tbuckley/cabot-search huggingface dataset:
Role of the enteric nervous system in the maintained hypersecretion induced by enterotoxin STa in the nutritionally deprived intestine.
Authors: H C Nzegwu, R J Levin
Journal: Gut (1994)

Electrogenic (Cl-) secretion was measured as the short circuit current (Isc, microA/cm2) across muscle-stripped sheets of jejunum and ileum incubated in vitro after removal from fed rats, rats starved for three days, and chronically undernourished rats (50% of fed control intake for 21 days). Concentration and Isc response curves for serially-added mucosal Escherichia coli STa enterotoxin showed that the rats which had undergone dietary deprivation had a larger secretory Isc maximum but the ED50 values were unchanged compared with fed animals. In fed intestine the action of STa was transient, with an Isc peak and subsequent decay to the baseline over 60 minutes but in the undernourished intestine the response consisted of a significantly greater peak than that of the fed state (jejunum = 94%; ileum = 168%) and the Isc was maintained at or near the peak for at least 60 minutes. The starved intestine had a less well developed maintenance of its enhanced peak Isc. Serosal tetrodotoxin (1 microM) had no effect on the initial peak Isc values but caused a decay of the maintained Isc down to the basal or fed levels in the starved and, especially, in the undernourished intestines. Thus, dietary deprivation, especially chronic undernutrition, enhances the maximum electrogenic secretion due to STa and creates a new neural path in the submucosal plexus that, when activated by STa, maintains its enhanced secretory action. Its putative role in exacerbating secretory diarrhoea in malnourished human subjects could be an important component underlying the known relation between malnourishment and the increased severity of diarrhoea.
Effect of Immunosuppression on Neonatally Diethylstilbestrol-Induced Genital Tract Lesion and Tumor Development in Female Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: S C Ways, H A Bern, P B Blair
Journal: JNCI Journal of the National Cancer Institute (1984)

Neonatal treatment of female rodents with the synthetic estrogen diethylstilbestrol [(DES) CAS: 56-53-1; alpha, alpha'-diethyl-4,4'-dimethoxystilbene] results in immunodeficiency that persists into adulthood, along with progressive development of genital tract lesions. DES-induced immunosuppression was examined as a possible promoter of genital tract lesion and tumor development in BALB/cCrgl female mice. Secondary suppression of T-cell immunity after neonatal DES treatment failed to increase lesion incidence or to promote genital tract tumor development in 8-month-old mice. Although hyperplastic lesions were present in 70% of the genital tracts from DES-treated mice at 8 months of age, apparently few neoplastic cells are present at this time, since transplantation of genital tracts from these animals into syngeneic hosts did not yield tumors. To reduce the possibility that potential tumors were too immunogenic to survive in the syngeneic hosts, genital tract pieces from 12-month-old DES-treated female mice were transplanted into immunosuppressed hosts; only 1 tumor resulted. The tumor was a mixed adenocarcinoma, squamous cell carcinoma, and sarcoma and was immunogenic. These results suggest that immunosurveillance by T-cells is relatively unimportant in DES-induced genital tract lesion development.
Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial
Authors: A. J. Wearden, C. Dowrick, C. Chew-Graham, R. P. Bentall, R. K. Morriss, S. Peters, L. Riste, G. Richardson, K. Lovell, G. Dunn
Journal: BMJ (2010)

