tbuckley/cabot-search huggingface dataset:
The Novel Combination of Chlorpromazine and Pentamidine Exerts Synergistic Antiproliferative Effects through Dual Mitotic Action
Authors: Margaret S. Lee, Lisa Johansen, Yanzhen Zhang, Amy Wilson, Mitchell Keegan, William Avery, Peter Elliott, Alexis A. Borisy, Curtis T. Keith
Journal: Cancer Research (2007)

Abstract Combination therapy has proven successful in treating a wide variety of aggressive human cancers. Historically, combination treatments have been discovered through serendipity or lengthy trials using known anticancer agents with similar indications. We have used combination high-throughput screening to discover the unexpected synergistic combination of an antiparasitic agent, pentamidine, and a phenothiazine antipsychotic, chlorpromazine. This combination, CRx-026, inhibits the growth of tumor cell lines in vivo more effectively than either pentamidine or chlorpromazine alone. Here, we report that CRx-026 exerts its antiproliferative effect through synergistic dual mitotic action. Chlorpromazine is a potent and specific inhibitor of the mitotic kinesin KSP/Eg5 and inhibits tumor cell proliferation through mitotic arrest and accumulation of monopolar spindles. Pentamidine treatment results in chromosomal segregation defects and delayed progression through mitosis, consistent with inhibition of the phosphatase of regenerating liver family of phosphatases. We also show that CRx-026 synergizes in vitro and in vivo with the microtubule-binding agents paclitaxel and vinorelbine. These data support a model where dual action of pentamidine and chlorpromazine in mitosis results in synergistic antitumor effects and show the importance of systematic screening for combinations of targeted agents. [Cancer Res 2007;67(23):11359–67]
Kinetics of the superficial perfusion and temperature in connection with photodynamic therapy of basal cell carcinomas using esterified and non-esterified 5-aminolaevulinic acid
Authors: S. Palsson, L. Gustafsson, N. Bendsoe, M. Soto Thompson, S. Andersson-Engels, K. Svanberg
Journal: British Journal of Dermatology (2003)

Summary Background Photodynamic therapy (PDT) is a local treatment modality with increasing indications for various malignant and non malignant diseases. The treatment parameters have not yet been optimized as there is a need for a better understanding of the process. The skin is an important target and serves as a good model for monitoring and evaluating the interaction of light with biological tissue. Objectives The tissue perfusion and the temperature of basal cell carcinomas were measured in connection with PDT in order to investigate the biological mechanisms involved. Methods An infrared camera was used during the treatment to measure skin temperature and a laser Doppler perfusion imaging device was used to image the superficial perfusion before and after treatment. Six hours after topical application of 5‐aminolaevulinic acid (ALA) or methyl esterified ALA (ALA–ME), 38 basal cell carcinomas were treated using light from a diode laser at 633 nm. Results In the lesions, the perfusion immediately after PDT was similar to that before PDT. One hour after the treatment the perfusion in the lesion was increased 50% compared with before PDT. However, in the skin surrounding the lesions the perfusion was doubled immediately after PDT and was still increasing 1 h after treatment. A temperature increase in the lesions of about 1–3 °C was observed for light fluence rates of 100–150 mW cm−2. In all patients treated, a diffuse temperature increase was visible outside the lesions. In some of the patients, the outlines of the blood vessels surrounding the treated lesions became visible in the thermal images. Measurements of temperature on healthy volunteers not administered photosensitizer, but illuminated with light of the same fluence rate, showed a similar increase in temperature in the illuminated spots. However, no temperature increase was observed outside the illuminated area. No statistically significant differences were found between the measurements on patients treated with ALA and ALA–ME. Conclusions The increased perfusion in the area surrounding the lesions after PDT, as seen by perfusion and temperature measurements, is the result of an inflammatory reaction to the PDT process. However, directly after PDT the perfusion in the lesions was the same as before irradiation. The combination of these observations suggests the presence of local blood stasis during and immediately after the treatment. The temperature measurements showed that the increased temperature was well below the temperature limit of hyperthermal damage. Furthermore, the measurements indicate that the increase in temperature was primarily a consequence of the heat absorbed in the tissue.
Primary chemotherapy with gemcitabine as prolonged infusion, non-pegylated liposomal doxorubicin and docetaxel in patients with early breast cancer: final results of a phase II trial
Authors: P. Schmid, J. Krocker, C. Jehn, K. Michniewicz, S. Lehenbauer-Dehm, H. Eggemann, V. Heilmann, S. Kümmel, C.O. Schulz, A. Dieing, M.B. Wischnewsky, S. Hauptmann, D. Elling, K. Possinger, B. Flath
Journal: Annals of Oncology (2005)
CD4+ Invariant T-Cell–Receptor+ Natural Killer T Cells in Bronchial Asthma
Authors: Omid Akbari, John L. Faul, Elisabeth G. Hoyte, Gerald J. Berry, Jan Wahlström, Mitchell Kronenberg, Rosemarie H. DeKruyff, Dale T. Umetsu
Journal: New England Journal of Medicine (2006)

