tbuckley/cabot-search huggingface dataset:
A Bispecific Recombinant Immunotoxin, DT2219, Targeting Human CD19 and CD22 Receptors in a Mouse Xenograft Model of B-Cell Leukemia/Lymphoma
Authors: Daniel A. Vallera, Deborah A. Todhunter, David W. Kuroki, Yanqun Shu, Andy Sicheneder, Hua Chen
Journal: Clinical Cancer Research (2005)

Abstract A novel bispecific single-chain fusion protein, DT2219, was assembled consisting of the catalytic and translocation domains of diphtheria toxin (DT390) fused to two repeating sFv subunits recognizing CD19 and CD22 and expressed in Escherichia coli. Problems with yield, purity, and aggregation in the refolding step were solved by incorporating a segment of human muscle aldolase and by using a sodium N-lauroyl-sarcosine detergent-based refolding procedure. Problems with reduced efficacy were addressed by combining the anti-CD19 and anti-CD22 on the same single-chain molecule. DT2219 had greater anticancer activity than monomeric or bivalent immunotoxins made with anti-CD19 and anti-CD22 sFv alone and it showed a higher level of binding to patient leukemia cells and to CD19+CD22+ Daudi or Raji cells than did anti-CD19 and anti-CD22 parental monoclonal antibodies. The resulting DT2219, mutated to enhance its avidity, was cytotoxic to Daudi cells in vitro (IC50 = 0.3 nmol/L). In vivo, DT2219 was effective in a flank tumor therapy model in which it significantly inhibited tumor growth (P &amp;lt; 0.05) and in a systemic model in which it significantly prolonged survival of severe combined immunodeficient mice with established Daudi (P &amp;lt; 0.008) compared with controls. DT2219 has broader reactivity in recognizing B-cell malignancies, has more killing power, and requires less toxin than using individual immunotoxin, which warrants further investigation as a new drug for treating B leukemia/lymphoma.
Effectiveness of screening older people for impaired vision in community setting: systematic review of evidence from randomised controlled trials
Authors: L. Smeeth, S. Iliffe
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To assess whether population screening for impaired vision among older people in the community leads to improvements in vision. <b>Design:</b> Systematic review of randomised controlled trials of population screening in the community that included any assessment of vision or visual function with at least 6 months9 follow up. <b>Subjects:</b> Adults aged 65 or over. <b>Main outcome measure:</b> Proportions with visual impairment in intervention and control groups with any method of assessing visual impairment. <b>Results:</b> There were no trials that primarily assessed visual screening. Outcome data on vision were available for 3494 people in five trials of multiphasic assessment. All the trials used self reported measures for vision impairment, both as screening tools and as outcome measures. The inclusion of a visual screening component in the assessments did not result in improvements in self reported visual problems (pooled odds ratio 1.04: 95% confidence interval 0.89 to 1.22). A small reduction (11%) in the number of older people with self reported visual problems cannot be excluded. <b>Conclusions:</b> Screening of asymptomatic older people in the community is not justified on present evidence. Visual impairment in this age group can usually be reduced with treatment. It is unclear why no benefit was seen. Further work is needed to clarify what interventions are appropriate for older people with unreported impairment of vision. <h3>Key messages</h3> Impaired vision is common among older people and has a variety of adverse associations General practitioners are currently obliged to offer an annual assessment of vision as part of the 75 and over programme Evidence for effectiveness of visual screening is lacking, but a small beneficial effect cannot be excluded The continued inclusion of screening for impaired vision in screening programmes for older people is not supported by the evidence Further work is needed to clarify appropriate interventions for older people with unreported visual impairment
Tuberculin responses and risk of pneumonia in immobile elderly patients
Authors: K. Nakayama
Journal: Thorax (2000)

