tbuckley/cabot-search huggingface dataset:
Relaxin inhibits effective collagen deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo
Authors: E J Williams
Journal: Gut (2001)

<h3>BACKGROUND</h3> Following liver injury, hepatic stellate cells (HSC) transform into myofibroblast-like cells (activation) and are the major source of type I collagen and the potent collagenase inhibitors tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) in the fibrotic liver. The reproductive hormone relaxin has been reported to reduce collagen and TIMP-1 expression by dermal and lung fibroblasts and thus has potential antifibrotic activity in liver fibrosis. <h3>AIMS</h3> To determine the effects of relaxin on activated HSC. <h3>METHODS</h3> Following isolation, HSC were activated by culture on plastic and exposed to relaxin (1–100 ng/ml). Collagen deposition was determined by Sirius red dye binding and radiolabelled proline incorporation. Matrix metalloproteinase (MMP) and TIMP expression were assessed by zymography and northern analysis. Transforming growth factor β1 (TGF-β1) mRNA and protein levels were quantified by northern analysis and ELISA, respectively. <h3>RESULTS</h3> Exposure of activated HSC to relaxin resulted in a concentration dependent decrease in both collagen synthesis and deposition. There was a parallel decrease in TIMP-1 and TIMP-2 secretion into the HSC conditioned media but no change in gelatinase expression was observed. Northern analysis demonstrated that primary HSC, continuously exposed to relaxin, had decreased TIMP-1 mRNA expression but unaltered type I collagen, collagenase (MMP-13), alpha smooth muscle actin, and TGF-β1 mRNA expression. <h3>CONCLUSION</h3> These data demonstrate that relaxin modulates effective collagen deposition by HSC, at least in part, due to changes in the pattern of matrix degradation.
TRIAL OF LOW-DOSE ASPIRIN PLUS DIPYRIDAMOLE VERSUS ANTICOAGULANTS FOR PREVENTION OF AORTOCORONARY VEIN GRAFT OCCLUSION
Authors: M Pfisterer, G Jockers, S Regenass, H.E Schmitt, K Skarvan, J Hasse, F Burkart, B Meyer, D Burckhardt, J Müller-Brand, P Stulz, E Grädel
Journal: The Lancet (1989)
Inhibition of gp130 Signaling in Breast Cancer Blocks Constitutive Activation of Stat3 and Inhibits <b> <i>in Vivo</i> </b> Malignancy
Authors: Katri S. Selander, Li Li, Latania Watson, Melinda Merrell, Heike Dahmen, Peter C. Heinrich, Gerhard Müller-Newen, Kevin W. Harris
Journal: Cancer Research (2004)

Abstract The cytokine receptor gp130 is the common signaling subunit of receptors used by the interleukin (IL)-6 cytokine family. gp130 is widely expressed in breast cancer cell lines and primary tumors. The role of gp130 in breast cancer in vivo is unknown. To study the effect of gp130 inhibition in breast cancer, endogenous gp130 signaling in breast cancer cell lines was blocked with a dominant-negative gp130 protein (DN gp130). DN gp130 inhibited constitutive Stat3 activation in breast cancer cells. Both gp130 and epidermal growth factor receptor (EGFR) have been implicated in constitutive Stat3 activation in breast cancer. There are known physical and functional interactions between gp130 and EGFR. Consistent with this, we show that DN gp130 inhibits signaling downstream of the EGFR in breast cancer cells. The effect of DN gp130 on breast cancer in vivo was assessed with an orthotopic nude mouse model. DN gp130 MDA-231 cells had markedly decreased engraftment, size, and metastasis compared with control cells. These results are particularly striking considering that DN gp130-expressing breast cancer cells grow faster in vitro. We hypothesized that DN gp130 expression results in inhibition of invasion and metastasis in vivo. Marked angiogenesis was present in tumors from control animals and was absent in tumors from DN gp130 animals. We additionally show that tissue inhibitor of metalloproteinase-3, an inhibitor of tumor invasion and angiogenesis, is up-regulated in both MDA-231 DN gp130 cells and tumors. These results, in light of the availability of several potential pharmacological inhibitors of gp130, suggest novel approaches to breast cancer therapy.
Zebrafish mutants in the von Hippel-Lindau tumor suppressor display a hypoxic response and recapitulate key aspects of Chuvash polycythemia
Authors: Ellen van Rooijen, Emile E. Voest, Ive Logister, Jeroen Korving, Thorsten Schwerte, Stefan Schulte-Merker, Rachel H. Giles, Fredericus J. van Eeden
Journal: Blood (2009)
Force-Velocity Relationship of Cat Cardiac Muscle, Studied by Isotonic and Quick-Release Techniques
Authors: MARK I. NOBLE, T. EARLE BOWEN, LLOYD L. HEFNER
Journal: Circulation Research (1969)

