tbuckley/cabot-search huggingface dataset:
Rat pancreatic stellate cells secrete matrix metalloproteinases: implications for extracellular matrix turnover
Authors: P A Phillips
Journal: Gut (2003)

<b>Background:</b> Pancreatic fibrosis is a characteristic feature of chronic pancreatic injury and is thought to result from a change in the balance between synthesis and degradation of extracellular matrix (ECM) proteins. Recent studies suggest that activated pancreatic stellate cells (PSCs) play a central role in pancreatic fibrogenesis via increased synthesis of ECM proteins. However, the role of these cells in ECM protein degradation has not been fully elucidated. <b>Aims:</b> To determine: (i) whether PSCs secrete matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) and, if so (ii) whether MMP and TIMP secretion by PSCs is altered in response to known PSC activating factors such as tumour necrosis factor α (TNF-α), transforming growth factor β1 (TGF-β1), interleukin 6 (IL-6), ethanol, and acetaldehyde. <b>Methods:</b> Cultured rat PSCs (n=3–5 separate cell preparations) were incubated at 37°C for 24 hours with serum free culture medium containing TNF-α (5–25 U/ml), TGF-β1 (0.5–1 ng/ml), IL-6 (0.001–10 ng/ml), ethanol (10–50 mM), or acetaldehyde (150–200 μM), or no additions (controls). Medium from control cells was examined for the presence of MMPs by zymography using a 10% polyacrylamide-0.1% gelatin gel. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine gene expression of MMP9 and the tissue inhibitors of metalloproteinases TIMP1 and TIMP2. Western blotting was used to identify a specific MMP, MMP2 (a gelatinase that digests basement membrane collagen and the dominant MMP observed on zymography) and a specific TIMP, TIMP2. Reverse zymography was used to examine functional TIMPs in PSC secretions. The effect of TNF-α, TGF-β1, and IL-6 on MMP2 secretion was assessed by densitometry of western blots. The effect of ethanol and acetaldehyde on MMP2 and TIMP2 secretion was also assessed by this method. <b>Results:</b> Zymography revealed that PSCs secrete a number of MMPs including proteinases with molecular weights consistent with MMP2, MMP9, and MMP13. RT-PCR demonstrated the presence of mRNA for metalloproteinase inhibitors TIMP1 and TIMP2 in PSCs while reverse zymography revealed the presence of functional TIMP2 in PSC secretions. MMP2 secretion by PSCs was significantly increased by TGF-β1 and IL-6, but was not affected by TNF-α. Ethanol and acetaldehyde induced secretion of both MMP2 and TIMP2 by PSCs. <b>Conclusions:</b> Pancreatic stellate cells have the capacity to synthesise a number of matrix metalloproteinases, including MMP2, MMP9, and MMP13 and their inhibitors TIMP1 and TIMP2. MMP2 secretion by PSCs is significantly increased on exposure to the proinflammatory cytokines TGF-β1 and IL-6. Both ethanol and its metabolite acetaldehyde increase MMP2 as well as TIMP2 secretion by PSCs. <b>Implication:</b> The role of pancreatic stellate cells in extracellular matrix formation and fibrogenesis may be related to their capacity to regulate the degradation as well as the synthesis of extracellular matrix proteins.
Age-related differences among patients with follicular lymphoma and the importance of prognostic scoring systems: analysis from a population-based non-Hodgkin’slymphoma registry
Authors: E. Maartense, S. le Cessie, H.C. Kluin-Nelemans, P.M. Kluin, S. Snijder, P.W. Wijermans, E.M. Noordijk
Journal: Annals of Oncology (2002)
