tbuckley/cabot-search huggingface dataset:
Antitumor and Antivascular Effects of AVE8062 in Ovarian Carcinoma
Authors: Tae Jin Kim, Murali Ravoori, Charles N. Landen, Aparna A. Kamat, Liz Y. Han, Chunhua Lu, Yvonne G. Lin, William M. Merritt, Nicholas Jennings, Whitney A. Spannuth, Robert Langley, David M. Gershenson, Robert L. Coleman, Vikas Kundra, Anil K. Sood
Journal: Cancer Research (2007)

Abstract The purpose of this study was to examine the therapeutic efficacy and underlying mechanisms of action of a vascular-disrupting agent, AVE8062, and to determine its effects on tumor metabolic activity. The in vitro and in vivo effects of AVE8062 alone and in combination with docetaxel were tested in chemotherapy-sensitive and chemotherapy-resistant ovarian cancer models. Tumors were analyzed for necrosis, microvessel density, endothelial cell apoptosis, and proliferation following treatment. The effect of AVE8062 on tumor regression and metabolic activity was examined by magnetic resonance (MR) or by [18F]fluorodeoxyglucose ([18F]FDG) uptake by positron emission tomography (PET) with MR imaging, respectively. AVE8062 monotherapy was effective in inhibiting tumor growth in all models (range 43–51% versus control; P &amp;lt; 0.05). Combination therapy was even more effective in inhibiting tumor growth (range 76–90% compared with controls, P &amp;lt; 0.01). AVE8062 in combination with chemotherapy significantly prolonged survival in HeyA8-injected mice (P &amp;lt; 0.001) compared with other groups. AVE8062-based therapy resulted in rapid development of central tumor necrosis, decreased microvessel density, decreased proliferation, and induction of apoptosis of tumor-associated endothelial cells. MR imaging showed regression of established HeyA8 ovarian tumors and [18F]FDG PET with MR showed rapid decrease in metabolic activity after AVE8062 therapy. Combination of AVE8062 plus docetaxel results in potent inhibition of ovarian cancer growth. These results suggest that AVE8062 may be useful as a clinical therapeutic approach for ovarian cancer patients and that functional [18F]FDG PET imaging may predict clinical response before an anatomic reduction in tumor size. [Cancer Res 2007;67(19):9337–45]
Structural characterization of antiidiotypic antibodies. Evidence that Ab2s are derived from the germline differently than Ab1s.
Authors: K Meek, C Hasemann, B Pollok, S S Alkan, M Brait, M Slaoui, J Urbain, J D Capra
Journal: The Journal of Experimental Medicine (1989)

We have found that syngeneic Ab2s in the antiarsonate system are serologically and structurally similar to one another. In contrast, the allogeneic Ab2 response is heterogeneous and derives from a large number of unrelated germline gene segments. The Ab2 response of the BALB/c strain to polyclonal A/J Ars A molecules can probably best be compared with a response to a foreign protein and might have been predicted in a strain that completely lacks the H chain V region gene from which the Ab1 derives. Partial variable region sequences of Ab2s from three other systems in addition to previously reported Ab2 structures indicates that this difference in allogeneic vs. syngeneic Ab2s may be a general phenomena. These data support Jerne's hypothesis of complementary V region genes existing in the germline. However, there is good evidence that these antiidiotypic antibodies are not derived directly from the germline, as somatic processes most likely play an important role in their generation. The D segments of Ab2s in the arsonate system as well as in other systems, are novel in structure and cannot easily be explained by previously described germline D segments. D-D fusion may play a role in the generation of the third hypervariable region in these antibodies.
The calcium-binding protein calretinin is a marker of the companion cell layer of the human hair follicle
Authors: E. Poblet, F. Jimenez, C. de Cabo, A. Prieto-Martin, R. Sanchez-Prieto
Journal: British Journal of Dermatology (2005)