Bronchial asthma is associated with an inflammatory process that is characterized by the presence in the airways of large numbers of CD4+ T cells producing interleukin-4 and interleukin-13. However, the CD4 antigen is expressed not only by class II major histocompatibility complex (MHC)-restricted CD4+ T cells, but also by a newly identified subgroup of T cells, CD1d-restricted natural killer T cells. These cells express a conserved (invariant) T-cell receptor and have a potent immunoregulatory function. Because mouse models of allergic asthma indicate that natural killer T cells are required for the development of allergen-induced airway hyperreactivity, we hypothesized that natural killer T cells play an important role in human asthma.We used CD1d-tetramers, antibodies specific for natural killer T cells, as well as reverse-transcriptase-polymerase-chain-reaction analysis of the invariant T-cell receptor of natural killer T cells to assess the frequency and distribution of natural killer T cells in the lungs and in the circulating blood of 14 patients with asthma.About 60 percent of the pulmonary CD4+CD3+ cells in patients with moderate-to-severe persistent asthma were not class II MHC-restricted CD4+ T cells but, rather, natural killer T cells. The natural killer T cells expressed an invariant T-cell receptor and produced type 2 helper cytokines. In contrast, the CD4+ T cells found in the lungs of patients with sarcoidosis were conventional CD4+CD3+ T cells, not natural killer T cells.Together with studies in mice indicating a requirement for natural killer T cells in the development of allergen-induced airway hyperreactivity, our results strongly suggest that CD4+ natural killer T cells play a prominent pathogenic role in human asthma.
Effect of daily corticosteroid treatment on CRP response to hip or knee replacement in patients with RA
Authors: K LAIHO
Journal: Annals of the Rheumatic Diseases (2001)

Serum C reactive protein (CRP) is an acute phase reactant which may be continuously increased in patients with persistently active rheumatoid arthritis (RA),1 or raised only temporarily to a high concentration for a few days as a normal response to uncomplicated hip or knee replacement in patients with osteoarthritis or RA.2 3 CRP usually decreases in patients with RA when inflammatory activity is treated with daily low dose corticosteroid. This prompts the question whether the CRP response to hip or knee replacement is decreased in patients with RA taking a daily low dose of oral corticosteroid compared with those not taking corticosteroid. This …
The microRNA-15 family inhibits the TGFβ-pathway in the heart
Authors: Anke J. Tijsen, Ingeborg van der Made, Maarten M. van den Hoogenhof, Wino J. Wijnen, Elza D. van Deel, Nina E. de Groot, Sergey Alekseev, Kees Fluiter, Blanche Schroen, Marie-José Goumans, Jolanda van der Velden, Dirk J. Duncker, Yigal M. Pinto, Esther E. Creemers
Journal: Cardiovascular Research (2014)

The overloaded heart remodels by cardiomyocyte hypertrophy and interstitial fibrosis, which contributes to the development of heart failure. Signalling via the TGFβ-pathway is crucial for this remodelling. Here we tested the hypothesis that microRNAs in the overloaded heart regulate this remodelling process via inhibition of the TGFβ-pathway. We show that the miRNA-15 family, which we found to be up-regulated in the overloaded heart in multiple species, inhibits the TGFβ-pathway by targeting of TGFBR1 and several other genes within this pathway directly or indirectly, including p38, SMAD3, SMAD7, and endoglin. Inhibition of miR-15b by subcutaneous injections of LNA-based antimiRs in C57BL/6 mice subjected to transverse aorta constriction aggravated fibrosis and to a lesser extent also hypertrophy. We identified the miR-15 family as a novel regulator of cardiac hypertrophy and fibrosis acting by inhibition of the TGFβ-pathway.
Every Newborn: health-systems bottlenecks and strategies to accelerate scale-up in countries
Authors: Kim E Dickson, Aline Simen-Kapeu, Mary V Kinney, Luis Huicho, Linda Vesel, Eve Lackritz, Joseph de Graft Johnson, Severin von Xylander, Nuzhat Rafique, Mariame Sylla, Charles Mwansambo, Bernadette Daelmans, Joy E Lawn
Journal: The Lancet (2014)
Rheumatoid adipose tissue is a potent source of cytokines
Authors: M Jastrzebska, E Kontny, I Janicka, W Maslinski, P Maldyk
Journal: Annals of the Rheumatic Diseases (2010)

