tbuckley/cabot-search huggingface dataset:
Vascular exchange in the kidney. Regional characterization by multiple indicator tomography.
Authors: C J Lumsden, M Silverman, A Zielinski, D G Potts, I Shafik, A S Brody, C I Whiteside, M Violante
Journal: Circulation Research (1993)

In previous work with the method of multiple indicator dilution (MID), we have established that a spatially distributed model of transcapillary exchange proposed by Goresky, Ziegler, and Bach (GZB) accurately describes, at the in vivo whole-organ level, the handling of extracellular indicators in the canine renal cortex. To date, however, it has not been possible to assess the key hypothesis that GZB corresponds to the actual local mechanism of exchange in vivo and is not just a compact summary of the kidney's average whole-organ behavior. By adapting the MID method to high speed computed tomography (CT), we are now able to report that the GZB mechanism is an accurate description of renal cortical transcapillary exchange down to volumes of cortical tissue comprising no more than a few per cent of the total cortical mass, i.e., containing no more than a few thousand nephrons. A small bolus of iohexol (radiopaque extracellular indicator) or iodipamide ethyl ester microparticles (radiopaque plasma indicator) injected into the renal artery was followed by CT as it passed through the kidney and into the renal vein. Time-attenuation value curves of the two contrast media obtained from the renal vein and from regions of interest in the cortex were then modeled with the GZB mechanism and with a more complex formulation that includes GZB as a limiting case. When applied to the data, the models converged to GZB as the best fit for each region examined. The GZB mechanism is found to provide excellent agreement with the regional data.
Copper-67 Radioimmunotherapy and Growth Inhibition by Anti–L1-Cell Adhesion Molecule Monoclonal Antibodies in a Therapy Model of Ovarian Cancer Metastasis
Authors: Karin Knogler, Jürgen Grünberg, Kurt Zimmermann, Susan Cohrs, Michael Honer, Simon Ametamey, Peter Altevogt, Mina Fogel, P. August Schubiger, Ilse Novak-Hofer
Journal: Clinical Cancer Research (2007)

Abstract Purpose: We examined the tumor-targeting and therapeutic effects of 67Cu-labeled single amino acid mutant forms of anti-L1 monoclonal antibody chCE7 in nude mice with orthotopically implanted SKOV3ip human ovarian carcinoma cells. Experimental Design: For radioimmunotherapy, chCE7 antibodies with a mutation of histidine 310 to alanine (chCE7H310A) and a mutation of asparagine 297 to glutamine (chCE7agl) were generated to achieve more rapid blood clearance. Biodistributions of 67Cu-4-(1,4,8,11-tetraazacyclotetradec-1-yl)-methyl benzoic acid tetrachloride (CPTA)–labeled mutant antibodies were measured in nude mice bearing SKOV3ip human ovarian cancer metastases. The effects of single i.v. injections of 67Cu-chCE7agl alone on tumor reduction and survival were investigated. In addition, a combination of low-dose 67Cu-radioimmunotherapy with unlabeled anti-L1 antibody L1-11A on survival was investigated. Results: 67Cu-CPTA-chCE7agl showed high (up to 49% ID/g) and persistent (up to 168 h) uptake in SKOV3ip metastases, with low levels in normal tissues. 67Cu-CPTA-chCE7H310A revealed a shorter half-life in the blood and a lower tumor uptake and retention. A single low dose of 4 MBq of 67Cu-chCE7agl reduced tumor growth but did not prolong survival significantly, whereas a single 10.5 MBq dose of 67Cu-chCE7agl reduced tumor growth and prolonged survival significantly. The combination of unlabeled monoclonal antibody L1-11A with a subtherapeutic dose of 67Cu-radioimmunotherapy also prolonged survival significantly. Conclusion: The results show improved pharmacokinetics and biodistributions as well as the therapeutic effect of the 67Cu-labeled single amino acid mutant chCE7agl. Therapeutic data indicate, for the first time, the feasibility of combining anti–L1-directed growth inhibition and 67Cu-radioimmunotherapy, thereby increasing the efficiency of antibody treatment of metastatic ovarian carcinoma.
Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis
Authors: Anil K. Sood, Guillermo N. Armaiz-Pena, Jyotsnabaran Halder, Alpa M. Nick, Rebecca L. Stone, Wei Hu, Amy R. Carroll, Whitney A. Spannuth, Michael T. Deavers, Julie K. Allen, Liz Y. Han, Aparna A. Kamat, Mian M.K. Shahzad, Bradley W. McIntyre, Claudia M. Diaz-Montero, Nicholas B. Jennings, Yvonne G. Lin, William M. Merritt, Koen DeGeest, Pablo E. Vivas-Mejia, Gabriel Lopez-Berestein, Michael D. Schaller, Steven W. Cole, Susan K. Lutgendorf
Journal: Journal of Clinical Investigation (2010)

Chronic stress is associated with hormonal changes that are known to affect multiple systems, including the immune and endocrine systems, but the effects of stress on cancer growth and progression are not fully understood. Here, we demonstrate that human ovarian cancer cells exposed to either norepinephrine or epinephrine exhibit lower levels of anoikis, the process by which cells enter apoptosis when separated from ECM and neighboring cells. In an orthotopic mouse model of human ovarian cancer, restraint stress and the associated increases in norepinephrine and epinephrine protected the tumor cells from anoikis and promoted their growth by activating focal adhesion kinase (FAK). These effects involved phosphorylation of FAKY397, which was itself associated with actin-dependent Src interaction with membrane-associated FAK. Importantly, in human ovarian cancer patients, behavioral states related to greater adrenergic activity were associated with higher levels of pFAKY397, which was in turn linked to substantially accelerated mortality. These data suggest that FAK modulation by stress hormones, especially norepinephrine and epinephrine, can contribute to tumor progression in patients with ovarian cancer and may point to potential new therapeutic targets for cancer management.
Poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) nanoparticles for local delivery of paclitaxel for restenosis treatment
Authors: Ulrich Westedt, Marc Kalinowski, Matthias Wittmar, Thomas Merdan, Florian Unger, Jutta Fuchs, Susann Schäller, Udo Bakowsky, Thomas Kissel
Journal: Journal of Controlled Release (2007)
Counting, analysing and reporting exacerbations of COPD in randomised controlled trials
Authors: S D Aaron, D Fergusson, G B Marks, S Suissa, K L Vandemheen, S Doucette, F Maltais, J F Bourbeau, R S Goldstein, M Balter, D O'Donnell, M FitzGerald
Journal: Thorax (2007)

Clinical trials measure exacerbations of chronic obstructive pulmonary disease (COPD) inconsistently. A study was undertaken to determine if different methods for ascertaining and analysing COPD exacerbations lead to biased estimates of treatment effects.Information on the methods used to count, analyse and report COPD exacerbation rates was abstracted from clinical trials of long-acting bronchodilators or long-acting bronchodilator/inhaled steroid combination products published between 2000 and 2006. Data from the Canadian Optimal Therapy of COPD Trial was used to illustrate how different analytical approaches can affect the estimate of exacerbation rates and their confidence intervals.22 trials (17,156 patients) met the inclusion criteria and were reviewed. None of the trials adjudicated exacerbations or determined independence of events. 14/22 studies (64%) introduced selection bias by not analysing outcome data for subjects who prematurely stopped study medications. Only 31% of trials used time-weighted analyses to calculate the mean number of exacerbations/patient-year and only 15% accounted for between-subject variation. In the Canadian Optimal Therapy of COPD Trial the rate ratio for exacerbations/patient-year was 0.85 when all data were included in a time-weighted analysis, but was overestimated as 0.79 when data for those who prematurely stopped study medications were excluded and was further overestimated as 0.46 when a time-weighted analysis was not conducted; p values ranged from 0.03 to 0.24 depending on how exacerbations were determined and analysed.Clinical trials have used widely different methods to define and analyse COPD exacerbations and this can lead to biased estimates of treatment effects. Future trials should strive to include blinded adjudication and assessment of the independence of exacerbation events, and trials should report time-weighted intention-to-treat analyses with adjustments for between-subject variation in COPD exacerbations.