Contractions of isolated cat papillary muscle were studied using a lever system with an electromagnetic load which allowed an on-line computer to control the experiment and to process all the data. Isotonic force-velocity curves were determined in 17 cat papillary muscles; the curves were not hyperbolic. Force-velocity curves at constant time in the contraction and constant contractile element length were obtained with a systolic quick-release technique in 9 muscles. The velocity of shortening after release to low force was almost always less than the maximum recorded following release to slightly higher force. When quick-release force-velocity curves determined at different times in the contraction were compared, the maximum velocity occurred at approximately 60% of the time to peak isometric force. The fall in velocity at lower forces was more marked later in the contraction. The shape of the quick-release force-velocity curves was found to depend on muscle length. At a constant time of release, and ignoring the low force end of the curves, the quick-release force-velocity relationships were not hyperbolic at muscle lengths appreciably below optimum, but near the optimal length the curves were hyperbolic. When these quick-release force-velocity curves were corrected for the presence of an elastic element in parallel with the contractile and series elastic elements, it was found that none of the contractile element force-velocity curves was hyperbolic.
Randomized Trial of High-Dose Chemotherapy and Blood Cell Autografts for High-Risk Primary Breast Carcinoma
Authors: Gabriel N. Hortobagyi, Aman U. Buzdar, Richard L. Theriault, Vicente Valero, Debra Frye, Daniel J. Booser, Frankie A. Holmes, Sergio Giralt, Issa Khouri, Borje Andersson, James L. Gajewski, Gabriela Rondon, Terry L. Smith, Sonja E. Singletary, Frederick C. Ames, Nour Sneige, Eric A. Strom, Marsha D. McNeese, Albert B. Deisseroth, Richard E. Champlin
Journal: JNCI Journal of the National Cancer Institute (2000)

Uncontrolled studies have reported encouraging outcomes for patients with high-risk primary breast cancer treated with high-dose chemotherapy and autologous hematopoietic stem cell support. We conducted a prospective randomized trial to compare standard-dose chemotherapy with the same therapy followed by high-dose chemotherapy.Patients with 10 or more positive axillary lymph nodes after primary breast surgery or patients with four or more positive lymph nodes after four cycles of primary (neoadjuvant) chemotherapy were eligible. All patients were to receive eight cycles of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC). Patients were stratified by stage and randomly assigned to receive two cycles of high-dose cyclophosphamide, etoposide, and cisplatin with autologous hematopoietic stem cell support or no additional chemotherapy. Tamoxifen was planned for postmenopausal patients with estrogen receptor-positive tumors and chest wall radiotherapy was planned for all. All P values are from two-sided tests.Seventy-eight patients (48 after primary surgery and 30 after primary chemotherapy) were registered. Thirty-nine patients were randomly assigned to FAC and 39 to FAC followed by high-dose chemotherapy. After a median follow-up of 6.5 years, there have been 41 relapses. In intention-to-treat analyses, estimated 3-year relapse-free survival rates were 62% and 48% for FAC and FAC/high-dose chemotherapy, respectively (P =.35), and 3-year survival rates were 77% and 58%, respectively (P =.23). Overall, there was greater and more frequent morbidity associated with high-dose chemotherapy than with FAC; there was one septic death associated with high-dose chemotherapy.No relapse-free or overall survival advantage was associated with the use of high-dose chemotherapy, and morbidity was increased with its use. Thus, high-dose chemotherapy is not indicated outside a clinical trial.
Emotion regulation predicts change of perceived health in patients with rheumatoid arthritis
Authors: H van Middendorp
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objectives:</b> To examine whether emotion regulation predicts change of perceived health in patients with rheumatoid arthritis (RA). <b>Methods:</b> Sixty six patients (44 female, 22 male; mean (SD) age 57.7 (11.6) years) participated in a prospective study. Hierarchical regression analysis was used to predict change of perceived health between study entry and follow up (1½ years later) from the emotion regulation styles ambiguity, control, orientation, and expression at study entry. <b>Results:</b> Valuing and intensely experiencing emotions (emotional orientation) predicted a decrease of positive affect. Difficulty recognising and expressing emotions (ambiguity) predicted an increase of perceived disease activity. Emotion regulation showed no associations with change of negative affect and social and physical functioning. <b>Conclusions:</b> Two styles of emotion regulation were shown to have a significant though modest role in the prediction of perceived health change in patients with RA. This suggests that the monitoring of emotion regulation may help to identify patients who are at risk for a reduction of perceived health. If our findings were confirmed by experimental research, improving emotion regulation skills might favourably affect perceived health.
Second-Line Therapy in Non–Small-Cell Lung Cancer: The DELTA Between Different Genotypes Widens
Authors: Alona Zer, Natasha B. Leighl
Journal: Journal of Clinical Oncology (2014)

