tbuckley/cabot-search huggingface dataset:
Tanshinone IIA inhibits metastasis after palliative resection of hepatocellular carcinoma and prolongs survival in part via vascular normalization
Authors: Wen-Quan Wang, Liang Liu, Hui-Chuan Sun, Yan-Ling Fu, Hua-Xiang Xu, Zong-Tao Chai, Qiang-Bo Zhang, Ling-Qun Kong, Xiao-Dong Zhu, Lu Lu, Zheng-Gang Ren, Zhao-You Tang
Journal: Journal of Hematology & Oncology (2012)

Abstract Background Promotion of endothelial normalization restores tumor oxygenation and obstructs tumor cells invasion, intravasation, and metastasis. We therefore investigated whether a vasoactive drug, tanshinone IIA, could inhibit metastasis by inducing vascular normalization after palliative resection (PR) of hepatocellular carcinoma (HCC). Methods A liver orthotopic double-tumor xenograft model in nude mouse was established by implantation of HCCLM3 (high metastatic potential) and HepG2 tumor cells. After removal of one tumor by PR, the effects of tanshinone IIA administration on metastasis, tumor vascularization, and survival were evaluated. Tube formation was examined in mouse tumor-derived endothelial cells (TECs) treated with tanshinone IIA. Results PR significantly accelerated residual hepatoma metastases. Tanshinone IIA did not inhibit growth of single-xenotransplanted tumors, but it did reduce the occurrence of metastases. Moreover, it inhibited PR-enhanced metastases and, more importantly, prolonged host survival. Tanshinone IIA alleviated residual tumor hypoxia and suppressed epithelial-mesenchymal transition (EMT) in vivo; however, it did not downregulate hypoxia-inducible factor 1α (HIF-1α) or reverse EMT of tumor cells under hypoxic conditions in vitro. Tanshinone IIA directly strengthened tube formation of TECs, associated with vascular endothelial cell growth factor receptor 1/platelet derived growth factor receptor (VEGFR1/PDGFR) upregulation. Although the microvessel density (MVD) of residual tumor tissue increased after PR, the microvessel integrity (MVI) was still low. While tanshinone IIA did not inhibit MVD, it did dramatically increase MVI, leading to vascular normalization. Conclusions Our results demonstrate that tanshinone IIA can inhibit the enhanced HCC metastasis associated with PR. Inhibition results from promoting VEGFR1/PDGFR-related vascular normalization. This application demonstrates the potential clinical benefit of preventing postsurgical recurrence.
Phase III multicenter randomized trial of amifostine as cytoprotectant in first-line chemotherapy in ovarian cancer patients
Authors: D. Lorusso, G. Ferrandina, S. Greggi, A. Gadducci, S. Pignata, S. Tateo, R. Biamonte, L. Manzione, G. Di Vagno, F. Ferrau’, G. Scambia
Journal: Annals of Oncology (2003)
Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport
Authors: Fatima Ferreirinha, Angelo Quattrini, Marinella Pirozzi, Valentina Valsecchi, Giorgia Dina, Vania Broccoli, Alberto Auricchio, Fiorella Piemonte, Giulia Tozzi, Laura Gaeta, Giorgio Casari, Andrea Ballabio, Elena I. Rugarli
Journal: Journal of Clinical Investigation (2004)

In several neurodegenerative diseases, axonal degeneration occurs before neuronal death and contributes significantly to patients’ disability. Hereditary spastic paraplegia (HSP) is a genetically heterogeneous condition characterized by selective degeneration of axons of the corticospinal tracts and fasciculus gracilis. HSP may therefore be considered an exemplary disease to study the local programs mediating axonal degeneration. We have developed a mouse model for autosomal recessive HSP due to mutations in the SPG7 gene encoding the mitochondrial ATPase paraplegin. Paraplegin-deficient mice are affected by a distal axonopathy of spinal and peripheral axons, characterized by axonal swelling and degeneration. We found that mitochondrial morphological abnormalities occurred in synaptic terminals and in distal regions of axons long before the first signs of swelling and degeneration and correlated with onset of motor impairment during a rotarod test. Axonal swellings occur through massive accumulation of organelles and neurofilaments, suggesting impairment of anterograde axonal transport. Retrograde axonal transport is delayed in symptomatic mice. We speculate that local failure of mitochondrial function may affect axonal transport and cause axonal degeneration. Our data suggest that a timely therapeutic intervention may prevent the loss of axons.
Risk of leukaemia in children infected with enterovirus: a nationwide, retrospective, population-based, Taiwanese-registry, cohort study
Authors: Jiun-Nong Lin, Cheng-Li Lin, Ming-Chia Lin, Chung-Hsu Lai, Hsi-Hsun Lin, Chih-Hui Yang, Fung-Chang Sung, Chia-Hung Kao
Journal: The Lancet Oncology (2015)
Progressive cavitating pulmonary changes in rheumatoid arthritis: a case report.
Authors: J D Macfarlane, C K Franken, A W van Leeuwen
Journal: Annals of the Rheumatic Diseases (1984)