Progressive impairment of regional myocardial perfusion after initial restoration of postischemic blood flow.
Authors: G Ambrosio, H F Weisman, J A Mannisi, L C Becker
Journal: Circulation (1989)

The "no-reflow" phenomenon, the occurrence of areas with very low flow in hearts reperfused after ischemia, is thought to be largely established at the time of reperfusion as a result of microvascular damage induced by ischemia. In the present study we sought to determine whether additional impairment of tissue perfusion might also occur during the course of reperfusion. Open-chest dogs were subjected to 90 minutes of left circumflex coronary artery occlusion and reperfused for 2 minutes (n = 7) or 3.5 hours (n = 8). Myocardial perfusion was visualized in left ventricular slices following in vivo injection of the fluorescent dye thioflavin-S just before killing. The area of impaired perfusion (absent thioflavin) averaged 9.5 +/- 3.0% of the risk region in dogs reperfused for 2 minutes, whereas it was nearly three times as large in dogs reperfused for 3.5 hours (25.9 +/- 8.2% of the risk region, p less than 0.05). Serial measurements of flow by microspheres during reperfusion demonstrated zones within the postischemic myocardium that were hyperemic 2 minutes after reperfusion, with adequate flow still present at 30 minutes, but with a subsequent marked fall in perfusion. After 3.5 hours these areas showed negligible flow (0.13 +/- 0.3 ml/min/g) and no thioflavin uptake. Tissue samples showing postischemic impairment in perfusion has received virtually no collateral flow during ischemia (less than 0.01 ml/min/g), whereas collateral flow was significantly higher in adjacent thioflavin-positive zones (0.04 +/- 0.01 ml/min/g in endocardial samples and 0.07 +/- 0.02 ml/min/g in samples from the midmyocardium, p less than 0.001 vs. thioflavin-negative areas). Areas that showed late impairment of flow invariably demonstrated contraction band necrosis, which contrasted with the pattern of coagulation necrosis observed in areas of "true" (i.e., immediate) no-reflow. Intracapillary erythrocyte stasis and marked intravascular neutrophil accumulation (to levels greater than 20-fold that found after 2 minutes reperfusion) were typically observed in areas of delayed impairment to flow. Obstruction to flow at the capillary level was confirmed in additional dogs in which the heart was injected postmortem with silicone rubber to delineate the microvascular filling pattern. Areas of absent capillary filling were much more extensive after 3.5 hours than after 2 minutes reperfusion. Thus, this study shows that the occurrence of areas of markedly impaired perfusion in postischemic myocardium is related only in part to an inability to reperfuse certain areas on reflow. A more important factor is represented by a delayed, progressive fall in flow to areas that initially received adequate reperfusion.(ABSTRACT TRUNCATED AT 400 WORDS)
Molecular evolution of a novel hyperactive Sleeping Beauty transposase enables robust stable gene transfer in vertebrates
Authors: Lajos Mátés, Marinee K L Chuah, Eyayu Belay, Boris Jerchow, Namitha Manoj, Abel Acosta-Sanchez, Dawid P Grzela, Andrea Schmitt, Katja Becker, Janka Matrai, Ling Ma, Ermira Samara-Kuko, Conny Gysemans, Diana Pryputniewicz, Csaba Miskey, Bradley Fletcher, Thierry VandenDriessche, Zoltán Ivics, Zsuzsanna Izsvák
Journal: Nature Genetics (2009)
Principles and Practice of Psychopharmacotherapy, Fifth Editionby JanicakPhilip G., M.D., MarderStephen R., M.D., and PavuluriMani N., M.D., Ph.D. Philadelphia, Lippincott Williams and Wilkins, 2010, 704 pp., $165.00.