Numerous cytokines and adipokines have a fundamental role in synovial inflammation and articular destruction characteristic of rheumatoid arthritis (RA). Cytokines are thought to originate from inflamed synovial tissue. Recently, adipose tissue has been suggested to play a role in chronic inflammatory joint diseases, but its ability to synthesise proinflammatory cytokines has not been well characterised. The aim of the present work was to investigate whether rheumatoid articular adipose tissue secretes cytokines and adipokines relevant to …
Preliminary analysis of the Very Early Diagnosis of Systemic Sclerosis (VEDOSS) EUSTAR multicentre study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis
Authors: Tünde Minier, Serena Guiducci, Silvia Bellando-Randone, Cosimo Bruni, Gemma Lepri, László Czirják, Oliver Distler, Ulrich A Walker, Jaap Fransen, Yannick Allanore, Christopher Denton, Maurizio Cutolo, Alan Tyndall, Ulf Müller-Ladner, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> The EULAR (European League Against Rheumatism) Scleroderma Trials and Research Group (EUSTAR) has identified preliminary criteria for very early diagnosis of systemic sclerosis (SSc). Our aim was to assess the prevalence of each proposed diagnostic item in a large observational patient cohort with Raynaud9s phenomenon (RP). <h3>Methods</h3> Baseline data of 469 RP patients enrolled into the Very Early Diagnosis of Systemic Sclerosis (VEDOSS) cohort are presented. <h3>Results</h3> 68% of all RP patients were antinuclear antibody (ANA) positive. ANA+ RP patients more frequently had previous or current puffy fingers (PuFi) (38.5% and 23.3%, p&lt;0.01) and an SSc pattern on nailfold capillaroscopy (NC) (53.6% and 13.4%, p&lt;0.001) than ANA− patients. Telangiectasia, current digital ulcers and digital pitting scars were also commoner in ANA+ RP patients. 38% of ANA+ patients presented with all three features, which should raise suspicion of very early SSc (ANA+RP+PuFi constitutes a 'red flag'). These patients more frequently exhibited an NC SSc pattern, sclerodactyly and telangiectases compared to ANA+ patients without PuFi. Almost 90% of patients with 'red flags' had anti-centromere or anti-topoisomerase I antibodies and/or an NC SSc pattern, and fulfilled the EUSTAR criteria for very early SSc. Previous or current PuFi were present in 23.3% of ANA− RP patients, eight of whom also had an NC SSc pattern. <h3>Conclusions</h3> In addition to well-characterised predictive factors, PuFi is an important sign raising suspicion for underlying very early SSc in patients with RP. The relevance of PuFi in ANA− RP patients should be clarified.
Recent Advances in Paediatrics Vol 5
Authors: J. Apley
Journal: BMJ (1976)

BACKGROUND: Patients with cystic fibrosis are known to have decreased mucociliary clearance. It has previously been shown that inhalation of a 7.0% solution of hypertonic saline significantly improved mucociliary clearance in a group of adult patients with cystic fibrosis. The aim of this study was to measure the response to increasing concentrations of inhaled hypertonic saline. METHODS: Ten patients (seven men) of mean (SE) age 22 (4) years and mean forced expiratory volume in one second (FEV1) 52.0 (6.7)% predicted completed the study. Mucociliary clearance was measured using a radioaerosol technique for 90 minutes after the interventions which comprised 0.9% NaCl + voluntary cough (control), 3.0% NaCl, 7.0% NaCl, and 12% NaCl. RESULTS: There was a significant increase in the amount of activity cleared from the right lung with all concentrations of hypertonic saline (HS) compared with control. The amount cleared at 90 minutes on the control day was 12.7% (95% confidence interval (CI) 9.8 to 17.2) compared with 19.7% (95% CI 13.6 to 29.5) for 3% HS, 23.8% (95% CI 15.9 to 36.7) for 7% HS and 26.0% (95% CI 19.8 to 35.9) for 12% HS. The improvement in mucociliary clearance was not solely due to coughing as the number of coughs recorded on the control day exceeded that recorded on any other day. The hypertonic saline did not induce a clinically significant change in FEV1. CONCLUSIONS: Within the range of concentrations examined in this study, the effect of hypertonic saline appears to be dose dependent. Inhalation of hypertonic saline remains a potentially useful treatment for patients with cystic fibrosis.
Association Between Thimerosal-Containing Vaccine and Autism
Authors: Anders Hviid, Michael Stellfeld, Jan Wohlfahrt, Mads Melbye
Journal: JAMA (2003)