Proton Beams in Radiation Therapy
Authors: H. Suit, M. Urie
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Proton Beams in Radiation Therapy Get access Herman Suit, Herman Suit * Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical SchoolBoston, Mass *Correspondence to : Herman D. Suit, M.D., Ph.D., Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114. Search for other works by this author on: Oxford Academic PubMed Google Scholar Marcia Urie Marcia Urie Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical SchoolBoston, Mass Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 3, 5 February 1992, Pages 155–164, https://doi.org/10.1093/jnci/84.3.155 Published: 05 February 1992 Article history Received: 21 September 1991 Accepted: 21 November 1991 Published: 05 February 1992
Association between polymorphism in regulatory region of gene encoding tumour necrosis factor α and risk of Alzheimer's disease and vascular dementia: a case-control study
Authors: Shauna M McCusker, Martin D Curran, Kevin B Dynan, Catriona D McCullagh, Duncan D Urquhart, Derek Middleton, Christopher C Patterson, Stephen P McIlroy, A Peter Passmore
Journal: The Lancet (2001)
ZEB1 Promotes Invasiveness of Colorectal Carcinoma Cells through the Opposing Regulation of uPA and PAI-1
Authors: Ester Sánchez-Tilló, Oriol de Barrios, Laura Siles, Pier G. Amendola, Douglas S. Darling, Miriam Cuatrecasas, Antoni Castells, Antonio Postigo
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Carcinoma cells enhance their invasive capacity through dedifferentiation and dissolution of intercellular adhesions. A key activator of this process is the ZEB1 transcription factor, which is induced in invading cancer cells by canonical Wnt signaling (β-catenin/TCF4). Tumor invasiveness also entails proteolytic remodeling of the peritumoral stroma. This study aimed to investigate the potential regulation by ZEB1 of the plasminogen proteolytic system constituted by the urokinase plasminogen activator (uPA), and its inhibitor, plasminogen activator inhibitor-1 (PAI-1). Experimental Design: Through multiple experimental approaches, colorectal carcinoma (CRC) cell lines and samples from human primary CRC and ZEB1 (−/−) mice were used to examine ZEB1-mediated regulation of uPA and PAI-1 at the protein, mRNA, and transcriptional level. Results: ZEB1 regulates uPA and PAI-1 in opposite directions: induces uPA and inhibits PAI-1. In vivo expression of uPA depends on ZEB1 as it is severely reduced in the developing intestine of ZEB1 null (−/−) mice. Optimal induction of uPA by Wnt signaling requires ZEB1 expression. ZEB1 binds to the uPA promoter and activates its transcription through a mechanism implicating the histone acetyltransferase p300. In contrast, inhibition of PAI-1 by ZEB1 does not involve transcriptional repression but rather downregulation of mRNA stability. ZEB1-mediated tumor cell migration and invasion depend on its induction of uPA. ZEB1 coexpresses with uPA in cancer cells at the invasive front of CRCs. Conclusions: ZEB1 promotes tumor invasiveness not only via induction in cancer cells of a motile dedifferentiated phenotype but also by differential regulation of genes involved in stroma remodeling. Clin Cancer Res; 19(5); 1071–82. ©2013 AACR.
<i>DROSOPHILA</i> NUTRIGENOMICS CAN PROVIDE CLUES TO HUMAN GENE-NUTRIENT INTERACTIONS
Authors: Douglas M. Ruden, Maria De Luca, Mark D. Garfinkel, Kerry L. Bynum, Xiangyi Lu
Journal: Annual Review of Nutrition (2005)

