tbuckley/cabot-search huggingface dataset:
Effector Cell-Derived Lymphotoxin α and Fas Ligand, but not Perforin, Promote Tc1 and Tc2 Effector Cell-Mediated Tumor Therapy in Established Pulmonary Metastases
Authors: Mark J. Dobrzanski, Joyce B. Reome, Joseph A. Hollenbaugh, James C. Hylind, Richard W. Dutton
Journal: Cancer Research (2004)

Abstract Cytolytic CD8+ effector cells fall into two subpopulations based on cytokine secretion. Type 1 CD8+ T cells (Tc1) secrete IFN-γ, whereas type 2 CD8+ T cells (Tc2) secrete interleukin (IL)-4 and IL-5. Although both effector cell subpopulations display Fas ligand (FasL) and tumor necrosis factor (TNF), tumor lysis is predominantly perforin dependent in vitro. Using an ovalbumin-transfected B16 lung metastasis model, we show that heightened numbers of adoptively transferred ovalbumin-specific Tc1 and Tc2 cells accumulated at the tumor site by day 2 after therapy and induced tumor regression that enhanced survival in mice with pulmonary metastases. Transfer of either TNF-α- or perforin-deficient Tc1 or Tc2 effector cells generated from specified gene-deficient mice showed no differences in therapeutic efficiency when compared with corresponding wild-type cells. In contrast, both Tc1 and Tc2 cells, derived from either FasL or TNF-α/lymphotoxin (LT) α double knockout mice, showed that therapeutic effects were dependent, in part, on effector cell-derived FasL or LTα. Six days after effector cell therapy, elevated levels of activated endogenous CD8/CD44High and CD4/CD44High T cells localized and persisted at sites of tumor growth, whereas donor cell numbers concomitantly decreased. Both Tc1 and Tc2 effector cell subpopulations induced endogenous antitumor responses that were dependent, in part, on recipient-derived IFN-γ and TNF-α. However, neither effector cell-mediated therapy was dependent on recipient-derived perforin, IL-4, IL-5, or nitric oxide. Collectively, tumor antigen-specific Tc1 and Tc2 effector cell-mediated therapy is initially dependent, in part, on effector cell-derived FasL or LTα that may subsequently potentiate endogenous recipient-derived type 1 antitumor responses dependent on TNF-α and IFN-γ.
Preventive Medicine for Our Ailing Health Care System
Authors: Alexander Leaf
Journal: JAMA (1993)

AS THE national debate about our health care system intensifies, it is timely to raise some important issues that should be seriously considered. I refer to the need for more preventive medicine, which should be part of the national debate, but with other basic problems may be passed over in the haste to deal just with cost issues. My aim is not to review the potential health benefits of preventive medicine but to indicate how health promotion should be an essential ingredient combined with curative medicine to create a comprehensive health care system. Although preventive medicine is not solely the domain of physicians, physicians should lead its practice. Preventive cardiology will be considered because heart disease continues to be the leading cause of premature death in our society, because the current practice of cardiology is a major item in our health costs, and because much is known about how to
Chemistry of the sex hormones.
Authors: Hubert R. Catchpole
Journal: JAMA (1963)

Whoever reads this volume gets a feeling that so slender a work should not have been included in what is flamboyantly called<i>American Lecture Series in Living Chemistry</i>. The author testifies in the preface that he had been pressured into writing this book. Perhaps his reasonable disclaimers should have been respected. What he himself modestly advanced as drawbacks to his authorship, the editor of the series exalts into virtues. "This unusual book," claims the dust jacket, "is written entirely from the point (sic) of the author's personal knowledge as a clinical endocrinologist." In actual content, the author briefly traces the organic chemistry of the steroids from methane to cyclopentenoperhydrophenanthrene with big, clear structural formulae (pp 3-19); similarly he displays formulae for the estrogens, androgens, and gestogens (pp 20-60), with clinical notes, doses, etc; he presents two chapters (pp 61-77) on urinary metabolites and metabolic pathways, and finally 11 pages of
Time-evolution and reversibility of strontium-induced osteomalacia in chronic renal failure rats
Authors: Line Oste, An R. Bervoets, Geert J. Behets, Geert Dams, Rita L. Marijnissen, Hilde Geryl, Ludwig V. Lamberts, Steven C. Verberckmoes, Viviane O. Van Hoof, Marc E. De Broe, Patrick C. D'Haese
Journal: Kidney International (2005)
FIRST GENERATION VERSUS NEWER GENERATIONS DRUG-ELUTING STENTS IN CHRONIC TOTAL OCCLUSION INTERVENTION
Authors: Amro Elnagar, Seung&ndash;Woon Rha, Byoung Geol Choi, sung il Im, Sunwon Kim, Jin Oh Na, Seongwoo Han, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Hong&ndash;Seog Seo, Chang Gyu Park, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2012)
Polycyclic aromatic hydrocarbon-induced cytotoxicity in cultured rat Sertoli cells involves differential apoptotic response.
Authors: Samir S Raychoudhury, Dana Kubinski
Journal: Environmental Health Perspectives (2002)