Progressive cavitating changes in the lung apices were found in a middle-aged man with seropositive rheumatoid arthritis. These findings were attributed at autopsy to a combination of nodule-type formation, necrosis, and mild fibrosis.
A randomized phase II study investigating the addition of the specific COX-2 inhibitor celecoxib to docetaxel plus carboplatin as first-line chemotherapy for stage IC to IV epithelial ovarian cancer, Fallopian tube or primary peritoneal carcinomas: the DoCaCel study
Authors: A.K.L. Reyners, L. de Munck, F.L.G. Erdkamp, W.M. Smit, K. Hoekman, R.I. Lalisang, H. de Graaf, A.N.M. Wymenga, M. Polee, H. Hollema, M.A.T.M. van Vugt, M. Schaapveld, P.H.B. Willemse
Journal: Annals of Oncology (2012)
Inhibition of reactive oxygen species downregulates the MAPK pathway in rat spinal cord after limb ischemia reperfusion injury
Authors: Eun Kyung Choi, Jin-Seok Yeo, Chan Yoon Park, Ho in Na, Jung a Lim, Jeong-Eun Lee, Seong Wook Hong, Sung-Sik Park, Dong Gun Lim, Kyung Hwa Kwak
Journal: International Journal of Surgery (2015)
Differentiation of human bone marrow-derived cells into buccal epithelial cells in vivo: a molecular analytical study
Authors: Simon D Tran, Stanley R Pillemer, Amalia Dutra, A John Barrett, Michael J Brownstein, Sharon Key, Evgenia Pak, Rose Anne Leakan, Albert Kingman, Kenneth M Yamada, Bruce J Baum, Eva Mezey
Journal: The Lancet (2003)
Implications of Widespread Covalent Modification of mRNA
Authors: Thomas A. Cooper
Journal: Circulation Research (2012)

W hole transcriptome analysis reveals that one third of human and mouse genes express mRNAs containing methylated adenosines.Fat mass and obesity-associated (FTO) gene, a risk gene for obesity and metabolic abnormalities, demethylates the modified residues, suggesting a link between RNA methylation and disease.Vertebrate ribosomal RNA (rRNA), transfer RNA (tRNA), messenger RNAs (mRNAs) as well as viral RNAs can be methylated at the N6 position of adenosines to produce N6methyladenosine (m6A).Although the presence of m6A modifications in mRNA has been known for decades and a handful of vertebrate m6A-modified mRNAs have been identified, the extent of m6A modification in mRNAs was unknown.Two recent articles using massively parallel sequencing found that mRNAs from more than one third of human and mouse genes contain m6A. 1,2N6-methyladenosines were found to be enriched near the translational stop codon, as well as in mRNA segments derived from large exons.Furthermore, the results showed that the genes modified and the distribution of modifications within mRNAs is conserved between mouse and humans.Particularly intriguing is the recent discovery that FTO gene, a risk gene for obesity and metabolic abnormalities, is an m6A demethylase.These results suggest a potential regulatory role for covalent modification of RNA and a link with metabolic disorders.Over the past 2 decades, RNA has been revealed as one of the most functionally diverse and information-rich molecules in the cell. 3RNA can function as a viral genome, message, decoding machine, guide to target proteins, enzyme, template and primer for DNA synthesis, and structural component.RNA carries information as primary nucleotide sequence and
Rupture of Rectus Abdominis during Pregnancy
Authors: J. B. Dawson
Journal: BMJ (1944)

