tbuckley/cabot-search huggingface dataset:
Relative Roles of Direct Regeneration Versus Paracrine Effects of Human Cardiosphere-Derived Cells Transplanted Into Infarcted Mice
Authors: Isotta Chimenti, Rachel Ruckdeschel Smith, Tao-Sheng Li, Gary Gerstenblith, Elisa Messina, Alessandro Giacomello, Eduardo Marbán
Journal: Circulation Research (2010)

Multiple biological mechanisms contribute to the efficacy of cardiac cell therapy. Most prominent among these are direct heart muscle and blood vessel regeneration from transplanted cells, as opposed to paracrine enhancement of tissue preservation and/or recruitment of endogenous repair.Human cardiac progenitor cells, cultured as cardiospheres (CSps) or as CSp-derived cells (CDCs), have been shown to be capable of direct cardiac regeneration in vivo. Here we characterized paracrine effects in CDC transplantation and investigated their relative importance versus direct differentiation of surviving transplanted cells.In vitro, many growth factors were found in media conditioned by human adult CSps and CDCs; CDC-conditioned media exerted antiapoptotic effects on neonatal rat ventricular myocytes, and proangiogenic effects on human umbilical vein endothelial cells. In vivo, human CDCs secreted vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor 1 when transplanted into the same SCID mouse model of acute myocardial infarction where they were previously shown to improve function and to produce tissue regeneration. Injection of CDCs in the peri-infarct zone increased the expression of Akt, decreased apoptotic rate and caspase 3 level, and increased capillary density, indicating overall higher tissue resilience. Based on the number of human-specific cells relative to overall increases in capillary density and myocardial viability, direct differentiation quantitatively accounted for 20% to 50% of the observed effects.Together with their spontaneous commitment to cardiac and angiogenic differentiation, transplanted CDCs serve as "role models," recruiting endogenous regeneration and improving tissue resistance to ischemic stress. The contribution of the role model effect rivals or exceeds that of direct regeneration.
Immune correlates of Varlilumab treated cancer patients are consistent with CD27 costimulatory activity
Authors: Timothy Bullock, Hillary McClintic, Se Jeong, Kelly Smith, Walt Olson, Venky Ramakrishna, Laura Vitale, Jennifer Green, Michael Yellin, Thomas Davis, Tibor Keler
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Varlilumab is a human IgG1 agonist anti-CD27 antibody designed to activate T cells through CD27 costimulation. Preclinical studies have shown that Varlilumab efficiently activates human T cells when combined with T cell receptor stimulation, enhances antigen specific CD8 T cell
PRL-3 Phosphatase Is Implicated in Ovarian Cancer Growth
Authors: Federica Polato, Annamaria Codegoni, Robert Fruscio, Patrizia Perego, Costantino Mangioni, Saurabh Saha, Alberto Bardelli, Massimo Broggini
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The PRL-3 phosphatase has been found expressed at higher levels in metastasis than in primary tumors of patients with colorectal cancer. In the present study, we evaluated the expression of PRL-3 in ovarian cancer tissue and its role in ovarian cancer cell growth. Experimental Design: PRL-3 phosphatase expression was evaluated in 84 ovarian tumor samples. PRL-3 expression has been knocked down using specific small interfering RNAs to determine its role in ovarian cancer cell growth in vitro. Results: In ovarian cancers, PRL-3 expression correlates with disease progression, being higher in advanced (stage III) than in early (stage I) tumors. In situ measurements of PRL-3 expression showed that it was confined to the epithelial neoplastic cells. The molecular mechanism underlying PRL-3 overexpression in ovarian cancers is independent from amplification of the corresponding genomic locus. Ovarian cancer cells growing in culture have high levels of expression of this phosphatase. PRL-3–specific knockdown using small interfering RNA severely impaired the growth of cells without affecting the expression of the closely related homologue PRL-1. Intriguingly, the growth of human colon carcinoma cells expressing lower levels of the PRL-3 was not affected by the PRL-3 knockdown. Conclusions: Altogether, these results show that PRL-3 expression is associated with ovarian cancer progression and point to a key role for this phosphatase in the control of ovarian cancer cells growth. This strongly suggests that PRL-3 should be considered as a target for the discovery of new anticancer agents to be tested against this malignancy.
Activation of oral keratinocytes by mercuric chloride: relevance to dental amalgam-induced oral lichenoid reactions
Authors: M.C. Little, R.E.B. Watson, M.N. Pemberton, C.E.M. Griffiths, M.H. Thornhill
Journal: British Journal of Dermatology (2001)