▪ Abstract Nutrigenomics refers to the complex effects of the nutritional environment on the genome, epigenome, and proteome of an organism. The diverse tissue- and organ-specific effects of diet include gene expression patterns, organization of the chromatin, and protein post-translational modifications. Long-term effects of diet range from obesity and associated diseases such as diabetes and cardiovascular disease to increased or decreased longevity. Furthermore, the diet of the mother can potentially have long-term health impacts on the children, possibly through inherited diet-induced chromatin alterations. Drosophila is a unique and ideal model organism for conducting nutrigenomics research for numerous reasons. Drosophila, yeast, and Caenorhabditis elegans all have sophisticated genetics as well as sequenced genomes, and researchers working with all three organisms have made valuable discoveries in nutrigenomics. However, unlike yeast and C. elegans, Drosophila has adipose-like tissues and a lipid transport system, making it a closer model to humans. This review summarizes what has already been learned in Drosophila nutrigenomics (with an emphasis on lipids and sterols), critically evaluates the data, and discusses fruitful areas for future research.
Factors Influencing Cholesterol Nucleation in Bile
Authors: Thomas R. Holzbach
Journal: Hepatology (1984)

Dilution induces structural alterations (i.e., vesicle formation) in the lipid particles of supersaturated human hepatic bile and in dilute model bile systems of comparable composition. These alterations strikingly increase both the degree and duration of metastable supersaturation. Concentrated normal human gallbladder bile also shows an increased but less striking degree and duration of metastability compared to comparable model biles. These differences, particularly with respect to gallbladder bile, cannot be attributed solely to compositional or lipid structural differences between native and model systems. They imply that additional factors are responsible for metastability. Furthermore, recent data suggest that biliary proteins may be involved. A limited number of these unidentified proteins have been shown to have the capacity to prolong metastability in supersaturated in vitro model systems. Thus, these recombined systems more nearly resemble the behavior of native bile. The mechanism of the nucleation inhibitory effect of these proteins is not clearly established.
No Treatment versus 24 or 60 Weeks of Antiretroviral Treatment during Primary HIV Infection: The Randomized Primo-SHM Trial
Authors: Marlous L. Grijsen, Radjin Steingrover, Ferdinand W. N. M. Wit, Suzanne Jurriaans, Annelies Verbon, Kees Brinkman, Marchina E. van der Ende, Robin Soetekouw, Frank de Wolf, Joep M. A. Lange, Hanneke Schuitemaker, Jan M. Prins
Journal: PLoS Medicine (2012)

In a three-arm randomized trial conducted among adult patients in HIV treatment centers in The Netherlands, Marlous Grijsen and colleagues examine the effects of temporary combination antiretroviral therapy during primary HIV infection.
Pharmacokinetics, Metabolism and Toxicity of Carbon Nanotubes for Biomedical Purposes
Authors: Sheng-Tao Yang, Jianbin Luo, Qinghan Zhou, Haifang Wang
Journal: Theranostics (2012)

Carbon nanotubes (CNTs) have attracted great interest of the nano community and beyond. However, the biomedical applications of CNTs arouse serious concerns for their unknown in vivo consequence, in which the information of pharmacokinetics, metabolism and toxicity of CNTs is essential. In this review, we summarize the updated data of CNTs from the biomedical view. The information shows that surface chemistry is crucial in regulating the in vivo behaviors of CNTs. Among the functionalization methods, PEGylation is the most efficient one to improve the pharmacokinetics and biocompatibility of CNTs. The guiding effects of the pharmacokinetics, metabolism and toxicity information on the biomedical applications of CNTs are discussed.
Response to Sunitinib Malate in Advanced Alveolar Soft Part Sarcoma
Authors: Silvia Stacchiotti, Elena Tamborini, Andrea Marrari, Silvia Brich, Sara Arisi Rota, Marta Orsenigo, Flavio Crippa, Carlo Morosi, Alessandro Gronchi, Marco A. Pierotti, Paolo G. Casali, Silvana Pilotti
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Alveolar soft part sarcoma (ASPS) is a rare, chemoresistant soft tissue sarcoma. ASPS harbors the t(17-X) (p11.2;q25) translocation, resulting in the ASPACR1-TFE3 fusion protein, causing MET autophosphorylation and activation of downstream signaling. The tumor vascular pattern prompted us to use sunitinib malate (SM), a tyrosine kinase inhibitor with antiangiogenic properties. Experimental Design: Since July 2007, five patients with progressive metastatic ASPS have been treated with continuous SM 37.5 mg/d on a named basis. Four patients are evaluable for response. In four cases, cryopreserved material was available. Upstream and downstream targets of receptor tyrosine kinase (RTK) pathways, as well as mechanisms of activation, were investigated by biochemical profiles, including human phospho-receptor RTK antibody arrays and immunoprecipitation/Western blotting, molecular analyses, immunohistochemistry, and fluorescence in situ hybridization analyses. Results: After 3 months, two patients had RECIST (response evaluation criteria in solid tumor) partial response, as well as positron emission tomography response and subjective improvement. One had a RECIST stable disease. One progressed and stopped treatment. One patient is still responding after 12 months. The upstream analysis showed activation of all the platelet-derived growth factor receptor (PDGFR) family members, as well as epidermal growth factor receptor, MET families, and RET. Vascular endothelial growth factor receptors (VEGFR1 and VEGFR2) were activated only in one case. The downstream target analysis showed strong activation of phosphatidylinositol 3-kinase/AKT, extracellular signal-regulated kinase 1/2, and mTOR and its targets (S6K and S6). The absence of any upstream mTOR effector deregulation and the presence of RTK cognate ligands support an autocrine-paracrine activation loop mechanism. Conclusion: SM may have antitumor activity in ASPS, possibly through a mechanism involving PDGFR and RET. The role of MET, epidermal growth factor receptor, and mTOR, as well as PDGFR inhibition, needs to be further explored.
Pulmonary hypertension and fenfluramine
Authors: HM Pouwels, JL Smeets, EC Cheriex, EF Wouters
Journal: European Respiratory Journal (1990)