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous and persistent environmental contaminants. Some PAHs are carcinogens and may affect the male reproductive system. Therefore, we exposed cultured rat Sertoli cells to a variety of PAHs to determine possible direct toxic effects on the cells of the seminiferous epithelium. Sertoli cells were chosen because they support germ cell development and maintain spermatogenesis. Sertoli cells were isolated from 19-21-day-old male rats and cultured in medium containing 0.08% dimethylsulfoxide as vehicle or in the presence of a variety of PAHs. In the first set of experiments, cultured Sertoli cells were incubated in the presence of 10(-4) M, 10(-6 )M, 10(-8) M, 10(-12) M, and 10(-16) M fluoranthene (FL) for 24 hr. After 24 hr, FL at 10(4), 10(-6), and 10(-8) M killed significant numbers of Sertoli cells as revealed by cell viability determinations. Sertoli cells cultured in the presence of 10(-6) M and 10(-8) M FL showed morphologic changes. Cell protein levels were decreased and lactate production in the medium increased in a concentration-dependent manner. In addition, Sertoli cells exposed to 10(6) M and 10(-8) M FL exhibited altered F-actin and alpha-tubulin distributions compared with untreated controls. Because FL killed about 62% of cells at 10(-4) M (100 micro g/mL) and 48% of cells at 10(-6) M (1 micro g/mL), increased lactate production about 3-fold at both concentrations, and decreased cell protein by half at 10(-4) M (100 micro g/mL), we decided to use a range of concentrations between 10 and 100 micro g/mL for the second set of experiments using benz[a]anthracene (BaA), benzo[a]pyrene (BaP), or benzo[b]fluoranthene (BbF). After 24 hr, BaA (100 micro g/mL), BaP (50 and 100 micro g/mL), and BbF (100 micro g/mL) significantly increased lactate level in the medium in a concentration-dependent manner. In a third set of experiments, cells were treated in culture uniformly with only 10 micro g/mL FL, BaA, BaP, or BbF for 24 hr. The cytotoxic effects exerted by these PAHs tested resulted in different apoptotic responses as characterized by in situ fluorescence staining. Microscopic analysis of apoptotic cells demonstrated nuclei of reduced size and labeled 3 -OH DNA ends when Sertoli cells had been incubated for 24 hr with 10 micro g BaP or BbF, but not with vehicle, media, FL, or BaA. Thus, our results demonstrate that the toxic effects of BaA and BbF on Sertoli cells are exerted through apoptosis, whereas FL and BaA do not elicit the apoptotic response.
Gangliosides Link the Acidic Sphingomyelinase-Mediated Induction of Ceramide to 12-Lipoxygenase-Dependent Apoptosis of Neuroblastoma in Response to Fenretinide
Authors: P. E. Lovat, F. Di Sano, M. Corazzari, B. Fazi, R. P. Donnorso, A. D. J. Pearson, A. G. Hall, C. P. F. Redfern, M. Piacentini
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: The lipid second messenger ceramide, which is generated by acidic and neutral sphingomyelinases or ceramide synthases, is a common intermediate of many apoptotic pathways. Metabolism of ceramide involves several enzymes, including glucosylceramide synthase and GD3 synthase, and results in the formation of gangliosides (GM3, GD3, and GT3), which in turn promote the generation of reactive oxygen species (ROS) and apoptosis. Fenretinide, a retinoic acid derivative, is thought to induce apoptosis via increases in ceramide levels, but the link between ceramide and subsequent apoptosis in neuroblastoma cells is unclear. Methods: SH-SY5Y and HTLA230 neuroblastoma cells were treated with fenretinide in the presence or absence of inhibitors of enzymes important in ceramide metabolism (fumonisin B 1 , inhibitor of ceramide synthase; desipramine, inhibitor of acidic and neutral sphingomyelinases; and PDMP, inhibitor of glucosylceramide). Small interfering RNAs were used to specifically block acidic sphingomyelinase or GD3 synthase activities. Apoptosis, ROS, and GD3 expression were measured by flow cytometry. Results: In neuroblastoma cells, ROS generation and apoptosis were associated with fenretinide-induced increased levels of ceramide, glucosylceramide synthase activity, GD3 synthase activity, and GD3. Fenretinide also induced increased levels of GD2, a ganglioside derived from GD3. Inhibition of acidic sphingomyelinase but not of neutral sphingomyelinase or ceramide synthase, blocked fenretinide-induced increases in ceramide, ROS, and apoptosis. Exogenous GD3 induced ROS and apoptosis in SH-SY5Y cells but not in SH-SY5Y cells treated with baicalein, a specific 12-lipoxygenase inhibitor. Exogenous GD2 did not induce apoptosis. Conclusions: A novel pathway of fenretinide-induced apoptosis is mediated by acidic sphingomyelinase, glucosylceramide synthase, and GD3 synthase, which may represent targets for future drug development. GD3 may be a key signaling intermediate leading to apoptosis via the activation of 12-lipoxygenase.
Anaemia to predict radiographic progression in rheumatoid arthritis
Authors: Hanna W van Steenbergen, Jessica A B van Nies, Annette H M van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2013)