Journal Article The calcium‐binding protein calretinin is a marker of the companion cell layer of the human hair follicle Get access E. Poblet, E. Poblet Department of Pathology, Hospital General Universitario de Albacete and Universidad de Castilla La Mancha, Spain *Dermatology, private practice, Las Palmas de Gran Canaria, Spain †Experimental Research Unit (Neuroscience), Hospital General Universitario de Albacete, Spain ‡Laboratorio de Oncologia Molecular, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla La Mancha, Spain Search for other works by this author on: Oxford Academic Google Scholar F. Jimenez, F. Jimenez Department of Pathology, Hospital General Universitario de Albacete and Universidad de Castilla La Mancha, Spain *Dermatology, private practice, Las Palmas de Gran Canaria, Spain †Experimental Research Unit (Neuroscience), Hospital General Universitario de Albacete, Spain ‡Laboratorio de Oncologia Molecular, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla La Mancha, Spain Francisco Jimenez. E‐mail: fjimenez@clinicadelpelo.com Search for other works by this author on: Oxford Academic Google Scholar C. De Cabo, C. De Cabo Department of Pathology, Hospital General Universitario de Albacete and Universidad de Castilla La Mancha, Spain *Dermatology, private practice, Las Palmas de Gran Canaria, Spain †Experimental Research Unit (Neuroscience), Hospital General Universitario de Albacete, Spain ‡Laboratorio de Oncologia Molecular, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla La Mancha, Spain Search for other works by this author on: Oxford Academic Google Scholar A. Prieto‐Martin, A. Prieto‐Martin Department of Pathology, Hospital General Universitario de Albacete and Universidad de Castilla La Mancha, Spain *Dermatology, private practice, Las Palmas de Gran Canaria, Spain †Experimental Research Unit (Neuroscience), Hospital General Universitario de Albacete, Spain ‡Laboratorio de Oncologia Molecular, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla La Mancha, Spain Search for other works by this author on: Oxford Academic Google Scholar R. Sánchez‐Prieto R. Sánchez‐Prieto Department of Pathology, Hospital General Universitario de Albacete and Universidad de Castilla La Mancha, Spain *Dermatology, private practice, Las Palmas de Gran Canaria, Spain †Experimental Research Unit (Neuroscience), Hospital General Universitario de Albacete, Spain ‡Laboratorio de Oncologia Molecular, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla La Mancha, Spain Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 6, 1 June 2005, Pages 1316–1320, https://doi.org/10.1111/j.1365-2133.2005.06603.x Published: 01 June 2005 Article history Accepted: 01 January 2005 Published: 01 June 2005
U.S. drinking water challenges in the twenty-first century.
Authors: Ronnie B Levin, Paul R Epstein, Tim E Ford, Winston Harrington, Erik Olson, Eric G Reichard
Journal: Environmental Health Perspectives (2002)

The access of almost all 270 million U.S. residents to reliable, safe drinking water distinguishes the United States in the twentieth century from that of the nineteenth century. The United States is a relatively water-abundant country with moderate population growth; nonetheless, current trends are sufficient to strain water resources over time, especially on a regional basis. We have examined the areas of public water infrastructure, global climate effects, waterborne disease (including emerging and resurging pathogens), land use, groundwater, surface water, and the U.S. regulatory history and its horizon. These issues are integrally interrelated and cross all levels of public and private jurisdictions. We conclude that U.S. public drinking water supplies will face challenges in these areas in the next century and that solutions to at least some of them will require institutional changes.
The feasibility of a home-based moderate-intensity physical activity intervention in obese children and adolescents
Authors: Louise S Conwell, Stewart G Trost, Luke Spence, Wendy J Brown, Jennifer A Batch
Journal: British Journal of Sports Medicine (2008)

To explore the feasibility of conducting a 10-week home-based physical activity (PA) programme and evaluate the changes in insulin sensitivity (S(I)) commensurate with the programme in obese young people.Open-labelled intervention.Home-based intervention with clinical assessments at a tertiary paediatric hospital.18 obese (body mass index (BMI)>International Obesity Task Force age and sex-specific cut-offs) children and adolescents (8-18 years, 11 girls/7 boys) were recruited. 15 participants (nine girls/six boys, mean+/-SE age 11.8+/-0.6 years, BMI-SD scores (BMI-SDS) 3.5+/-0.1, six prepubertal/nine pubertal) completed the intervention.The programme comprised biweekly home visits over 10 weeks with personalised plans implemented aiming to increase moderate-intensity PA. Pedometers and PA diaries were used as self-monitoring tools. The goals were to (1) teach participants behavioural skills related to adopting and maintaining an active lifestyle and (2) increase daily participation in PA.Mean steps/day were assessed. S(I) assessed by the frequently sampled intravenous glucose tolerance test and other components of the insulin resistance syndrome were measured.Mean steps/day increased significantly from 10 363+/-927 (baseline) to 13 013+/-1131 (week 10) (p<0.05). S(I) was also significantly increased, despite no change in BMI-SDS, and remained so after an additional 10-week follow-up.The results suggest that such a home-based PA programme is feasible. S(I) improved without changes in BMI-SDS. More rigorous evaluations of such programmes are warranted.
Phase II Trial of Erlotinib Plus Concurrent Whole-Brain Radiation Therapy for Patients With Brain Metastases From Non–Small-Cell Lung Cancer
Authors: James W. Welsh, Ritsuko Komaki, Arya Amini, Mark F. Munsell, Wyatt Unger, Pamela K. Allen, Joe Y. Chang, Jeffrey S. Wefel, Susan L. McGovern, Linda L. Garland, Su S. Chen, Jamie Holt, Zhongxing Liao, Paul Brown, Erik Sulman, John V. Heymach, Edward S. Kim, Baldassarre Stea
Journal: Journal of Clinical Oncology (2013)