Authors: Megan Schabbing
Journal: American Journal of Psychiatry (2011)
Patient Selection in Heart Failure With Preserved Ejection Fraction Clinical Trials
Authors: Jacob P. Kelly, Robert J. Mentz, Alexandre Mebazaa, Adriaan A. Voors, Javed Butler, Lothar Roessig, Mona Fiuzat, Faiez Zannad, Bertram Pitt, Christopher M. O’Connor, Carolyn S.P. Lam
Journal: Journal of the American College of Cardiology (2015)
Preoperative prediction of type 2 diabetes remission after Roux-en-Y gastric bypass surgery: a retrospective cohort study
Authors: Christopher D Still, G Craig Wood, Peter Benotti, Anthony T Petrick, Jon Gabrielsen, William E Strodel, Anna Ibele, Jamie Seiler, Brian A Irving, Melisa P Celaya, Robin Blackstone, Glenn S Gerhard, George Argyropoulos
Journal: The Lancet Diabetes & Endocrinology (2013)
Effects of Screening and Systemic Adjuvant Therapy on ER-Specific US Breast Cancer Mortality
Authors: Diego Munoz, Aimee M. Near, Nicolien T. van Ravesteyn, Sandra J. Lee, Clyde B. Schechter, Oguzhan Alagoz, Donald A. Berry, Elizabeth S. Burnside, Yaojen Chang, Gary Chisholm, Harry J. de Koning, Mehmet Ali Ergun, Eveline A. M. Heijnsdijk, Hui Huang, Natasha K. Stout, Brian L. Sprague, Amy Trentham-Dietz, Jeanne S. Mandelblatt, Sylvia K. Plevritis
Journal: JNCI Journal of the National Cancer Institute (2014)

Molecular characterization of breast cancer allows subtype-directed interventions. Estrogen receptor (ER) is the longest-established molecular marker.We used six established population models with ER-specific input parameters on age-specific incidence, disease natural history, mammography characteristics, and treatment effects to quantify the impact of screening and adjuvant therapy on age-adjusted US breast cancer mortality by ER status from 1975 to 2000. Outcomes included stage-shifts and absolute and relative reductions in mortality; sensitivity analyses evaluated the impact of varying screening frequency or accuracy.In the year 2000, actual screening and adjuvant treatment reduced breast cancer mortality by a median of 17 per 100000 women (model range = 13-21) and 5 per 100000 women (model range = 3-6) for ER-positive and ER-negative cases, respectively, relative to no screening and no adjuvant treatment. For ER-positive cases, adjuvant treatment made a higher relative contribution to breast cancer mortality reduction than screening, whereas for ER-negative cases the relative contributions were similar for screening and adjuvant treatment. ER-negative cases were less likely to be screen-detected than ER-positive cases (35.1% vs 51.2%), but when screen-detected yielded a greater survival gain (five-year breast cancer survival = 35.6% vs 30.7%). Screening biennially would have captured a lower proportion of mortality reduction than annual screening for ER-negative vs ER-positive cases (model range = 80.2%-87.8% vs 85.7%-96.5%).As advances in risk assessment facilitate identification of women with increased risk of ER-negative breast cancer, additional mortality reductions could be realized through more frequent targeted screening, provided these benefits are balanced against screening harms.