Delayed type hypersensitivity (DTH) response to tuberculin is an important marker of T helper 1 (Th1) mediated acquired immunity against tuberculosis. Depressed DTH responses to tuberculin are observed in immobile elderly individuals with reduced activities of daily living (ADL) scores. Immobility in older people increases the risk of pneumonia related mortality. The decline in the competence of the immune system might be a reason for the increased susceptibility to infection in the elderly and the depressed DTH response to tuberculin might be a predictor for increased risk of pneumonia.The DTH responses to tuberculin were examined in 49 older patients with limited ADL of similar severity, all of whom had a past history of positive DTH responses to tuberculin. Responses with an induration diameter of >/=10 mm were considered positive. Reactivities of Th1 and Th2 lymphocytes taken from the peripheral blood of each subject were also examined and compared between the positive tuberculin responders and the negative tuberculin responders. The rates of pneumonia in these groups were then compared prospectively for two years.The number of CD4 lymphocytes differed significantly between patients with a positive tuberculin response (n=22, mean (SE) 1018 (118) x 10(6)/l) and those with a negative response (n=27, 666 (80) x 10(6)/l, p=0.02). Likewise, the number of Th1 cells was significantly higher in positive tuberculin responders than in negative responders (276 (5.8) x 10(6)/l versus 149 (14) x 10(6)/l, p=0.01). However, the numbers of Th2 cells were similar between patients with positive and negative responses (22 (3) x 10(6)/l versus 19 (3) x 10(6)/l, p=0.41). During the follow up period new pneumonia was diagnosed in 18 (67%) of the 27 negative tuberculin responders and in seven (31%) of the 22 positive tuberculin responders. According to the Cox regression model, a hazard ratio of developing pneumonia in patients with a negative tuberculin response compared with those with a positive tuberculin response was 2.57 (95% CI 1.12 to 6.17, p=0.03).The diminished DTH response to tuberculin may be a predictor for increased risk of pneumonia in elderly disabled patients.
Cediranib combined with carboplatin and paclitaxel in patients with metastatic or recurrent cervical cancer (CIRCCa): a randomised, double-blind, placebo-controlled phase 2 trial
Authors: R Paul Symonds, Charlie Gourley, Susan Davidson, Karen Carty, Elaine McCartney, Debbie Rai, Susana Banerjee, David Jackson, Rosemary Lord, Mary McCormack, Emma Hudson, Nicholas Reed, Maxine Flubacher, Petra Jankowska, Melanie Powell, Caroline Dive, Catharine M L West, James Paul
Journal: The Lancet Oncology (2015)

Patients treated with standard chemotherapy for metastatic or relapsed cervical cancer respond poorly to conventional chemotherapy (response achieved in 20-30% of patients) with an overall survival of less than 1 year. High tumour angiogenesis and high concentrations of intratumoural VEGF are adverse prognostic features. Cediranib is a potent tyrosine kinase inhibitor of VEGFR1, 2, and 3. In this trial, we aimed to assess the effect of the addition of cediranib to carboplatin and paclitaxel chemotherapy in patients with metastatic or recurrent cervical cancer.
Steady-state mRNA levels of the sarcolemmal Na(+)-Ca2+ exchanger peak near birth in developing rabbit and rat hearts.
Authors: S R Boerth, D B Zimmer, M Artman
Journal: Circulation Research (1994)

To functionally compensate for an underdeveloped sarcoplasmic reticulum in immature cardiomyocytes, it has been proposed that the sarcolemmal Na(+)-Ca2+ exchanger may assume a more predominant role for regulating cytosolic Ca2+. Previous studies using sarcolemma prepared from developing rabbit hearts demonstrated that Na(+)-dependent Ca2+ uptake and exchanger protein content were highest at birth and declined postnatally. To further investigate the significance of the Na(+)-Ca2+ exchanger during normal myocardial development, steady-state mRNA levels of the cardiac Na(+)-Ca2+ exchanger were quantitated by Northern blot and slot-blot analyses using poly(A+) RNA isolated from rabbit and rat ventricles at various fetal and postnatal ages. Northern analyses were performed with a 1.35-kb guinea pig cardiac Na(+)-Ca2+ exchanger cDNA probe. Exchanger mRNA levels were quantitated by densitometric scans of the slot blots, and results were normalized by reprobing the same blots with 32P 5'-end-labeled oligo(dT). In both species, exchanger mRNA levels peaked near birth and declined postnatally. Maximal levels were approximately sixfold greater in the late fetal rabbit (gestational day 29) and eightfold greater in the early newborn rat (postnatal day 1) compared with adults of the respective species. The parallel changes in exchanger mRNA and protein levels suggest that developmental regulation of cardiac Na(+)-Ca2+ exchanger expression involves pretranslational control mechanisms. These results support the concept that during normal cardiac development, Na(+)-Ca2+ exchanger expression is maximal near the time of birth and then declines postnatally as Ca2+ regulation by the sarcoplasmic reticulum reaches functional maturity.
Evidence that Resistance to Nilotinib May Be Due to BCR-ABL, Pgp, or Src Kinase Overexpression
Authors: François-Xavier Mahon, Sandrine Hayette, Valérie Lagarde, Francis Belloc, Béatrice Turcq, Franck Nicolini, Coralie Belanger, Paul W. Manley, Cédric Leroy, Gabriel Etienne, Serge Roche, Jean-Max Pasquet
Journal: Cancer Research (2008)