Mercuric compounds are nephrotoxic and neurotoxic at high doses. Thimerosal, a preservative used widely in vaccine formulations, contains ethylmercury. Thus it has been suggested that childhood vaccination with thimerosal-containing vaccine could be causally related to neurodevelopmental disorders such as autism.To determine whether vaccination with a thimerosal-containing vaccine is associated with development of autism.Population-based cohort study of all children born in Denmark from January 1, 1990, until December 31, 1996 (N = 467 450) comparing children vaccinated with a thimerosal-containing vaccine with children vaccinated with a thimerosal-free formulation of the same vaccine.Rate ratio (RR) for autism and other autistic-spectrum disorders, including trend with dose of ethylmercury.During 2 986 654 person-years, we identified 440 autism cases and 787 cases of other autistic-spectrum disorders. The risk of autism and other autistic-spectrum disorders did not differ significantly between children vaccinated with thimerosal-containing vaccine and children vaccinated with thimerosal-free vaccine (RR, 0.85 [95% confidence interval [CI], 0.60-1.20] for autism; RR, 1.12 [95% CI, 0.88-1.43] for other autistic-spectrum disorders). Furthermore, we found no evidence of a dose-response association (increase in RR per 25 microg of ethylmercury, 0.98 [95% CI, 0.90-1.06] for autism and 1.03 [95% CI, 0.98-1.09] for other autistic-spectrum disorders).The results do not support a causal relationship between childhood vaccination with thimerosal-containing vaccines and development of autistic-spectrum disorders.
AKR1B10: A New Diagnostic Marker of Non–Small Cell Lung Carcinoma in Smokers
Authors: Trevor M. Penning
Journal: Clinical Cancer Research (2005)

Lung cancer is a leading cause of cancer death worldwide, and non–small cell lung carcinoma (NSCLC) accounts for 80% of the cases. Even the most innovative therapeutic regimens do not increase overall 5-year survival rates for NSCLC to >15%. Early detection methods could lead to intervention
Noninvasive detection of fetal trisomy 21: systematic review and report of quality and outcomes of diagnostic accuracy studies performed between 1997 and 2012
Authors: E. Mersy, L.J.M. Smits, L.A.A.P. van Winden, C.E.M. de Die-Smulders, A.D.C. Paulussen, M.V.E. Macville, A.B.C. Coumans, S.G.M. Frints
Journal: Human Reproduction Update (2013)

Research on noninvasive prenatal testing (NIPT) of fetal trisomy 21 is developing fast. Commercial tests have become available. To provide an up-to-date overview of NIPT of trisomy 21, an evaluation of the methodological quality and outcomes of diagnostic accuracy studies was made. We undertook a systematic review of the literature published between 1997 and 2012 after searching PubMed, using MeSH terms 'RNA', 'DNA' and 'Down Syndrome' in combination with 'cell-free fetal (cff) RNA', 'cffDNA', 'trisomy 21' and 'noninvasive prenatal diagnosis' and searching reference lists of reported literature. From 79 abstracts, 16 studies were included as they evaluated the diagnostic accuracy of a molecular technique for NIPT of trisomy 21, and the test sensitivity and specificity were reported. Meta-analysis could not be performed due to the use of six different molecular techniques and different cutoff points. Diagnostic parameters were derived or calculated, and possible bias and applicability were evaluated utilizing the revised tool for Quality Assessment of Diagnostic Accuracy (QUADAS-2). Seven of the included studies were recently published in large cohort studies that examined massively parallel sequencing (MPS), with or without pre-selection of chromosomes, and reported sensitivities between 98.58% [95% confidence interval (CI) 95.9–99.5%] and 100% (95% CI 96–100%) and specificities between 97.95% (95% CI 94.1–99.3%) and 100% (95% CI 99.1–100%). None of these seven large studies had an overall low risk of bias and low concerns regarding applicability. MPS with or without pre-selection of chromosomes exhibits an excellent negative predictive value (100%) in conditions with disease odds from 1:1500 to 1:200. However, positive predictive values were lower, even in high-risk pregnancies (19.7–100%). The other nine cohort studies were too small to give precise estimates (number of trisomy 21 cases: ≤25) and were not included in the discussion. NIPT of trisomy 21 by MPS with or without pre-selection of chromosomes is promising and likely to replace the prenatal serum screening test that is currently combined with nuchal translucency measurement in the first trimester of pregnancy. Before NIPT can be introduced as a screening test in a social insurance health-care system, more evidence is needed from large prospective diagnostic accuracy studies in first trimester pregnancies. Moreover, we believe further assessment, of whether NIPT can be provided in a cost-effective, timely and equitable manner for every pregnant woman, is required.
Exenatide Treatment for 6 Months Improves Insulin Sensitivity in Adults With Type 1 Diabetes
Authors: Gayatri Sarkar, May Alattar, Rebecca J. Brown, Michael J. Quon, David M. Harlan, Kristina I. Rother
Journal: Diabetes Care (2013)