Staphylococcal Septicaemia treated with PenicillinThe following record of a case of septicaemia which responded to treatment with penicillin may be of interest.CASE HISTORY The patient, a lance-corporal aged 21, had been treated for sinusitis two months before the present illness, and had had 'several examinations on account of chronic cough; these were Tb.-negative.Two weeks before admission to hospital he had had a boil on the neck, which healed on being opened and drained.Five days before admission he reported sick with acute pain over the right sacro-iliac region.There were no other symptoms, and no pyrexia.He was treated at home with local heat.An unusual feature was the extreme I would like to thank Mr.
Intestinal GUCY2C Prevents TGF-β Secretion Coordinating Desmoplasia and Hyperproliferation in Colorectal Cancer
Authors: Ahmara V. Gibbons, Jieru E. Lin, Gilbert W. Kim, Glen P. Marszalowicz, Peng Li, Brian A. Stoecker, Erik S. Blomain, Satish Rattan, Adam E. Snook, Stephanie Schulz, Scott A. Waldman
Journal: Cancer Research (2013)

Abstract Tumorigenesis is a multistep process that reflects intimate reciprocal interactions between epithelia and underlying stroma. However, tumor-initiating mechanisms coordinating transformation of both epithelial and stromal components are not defined. In humans and mice, initiation of colorectal cancer is universally associated with loss of guanylin and uroguanylin, the endogenous ligands for the tumor suppressor guanylyl cyclase C (GUCY2C), disrupting a network of homeostatic mechanisms along the crypt-surface axis. Here, we reveal that silencing GUCY2C in human colon cancer cells increases Akt-dependent TGF-β secretion, activating fibroblasts through TGF-β type I receptors and Smad3 phosphorylation. In turn, activating TGF-β signaling induces fibroblasts to secrete hepatocyte growth factor (HGF), reciprocally driving colon cancer cell proliferation through cMET-dependent signaling. Elimination of GUCY2C signaling in mice (Gucy2c−/−) produces intestinal desmoplasia, with increased reactive myofibroblasts, which is suppressed by anti-TGF-β antibodies or genetic silencing of Akt. Thus, GUCY2C coordinates intestinal epithelial–mesenchymal homeostasis through reciprocal paracrine circuits mediated by TGF-β and HGF. In that context, GUCY2C signaling constitutes a direct link between the initiation of colorectal cancer and the induction of its associated desmoplastic stromal niche. The recent regulatory approval of oral GUCY2C ligands to treat chronic gastrointestinal disorders underscores the potential therapeutic opportunity for oral GUCY2C hormone replacement to prevent remodeling of the microenvironment essential for colorectal tumorigenesis. Cancer Res; 73(22); 6654–66. ©2013 AACR.
Development of Quality Indicators for Patients Undergoing Colorectal Cancer Surgery
Authors: Marcia L. McGory, Paul G. Shekelle, Clifford Y. Ko
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Colorectal cancer is the second most common cancer type among new cancer diagnoses in the United States. Attention to the quality of surgical care for colorectal cancer is of particular importance given the increasing numbers of colorectal cancer resections performed in the aging population. A National Cancer Institute–sponsored consensus panel produced guidelines for colorectal cancer surgery in 2000. We have updated and extended that work by using a formal process to identify and rate quality indicators as valid for care during the preoperative, intraoperative, and postoperative periods. Methods: Using a modification of the RAND/UCLA Appropriateness Methodology, we carried out structured interviews with leaders in the field of colorectal cancer surgery and systematic reviews of the literature to identify candidate quality indicators addressing perioperative care for patients undergoing surgery for colorectal cancer. A panel of 14 colorectal surgeons, general surgeons, and surgical oncologists then evaluated and formally rated the indicators using the modified Delphi method to identify valid indicators. Results: A total of 142 candidate indicators were identified in six broad domains: privileging (which addresses surgical credentials), preoperative evaluation, patient–provider discussions, medication use, intraoperative care, and postoperative management. The expert panel rated 92 indicators as valid. These indicators address all domains of perioperative care for patients undergoing surgery for colorectal cancer. Conclusions: The RAND/UCLA Appropriateness Methodology can be used to identify and rate indicators of high-quality perioperative care for patients undergoing surgery for colorectal cancer. The indicators can be used as quality performance measures and for quality-improvement programs.
Surgery of the Anus, Rectum and Colon
Authors: R. PHILLIPS
Journal: Gut (2000)

Surgery of the Anus, Rectum and Colon . 2nd ed. Vol 1 & 2. Edited by Keighley MRB, Williams NS. (Pp 2872; illustrated; £285.) United Kingdom: Harcourt Brace, 1999. ISBN 0 70202 335 3.

The last dinosaur disappeared from Earth over 66 million years ago, wiped out in some cataclysm that changed the world and its climate for ever.

