)

Colloidal lipid particles such as solid lipid nanoparticles and liquid crystalline nanoparticles have great opportunities as drug carriers especially for lipophilic drugs intended for intravenous administration. In order to evaluate drug release from these nanoparticles and determine their behavior after administration, emulsion droplets were used as a lipophilic compartment to which the transfer of a model drug was measured. The detection of the model drug transferred from monoolein cubic particles and trimyristin solid lipid nanoparticles into emulsion droplets was performed using a flow cytometric technique. A higher rate and amount of porphyrin transfer from the solid lipid nanoparticles compared to the monoolein cubic particles was observed. This difference might be attributed to the formation of a highly ordered particle which leads to the expulsion of drug to the surface of the crystalline particle. Furthermore, the sponge-like structure of the monoolein cubic particles decreases the rate and amount of drug transferred. In conclusion, the flow cytometric technique is a suitable technique to study drug transfer from these carriers to large lipophilic acceptors. Monoolein cubic particles with their unique structure can be used successfully as a drug carrier with slow drug release compared with trimyristin nanoparticles.
Mending a Faltering Heart
Authors: Mo Li, Juan Carlos Izpisua Belmonte
Journal: Circulation Research (2016)

More people die every year from ischemic heart disease than any other disease. Because the human heart lacks sufficient ability to replenish the damaged cardiac muscles, extensive research has been devoted toward understanding the homeostatic and regenerative potential of the heart and to develop regenerative therapies for heart disease. Here, we discuss recent advances in the understanding of mechanisms governing heart growth during homeostasis or injury, including those from observational studies in humans and experimental research in animal models of cardiac regeneration. We also discuss how progress in stem cell biology and cellular reprogramming has enabled exciting new strategies for cardiac regeneration.
Anti-inflammatory effects of garenoxacin on IL-8 production and ERK1/2 activation induced by lipopolysaccharides in A549 and THP-1 cells
Authors: Shintaro Hara, Yuji Ishimatsu, Hiroshi Mukae, Noriho Sakamoto, Tomoyuki Kakugawa, Hanako Fujita, Atsuko Hara, Shigeru Kohno
Journal: European Respiratory Journal (2011)

Objective: The anti-inflammatory properties of macrolides have been applied to the treatment of inflammatory airway diseases. Although the anti-inflammatory properties of fluoroquinolones have been reported, no reports are available regarding a newly developed fluoroquinolone, garenoxacin (GRNX). To examine the immunomodulatory effect of GRNX, we examined the transcription and secretion of inflammatory cytokines by human airway epithelial cells and monocytes stimulated with lipopolysaccharide (LPS).

Methods: A human lung epithelial cell line (A549) and a human monocyte cell line (THP-1) were stimulated with LPS and exposed to different concentrations of GRNX. The transcription of interleukin 8 (IL-8) at 3 h was measured in cell lysates using real-time PCR. The secretion of IL-8 was measured in the supernatants of the cell cultures at 24 h (A549 cells) or 9 h (THP-1 cells) using an enzyme-linked immunosorbent assay.

Results: LPS stimulation resulted in a significant increase in the transcription and secretion of IL-8 by A549 and THP-1 cells. Treatment with GRNX significantly inhibited the transcription and secretion of IL-8 by LPS-stimulated cells through inhibition of LPS-induced ERK1/2 phosphorylation.

Conclusions: GRNX has an anti-inflammatory activity through its capacity to alter the secretion of IL-8 from A549 and THP-1 cell lines.