Article Tools ONCOLOGY GRAND ROUNDS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2013.54.4270 Journal of Clinical Oncology - published online before print May 19, 2014 PMID: 24841982 Second-Line Therapy in Non–Small-Cell Lung Cancer: The DELTA Between Different Genotypes Widens Alona ZerxAlona ZerSearch for articles by this author , Natasha B. LeighlxNatasha B. LeighlSearch for articles by this author Show More Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada https://doi.org/10.1200/JCO.2013.54.4270 First Page Full Text PDF Figures and Tables © 2014 by American Society of Clinical Oncology
EUS and clinical characteristics of cystic pancreatic neuroendocrine tumors
Authors: P. Kongkam, M. Al-Haddad, S. Attasaranya, J. O’Neil, S. Pais, S. Sherman, J. DeWitt
Journal: Endoscopy (2008)

Pancreatic neuroendocrine tumors (PNETs) may rarely appear as cystic or mixed solid-cystic masses. The endoscopic ultrasound (EUS) morphology and cyst fluid characteristics of these tumors are not well clarified. We retrospectively identified nine adult patients with nine single cystic pancreatic neuroendocrine tumors (CNETs). These nine included 0.67 % of the 1344 patients with pancreatic cystic lesions and 9.5 % of the 95 confirmed PNETs evaluated over the 12-year study period. At presentation, four patients were asymptomatic and five had known acute pancreatitis (n = 2), MEN-1 syndrome with hypoglycemia (n = 1), and abdominal pain (n = 2). Median maximal tumor diameter was 26 mm (range 20 – 64 mm). EUS morphology was mixed solid and cystic (n = 4) or cystic alone (n = 5). Cytology from EUS-fine-needle aspiration (FNA) (median 2 passes; range 1 – 6) demonstrated a PNET, and immunocytochemistry was confirmatory in all patients. Cyst fluid carcinoembryonic antigen (CEA) (n = 4) and amylase (n = 5) ranged from 0.1 to 1.8 ng/ml (normal 0 – 2.5 ng/ml) and 72 to 1838 U/L (normal 25 – 161 U/L), respectively. Six patients underwent surgery, and the preoperative diagnosis was confirmed in all.
Characteristics of US Patients with Myelodysplastic Syndromes: Results of Six Cross-sectional Physician Surveys
Authors: Mikkael A. Sekeres, W. Marieke Schoonen, Hagop Kantarjian, Alan List, Jon Fryzek, Ronald Paquette, Jaroslaw P. Maciejewski
Journal: JNCI Journal of the National Cancer Institute (2008)