The tetracyclines are effective antibiotics for the treatment of exacerbations of chronic bronchitis and are also extensively used for the long-term treatment of acne vulgaris. Their more general use has, however, diminished because of an increasing incidence of tetracycline resistance among many formerly susceptible bacteria and because their effects on developing teeth contraindicate their use in pregnancy and childhood. Moreover in patients with pyelonephritis tetracyclines may further impair renal function.<sup>1</sup> New tetracyclines are of special interest if they have any advantage over existing preparations in these respects.
Nm23 Protein Expression in Ductal In Situ and Invasive Human Breast Carcinoma
Authors: J. A. Royds, T. J. Stephenson, R. C. Rees, A. J. Shorthouse, P. B. Silcocks
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Nm23 Protein Expression in Ductal In Situ and Invasive Human Breast Carcinoma Get access Janice A. Royds, Janice A. Royds 1Department of Pathology, University of SheffieldSheffield, England Search for other works by this author on: Oxford Academic PubMed Google Scholar Timothy J. Stephenson, Timothy J. Stephenson 1Department of Pathology, University of SheffieldSheffield, England Correspondence to: Timothy J. Stephenson, M.D., Department of Pathology, University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, England. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert C. Rees, Robert C. Rees 2Institute for Cancer Studies, University of SheffieldSheffield, England Search for other works by this author on: Oxford Academic PubMed Google Scholar Andrew J. Shorthouse, Andrew J. Shorthouse 4Royal Hallamshire HospitalSheffield, England Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul B. Silcocks Paul B. Silcocks 3Department of Public Health Medicine, University of SheffieldSheffield, England Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 9, 5 May 1993, Pages 727–731, https://doi.org/10.1093/jnci/85.9.727 Published: 05 May 1993 Article history Received: 16 October 1992 Revision received: 13 January 1993 Accepted: 25 January 1993 Published: 05 May 1993
Endothelin receptors in cultured adult rat cardiac fibroblasts
Authors: L. C Katwa, E. Guarda, K. T Weber
Journal: Cardiovascular Research (1993)

Objectives: Endothelins, released by vascular endothelial cells, are known growth promoters of various mesenchymal cells that contribute to stromal protein accumulation. Whether endothelins could contribute to myocardial fibrosis depends, in part on whether cardiac fibroblasts have endothelin receptors. The identification and binding characteristics of endothelin-1 and endothelin-3 and their ETA and ETB receptor subtypes in cultured adult rat cardiac fibroblasts represented study objectives. Methods: Cultured rat cardiac fibroblasts (passages 5-10) grown until confluence were used to study radioligand binding assays, receptor subtypes, association and dissociation, effects of agonist and antagonist on binding kinetics, and affinity cross linking. Results: Binding association of 125I-endothelin-l and l25I-endothelin-3 was rapid, specific, and saturable within 60 minutes. The dissociation of receptor bound 125I-endothelin-l was slow and partially reversible (30%-40%), suggesting more than one class of endothelin receptors, whereas the dissociation of 125I-endothelin-3 was time dependent and reversible. Competitive displacement with unlabelled endothelin-1, endothelin-3, endothelin-receptor non-selective sarafotoxin (S6b), and ETA receptor selective antagonist PED-3512-PI were used to identify receptor subtypes. Displacement of l25I-endothelin-l by cold endothelin-1, resulted in a low affinity, high binding site (IC50 5.4 × 10−9 M; 3.6 × 104 binding sites·cell−1) and a high affinity, low binding site (IC50 4.2 × 10−4 M; 11 830 binding sites·cell−1). With 125I-endothelin-l the IC50 s for sarafotoxin, endothelin-3, and PED-3512-PI were 1.8 × 10−10, 1.7 × 10−9, and 3.7 × 10−9 M, respectively; for 125I-endothelin-3 these IC50s were 2.28 × 10−11, 1.9 × 10−10, and 1.7 × 10−9 M, respectively. Endothelin receptor subunits of 53, 37, 34, and 24 kDa were identified by affinity cross linking. Conclusion: Endothelin-1 and endothelin-3 binding and ETA and ETB receptor subtypes are present in cardiac fibroblasts with ETB predominant. The presence of these receptors support the hypothesis that endothelins may regulate cardiac fibroblast function. Cardiovascular Research 1993;27:21-25-2129
Randomized Controlled Trial of Outpatient Mentalization-Based Treatment Versus Structured Clinical Management for Borderline Personality Disorder
Authors: Anthony Bateman, Peter Fonagy
Journal: American Journal of Psychiatry (2009)