The severity of rheumatoid arthritis (RA) is highly variable between patients and currently known risk factors explain only part of this variance.1 Much research is dedicated to identify additional new risk factors. Such factors may shed light on the processes underlying progression of RA and many risk factors together may enable risk stratification and individualised treatment of RA.

With interest we read the study by Moller et al ,2 showing that patients with RA with anaemia have more severe radiological progression. Although anaemia in RA is generally considered to be a consequence of chronic inflammation, this recent study based on patients with RA included in the Swiss SCQM-database- observed that the association between anaemia and joint damage was independent of the association between disease activity (measured with the Disease Activity Score including the 28-swollen joint count and erythrocyte sedimentation rate (DAS28ESR) and clinical Disease Activity Index (cDAI)) and joint damage. This led to the presumptions that anaemia in RA captures disease processes that are unmeasured …
Abstract 2050: MicroRNA-124a: A master regulator of glioblastoma migration
Authors: Kerrie L. McDonald, Adam Fowler, Daniel Thomson, Keith Giles, Peter Leedman, Bruce G. Robinson
Journal: Cancer Research (2010)

Abstract For most patients diagnosed with a glioblastoma multiforme (GBM), the invasiveness of this tumor and its resistance to treatment predicts a poor outcome with no realistic possibility of a cure. Although brain tumor cells rarely metastasize outside the brain, they have an extraordinary capacity to migrate long distances and infiltrate normal brain, making complete surgical removal impossible. New therapeutic strategies are needed to target the invading cell population to further reduce tumor cell spread and a better understanding of the mechanisms promoting tumor migration and invasion are urgently needed. MiR-124a, a microRNA, normally abundantly expressed in normal adult brain tissue, shows marked down regulation (&amp;gt;1000 fold) in GBM cell lines (A172, T98G, MO59J, MO59K and U87MG). Conversely, a predicted miR-124a target, IQGAP1, is over-expressed in GBM cell lines and tissue samples. We previously demonstrated IQGAP1 overexpression in 86% of GBM patients and associated high levels with poor prognosis. IQGAP1 expression was prominent in the actively migrating and rapidly dividing palisading neoplastic cells that surround the necrotic foci. We hypothesized a reciprocal interaction between miR-124a and IQGAP1. To show this, GBM cell lines were transfected with a synthetic miR-124a precursor molecule to increase endogenous miR-124a expression. Cell migration was measured by impedence of a current (ECIS 9600) and tumor cell invasion was measured using transwell inserts. The interaction between miR-124a and IQGAP1 was ascertained using quantitative PCR, Western Blot analysis and luciferase reporter assays. Transfected miR-124a-GBM cells did not show any alterations in cell proliferation however significant reductions in tumor cell migration and invasion were observed when compared to control cells. Reducedmigration and invasion was also observed when GBM cells were transiently transfected with siRNA directed at IQGAP1. A direct effect of miR-124a on IQGAP1 expression levels was demonstrated at the mRNA and protein levels via miR-124a targeting the IQGAP1 mRNA 3’-UTR. In summary, we show that miR-124 functions as a tumour suppressor miRNA being downregulated in GBM which results in overexpression of IQGAP1. Additional migratory proteins commonly overexpressed in GBM also possess predicted miR-124a target sites and are currently been evaluated. miR-124a may therefore act as a master regulator of GBM invasiveness. Furthermore, delivery of miR-124a into GBMs may represent as a novel therapeutic approach to limit GBM invasion both alone and in combination with convential chemotherapy treatments. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2050.
INDUCTION OF LEFT VENTRICULAR DYSSYNCHRONY AND ITS POTENTIAL CONSEQUENCES ON PROGNOSIS OF PATIENTS TREATED WITH CARDIAC RESYNCHRONIZATION THERAPY
Authors: Dominique Auger, Victoria Delgado, Gabe B. Bleeker, Matteo Bertini, Rutger J. van Bommel, See Hooi Ewe, Tomasz G. Witkowski, Arnold CT Ng, Martin J. Schalij, Jeroen J. Bax
Journal: Journal of the American College of Cardiology (2011)
Vectors based on Semliki Forest virus for rapid and efficient gene transfer into non-endothelial cardiovascular cells: comparison to adenovirus
Authors: A Roks
Journal: Cardiovascular Research (1997)