Mankind gradually evolved, competing in a hostile environment, winning because …
Once-Daily Bronchodilators for Chronic Obstructive Pulmonary Disease
Authors: James F. Donohue, Charles Fogarty, Jan Lötvall, Donald A. Mahler, Heinrich Worth, Arzu Yorgancioğlu, Amir Iqbal, James Swales, Roger Owen, Mark Higgins, Benjamin Kramer
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Indacaterol is the first once-daily, long-acting inhaled beta(2)-agonist bronchodilator studied in patients with chronic obstructive pulmonary disease (COPD).To demonstrate greater efficacy of indacaterol versus placebo on FEV(1) at 24 hours post dose (trough) after 12 weeks, to compare efficacy with placebo and tiotropium, and to evaluate safety and tolerability over 26 weeks.Patients with moderate-to-severe COPD were randomized to double-blind indacaterol 150 or 300 microg or placebo, or open-label tiotropium 18 microg, all once daily, for 26 weeks. The primary efficacy outcome was trough FEV(1) at 12 weeks. Additional analyses (not adjusted for multiplicity) included transition dyspnea index (TDI), health status (St George's Respiratory Questionnaire [SGRQ]), and exacerbations. Serum potassium, blood glucose, and QTc interval were measured.A total of 1,683 patients (age, 63.3 yr; post-bronchodilator FEV(1), 56% predicted; FEV(1)/FVC, 0.53) were randomized to the four treatment arms. Trough FEV(1) at Week 12 increased versus placebo by 180 ml with both indacaterol doses and by 140 ml with tiotropium (all P < 0.001 vs. placebo). At Week 26, for indacaterol 150/300 microg, respectively, versus placebo, TDI increased (1.00/1.18, P < 0.001) and SGRQ total score decreased (-3.3/-2.4, P < 0.01); corresponding results with tiotropium were 0.87 (P < 0.001) for TDI and (-1.0, P = not significant) for SGRQ total score. The incidence of adverse events, low serum potassium, high blood glucose, and prolonged QTc interval was similar across treatments.Indacaterol was an effective once-daily bronchodilator and was at least as effective as tiotropium in improving clinical outcomes for patients with COPD. Clinical trial registered with clinicaltrials.gov (NCT 00463567).
Behavioral Science Research in Diabetes: Lifestyle changes related to obesity, eating behavior, and physical activity
Authors: R. R. Wing, M. G. Goldstein, K. J. Acton, L. L. Birch, J. M. Jakicic, J. F. Sallis, D. Smith-West, R. W. Jeffery, R. S. Surwit
Journal: Diabetes Care (2001)

Lifestyle factors related to obesity, eating behavior, and physical activity play a major role in the prevention and treatment of type 2 diabetes. In recent years, there has been progress in the development of behavioral strategies to modify these lifestyle behaviors. Further research, however, is clearly needed, because the rates of obesity in our country are escalating, and changing behavior for the long term has proven to be very difficult. This review article, which grew out of a National Institute of Diabetes and Digestive and Kidney Diseases conference on behavioral science research in diabetes, identifies four key topics related to obesity and physical activity that should be given high priority in future research efforts: 1) environmental factors related to obesity, eating, and physical activity; 2) adoption and maintenance of healthful eating, physical activity, and weight; 3) etiology of eating and physical activity; and 4) multiple behavior changes. This review article discusses the significance of each of these four topics, briefly reviews prior research in each area, identifies barriers to progress, and makes specific research recommendations.
Repertoire, diversity, and differentiation of specific CD8 T cells are associated with immune protection against human cytomegalovirus disease
Authors: Karim Sacre, Guislaine Carcelain, Nathalie Cassoux, Anne-Marie Fillet, Dominique Costagliola, Daniel Vittecoq, Dominique Salmon, Zahir Amoura, Christine Katlama, Brigitte Autran
Journal: The Journal of Experimental Medicine (2005)