Trimethoprim-Sulfamethoxazole in Listeria monocytogenes Meningitis
Authors: Germaine Jacquette, Penelope H. Dennehy
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 June 1985Trimethoprim-Sulfamethoxazole in Listeria monocytogenes MeningitisGERMAINE JACQUETTE, M.D., PENELOPE H. DENNEHY, M.D.GERMAINE JACQUETTE, M.D.Search for more papers by this author, PENELOPE H. DENNEHY, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-6-866_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In their review of the use of trimethoprim-sulfamethoxazole in the treatment of bacterial meningitis, Levitz and Quintiliani (1) conclude that it may play a major role in treatment of resistant gram-negative and Staphylococcus aureus meningitides. They also cite two reports of successful use of the drug in Listeria monocytogenes meningitis. We report our experience and note additional cases in the literature indicating that trimethoprim-sulfamethoxazole should be considered in the treatment of Listeria meningitis in appropriate situations.A 73-year-old man with a history of resected renal cell Carcinoma, prostatectomy, recurrent urinary tract infections, and mild renal insufficiency was...References1. LEVITZQUINTILIANI RR. Trimethoprim-sulfamethoxazole for bacterial meningitis. Ann Intern Med. 1984;100:881-90. LinkGoogle Scholar2. IWARSONLIDIN-JAMSONSVENSSON SGR. Listeria meningitis in the non-compromised host. Infection. 1977;5:204-6. CrossrefMedlineGoogle Scholar3. SCHEERHIRSCHMAN MS. Oral and ambulatory therapy of Listeria bacteremia and meningitis with trimethoprim-sulfamethoxazole. Mt Sinai Med J. 1982;49:411-4. MedlineGoogle Scholar4. LARSSONCRONBERGWINBLAD SSS. Clinical aspects of 64 cases of juvenile and adult listeriosis in Sweden. Acta Med Scand. 1978;204:503-8. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByListeria Rhomboencephalitis in an Immunocompetent HostListeria monocytogenes encephalitis mimicking west nile encephalitisAcute Bacterial Meningitis in Adults: A 12-Year ReviewCentral Nervous System Infection with Listeria monocytogenes : 33 Yearsʼ Experience at a General Hospital and Review of 776 Episodes from the LiteratureMeningites bacteriennes non tuberculeuses du sujet age de plus de 60 ansCentral Nervous System Infections in the Compromised HostTraitement des méningo-encéphalites à Listeria monocytogenes de l'adulte par le cotrimoxazole en monothérapie 1 June 1985Volume 102, Issue 6Page: 866-867KeywordsBacterial meningitisDrugsMeningitisProstatectomyRenal cell carcinomaStaphylococcus aureus Issue Published: 1 June 1985 PDF DownloadLoading ...
Effect of hemithorax irradiation alone or combined with doxorubicin and cyclophosphamide in 47 pleural mesotheliomas: a nonrandomized phase II study
Authors: CJ Linden, C Mercke, U Albrechtsson, L Johansson, SB Ewers
Journal: European Respiratory Journal (1996)

In order to assess the value of radiotherapy in the treatment of pleural mesotheliomas, we studied tumour response and survival after hemithorax irradiation alone (RT), or radiotherapy combined with doxorubicin and cyclophosphamide chemotherapy (RTCT). Forty seven patients with pleural mesotheliomas received irradiation of the diseased hemithorax at 8 MV (megavolt) photons to a total dose of 40 Gy, administered in 20 daily fractions of 2 Gy for 5 days a week. One month after RT, patients aged &lt; or = 70 yrs with a good performance status were offered supplementary chemotherapy (CT) with doxorubicin 30 mg.m-2 body surface on Day 1 and Day 8, combined with cyclophosphamide 600 mg.m-2 on Day 1, in cycles of 21 days. Tumour response was evaluated by computed axial tomography (CAT) before and 1 month after RT and/or CT. Only 3 of the 47 (95% confidence interval (95% CI)-0.6-13%) irradiated tumours responded with a partial response (PR). In 31 patients treated with RT alone, one PR was observed; whereas, in the combined treatment group, 2 out of 16 responded with PR to RT. CT with doxorubicin and cyclophosphamide induced only 2 out of 16 PRs (95% CI -3.4-28.4%), and the combined treatment consisting of RT followed by CT induced 2 out of 16 PRs. The median survival following the initiation of RT was 7 months in all patients (n = 47), 6 months in the RT group (n = 31), and 13 months in the combined RTCT group (n = 16). Chest pain, performance status and body weight were not favourably affected by the radiotherapy. We conclude that hemithorax irradiation of pleural mesotheliomas with a moderately high dose is not useful, since it produces no improvement in chest pain, few objective tumour responses and no prolongation of survival.