Despite the benefits of mercury-containing amalgam dental fillings there are growing concerns regarding the potential adverse health effects arising from exposure to mercury released from fillings. In some individuals this process may result in a local lichenoid reaction of the oral mucosa.The aim of this study was to investigate the possibility that mercury salts released from amalgam fillings might act directly on oral keratinocytes to induce changes that could promote the development of such lesions.In vitro experiments were performed in which normal oral and cutaneous keratinocytes were cultured in the presence of mercuric chloride (HgCl2). ICAM-1 expression and the release of cytokines was determined by enzyme-linked immunosorbent assay techniques. T-cell binding to HgCl2-pretreated keratinocytes was assessed using a colorimetric method.Subcytotoxic concentrations of HgCl2 induced a concentration-related increase in ICAM-1 expression and consequent T-cell binding on oral, but not cutaneous, keratinocytes. HgCl2 also stimulated the release of low levels of tumour necrosis factor-alpha and interleukin-8 (but not RANTES), and inhibited the release of interleukin-1alpha by oral keratinocytes.This study provides evidence that oral keratinocytes may play an integral part in initiating the pathogenesis of amalgam-induced lichenoid reactions.
The epidermal disorder in lichen planus: an in vitro study*
Authors: D.G.C. PRESBURY, R. MARKS
Journal: British Journal of Dermatology (2006)

The epidermal component of lichen planus seems to result from a continuous process of erosion of the basal zone, and repopulation of the ‘wounded’ area by cells from nearby uninvolved epidermis. In order to investigate these migrating cells further, we have studied tissue slices from forty papules of lichen planus derived from twenty-nine patients. The tissue slices were cultured for periods of 24 or 48 h. Marked migration of fusiform and spindle-shaped cells into the eroded dermo-epidermal zone appeared to have taken place. In general, the changes represented an exaggeration of those usually present in vivo. Cytochalasin B, in concentrations of 5 μg/ml or greater in the culture medium, prevented cell migration. This effect, and the fact that autoradiographic studies showed few cells to be synthesizing DNA, suggested that cell migration took place by movement rather than by mitotic activity. Lichen planus (LP) seems unusual in that, although there is destruction in the basal generative layer, there is at the same time epidermal thickening. A recent study by Marks, Black & Wilson Jones (1973) has produced evidence suggesting that kcratinocytes migrate into the LP lesion from nearby uninvolved epidermis, and then repopulate the damaged basal zone in an attempt at healing the ‘microwound’ due to the erosive LP process. We have tried to learn more about these epidermal changes, by studying in vitro tissue slices from LP papules. During this study we have made observations that we believe support the concept that the epidermal changes in LP are a mixture of continuous damage and of attempts at repopulation by migrating epidermal cells.
Letter in response to TB during TNF- inhibitor therapy, despite screening
Authors: K. Manalan, A. Singanayagam, M. Wickremasinghe, O. M. Kon
Journal: Thorax (2014)

We read the case-based discussion published in Thorax by Hofland et al 1 with great interest. The case studies reported by the authors raise a very important point about the necessity for continued monitoring of patients on tumour necrosis factor (TNF)-α antagonist therapy, even in the absence of evidence of latent TB infection (LTBI) at the onset of therapy and this is a point that is not discussed in the most recent British Thoracic society (BTS) guidance document on TB and anti-TNF α treatment.2

The two cases described in the article would be classified as ‘low risk’ and thus not offered chemoprophylaxis if managed according to current BTS recommendations. …
Intramolecular Epitope Spreading in Heymann Nephritis
Authors: Pallavi Shah, Alfonso Tramontano, Sudesh P. Makker
Journal: Journal of the American Society of Nephrology (2007)