To determine the correlates of immune recovery from active human CMV (HCMV) disease, we compared the antigenic repertoire, diversity, magnitude, and differentiation of HCMV-specific CD8+ T cells in HIV-HCMV coinfected subjects with no, cured, or active HCMV disease and in healthy HIV-negative HCMV-positive controls. ELISPOT–IFN-γ assays using peptide pools spanning the pp65 and immediate early 1 (IE1) HCMV proteins showed that HCMV-specific CD8+ T cells had a significantly broader antigenic repertoire and greater diversity in HIV-positive patients controlling HCMV replication than in those with active HCMV disease, but the magnitude of the CD8 T cell response did not differ between the different groups. HCMV-specific T cells mainly were focused against IE1 during the short-term recovery from retinitis, and switched toward pp65 during long-term recovery. HCMV-specific T cells displaying an “early” (CD8+CD27+CD28+) and “intermediate” (CD8+CD27−CD28+) differentiation phenotype were increased significantly during long-term recovery compared with other HIV-positive patients and were nearly undetectable during active HCMV disease. HCMV-specific T cells with a “late” (CD8+CD27−28−) differentiation phenotype predominated in all cases. Therefore, restoration of immune protection against HCMV after active HCMV disease in immunodeficient individuals is associated with enlarged repertoire and diversity, and with early differentiation of virus-specific CD8+ T cells, thus defining immune correlates of protection against diseases caused by persistent viruses.
Multiphoton Imaging of the Functioning Kidney
Authors: Andrew M. Hall, Carol Crawford, Robert J. Unwin, Michael R. Duchen, Claire M. Peppiatt-Wildman
Journal: Journal of the American Society of Nephrology (2011)

Translating discoveries made in isolated renal cells and tubules to the in vivo situation requires the assessment of cellular function in intact live organs. Multiphoton imaging is a form of fluorescence microscopy that is ideally suited to working with whole tissues and organs, but adequately loading cells with fluorescence dyes in vivo remains a challenge. We found that recirculation of fluorescence dyes in the rat isolated perfused kidney (IPK) resulted in levels of intracellular loading that would be difficult to achieve in vivo. This technique allowed the imaging of tubular cell structure and function with multiphoton microscopy in an intact, functioning organ. We used this approach to follow processes in real time, including (1) relative rates of reactive oxygen species (ROS) production in different tubule types, (2) filtration and tubular uptake of low-molecular-weight dextrans and proteins, and (3) the effects of ischemia-reperfusion injury on mitochondrial function and cell structure. This study demonstrates that multiphoton microscopy of the isolated perfused kidney is a powerful technique for detailed imaging of cell structure and function in an intact organ.
Anonymous Mycobacteria in the Etiology of Sarcoidosis
Authors: HERBERT W. BERGER
Journal: Annals of Internal Medicine (1968)

A case is reported of a 17-year-old negro boy with typical clinical evidence of sarcoidosis. Biopsy of a cervical lymph node showed noncaseating epithelioid cell granuloma consistent with the diagnosis of sarcoidosis; the Kveim test was positive. Culture of the biopsied lymph node revealed two colonies of scotochromogenic mycobacteria. The possible role of anonymous mycobacteria as a causal agent of sarcoidosis is discussed, and the literature on this subject reviewed.
Viruses and lymphocytes in rheumatoid arthritis. II. Examination of lymphocytes and sera from patients with rheumatoid arthritis for evidence of retrovirus infection.
Authors: H Hart, J N McCormick, B P Marmion
Journal: Annals of the Rheumatic Diseases (1979)

The possible involvement of retroviruses in the aetiology of rheumatoid arthritis (RA) was investigated.Retrovirus antigens were not expressed on rheumatoid synovial and peripheral blood lymphocytes as judged by membrane immunofluorescence, radioimmunoassay, and comple- ment-mediated cytotoxicity.The specific antiretroviral (anti-RD-144 and anti-SSAV) sera used in this study were produced in rabbits immunised with viral antigens grown in a homologous system (rabbit cells and medium supplemented with normal rabbit serum), avoiding non-specific immunofluorescence previously detected with donated antiretroviral sera.Immune complexes lodged in the rheumatoid synovial membranes did not contain, and other cells within the membranes did not express, retroviral antigens.Antibodies cross-reacting with primate retrovirus antigens were sought in sera from patients with 'autoimmune' diseases by means of solid phase radioimmunoassay.There were no retrovirus antibodies in the 3 groups of patients studied, that is, those with rheumatoid arthritis, systemic lupus erythematosus, and with non-RA conditions.Absorption of rheumatoid factor did not alter this conclusion.These results give little support to the hypothesis that activation of endogenous human retroviruses or an infection with horizontally transmitted retroviruses is associated with the rheumatoid process.
Anecortave Acetate (15 Milligrams) versus Photodynamic Therapy for Treatment of Subfoveal Neovascularization in Age-Related Macular Degeneration
Authors: Jason S. Slakter, Thomas Bochow, Donald J. D’Amico, Bethany Marks, Janice Jerdan, E. Kenneth Sullivan
Journal: Ophthalmology (2005)