Objective: Replication-deficient, recombinant adenovirus is used as a carrier for gene transfer, but it is unspecific and the onset of transgene expression is relatively late. Here, we evaluated the efficiency and selectivity of gene transfer mediated by recombinant Semliki Forest virus (SFV). Methods: We compared the efficiency of a SFV-based vector with an adenoviral vector, using LacZ as a reporter gene. Firstly, the affinity for vascular smooth muscle cells, endothelial cells and cardiac myocytes was assessed. Secondly, we compared the time course of LacZ expression and cytotoxicity in vascular smooth muscle cells. Results: The SFV-based vector infects vascular smooth muscle cells and cardiomyocytes as efficiently as adenovirus. In contrast to adenovirus, SFV hardly transfers LacZ to endothelial cells (2.6% or less). SFV-mediated expression was visible after 1 h, reaching a maximum after 6 h. In contrast, adenovirus-mediated expression became visible after 6 h, and reached a maximum after 48–72 h. Both vectors were cytotoxic. Conclusions: We demonstrate that SFV efficiently transfers LacZ to vascular smooth muscle cells and cardiomyocytes, but not to endothelial cells. In contrast, adenovirus causes efficient transgene expression in all cell types tested. Furthermore, SFV-mediated expression is faster than adenovirus-mediated expression. Therefore, SFV-mediated gene transfer may be a suitable alternative to adenovirus, providing a fast expression in non-endothelial cardiovascular cell types.
Raw milk cheeses and salmonella
Authors: A. Rampling
Journal: BMJ (1996)

In this week's BMJ Desenclos et al (p 91) describe a nationwide outbreak in France of 273 confirmed infections with Salmonella paratyphi B.1 The source of the infections was traced to cheese made from unpasteurised goats' milk. A third of the patients were so ill that they were admitted to hospital, and one died. As with most outbreaks of food poisoning, the patients with confirmed infection were probably only a minority of those affected. The outbreak began during the second week of August 1993 and continued until the second week of October, two months later. The questions that must be asked are, how could an outbreak of infection with such a serious pathogen with a common source have continued uncontrolled for so long and why was the source not identified sooner?

It was estimated by the authors that production of contaminated cheese started in mid-June; but the producer's protocol for internal quality control depended on sampling six finished cheeses from one batch each week, and it was not until 6 October that tests detected S paratyphi B in a sample of cheese. S paratyphi was then found in milk pooled from the 40 suppliers on 6 and 9 October and from milk from a tank on the farm of one supplier. The company took immediate steps to prevent further contamination of the cheese and also destroyed all batches that were still in store at the plant. It was …
Interleukin-22 Is Frequently Expressed in Small- and Large-Cell Lung Cancer and Promotes Growth in Chemotherapy-Resistant Cancer Cells
Authors: Sebastian Kobold, Stefanie Völk, Till Clauditz, Natascha Jennifer Küpper, Sarah Minner, Amanda Tufman, Peter Düwell, Michael Lindner, Ina Koch, Simon Heidegger, Simon Rothenfußer, Max Schnurr, Rudolf Maria Huber, Waldemar Wilczak, Stefan Endres
Journal: Journal of Thoracic Oncology (2013)