Brain metastasis (BM) is a leading cause of death from non-small-cell lung cancer (NSCLC). Reasoning that activation of the epidermal growth factor receptor (EGFR) contributes to radiation resistance, we undertook a phase II trial of the EGFR inhibitor erlotinib with whole-brain radiation therapy (WBRT) in an attempt to extend survival time for patients with BM from NSCLC. Additional end points were radiologic response and safety.Eligible patients had BM from NSCLC, regardless of EGFR status. Erlotinib was given at 150 mg orally once per day for 1 week, then concurrently with WBRT (2.5 Gy per day 5 days per week, to 35 Gy), followed by maintenance. EGFR mutation status was tested by DNA sequencing at an accredited core facility.Forty patients were enrolled and completed erlotinib plus WBRT (median age, 59 years; median diagnosis-specific graded prognostic assessment score, 1.5). The overall response rate was 86% (n = 36). No increase in neurotoxicity was detected, and no patient experienced grade ≥ 4 toxicity, but three patients required dose reduction for grade 3 rash. At a median follow-up of 28.5 months (for living patients), median survival time was 11.8 months (95% CI, 7.4 to 19.1 months). Of 17 patients with known EGFR status, median survival time was 9.3 months for those with wild-type EGFR and 19.1 months for those with EGFR mutations.Erlotinib was well tolerated in combination with WBRT, with a favorable objective response rate. The higher-than-expected rate of EGFR mutations in these unselected patients raises the possibility that EGFR-mutated tumors are prone to brain dissemination.
THE HONORARY STAFF OF THE MOUNT VERNON HOSPITAL AND THE COMMITTEE OF MANAGEMENT.
Authors: Hermann Weber, Clifford. Allbutt, Watson. Cheyne, F.W. Tunnicliffe, Arthur Latham, F.W.F.W. Pricetunnicliffe, A.J. Whiting, James Berry, H.J. Scharlieb, C. Harrison Orton, Arnold Gabriel, E.D.D. Davis, J.W. Linnell
Journal: The Lancet (1913)
Eosinophil cationic granule proteins impair thrombomodulin function. A potential mechanism for thromboembolism in hypereosinophilic heart disease.
Authors: A Slungaard, G M Vercellotti, T Tran, G J Gleich, N S Key
Journal: Journal of Clinical Investigation (1993)

Thromboembolism is a prominent but poorly understood feature of eosinophilic, or Loeffler's endocarditis. Eosinophil (EO) specific granule proteins, in particular major basic protein (MBP), accumulate on endocardial surfaces in the course of this disease. We hypothesized that these unusually cationic proteins promote thrombosis by binding to the anionic endothelial protein thrombomodulin (TM) and impairing its anticoagulant activities. We find that MBP potently (IC50 of 1-2 microM) inhibits the capacity of endothelial cell surface TM to generate the natural anticoagulant activated protein C (APC). MBP also inhibits APC generation by purified soluble rabbit TM with an IC50 of 100 nM without altering its apparent Kd for thrombin or Km for protein C. This inhibition is reversed by polyanions such as chondroitin sulfate E and heparin. A TM polypeptide fragment comprising the extracellular domain that includes its naturally occurring anionic glycosaminoglycan (GAG) moiety (TMD-105) is strongly inhibited by MBP, whereas its counterpart lacking the GAG moiety (TMD-75) is not. MBP also curtails the capacity of TMD-105 but not TMD-75 to prolong the thrombin clotting time. Thus, EO cationic proteins potently inhibit anticoagulant activities of the glycosylated form of TM, thereby suggesting a potential mechanism for thromboembolism in hypereosinophilic heart disease.
Drug Treatment of Hyperlipidemia in Women
Authors: Judith M. E. Walsh
Journal: JAMA (2004)