Myelodysplastic syndromes (MDS) comprise a group of pathologically and cytogenetically distinct bone marrow disorders. Little is known about the characteristics of MDS patients, including their pathological and prognostic classifications, cytopenias, transfusion and supportive care needs, and treatment regimens. We describe these characteristics in a large group of recently diagnosed and existing (ie, established) MDS patients.We conducted six consecutive cross-sectional surveys among US hematology and medical oncology specialists (identified from an American Medical Association [AMA] database of physicians who administer chemotherapy) between June 2005 and January 2007. A questionnaire collected data on the characteristics and treatment patterns of the 4-10 most recently seen MDS patients for each physician, including demographic data, transfusion needs, treatment approaches, and consideration for clinical trials or bone marrow transplantation.A panel of 101 physicians who were geographically representative of physicians registered with the AMA characterized 614-827 patients per survey, for a total of 4514 responses. Among recently diagnosed patients, 55% were male (95% confidence interval [CI] = 52% to 59%), the median age at diagnosis was 71 years (range = 65-80 years), and 10% (95% CI = 8% to 12%) had MDS secondary to chemotherapy, radiation therapy, or environmental exposure. The median duration of MDS in established patients ranged from 13 to 16 months over the six surveys. Among recently diagnosed MDS patients, fewer patients with lower-risk disease than with higher-risk disease were dependent on either red blood cell transfusions (22% vs 68%) or platelet transfusions (6% vs 33%). More than 50% of all newly diagnosed and established patients used erythropoiesis-stimulating agents. A small percentage of all patients either had had or were being considered for bone marrow transplantation (recently diagnosed: 4%; established: 4% or less) or were being treated on clinical trials (recently diagnosed: 1%; established: 4% or less).MDS patients in the United States have substantial transfusion needs, and use of erythropoiesis-stimulating agents and are seldom considered for bone marrow transplantation or clinical trials. These data may be useful in characterizing the health care resource use and pharmacoeconomic impact of MDS in the United States.
Vinorelbine Plus Cisplatin Versus Docetaxel Plus Gemcitabine in Advanced Non-Small-Cell Lung Cancer: A Phase III Randomized Trial
Authors: Vassilis Georgoulias, Alexandros Ardavanis, Xanthi Tsiafaki, Athina Agelidou, Penelope Mixalopoulou, Ourania Anagnostopoulou, Panagiotis Ziotopoulos, Michael Toubis, Kostas Syrigos, Nikolaos Samaras, Aris Polyzos, Anna Christou, Stylianos Kakolyris, Charalambos Kouroussis, Nikolaos Androulakis, George Samonis, Dora Chatzidaki
Journal: Journal of Clinical Oncology (2005)

PURPOSE To compare the activity and tolerability of docetaxel/gemcitabine (DG) and vinorelbine/cisplatin (VC) combinations in chemotherapy-naive non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS Patients with advanced NSCLC were randomly assigned to receive either DG (gemcitabine 1,000 mg/m(2) [days 1 and 8] plus docetaxel 100 mg/m(2) [day 8]) or VC (vinorelbine 30 mg/m(2) [days 1 and 8] plus cisplatin 80 mg/m(2) [day 8]) and prophylactic recombinant human granulocyte colony-stimulating factor (150 microg/m(2) subcutaneously [day 9 through 15]) every 3 weeks. Results A total of 413 randomly assigned patients were analyzed for response and toxicity (DG, n = 197; VC, n = 192). Median survival was 9.0 and 9.7 months (P = .965) for DG and VC arms, respectively; the corresponding 1-year survival rates were 34.3% and 40.8%, respectively. Overall response rate was 30% (95% CI, 23.9% to 36.3%) and 39.2% (95% CI, 32.5% to 45.9%; P = .053) for DG and VC, respectively. Toxicity was as follows (DG v VC): grade 2 to 4 anemia, 34% v 55% (P = .0001); grade 3 to 4 neutropenia, 16% v 37% (P = .0001); febrile neutropenia, 6% v 11% (P = .009); and grade 3 to 4 nausea and vomiting, 1% v 15% (P = .003). Nephrotoxicity occurred in 8% and ototoxicity in 2% of VC-treated patients. There were five and six treatment-related deaths in the DG and VC arms, respectively. Quality of life was improved in DG but not in VC patients. CONCLUSION Although the two regimens produced comparable overall survival, the DG regimen had a better toxicity profile. Therefore, DG could be used in the first-line setting of advanced NSCLC, especially for patients who cannot tolerate cisplatin.
OC-033 Taurolidine significantly reduces the incidence of catheter related blood stream infections in patients on home parenteral nutrition: Abstract OC-033 Table 1
Authors: J A Saunders, M Naghibi, T R Smith, A T King, Z B Leach, M A Stroud
Journal: Gut (2012)