Fenfluramine is a widely prescribed anorectic drug as adjuvant therapy for obesity. Pulmonary vascular hypertension after use of fenfluramine is rarely reported. We present a patient with pulmonary hypertension and right heart failure after treatment with fenfluramine. Pulmonary hypertension resolved after withdrawal of the drug.
Twin Interactions in a Normal Nursery School
Authors: MARIA PALUSZNY, RALPH GIBSON
Journal: American Journal of Psychiatry (1974)

The authors studied ten sets of middle-class fraternal twins in an effort to determine what factors influenced the twinning relationship. They found that five sets of twins showed some form of mutual dependency and that two showed one-sided dependency; in each case mother-child dependency was excessive. Three pairs of twins showed minimal or no dependency. Each of these groups is illustrated with a case report. Follow-up of six sets of twins revealed an unexpectedly high incidence of neurotic problems that were not significantly related to dependency. The authors offer several possible explanations for this finding.
Relation of Arterial Blood Pressure to the Transverse Diameter of the Heart in Compensated Hypertensive Heart Disease
Authors: ELI A. RAMIREZ, PEDRO H. GARCIA PONT
Journal: Circulation (1965)

In 535 male hypertensive patients the correlation coefficient between the corrected transverse diameter of the heart and the systolic pressure was +0.301. With diastolic pressure the correlation coefficient was +0.209. Both coefficients were significant ( p &lt;0.001), but the association between the variables was quite small in both correlations. The correlation between the corrected transverse diameter and the systolic pressure was significantly better than with the diastolic pressure, ( p &lt;0.001). The correlation between the corrected transverse diameter and the systolic pressure was independent of age.
Pulmonary Fibrosis Masking Polymyositis
Authors: D. Robert Webb
Journal: JAMA (1972)

A case of polymyositis with pulmonary fibrosis was unusual in that a striking remission occurred after high-dosage therapy with corticosteroids was instituted. This remission has persisted now for some 20 months. The presence of muscle disease in this patient and in several patients previously reported was masked by the more impressive symptoms of pulmonary disease. A search for occult muscle disease in patients with pulmonary fibrosis is recommended. The presence of inflammatory muscle disease in patients with pulmonary fibrosis suggests high-dosage therapy with corticosteroid (80 to 100 mg prednisone daily) may be required for therapeutic response.
STUDIES ON EXPERIMENTAL HYPERTENSION
Authors: Harry Goldblatt, Harry Weinstein, Joseph R. Kahn
Journal: The Journal of Experimental Medicine (1941)

By means of a silver chain attached to a silver ring around the main renal artery, intermittent renal arterial occlusion, up to 30 minutes daily, was practiced for as long as 5 months in unilaterally nephrectomized dogs. This did not result in the development of persistently elevated blood pressure. Persistent moderate constriction of the renal artery of such animals by a silver clamp, after intermittent temporary occlusion had failed to affect the blood pressure, produced the usual rise of blood pressure, without accompanying significant impairment of renal excretory function. When the renal artery accidentally became persistently constricted to a great degree, or actually occluded, or if occlusion was deliberately produced by continuous pulling of the chain, hypertension and renal insufficiency (the malignant phase) quickly developed. The results do not lend support to the view that brief daily periods of renal ischemia from intrarenal vasospasm, or from any other cause, can produce persistent hypertension of renal origin.
Diet supplements and gene therapy tried for Parkinson's disease
Authors: J. Hopkins Tanne
Journal: BMJ (2002)

Two new experimental approaches—dietary supplements and gene therapy—might be useful in the treatment of Parkinson's disease, scientists from the United States and New Zealand said last week.