Several clinical trials have evaluated the effects of lipid-lowering medications on coronary heart disease (CHD). Many of the trials have not included enough women to allow sex-specific analyses or have not reported results in women separately.To assess and synthesize the evidence regarding drug treatment of hyperlipidemia for the prevention of CHD events in women and to conduct a meta-analysis of the effect of drug treatment on mortality.We searched MEDLINE, the Cochrane Database, and the Database of Abstracts of Reviews of Effectiveness for articles published from 1966 through December 2003. We reviewed reference lists of articles and consulted content experts.Studies of outpatients that had a treatment duration of at least 1 year, assessed the impact of lipid lowering on clinical outcomes, and reported results by sex were included. Outcomes evaluated were total mortality, CHD mortality, nonfatal myocardial infarction, revascularization, and total CHD events. Summary estimates of the relative risks (RRs) with therapy were calculated using a random-effects model for patients with and without a previous history of cardiovascular disease.Thirteen studies were included. Six trials included a total of 11 435 women without cardiovascular disease and assessed the effects of lipid-lowering medications. Lipid lowering did not reduce total mortality (RR, 0.95; 95% confidence interval [CI], 0.62-1.46), CHD mortality (RR, 1.07; 95% CI, 0.47-2.40), nonfatal myocardial infarction (RR, 0.61; 95% CI, 0.22-1.68), revascularization (RR, 0.87; 95% CI, 0.33-2.31), or CHD events (RR, 0.87; 95% CI, 0.69-1.09). However, some analyses were limited by too few CHD events in the available trials. Eight trials included 8272 women with cardiovascular disease and assessed the effects of lipid-lowering medications. Lipid lowering did not reduce total mortality in women with cardiovascular disease (RR, 1.00; 95% CI, 0.77-1.29). However, lipid lowering reduced CHD mortality (RR, 0.74; 95% CI, 0.55-1.00), nonfatal myocardial infarction (RR, 0.71; 95% CI, 0.58-0.87), revascularization (RR, 0.70; 95% CI, 0.55-0.89), and total CHD events (RR, 0.80; CI, 0.71-0.91).For women without cardiovascular disease, lipid lowering does not affect total or CHD mortality. Lipid lowering may reduce CHD events, but current evidence is insufficient to determine this conclusively. For women with known cardiovascular disease, treatment of hyperlipidemia is effective in reducing CHD events, CHD mortality, nonfatal myocardial infarction, and revascularization, but it does not affect total mortality.
AN ULTRASTRUCTURAL STUDY OF LYMPHOCYTES WITH SURFACE-BOUND IMMUNOGLOBULIN
Authors: William D. Perkins, Morris J. Karnovsky, Emil R. Unanue
Journal: The Journal of Experimental Medicine (1972)

This report is on a radioautographic study of lymphocytes exposed to (125)I-labeled anti-Ig in an attempt to identify surface-bound Ig molecules. The results as studied by ultrastructural radioautography confirmed the presence of surface-bound Ig on a certain population of lymphocytes. The specificity of the anti-Ig was determined by using appropriate controls that included the use of an absorbed anti-Ig and anti-hemocyanin antibody. The labeling pattern resulting from the interaction of labeled anti-Ig and Ig was found to be specifically associated with the cell surface and random in its distribution. Morphological differences were not apparent between labeled and nonlabeled lymphocytes in the spleen and lymph nodes. In the thymus, most lymphocytes did not exhibit detectable Ig. The few thymic lymphocytes that were labeled had unique morphological characteristics that included fewer ribosomes, many of which were monoribosomes. Relative to the amount in their cytoplasmic organelles, plasma cells had surface Ig but to a lesser degree than lymphocytes. Finally, macrophages were nonspecifically labeled and contained antibody on their membranes as well as intracellularly.
Solutions for swimmer's shoulder, baseballer's elbow and runner's upper respiratory tract infection
Authors: Karim M Khan
Journal: British Journal of Sports Medicine (2010)

Warm upstrikes at a critical time.And infections are most common immediately before or after high-level competition.Diffl am throat spray was tested as a way to prevent upper respiratory symptoms in association with a half-marathon race 3 (see page 127). Economics in sports and exercise medicine -here to stay!A Canadian systematic review (on which I am an author) has already been tabled in the New Zealand parliament as sensible folks tried to help Prime Minister John Key make a quality decision.The issue was to keep funding exercise classes, which save the nation money by reducing fall-related injuries in seniors 4 (see page 80).The days of anyone arguing that that health economics is not sports medicine are patently over.Ask the Australasian College of Sports Physicians as they negotiate with the Rudd government to fund their specialty -a specialty that has the potential to limit the economic burden of physical inactivity.Physical inactivity costs the US over $1 trillion annually; clearly exercise is medicine -and good value at that. Conference preview -book now for AMSSM in Cancun!Sign up to be a part of AMSSM's excellent conference in Cancun, in Mexico's Mayan Riviera.Your family will love you for that!At this friendly and value-packed conference you will hear the latest from Tim Hewett 5 , Bert Mandelbaum, Kevin Guskiewicz (concussion) and many more; even more importantly, the AMSSM conference is renowned for letting you get up close and personal to ask your specifi c questions -one-on-one time with these folks and others.And that's really something you can't get any other way.
Activation of Mitogen-Activated Protein Kinase in Porcine Carotid Arteries
Authors: Leonard P. Adam, Michael T. Franklin, Gregory J. Raff, David R. Hathaway
Journal: Circulation Research (1995)