Immunization with megalin induces active Heymann nephritis, which reproduces features of human idiopathic membranous glomerulonephritis. Megalin is a complex immunological target with four discrete ligand-binding domains (LBDs) that may contain epitopes to which pathogenic autoantibodies are directed. Recently, a 236-residue N-terminal fragment, termed "L6," that spans the first LBD was shown to induce autoantibodies and severe disease. We used this model to examine epitope-specific contributions to pathogenesis. Sera obtained from rats 4 weeks after immunization with L6 demonstrated reactivity only with the L6 fragment on Western blot, whereas sera obtained after 8 weeks demonstrated reactivity with all four recombinant fragments of interest (L6 and LBDs II, III, and IV). We demonstrated that the L6 immunogen does not contain the epitopes responsible for the reactivity to the LBD fragments. Therefore, the appearance of antibodies directed at LBD fragments several weeks after the primary immune response suggests intramolecular epitope spreading. In vivo, we observed a temporal association between increased proteinuria and the appearance of antibodies to LBD fragments. These data implicate B cell epitope spreading in antibody-mediated pathogenesis of active Heymann nephritis, a model that should prove valuable for further study of autoimmune dysregulation.
House dust mite extract downregulates C/EBP in asthmatic bronchial smooth muscle cells
Authors: N. Miglino, M. Roth, M. Tamm, P. Borger
Journal: European Respiratory Journal (2010)

Reduced translation of CEBPA mRNA has been associated with increased proliferation of bronchial smooth muscle (BSM) cells of asthma patients. Here, we assessed the effect of house dust mite (HDM) extracts on the cell proliferation ([ 3 H]-thymidine incorporation), inflammation (interleukin (IL)-6 release) and upstream translation regulatory proteins of CCAAT/enhancer-binding protein (C/EBP)α in human BSM cells of healthy controls and asthmatic patients. HDM extract significantly increased IL-6 protein and proliferation of BSM cells of asthma patients only. HDM extract reduced the C/EBPα expression in BSM cells of asthma patients, which coincided with significantly increased levels of calreticulin (CRT) protein, an inhibitor of CEBPA mRNA translation. HDM extract elicited both protease-dependent and -independent responses, which were mediated via protease-activated receptor (PAR)2 and CRT, respectively. In conclusion, HDM extract reduced CEBPA mRNA translation, specifically in asthmatic BSM cells, and 1) upregulated CRT, 2) activated PAR2, and increased 3) IL-6 expression and 4) the proliferation of asthmatic BSM cells. Hence, HDM exposure contributes to inflammation and remodelling by a nonimmune cell-mediated mechanism via a direct interaction with BSM cells. These findings may potentially explain several pathological features of this disease, in particular BSM cell hyperplasia.
Comparison of reported prevalences of recent asthma in longitudinal and cross-sectional studies
Authors: MR Sears, S Lewis, GP Herbison, B Robson, EM Flannery, MD Holdaway, N Pearce, J Crane, PA Silva
Journal: European Respiratory Journal (1997)

A potential source of bias in prevalence rates reported for symptoms and diagnoses of asthma in longitudinal studies could arise if repeated questioning of subjects or previous experience of lung function and airway responsiveness tests increased awareness of respiratory symptoms. We wished to determine the extent of any such bias by comparing reported prevalence rates from a longitudinal and cross-sectional study within similar populations. The prevalences of wheezing in the last year, waking with chest tightness, waking with shortness of breath, waking with coughing, having an attack of asthma in the last year, and current use of medications for asthma were determined using identical questions in two populations. Self-completed questionnaire responses of 946 subjects, 21 yrs of age, participating in the seventh respiratory assessment in the longitudinal Dunedin Multidisciplinary Health and Development Research Study were compared with responses provided by 991 subjects, aged 20-22 yrs, completing a postal questionnaire on one occasion only for the New Zealand section of the European Community Respiratory Health Study. The prevalence rates were not significantly different between the two populations, for all of the reported symptoms and for medication use. Differences in responses between genders were similar in each study, with all responses being more common in females. We conclude that repeated questioning regarding respiratory symptoms and repeated lung function and bronchial challenge testing in a longitudinal study of asthma did not bias prevalence rates compared with those obtained in a similar population of the same age studied on only one occasion.
A Concise History of the Cancer and Leukemia Group B
Authors: Richard L. Schilsky, O. Ross McIntyre, James F. Holland, Emil Frei
Journal: Clinical Cancer Research (2006)