Abstract Targeting the tyrosine kinase activity of Bcr-Abl is an attractive therapeutic strategy in chronic myeloid leukemia (CML) and in Bcr-Abl–positive acute lymphoblastic leukemia. Whereas imatinib, a selective inhibitor of Bcr-Abl tyrosine kinase, is now used in frontline therapy for CML, second-generation inhibitors of Bcr-Abl tyrosine kinase such as nilotinib or dasatinib have been developed for the treatment of imatinib-resistant or imatinib-intolerant disease. In the current study, we generated nilotinib-resistant cell lines and investigated their mechanism of resistance. Overexpression of BCR-ABL and multidrug resistance gene (MDR-1) were found among the investigated mechanisms. We showed that nilotinib is a substrate of the multidrug resistance gene product, P-glycoprotein, using verapamil or PSC833 to block binding. Up-regulated expression of p53/56 Lyn kinase, both at the mRNA and protein level, was found in one of the resistant cell lines and Lyn silencing by small interfering RNA restored sensitivity to nilotinib. Moreover, failure of nilotinib treatment was accompanied by an increase of Lyn mRNA expression in patients with resistant CML. Two Src kinase inhibitors (PP1 and PP2) partially removed resistance but did not significantly inhibit Bcr-Abl tyrosine kinase activity. In contrast, dasatinib, a dual Bcr-Abl and Src kinase inhibitor, inhibited the phosphorylation of both BCR-ABL and Lyn, and induced apoptosis of the Bcr-Abl cell line overexpressing p53/56 Lyn. Such mechanisms of resistance are close to those observed in imatinib-resistant cell lines and emphasize the critical role of Lyn in nilotinib resistance. [Cancer Res 2008;68(23):9809–16]
Variations in Patient Management and Outcomes for Acute Myocardial Infarction in the United States and Other Countries
Authors: Frans Van de Werf
Journal: JAMA (1995)

<h3>Objective.</h3> —To examine differences in outcomes and patient management between patients in the United States and outside the United States undergoing thrombolysis for acute myocardial infarction. <h3>Design, Setting, and Patients.</h3> —Patients in the United States (n=23105) and 14 other countries (n=17 916) were randomized to receive streptokinase plus either subcutaneous or intravenous (IV) heparin, accelerated recombinant tissue-type plasminogen activator (rt-PA) plus IV heparin, or combined streptokinase and rt-PA plus IV heparin. <h3>Outcome Measures.</h3> —Differences in 30-day mortality and patient management were compared among treatments and between US and non-US patients. Treatment-by-country interactions were assessed by logistic regression analyses. Expected mortality of US and non-US patients was estimated using a predictive model and was compared with observed mortality. <h3>Results.</h3> —Mortality reduction with accelerated rt-PA vs streptokinase was greater in the United States (1.2% absolute decrease vs 0.7% elsewhere), but the test for treatment-by-country interaction against streptokinase was not significant (<i>P</i>=.30). Benefits of accelerated rt-PA over combination therapy were observed in the United States, but not in other countries (<i>P</i>=.02). Despite differences in baseline characteristics and patient management, 30-day mortality was not significantly different: 6.8% in the United States vs 7.2% elsewhere (<i>P</i>=.09). After adjustment for baseline differences, observed vs predicted outcomes were slightly better in the United States (6.8% vs 7.0%) than elsewhere (7.2% vs 7.0%), indicating that enrollment in the United States was a marginally significant predictor of better survival (<i>P</i>=.047). <h3>Conclusions.</h3> —No significant evidence for a differentially greater benefit of accelerated rt-PA over streptokinase was found in US vs non-US patients. However, increased procedure and treatment use in the United States was associated with only a small decrease in short-term mortality. Long-term follow-up is required to clarify the relationship between survival and the more intensive US management approach. (<i>JAMA</i>. 1995;273:1586-1591)
Primary Pituitary Lymphoma: A Histological, Immunohistochemical, and Ultrastructural Study with Literature Review
Authors: Olga Moshkin, Paul Muller, Bernd W. Scheithauer, Jonathan Juco, Eva Horvath, Bruce J. Patterson, Suzzane Kamel-Reid, Kalman Kovacs
Journal: Endocrine Pathology (2009)
New Concepts in Von Willebrand Disease
Authors: J. Evan Sadler
Journal: Annual Review of Medicine (2004)