The thin-filament protein h-caldesmon (the high molecular weight isoform of caldesmon) is phosphorylated in resting and contracted porcine carotid arteries. Phosphorylation of h-caldesmon in intact tissue occurs at sites that are covalently modified by mitogen-activated protein kinase (MAPK) in vitro. In this study, we have evaluated MAPK activation in arteries in response to mechanical load and pharmacological stimulation. MAPK was extracted from resting and stimulated porcine carotid arteries and then partially purified by anion-exchange fast-performance liquid chromatography. MAPK activity was separated into two peaks corresponding to the tyrosine-phosphorylated 42- and 44-kD isoforms of MAPK (p42MAPK and p44MAPK, respectively). Of the total MAPK activity, 42% was associated with p42MAPK, and 58% was associated with p44MAPK, this percentage was not altered by stimulation of the muscles with either KCl (110 mmol/L) or phorbol 12,13-dibutyrate (PDBu, 1 mumol/L). Both p42MAPK and p44MAPK, purified from porcine carotid arteries, phosphorylated h-caldesmon at the same sites and to levels approaching or > 1 mol phosphate per mole protein. In unloaded muscle strips, MAPK activity was 39 pmol.min-1.mg protein-1 when assayed with the peptide substrate APRTPG-GRR. MAPK activity increased in response to incremental mechanical loading to a maximum of 99 pmol.min-1.mg protein-1 at 16 x 10(3) N/m2. MAPK activity could be further increased in loaded muscles by pharmacological stimulation. With KCl stimulation, MAPK activities rose to a peak of 205 pmol.min-1.mg protein-1 at 10 minutes and then declined to basal values at 30 and 60 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)
New advances in the use of noninvasive ventilation for acute hypoxaemic respiratory failure
Authors: M. Antonelli, M.A. Pennisi, G. Conti
Journal: European Respiratory Journal (2003)

Noninvasive ventilation (NIV) includes various techniques for augmenting alveolar ventilation without an endotracheal airway. The theoretical advantages of this approach include avoiding the complications associated with endotracheal intubation, improving patient comfort, preserving airway defence mechanisms, speech and swallowing. The successful application of NIV in hypoxaemic acute respiratory failure (ARF) of varied etiologies has been extensively described but success rate is strictly dependent on ARF etiology and until today the application of NIV strategies in the setting of hypoxaemic ARF is controversial. Larger, controlled studies are required to clarify the role of NIV in the setting of hypoxaemic ARF. The correct choice of the patient ventilator interface is a crucial issue in noninvasive ventilation. The study of new interfaces could improve tolerability reducing the noninvasive ventilation failure rate.
Metabolic Syndrome, Obesity, and Mortality
Authors: Peter T. Katzmarzyk, Timothy S. Church, Ian Janssen, Robert Ross, Steven N. Blair
Journal: Diabetes Care (2005)

OBJECTIVE—To determine in normal weight, overweight, and obese men the risk of all-cause and cardiovascular disease (CVD) mortality associated with the metabolic syndrome (MetS) and the influence of cardiorespiratory fitness (CRF). RESEARCH DESIGN AND METHODS—This observational cohort study included 19,173 men who underwent a clinical examination, including a maximal exercise test. MetS was defined according to National Cholesterol Education Program guidelines. RESULTS—At baseline 19.5% of the men had MetS. The ORs of the metabolic syndrome at baseline were 4.7 (95% CI 4.2–5.3) in overweight and 30.6 (26.7–35.0) in obese men compared with normal weight men. A total of 477 deaths (160 CVD) occurred in 10.2 years of follow-up. The risks of all-cause mortality were 1.11 (0.75–1.17) in normal weight, 1.09 (0.82–1.47) in overweight, and 1.55 (1.14–2.11) in obese men with MetS compared with normal weight healthy men. The corresponding risks for CVD mortality were 2.06 (0.92–4.63) in normal weight, 1.80 (1.10–2.97) in overweight, and 2.83 (1.70–4.72) in obese men with the MetS compared with normal weight healthy men. After the inclusion of CRF in the model, the risks associated with obesity and MetS were no longer significant. CONCLUSIONS—Obesity and MetS are associated with an increased risk of all-cause and CVD mortality; however; these risks were largely explained by CRF.