Abstract A formal National Cancer Institute Clinical Trials Cooperative Group Program was conceived in 1955 when Dr. Sidney Farber, Mary Lasker, and others approached Congress with a proposal to increase support for studies of chemotherapy of cancer. In response, Congress awarded US $5 million to the National Cancer Institute to establish the Chemotherapy National Service Center. The founders of the Cancer and Leukemia Group B, James Holland and Emil (Tom) Frei, III, envisioned that successful chemotherapy for leukemia and other hematologic malignancies could be expeditiously realized through carefully designed clinical trials executed uniformly as a cooperative effort among several institutions. In 1956, the group was designated the Acute Leukemia Group B by the Chemotherapy National Service Center Clinical Studies Panel, and Frei was elected chairman. In the ensuing 50 years, the Cancer and Leukemia Group B has expanded to national and even international membership, and its research programs have expanded to include all of the common adult solid tumors and hematologic malignancies in a multidisciplinary effort to improve the outcomes for patients with cancer and to better understand the biology of malignant disease.
HTLV-III ANTIBODY IN PROSTITUTES
Authors: S.E. Barton, G.S. Underhill, C. Gilchrist, D.J. Jeffries, J.R.W. Harris, Dominique Brenky-Faudeux, André Fribourg-Blanc, Umberto Tirelli, Emanuela Vaccher, Antonio Carbone, PaoloDe Paoli, Gianfranco Santini, Silvio Monfardini, None AIDS and Related Syndromes Study Group
Journal: The Lancet (1985)
Association of ground hardness with injuries in rugby union
Authors: Masahiro Takemura, Anthony G Schneiders, Melanie L Bell, Peter D Milburn
Journal: British Journal of Sports Medicine (2007)

Ground hardness is considered one of the possible risk factors associated with rugby injuries.To examine the contribution of ground hardness, rainfall and evapotranspiration to the incidence of injury, and to investigate seasonal injury bias throughout one full season of rugby union.A prospective epidemiological study of rugby injuries was performed on 271 players from rugby union teams involved in the premier grade rugby competition in Dunedin, New Zealand. Ground hardness was measured before each match over 20 rounds with an industrial penetrometer, and local weather information was collected through the National Institute of Weather and Atmospheric Research and the Otago Regional Council. Poisson mixed models were used to describe injury incidence as a function of ground hardness throughout the season.The overall injury incidence during the season was 52 injuries per 1000 match player-hours (95% CI 42 to 65). Although injury incidence decreased gradually by round with a rate ratio of 0.98 (95% CI 0.96 to 0.99) (p = 0.036), and the hardness of match grounds decreased significantly over the season (0.16 MPa/round, 95% CI 0.12 to 0.21, p<0.001), a non-significant association was demonstrated between injury incidence and ground hardness. Injury incidence was not associated with a combination of ground hardness, rainfall and evapotranspiration on the day of the match or cumulative rainfall and evapotranspiration before each match.Seasonal change in ground hardness and an early-season bias of injuries was demonstrated. Although the contribution of ground hardness to injury incidence was not statistically significant, match round and injury incidence were highly correlated, confirming a seasonal bias, which may confound the relationship of injury to ground condition.
Pulse Pressure Predicts Incident Cardiovascular Disease but Not Diabetic Nephropathy in Patients With Type 1 Diabetes (The FinnDiane Study)
Authors: Daniel Gordin, Johan Wadén, Carol Forsblom, Lena Thorn, Milla Rosengård-Bärlund, Nina Tolonen, Markku Saraheimo, Valma Harjutsalo, Per-Henrik Groop
Journal: Diabetes Care (2011)