Active Immunotherapy Induces Antibody Responses That Target Tumor Angiogenesis
Authors: Jonathan Schoenfeld, Masahisa Jinushi, Yukoh Nakazaki, Daniel Wiener, Joosang Park, Robert Soiffer, Donna Neuberg, Martin Mihm, F. Stephen Hodi, Glenn Dranoff
Journal: Cancer Research (2010)

Abstract The inhibition of VEGF signaling with antibodies or small molecules achieves clinical benefits in diverse solid malignancies. Nonetheless, therapeutic effects are usually not sustained, and most patients eventually succumb to progressive disease, indicating that antiangiogenic strategies require additional optimization. Vaccination with lethally irradiated, autologous tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GM-CSF) and antibody blockade of cytotoxic T lymphocyte–associated antigen-4 (CTLA-4) trigger a tumor vasculopathy in some long-term responding subjects. These reactions are characterized by disrupted tumor blood vessels in association with lymphocyte and granulocyte infiltrates and zonal areas of ischemic tumor necrosis. However, the mechanisms underlying this immune-mediated destruction of the tumor vasculature remain to be clarified. Here, we show that GM-CSF–secreting tumor cell vaccines and CTLA-4 blockade elicit a functionally important humoral reaction against multiple angiogenic cytokines. Antibodies to angiopoietin-1 and angiopoietin-2 block Tie-2 binding, downstream signaling, endothelial cell tube formation, and macrophage chemotaxis. Antibodies to macrophage inhibitory factor (MIF) attenuate macrophage Tie-2 expression and matrix metalloproteinase-9 (MMP-9) production. Together, these results delineate an immunotherapy-induced host response that broadly targets the angiogenic network in the tumor microenvironment. Cancer Res; 70(24); 10150–60. ©2010 AACR.
T cell suppressors of antitumor immunity. The production of Ly-1-,2+ suppressors of delayed sensitivity precedes the production of suppressors of protective immunity.
Authors: A DiGiacomo, R J North
Journal: The Journal of Experimental Medicine (1986)

The results of this study show that during growth of the immunogenic Meth A fibrosarcoma, two different types of suppressor T lymphocytes are generated in sequence. One type is generated during early tumor growth, reaches peak number around day 6, and is progressively lost thereafter. It is defined by its ability, upon passive transfer, to suppress the expression of a DTH reaction to tumor antigens in tumor-immunized recipients. It bears the Ly1-,2+ membrane phenotype and is sensitive to relatively low doses of cyclophosphamide. In contrast, the second type of suppressor cell is not detected until after day 9 of tumor growth, and is defined by its ability to inhibit, upon passive transfer, the expression of adoptive immunity against an established tumor in T cell-deficient recipients. According to previous studies it bears the Ly1+,2-, L3T4a+ membrane phenotype and is less sensitive to cyclophosphamide than the T cell suppressor of DTH. It is argued that this second type of suppressor T cell seems likely to be responsible for the escape of immunogenic tumors from antitumor immunity, because it can suppress the expression of a powerful mechanism of antitumor immunity in recipient mice, and is generated progressively as the tumor-bearing host loses concomitant immunity. In contrast, although the Ly-1-,2+ T cell suppressors of DTH can efficiently suppress a DTH reaction to an implant of living tumor cells, they fail to suppress the expression of immunity to the same implant.