Objective: This randomized controlled trial tested the effectiveness of an 18-month mentalization-based treatment (MBT) approach in an outpatient context against a structured clinical management (SCM) outpatient approach for treatment of borderline personality disorder. Method: Patients (N=134) consecutively referred to a specialist personality disorder treatment center and meeting selection criteria were randomly allocated to MBT or SCM. Eleven mental health professionals equal in years of experience and training served as therapists. Independent evaluators blind to treatment allocation conducted assessments every 6 months. The primary outcome was the occurrence of crisis events, a composite of suicidal and severe self-injurious behaviors and hospitalization. Secondary outcomes included social and interpersonal functioning and self-reported symptoms. Outcome measures, assessed at 6-month intervals, were analyzed using mixed effects logistic regressions for binary data, Poisson regression models for count data, and mixed effects linear growth curve models for self-report variables. Results: Substantial improvements were observed in both conditions across all outcome variables. Patients randomly assigned to MBT showed a steeper decline of both self-reported and clinically significant problems, including suicide attempts and hospitalization. Conclusions: Structured treatments improve outcomes for individuals with borderline personality disorder. A focus on specific psychological processes brings additional benefits to structured clinical support. Mentalization-based treatment is relatively undemanding in terms of training so it may be useful for implementation into general mental health services. Further evaluations by independent research groups are now required.
Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial
Authors: JL Mega, E Braunwald, S Mohanavelu, P Burton, R Poulter, F Misselwitz, V Hricak, ES Barnathan, P Bordes, A Witkowski, V Markov, L Oppenheimer, CM Gibson
Journal: The Lancet (2009)
Intrachromosomal Amplification of Chromosome 21 Is Associated With Inferior Outcomes in Children With Acute Lymphoblastic Leukemia Treated in Contemporary Standard-Risk Children's Oncology Group Studies: A Report From the Children's Oncology Group
Authors: Nyla A. Heerema, Andrew J. Carroll, Meenakshi Devidas, Mignon L. Loh, Michael J. Borowitz, Julie M. Gastier-Foster, Eric C. Larsen, Leonard A. Mattano, Kelly W. Maloney, Cheryl L. Willman, Brent L. Wood, Naomi J. Winick, William L. Carroll, Stephen P. Hunger, Elizabeth A. Raetz
Journal: Journal of Clinical Oncology (2013)

Purpose Five-year overall survival (OS) for children with B-cell precursor acute lymphoblastic leukemia (B-ALL) exceeds 90% with risk-adapted therapy. Age, initial WBC count, genetic aberrations, and minimal residual disease (MRD) are used for risk stratification. Intrachromosomal amplification of a region of chromosome 21 (iAMP21; three or more extra copies of RUNX1 on an abnormal chromosome 21) is a recently identified recurrent genomic lesion associated with inferior outcome in some studies. We investigated the impact of iAMP21 in a large cohort treated in contemporary Children's Oncology Group (COG) ALL trials. Patients and Methods Fluorescent in situ hybridization for specific genetic aberrations was required at diagnosis. MRD was measured by flow cytometry at end induction. Outcome was measured as event-free survival (EFS) and OS. Results iAMP21 was found in 158 (2%) of 7,793 patients with B-ALL age ≥ 1 year; 74 (1.5%) of 5,057 standard-risk (SR) patients, and 84 (3.1%) of 2,736 high-risk (HR) patients. iAMP21 was associated with age ≥ 10 years, WBC less than 50,000/μL, female sex, and detectable MRD at day 29. Four-year EFS and OS were significantly worse for patients with iAMP21 and SR B-ALL, but iAMP21 was not a statistically significant prognostic factor in HR patients. There was no interaction between MRD and iAMP21. Among SR patients, day 29 MRD ≥ 0.01% and iAMP21 were associated with the poorest EFS and OS; absence of both was associated with the best outcome. Conclusion iAMP21 is associated with inferior outcome in pediatric B-ALL, particularly SR patients who require more intensive therapy and are now treated on HR COG ALL protocols.
Influence of Digitoxin on Labile and Inorganic Phosphates, Lactate, Glycogen, Potassium and Sodium in Dog Ventricle
Authors: JOHN REBAR, BLANCHE T. REBAR, AKIRA OMACHI
Journal: Circulation Research (1957)

This communication deals with the effects produced by digitoxin on the metabolism of the dog's ventricles as indicated by changes in labile and inorganic phosphates, lactate, glycogen, potassium and sodium content of the myocardium immediately frozen after excision. The results suggest increased turnover of high energy phosphate and glycogen by nontoxic doses.
The roles of mesenchymal stem cells in tumor inflammatory microenvironment
Authors: Zhao Sun, Shihua Wang, Robert Chunhua Zhao
Journal: Journal of Hematology & Oncology (2014)