Von Willebrand factor (VWF) behaves as an extracellular adapter molecule, linking platelets to the extracellular matrix at sites of vascular injury. These interactions are crucial for hemostasis. Too little platelet adhesion causes bleeding that is typical of von Willebrand disease, whereas too much platelet adhesion may cause thrombotic thrombocytopenic purpura. Mutations in VWF or platelet glycoprotein Ib can either reduce or increase the affinity of platelet binding. Paradoxically, affinity changes in either direction cause bleeding. Crystallographic studies now suggest molecular explanations for all of these phenotypes. Clinical investigations of von Willebrand disease type 1 are defining the relationship between plasma VWF level and the risk of bleeding or thrombosis. Emerging data suggest that VWF level is a useful biomarker for the risk of either bleeding or thrombosis and could be incorporated into a comprehensive approach to treat or prevent these adverse events.
Three-dimensional Imaging of the Foveal Photoreceptor Layer in Central Serous Chorioretinopathy Using High-speed Optical Coherence Tomography
Authors: Yumiko Ojima, Masanori Hangai, Manabu Sasahara, Norimoto Gotoh, Ryo Inoue, Yoshiaki Yasuno, Shuichi Makita, Toyohiko Yatagai, Akitaka Tsujikawa, Nagahisa Yoshimura
Journal: Ophthalmology (2007)
Intensive Glycemic Control and the Prevention of Cardiovascular Events: Implications of the ACCORD, ADVANCE, and VA Diabetes Trials
Authors: Jay S. Skyler, Richard Bergenstal, Robert O. Bonow, John Buse, Prakash Deedwania, Edwin A.M. Gale, Barbara V. Howard, M. Sue Kirkman, Mikhail Kosiborod, Peter Reaven, Robert S. Sherwin
Journal: Journal of the American College of Cardiology (2009)
THE EFFECT OF ALLOXAN DIABETES ON EXPERIMENTAL CHOLESTEROL ATHEROSCLEROSIS IN THE RABBIT
Authors: G. Lyman Duff, Doris J. H. Brechin, W. E. Finkelstein
Journal: The Journal of Experimental Medicine (1954)

Experiments were undertaken to ascertain whether the previously demonstrated inhibition of the development of experimental aortic atherosclerosis in alloxan-diabetic rabbits fed cholesterol was due to the injection of alloxan per se or to the existence of the diabetic state produced by alloxan. It was established that, by treating the diabetic state with insulin, the diabetic state could be ameliorated and the inhibitory effect obviated. It was therefore concluded that the inhibitory phenomenon was not due to the injection of alloxan per se but that it was associated with one or more factors that characterize the alloxan diabetic state in the rabbit and that are reversible by insulin therapy. In the course of the experiment it was demonstrated that the inhibitory effect was apparent in cholesterol-fed diabetic rabbits whether or not their diet was supplemented with vegetable oil. The previously reported metabolic abnormalities of the diabetic animals were confirmed. It was established that suitable treatment of the cholesterol-fed diabetic animals with insulin would bring all the metabolic aberrations, including those of the serum lipids, into reasonably close correspondence with those observed in non-diabetic rabbits fed cholesterol.
Monocytosis in the BXSB model for systemic lupus erythematosus.
Authors: D Wofsy, C E Kerger, W E Seaman
Journal: The Journal of Experimental Medicine (1984)

Autoimmunity in BXSB mice is associated with a progressive increase in the number of peripheral blood mononuclear cells (PBMC). This is due to a marked rise in circulating monocytes, identified by: (a) their appearance on light and electron microscopy; (b) their surface antigenic characteristics; (c) their expression of Fc receptors; and (d) their capacity for phagocytosis. Among murine models for systemic lupus erythematosus, only the BXSB strain is characterized by monocytosis, suggesting that cells of monocytic lineage may contribute significantly to the pathogenesis of autoimmune disease in BXSB mice.
Analysis of Changes in Eating Behavior and Weight Loss in Type II Diabetic Patients: Which Behaviors to Change
Authors: John C Guare, Rena R Wing, Marsha D Marcus, Leonard H Epstein, Lisa R Burton, William E Gooding
Journal: Diabetes Care (1989)