<h3>Introduction</h3> Catheter related blood stream infections (CRBSI) in patients receiving home parenteral nutrition (HPN) cause significant morbidity, are potentially life-threatening and through repeated line replacements may compromise venous access. We introduced products containing taurolidine as preventative antimicrobial line locks in 2006 for HPN patients who had repeated episodes of CRBSI and report the incidence of CRBSI before and after. <h3>Methods</h3> Data were retrospectively collected from electronic and paper records for all adult HPN patients between January 2001 and October 2011. <h3>Results</h3> Data were available for 19/22 HPN patients receiving taurolidine locks for a period of 51.9 patient years (21.5 years pre-taurolidine and 30.4 years post-taurolidine). Patients were offered taurolidine if they had: (1) two or more episodes of community borne CRBSI (2) one episode of CRBSI in patients with a persistent source of intra-abdominal sepsis (3) significantly compromised vascular access. The use of taurolidine significantly reduced the rate of CRBSI from 4.59 to 0.81 episodes per 1000 days (p&lt;0.0001). Nine episodes of recurrent CRBSI occurred in five patients despite taurolidine (one patient had four further infections in 5.6 years). The organisms responsible were coag neg staph. (four episodes), pseudomonas (one episode), candida (one episode), mixed coliform and coag neg staph (one episode) and two cases which were culture negative. <h3>Conclusion</h3> Our experience shows that taurolidine significantly reduces the rate of CRBSI, particularly in patients who have had at least two previous infections. It may also have a role in preventing infection in patients with foci of potential abdominal sepsis in the context of type 2 IF. Despite this, it should not be seen as a substitute for meticulous line access techniques as some patients continue to develop recurrent infections while on treatment. <h3>Competing interests</h3> None declared.
Clinical course of alcoholic liver cirrhosis: A Danish population-based cohort study
Authors: Peter Jepsen, Peter Ott, Per Kragh Andersen, Henrik Toft Sørensen, Hendrik Vilstrup
Journal: Hepatology (2009)

The clinical course of alcoholic cirrhosis, a condition with a high mortality, has not been well described. We examined prevalence, risk, chronology, and mortality associated with three complications of cirrhosis: ascites, variceal bleeding, and hepatic encephalopathy. We followed a population-based cohort of 466 Danish patients diagnosed with alcoholic cirrhosis in 1993–2005, starting from the date of hospital diagnosis and ending in August 2006. Data were extracted from medical charts during the follow-up period. Risk and mortality associated with complications were calculated using competing-risks methods. At diagnosis of alcoholic cirrhosis, 24% of patients had no complications, 55% had ascites alone, 6% had variceal bleeding alone, 4% had ascites and variceal bleeding, and 11% had hepatic encephalopathy. One-year mortality was 17% among patients with no initial complications, 20% following variceal bleeding alone, 29% following ascites alone, 49% following ascites and variceal bleeding (from the onset of the later of the two complications), and 64% following hepatic encephalopathy. Five-year mortality ranged from 58% to 85%. The risk of complications was about 25% after 1 year and 50% after 5 years for all patients without hepatic encephalopathy. The complications under study did not develop in any predictable sequence. Although patients initially without complications usually developed ascites first (12% within 1 year), many developed either variceal bleeding first (6% within 1 year) or hepatic encephalopathy first (4% within 1 year). Subsequent complications occurred in an unpredictable order among patients with ascites or variceal bleeding. Conclusion: Patients with alcoholic cirrhosis had a high prevalence of complications at the time of cirrhosis diagnosis. The presence and type of complications at diagnosis were predictors of mortality, but not of the risk of subsequent complications. (Hepatology 2010.)
Bugs and boats: an athlete's view
Authors: Shaun Pearce
Journal: British Journal of Sports Medicine (1997)

<h3>SUMMARY</h3> Tissue-resident macrophages are of vital importance as they preserve tissue homeostasis in all mammalian organs. Nevertheless, appropriate cell culture models are still limited. Here, we propose a novel culture model to study and expand murine primary alveolar macrophages (AMs), the tissue-resident macrophages of the lung, in vitro over several months. By providing a combination of GM-CSF, TGFβ and the PPARγ activator rosiglitazone, we maintain and expand mouse ex vivo cultured AMs, short mexAMs, over several months. MexAMs maintain typical morphologic features and stably express primary AM surface markers throughout in vitro culture. They respond to microbial ligands and exhibit an AM-like transcriptional profile, including the expression of AM specific transcription factors. Furthermore, when transferred into AM deficient mice, mexAMs efficiently engraft in the lung and fulfill key macrophage functions leading to a significantly reduced surfactant load in those mice. Altogether, mexAMs provide a novel, simple and versatile tool to study AM behavior in homeostasis and disease settings. <h3>KEYPOINTS</h3> A novel method to culture and expand primary alveolar macrophages over several months ex vivo Murine ex vivo cultured alveolar macrophages (mexAMs) restore lung function in a murine pulmonary alveolar proteinosis model