Tumor behavior is not entirely determined by tumor cells. Studies have demonstrated that a variety of non-tumor cells in the tumor microenvironment affect tumor behavior; thus, a new focus of cancer research has been the development of novel cancer treatment ideas and therapeutic targets based on the effects of these cells. Mesenchymal stem cells (MSCs) are an important component of the tumor microenvironment; however, previous studies have produced controversial results regarding whether MSCs promote or inhibit tumor growth and progression. In particular, Naïve MSCs and tumor-derived MSCs (T-MSCs) have different functions. Naïve MSCs could exert bidirectional effects on tumors because these cells can both promote and inhibit tumor progression while T-MSCs promote tumor progression due to influences from the tumor itself and from the inflammatory tumor microenvironment. As an unhealed wound, tumor produces a continuous source of inflammatory mediators and causes aggregation of numerous inflammatory cells, which constitute an inflammatory microenvironment. Inflammatory factors can induce homing of circulating MSCs and MSCs in adjacent tissues into tumors, which are then being "educated" by the tumor microenvironment to support tumor growth. T-MSCs could recruit more immune cells into the tumor microenvironment, increase the proportion of cancer stem cells and promote tumor angiogenesis, further supporting tumor progression. However, as plasticity is a fundamental feature of MSCs, MSCs can also inhibit tumors by activating various MSC-based signaling pathways. Studies of the mechanisms by which interactions among tumors, MSCs, and the inflammatory microenvironment occur and methods to disrupt these interactions will likely reveal new targets for cancer therapy.
Potentiation of Cytotoxic T-Cell Function by Virus 2
Authors: Carol L. Reinisch, Stuart F. Schlossman
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Potentiation of Cytotoxic T-Cell Function by Virus Get access Carol L. Reinisch, Carol L. Reinisch Search for other works by this author on: Oxford Academic PubMed Google Scholar Stuart F. Schlossman Stuart F. Schlossman 3Division of Tumor Immunology, Sidney Farber Cancer Center, and Department of Medicine, Harvard Medical School, Boston, Mass. 02115 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 6, December 1976, Pages 1277–1281, https://doi.org/10.1093/jnci/57.6.1277 Published: 01 December 1976 Article history Received: 20 January 1976 Revision received: 10 May 1976 Published: 01 December 1976
Screening for Hereditary Hemochromatosis: A Systematic Review for the U.S. Preventive Services Task Force
Authors: Evelyn P. Whitlock, Betsy A. Garlitz, Emily L. Harris, Tracy L. Beil, Paula R. Smith
Journal: Annals of Internal Medicine (2006)

Background: The U.S. Preventive Services Task Force (USPSTF) has not previously considered screening for hereditary hemochromatosis for a recommendation as a clinical preventive service for primary care clinicians. Purpose: To conduct a focused systematic review of heredita-ry hemochromatosis screening relating to 2 USPSTF criteria, the burden of suffering and the potential effectiveness of a preven-tive intervention, to determine whether evidence is sufficient for a USPSTF recommendation. Data Sources: MEDLINE, CINAHL, and Cochrane Library databases from 1966 through February 2005. The authors supplemented literature searches with source materials from experts in the field and the bibliographies of key reviews and included studies. Study Selection: Studies were retrieved to answer 3 key questions: 1) What is the risk for developing clinical hemochromatosis among those with a homozygous C282Y genotype? 2) Does earlier therapeutic phlebotomy of individuals with primary iron overload due to hereditary hemochromatosis reduce morbidity and mortality compared with treatment after diagnosis in routine clinical care? 3) Are there groups at increased risk for developing hereditary hemochromatosis that can be readily identified before genetic screening? The authors critically appraised studies using quality criteria specific to their design. Data Extraction: The authors abstracted all studies into evidence tables using condition definitions and diagnostic criteria. Data Synthesis: Data were insufficient to define a very precise estimate of penetrance. Available data suggest that up to 38% to 50% of C282Y homozygotes may develop iron overload, with up to 10% to 33% eventually developing hemochromatosis-associated morbidity. Prevalence of C282Y homozygosity is higher in family members of probands and other high-risk patient groups defined by signs, symptoms, and phenotypic screening. Limitations: This review considered genetic screening for HFE-related hereditary hemochromatosis in C282Y homozygotes only. Available research is limited, is based solely on observational designs, and is plagued by poor or inconsistent reporting. Conclusions: Research addressing genetic screening for hereditary hemochromatosis remains insufficient to confidently project the impact of, or estimate the benefit from, widespread or high-risk genetic screening for hereditary hemochromatosis.
835-4 Comparison of the effects of metoprolol and carvedilol on symptoms, well-being, and quality-adjusted life-years: A description of the patient-journey in COMET
Authors: John G Cleland, Karl Swedberg, Andrea Di Lenarda, Peter Hanrath, Michel Komajda, Beatrix Lutiger, Jacobus Lubsen, Marco Metra, Willem J Remme, Armin Scherhag, Andrew Charlesworth, Christian Torp-Pedersen, Philip A Poole-Wilson
Journal: Journal of the American College of Cardiology (2004)
Quantitative studies of the fate of epidermal Langerhans cells after X-irradiation of guinea-pig and mouse footpad skin
Authors: SHIRLEY COLE, J.M. FAIRWEATHER, K.M.S. TOWNSEND
Journal: British Journal of Dermatology (1987)