To identify the behavior-change strategies that are most clearly related to weight loss, 106 patients with type II (non-insulin-dependent) diabetes completed the Eating Behavior Inventory (EBI) before and after participating in a behavioral weight-loss program and at 1-yr follow-up. The EBI is a standardized questionnaire that assesses behavioral strategies typically taught in a behavioral weight-loss program. Pretreatment scores on the EBI were not related to weight-loss outcome, but changes on the EBI in the direction of more frequent use of appropriate strategies were related to weight loss at both posttreatment and 1-yr follow-up. Specific strategies related to weight loss at both times were 7) eating foods that help in losing weight, 2) recording foods eaten, 3) refusing food offered by others, and 4) being able to stop eating when appropriate. However, few patients maintained frequent use of these strategies at follow-up. It is concluded that weight-loss programs should focus on the strategies most strongly related to weight loss and try to improve long-term use of these techniques.
Reactive dilation of large coronary arteries in conscious dogs.
Authors: T H Hintze, S F Vatner
Journal: Circulation Research (1984)

To study the response of large coronary arteries to short periods of myocardial ischemia a pair of ultrasonic dimension transducers, a flow probe and a hydraulic occluder were implanted around the left circumflex coronary artery for the instantaneous and continuous measurement of external coronary artery dimensions and coronary blood flow, respectively. At 6.1 +/- 0.4 seconds after release of a 15-second occlusion, mean coronary blood flow increased by 255 +/- 30% from a preocclusion flow of 32 +/- 4.1 ml/min. At this time, large coronary arterial cross-sectional area was unchanged but increased slowly, reaching a peak 28 +/- 4.4% above preocclusion levels 61 +/- 3.2 seconds after occlusion, i.e., reactive dilation. During maximal reactive dilation, coronary blood flow had already returned to control levels, and heart rate, mean arterial pressure, left ventricular systolic pressure, and left ventricular dP/dt were not different from control. The reactive dilation was not affected if the occlusion occurred proximal or distal to where diameter was measured, or by combined alpha- and beta-adrenergic receptor blockade, ganglionic blockade, inhibition of prostaglandin synthesis, or by aminophylline. When the reactive hyperemia was prevented by constricting the coronary artery upon release of the coronary occlusion, the reactive dilation was not observed. Thus, large coronary arteries respond to brief periods of occlusion with reactive dilation. The time course of this response is distinctly different from the accompanying reactive hyperemia, and could be eliminated by preventing the marked increase in coronary blood flow following release from the brief period of coronary artery occlusion.
Recurrent hemolytic uremic syndrome in an adult renal allograft recipient
Authors: A Agarwal, S M Mauer, A J Matas, K A Nath
Journal: Journal of the American Society of Nephrology (1995)

Acute renal insufficiency in the setting of hemolysis and thrombocytopenia, a triad that constitutes adult or pediatric hemolytic uremic syndrome, can be associated with or triggered by diverse conditions such as verocytotoxin-producing Escherichia coli, viral infections, pregnancy, malignant hypertension, scleroderma, renal radiation, allograft rejection, lupus erythematosus, and assorted medications such as mitomycin C, cyclosporine, and oral contraceptives. Recurrent and de novo hemolytic uremic syndrome occur after renal transplantation. Relapses are also common and probably reflect incomplete resolution of the initial episode. The major differential diagnoses of hemolytic uremic syndrome in the renal allograft include acute vascular rejection, cyclosporine, FK506 or antilymphocyte antibody nephrotoxicity, and malignant hypertension, all of which may display overlapping clinical and histologic features with primary hemolytic uremic syndrome; in such instances, the exact diagnosis may be quite difficult. It is possible that the risk of recurrence may be reduced by proper timing of transplantation and suitable choice of immunosuppressive agents. Intensive plasmapheresis in conjunction with fresh frozen plasma and supportive management of renal failure may lessen mortality and morbidity even in recurrent hemolytic uremic syndrome after transplantation.
Sentinel lymph node biopsy: in support of equity of access, informed shared decision making and patient choice
Authors: J.K. Schofield
Journal: British Journal of Dermatology (2015)

Journal Article Sentinel lymph node biopsy: in support of equity of access, informed shared decision making and patient choice Get access J.K. Schofield J.K. Schofield Department of dermatology United Lincolnshire Hospitals NHS Trust Lincoln County Hospital Greetwell Road Lincoln LN2 5QY, U.KSchool of Postgraduate Medicine University of Hertfordshire Hatfield U.K E‐mail: j.k.schofield@herts.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 3, 1 September 2015, Pages 863–864, https://doi.org/10.1111/bjd.13921 Published: 01 September 2015