In lung cancer, interleukin-22 (IL-22) expression within primary tissue has been demonstrated, but the frequency and the functional consequence of IL-22 signaling have not been addressed. This study aims at analyzing the cellular effects of IL-22 on lung carcinoma cell lines and the prognostic impact of IL-22 tissue expression in lung cancer patients.Biological effects of IL-22 signaling were investigated in seven lung cancer cell lines by Western blot, flow cytometry, real-time polymerase chain reaction, and proliferation assays. Tumor tissue specimens of two cohorts with a total of 2300 lung cancer patients were tested for IL-22 expression by immunohistochemistry. IL-22 serum concentrations were analyzed in 103 additional patients by enzyme-linked immunosorbent assay.We found the IL-22 receptor 1 (IL-22-R1) to be expressed in six of seven lung cancer cell lines. However IL-22 signaling was functional in only four cell lines, where IL-22 induced signal transducer activator of transcription 3 phosphorylation and increased cell proliferation. Furthermore, IL-22 induced the expression of antiapoptotic B-cell lymphoma 2, but did not rescue tumor cells from carboplatin-induced apoptosis. Cisplatin-resistant cell lines showed a significant up-regulation of IL-22-R1 along with a stronger proliferative response to IL-22 stimulation. IL-22 was preferentially expressed in small- and large-cell lung carcinoma (58% and 46% of cases, respectively). However, no correlation between IL-22 expression by immunohistochemistry and prognosis was observed.IL-22 is frequently expressed in lung cancer tissue. Enhanced IL-22-R1 expression and signaling in chemotherapy-refractory cell lines are indicative of a protumorigenic function of IL-22 and may contribute to a more aggressive phenotype.
Moderate Hypoxia Potentiates Interleukin-1β Production in Activated Human Macrophages
Authors: Eduardo J. Folco, Galina K. Sukhova, Thibaut Quillard, Peter Libby
Journal: Circulation Research (2014)

Rationale : Inflammation drives atherogenesis. Animal and human studies have implicated interleukin-1β (IL-1β) in this disease. Moderate hypoxia, a condition that prevails in the atherosclerotic plaque, may conspire with inflammation and contribute to the evolution and complications of atherosclerosis through mechanisms that remain incompletely understood. Objective : This study investigated the links between hypoxia and inflammation by testing the hypothesis that moderate hypoxia modulates IL-1β production in activated human macrophages. Methods and Results : Our results demonstrated that hypoxia enhances pro-IL-1β protein, but not mRNA, expression in lipopolysaccharide-stimulated human macrophages. We show that hypoxia limits the selective targeting of pro-IL-1β to autophagic degradation, thus prolonging its half-life and promoting its intracellular accumulation. Furthermore, hypoxia increased the expression of NLRP3, a limiting factor in NLRP3 inflammasome function, and augmented caspase-1 activation in lipopolysaccharide-primed macrophages. Consequently, hypoxic human macrophages secreted higher amounts of mature IL-1β than did normoxic macrophages after treatment with crystalline cholesterol, an endogenous danger signal that contributes to atherogenesis. In human atherosclerotic plaques, IL-1β localizes predominantly to macrophage-rich regions that express activated caspase-1 and the hypoxia markers hypoxia-inducible factor 1α and hexokinase-2, as assessed by immunohistochemical staining of carotid endarterectomy specimens. Conclusions : These results indicate that hypoxia potentiates IL-1β expression in cultured human macrophages and in the context of atheromata, therefore unveiling a novel proinflammatory mechanism that may participate in atherogenesis.
Coupling interval, exit block, and periodicity of ventricular parasystolic rhythm
Authors: C. W. VELLANI, A. MURRAY, J. M. NEILSON
Journal: Cardiovascular Research (1979)

The electrocardiograms in this study of parasystolic rhythm were tape recorded and then analysed with a special purpose hybrid computer. The rate of appearance of specific inter-ectopic intervals was shown to change significantly with small changes in either the sinus or parasystolic pacemaker period. Natural changes in the period of the ectopic pacemakers were observed over several hours. Changes amounting to 14% within 10 min and 18% overall were observed in one patient, and a gradual lengthening of 10% over 3 h in another. A previously undescribed form of exit block has been discovered in one patient where the block remained active for a given time only after propagation from the parasystolic focus. Different interectopic intervals were shown to contribute to specific and restricted coupling interval locations in diastole. Hence this form of exit block, by preventing some inter-ectopic intervals from propagating, limited the locations in diastole in which parasystolic ectopic complexes could appear. In this case later diastolic complexes were inhibited and hence fusion complexes were completely absent. Parasystolic rhythm, with and without the exit block described, was simulated successfully by a digital computer. The simulations aided our understanding of the clinical data.