OBJECTIVE Exenatide treatment improves glycemia in adults with type 2 diabetes and has been shown to reduce postprandial hyperglycemia in adolescents with type 1 diabetes. We studied the effects of exenatide on glucose homeostasis in adults with long-standing type 1 diabetes. RESEARCH DESIGN AND METHODS Fourteen patients with type 1 diabetes participated in a crossover study of 6 months' duration on exenatide (10 μg four times a day) and 6 months off exenatide. We assessed changes in fasting and postprandial blood glucose and changes in insulin sensitivity before and after each study period. RESULTS High-dose exenatide therapy reduced postprandial blood glucose but was associated with higher fasting glucose concentrations without net changes in hemoglobin A1c. Exenatide increased insulin sensitivity beyond the effects expected as a result of weight reduction. CONCLUSIONS Exenatide is a promising adjunctive agent to insulin therapy because of its beneficial effects on postprandial blood glucose and insulin sensitivity in patients with type 1 diabetes.
A randomized trial of four cycles of adjuvant AC (adriamycin + cyclophosphamide) ± two cycles of EP (etoposide + cisplatin) in node positive patients with breast cancer
Authors: F Içli, H Akbulut, D Dinçol, H Onur, A Demirkazik, R Cam, F Cay, S Demirci, A Uner, S Erekul
Journal: Annals of Oncology (2001)
Genomewide Screen for Pulmonary Function in 200 Families Ascertained for Asthma
Authors: Dirkje S. Postma, Deborah A. Meyers, Hajo Jongepier, Timothy D. Howard, Gerard H. Koppelman, Eugene R. Bleecker
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Changes in pulmonary function are important in determining asthma outcome. Genetic factors may influence airway obstruction in asthma. We performed a genomewide screen in 200 families of probands objectively diagnosed with asthma in the 1960s to identify chromosomal regions related to changes in pre- and postbronchodilator lung function (FEV1, VC, and FEV1%VC) and assess influences of early-life smoke exposure. Smoking (pack-years), age, sex, and height were covariates in variance component analyses. Significant evidence for linkage of pre- and postbronchodilator FEV1%VC was obtained for chromosome 2q32 (LOD,4.9, increasing to 6.03 with additional fine-mapping markers, and 3.2, respectively). Linkage existed for chromosome 5q for pre- and postbronchodilator VC (likelihood of disease [LOD], 1.8 and 2.6, respectively). Results for pre- and postbronchodilator FEV1 were less significant (LOD, 1.5 and 1.6, chromosomes 11p and 10q, respectively). Results were not affected by passive smoke exposure. There is significant evidence for linkage of FEV1%VC to chromosome 2q32 in families of probands with asthma, 35 cM proximal from linkage previously observed in families of probands with early-onset chronic obstructive pulmonary disease. Thus, there may be multiple genes on chromosome 2q that are important in determining presence and degree of airflow limitation in families ascertained for obstructive airway disease.
Multiple scales of brain-mind interactions
Authors: Lester Ingber
Journal: Behavioral and Brain Sciences (1995)

Abstract Posner &amp; Raichle's Images of mind is an excellent educational book and very well written. Some flaws as a scientific publication are: (a) the accuracy of the linear subtraction method used in PET is subject to scrutiny by further research at finer spatial-temporal resolutions; (b) lack of accuracy of the experimental paradigm used for EEG complementary studies.