OBJECTIVE Pulse pressure (PP), an estimate of arterial stiffness, has been shown to be associated with incident cardiovascular disease (CVD) in patients with type 1 diabetes (T1D). However, diabetic kidney disease, a strong predictor of CVD, was not previously taken into account. Furthermore, the role of PP as a predictor of diabetic nephropathy is not known. Therefore, we prospectively investigated the associations between PP and these diabetes complications in patients with T1D. RESEARCH DESIGN AND METHODS A total of 4,509 patients from the FinnDiane Study participated. Follow-up data on incident CVD events and renal status (median 5.3 years) were available in 69 and 76% of the patients, respectively. Altogether, 269 patients (8.6%) had an incident CVD event and 370 patients (10.8%) progressed to a higher level of albuminuria or to end-stage renal disease. RESULTS PP was higher at baseline in patients who experienced a CVD event (66 ± 18 vs. 52 ± 14 mmHg; P &amp;lt; 0.001) or progressed in their renal status (58 ± 18 vs. 54 ± 15 mmHg; P &amp;lt; 0.01) during follow-up. In a Cox regression model, PP was independently associated with a first ever CVD event (hazard ratio per 10 mmHg 1.22 [95% CI 1.10–1.34]) but not progression of renal disease (1.00 [0.89–1.12]) after adjustments for traditional risk factors. CONCLUSIONS PP, a marker of arterial stiffness, is a risk factor for cardiovascular complications but not for diabetic nephropathy in patients with T1D.
High levels of BAX, low levels of MRP-1, and high platelets are independent predictors of response to imatinib in myeloid blast crisis of CML
Authors: Thoralf Lange, Christine Günther, Thomas Köhler, Rainer Krahl, Scarlet Musiol, Sabine Leiblein, Haifa-Kathrin Al-Ali, Iris van Hoomissen, Dietger Niederwieser, Michael W. N. Deininger
Journal: Blood (2003)
Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis
Authors: Dorothy A Machalek, Mary Poynten, Fengyi Jin, Christopher K Fairley, Annabelle Farnsworth, Suzanne M Garland, Richard J Hillman, Kathy Petoumenos, Jennifer Roberts, Sepehr N Tabrizi, David J Templeton, Andrew E Grulich
Journal: The Lancet Oncology (2012)
The colonic mucus protection depends on the microbiota
Authors: Ana M Rodríguez-Piñeiro, Malin E V Johansson
Journal: Gut Microbes (2015)

The intestinal mucus is a pivotal part of our intestinal protection. It provides slow diffusion of protective molecules, trapping of luminal material as bacteria and smooth transport in the small intestine. In colon it restricts bacterial access to the epithelium limiting the responses to the enormous bacterial load present at this location. The development of these systems depends on the microbiota composition as seen in our recent study comparing the mucus phenotype in 2 colonies kept in different husbandries within the same SPF animal facility. One colony had impenetrable colonic mucus while the other colony had more penetrable mucus. The mucus phenotypes were transmitted via the microbiota and clear differences in its composition could be detected. Candidates associated with the different colonies were identified but the observed mucus difference could not be assigned to a specific bacterium.
Ultrastructure of Meningeal Tumors Induced in Dogs With Rous Sarcoma Virus
Authors: Emilio Bucciarelli, Giancarlo F. Rabotti, Albert J. Dalton
Journal: JNCI Journal of the National Cancer Institute (1967)

Leptomeningeal tumors induced in 11 dogs by intracerebral inoculation of Rous sarcoma virus (RSV) were studied with the electron microscope. The strains of RSV used were: Schmidt-Ruppin, Bryan high-titer, and CT559. Two main types of tumors were recognized from their ultrastructure: 1) meningothelial meningiomas consisting of cells closely similar to the normal arachnocyte and having the ultrastructural characteristics observed in human meningiomas; 2) meningeal sarcomas consisting predominantly of a fibroblastic type of cell showing various degrees of anaplasia. The histogenesis of the leptomeningeal sarcoma from the arachnocytes, rather than from the endothelial or the adventitial cells of blood vessels, is suggested. Viral particles morphologically indistinguishable from those associated with the avian-leukosis-virus complex were noted in the tumors of 5 of the 11 dogs. Cytoplasmic crystalline aggregates were observed in the neoplastic cells of 10 dogs. The nature of these formations remains unknown. No viral particles or crystals were observed in the meninges of 3 normal dogs.