Langerhans cell numbers, morphology and distribution were observed in cross sections of footpad epidermis at intervals from 1 to 28 days after exposure of the hind feet of CBA/H mice or albino guinea-pigs to a single absorbed dose of 20 Gy (2000 rad) of X-rays. In mice, the number of Langerhans cells reactive with anti-macrophage F4/80 monoclonal antibody steadily declined by approximately 85% within 10 days after irradiation, consistent with previous studies, in which Langerhans cells were identified in epidermal sheets by ATPase activity or presence of Birbeck granules. Remaining Langerhans cells were exceptionally dendritic. Very few Birbeck granule-containing cells were found in murine popliteal lymph nodes before or after irradiation but damaged cells were present in superficial strata of irradiated epidermis. The morphology and number of epidermal F4/80-positive cells approached normal by 15 days after irradiation. In guinea-pigs, gradual suprabasal movement and loss of rounded, ATPase-positive Langerhans cells from the epidermis were detectable from 5 to 20 days after irradiation but the magnitude of the cell loss and redistribution was partially obscured by the simultaneous appearance of clusters of replacement Langerhans cells in the basal layer and by keratinocyte hyperplasia.
Time Between the First Day of Chemotherapy and the Last Day of Chest Radiation Is the Most Important Predictor of Survival in Limited-Disease Small-Cell Lung Cancer
Authors: Dirk De Ruysscher, Madelon Pijls-Johannesma, Søren M. Bentzen, André Minken, Rinus Wanders, Ludy Lutgens, Monique Hochstenbag, Liesbeth Boersma, Bradly Wouters, Guido Lammering, Johan Vansteenkiste, Philippe Lambin
Journal: Journal of Clinical Oncology (2006)

To identify time factors for combined chemotherapy and radiotherapy predictive for long-term survival of patients with limited-disease small-cell lung cancer (LD-SCLC).A systematic overview identified suitable phase III trials. Using meta-analysis methodology to compare results within trials, the influence of the timing of chest radiation and the start of any treatment until the end of radiotherapy (SER) on local tumor control, survival, and esophagitis was analyzed. For comparison between studies, the equivalent radiation dose in 2-Gy fractions, corrected for the overall treatment time of chest radiotherapy, was analyzed.The SER was the most important predictor of outcome. There was a significantly higher 5-year survival rate in the shorter SER arms (relative risk [RR] = 0.62; 95% CI, 0.49 to 0.80; P = .0003), which was more than 20% when the SER was less than 30 days (upper bound of 95% CI, 90 days). A low SER was associated with a higher incidence of severe esophagitis (RR = 0.55; 95% CI, 0.42 to 073; P < .0001). Each week of extension of the SER beyond that of the study arm with the shortest SER resulted in an overall absolute decrease in the 5-year survival rate of 1.83% +/- 0.18% (95% CI).A low time between the first day of chemotherapy and the last day of chest radiotherapy is associated with improved survival in LD-SCLC patients. The novel parameter SER, which takes into account accelerated proliferation of tumor clonogens during both radiotherapy and chemotherapy, may facilitate a more rational design of combined-modality treatment in rapidly proliferating tumors.