Functional decline in early Parkinson's disease may be slowed by dietary supplementation with the coenzyme Q10, a naturally occurring compound, says a report in the Archives of Neurology 

(2002;59:1541-50), while the Food and Drug Administration has just approved the first gene therapy trial for advanced Parkinson's disease. The FDA's decision comes after the report of a successful experiment in gene therapy carried out in rats …
Prolonged Continuous Acyclovir Treatment of Normal Adults With Frequently Recurring Genital Herpes Simplex Virus Infection
Authors: Lisa G. Kaplowitz
Journal: JAMA (1991)

In this 3-year study of suppressive acyclovir for recurrent genital herpes, patients with more than six recurrences per year were randomized initially to 400 mg of acyclovir or placebo orally two times per day, with recurrences treated with 200 mg of acyclovir five times per day for 5 days. In the second year of the study, all patients received acyclovir as a daily suppressive or intermittent acute therapy; in the third year, all received daily acyclovir. Among 525 patients completing 3 study years, 289 received 3 years of suppressive therapy and 236 received 1 year of acute therapy followed by 2 years of suppressive therapy. Of those who completed the third year, 61% were recurrence free that year; 25% of the suppressive therapy—only group were recurrence free for all 3 years. The annual recurrence rate dropped from more than 12 recurrences per year at baseline to 1.0 (suppressive therapy) and 1.4 (acute and suppressive therapy) recurrences during the third year. No significant toxic effects were detected. Daily suppressive acyclovir therapy was effective and well tolerated. (<i>JAMA</i>. 1991;265:747-751)
Discordance Between Conclusions Stated in the Abstract and Conclusions in the Article: Analysis of Published Randomized Controlled Trials of Systemic Therapy in Lung Cancer
Authors: Abdullah K. Altwairgi, Christopher M. Booth, Wilma M. Hopman, Tara D. Baetz
Journal: Journal of Clinical Oncology (2012)

Clinicians may read only the abstract of an article to keep abreast of newly published randomized controlled trials (RCTs). However, discordances have been noticed in summary conclusions in the abstracts and the main body of some articles. This article evaluated such discordances in detail.RCTs of systemic therapy for lung cancer published between 2004 and 2009 were considered. Conclusions in the body of the articles and those in the abstracts were graded by using a 7-point Likert scale; 1 for strong endorsement of the control arm, 4 for a neutral statement, and 7 for strong endorsement of the experimental arm. Conclusions were classified as discordant if the difference in scores was ≥ 2. χ(2) tests and logistic regression were used to identify factors associated with discordance.From among 114 eligible RCTs identified (90 for non-small-cell and 24 for small-cell lung cancer), 11 (10%) articles presented discordant conclusions in the abstract and in the body of the articles. Discordance was most common when the experimental arm was strongly supported in the abstract but not in the body of the article (nine of 11; 82%); however, the converse was much less common (two of 11; 18%; P < .001). Intraclass correlations for the two reviewers were ≥ 0.9. The discordances were found to be independent of trial-related factors.Conclusive statements in the abstract can differ from those in the full text. Clinicians should use caution when they consider making changes in their practice on the basis of reading only the abstract of a published RCT.
The Epidemiology of Intensive Care Unit Readmissions in the United States
Authors: Sydney E. S. Brown, Sarah J. Ratcliffe, Jeremy M. Kahn, Scott D. Halpern
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

The incidence of intensive care unit (ICU) readmissions across the United States is unknown.To determine incidence of ICU readmissions in United States hospitals, and describe the distribution of time between ICU discharges and readmissions.This retrospective cohort study used 196,202 patients in 156 medical and surgical ICUs in 106 community and academic hospitals participating in Project IMPACT from April 1, 2001, to December 31, 2007. We used mixed-effects logistic regression, adjusting for patient and hospital characteristics, to describe how ICU readmission rates differed across patient types, ICU models, and hospital types.Measurements consisted of 48- and 120-hour ICU readmission rates and time to readmission. A total of 3,905 patients (2%) were readmitted to the ICU within 48 hours, and 7,171 (3.7%) within 120 hours. In adjusted analysis, there was no difference in ICU readmissions across patient types or ICU models. Among medical patients, those in academic hospitals had higher odds of 48- and 120-hour readmission than patients in community hospitals without residents (1.51 [95% confidence interval, 1.12-2.02] and 1.63 [95% confidence interval, 1.24-2.16]). Median time to ICU readmission was 3.07 days (interquartile range, 1.27-6.58). Closed ICUs had the longest times to readmission (3.55 d [interquartile range, 1.42-7.50]).Approximately 2% and 4% of ICU patients discharged to the ward are readmitted within 48 and 120 hours, within a median time of 3 days. Medical patients in academic hospitals are more likely to be readmitted than patients in community hospitals without residents. ICU readmission rates could be useful for policy makers and investigations into their causes and consequences.