tbuckley/cabot-search huggingface dataset:
Hepatic Arterial Infusion Versus Systemic Therapy for Hepatic Metastases From Colorectal Cancer: A Randomized Trial of Efficacy, Quality of Life, and Molecular Markers (CALGB 9481)
Authors: Nancy E. Kemeny, Donna Niedzwiecki, Donna R. Hollis, Heinz-Josef Lenz, Robert S. Warren, Michelle J. Naughton, Jane C. Weeks, Elin R. Sigurdson, James E. Herndon, Chunfeng Zhang, Robert J. Mayer
Journal: Journal of Clinical Oncology (2006)

Purpose Hepatic metastases derive most of their blood supply from the hepatic artery; therefore, for patients with hepatic metastases from colorectal cancer, hepatic arterial infusion (HAI) of chemotherapy may improve outcome. Methods In a multi-institutional trial, 135 patients were randomly assigned to receive HAI versus systemic bolus fluorouracil and leucovorin. The primary end point was survival; secondary end points were response, recurrence, toxicity, quality of life, cost, and the influence of molecular markers. Results Overall survival was significantly longer for HAI versus systemic treatment (median, 24.4 v 20 months; P = .0034), as were response rates (47% and 24%; P = .012) and time to hepatic progression (THP; 9.8 v 7.3 months; P = .034). Time to extrahepatic progression (7.7 v 14.8 months; P = .029) was significantly shorter in the HAI group. Quality-of-life measurements showed improved physical functioning in the HAI group at the 3- and 6-month follow-up assessments. Toxicity included grade ≥ 3 neutropenia (2% and 45%; P &lt; .01), stomatitis (0% and 24%; P &lt; .01), and bilirubin elevation (18.6% and 0; P &lt; .01) in the HAI and systemic treatment groups, respectively. A greater proportion of men versus women receiving HAI experienced biliary toxicity (37% and 15%, respectively; P = .05). For HAI patients with thymidylate synthase levels in tumor less than or ≥ 4, the median survival was 24 and 14 months, respectively (P = .17). Conclusion HAI therapy increased overall survival, response rate, THP, and was associated with better physical functioning compared with systemic therapy. Additional studies need to address the overall benefit and cost of new chemotherapy agents versus HAI alone or the combination of HAI with new agents.
Direct adhesion to bone marrow stroma via fibronectin receptors inhibits hematopoietic progenitor proliferation.
Authors: R W Hurley, J B McCarthy, C M Verfaillie
Journal: Journal of Clinical Investigation (1995)

In long-term bone marrow cultures, stroma-adherent progenitors proliferate significantly less than nonadherent progenitors. Thus, close progenitor-stroma interactions may serve to regulate or restrict rather than promote hematopoietic progenitor proliferation. We hypothesized that signaling through adhesion receptors on hematopoietic cells may contribute to the inhibition of proliferation observed when progenitors are in contact with stroma. We demonstrate that progenitors cultured physically separated from stroma in a transwell proliferate significantly more than progenitors adherent to stroma. Furthermore, proliferation of colony forming cells (CFC) is reduced after specific adhesion to stroma, metabolically inactivated glutaraldehyde-fixed stroma, stromal-extracellular matrix, or the COOH-terminal heparin-binding domain of fibronectin. Nonspecific adhesion to poly-L-lysine fails to inhibit CFC proliferation. That the VLA-4 integrin is one of the receptors that transfers proliferation inhibitory signals was shown using blocking anti-alpha 4 monomeric F(ab) fragments. Furthermore, when synthetic peptides representing specific cell attachment sites within the heparin-binding domain of fibronectin were added to Dexter-type marrow cultures, significantly increased recovery and proliferation of CFC was observed, suggesting that these peptides disrupt adhesion-mediated proliferation inhibitory events. Thus, negative regulation of hematopoiesis may not only depend on the action of growth inhibitory cytokines but also on growth inhibitory signals resulting from direct adhesive interactions between progenitors and marrow stroma.
Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque
Authors: Diana Bonderman, Alexander Teml, Johannes Jakowitsch, Christopher Adlbrecht, Mariann Gyöngyösi, Wolfgang Sperker, Harald Lass, Wilhelm Mosgoeller, Dietmar H. Glogar, Peter Probst, Gerald Maurer, Yale Nemerson, Irene M. Lang
Journal: Blood (2002)
Tumour necrosis factor α secretion induces protease activation and acinar cell necrosis in acute experimental pancreatitis in mice
Authors: Matthias Sendler, Annegret Dummer, Frank U Weiss, Burkhard Krüger, Thomas Wartmann, Karin Scharffetter-Kochanek, Nico van Rooijen, Sudarshan Ravi Malla, Ali Aghdassi, Walter Halangk, Markus M Lerch, Julia Mayerle
Journal: Gut (2012)

<h3>Background</h3> Acute pancreatitis has long been considered a disorder of pancreatic self-digestion, in which intracellular activation of digestive proteases induces tissue injury. Chemokines, released from damaged pancreatic cells then attract inflammatory cells, whose systemic action ultimately determines the disease severity. In the present work the opposite mechanism is investigated; that is, whether and how inflammatory cells can activate intracellular proteases. <h3>Design</h3> Using mice either deficient for the CD18-α subunit of the membrane attack complex-1 (MAC-1) complex or tumour necrosis factor (TNF)α, as well as after depletion of leucocyte subpopulations, pancreatitis was induced by 7-hourly caerulein injections (50 μg/kg, intraperitoneally). Pancreatic acini were coincubated in vitro from wild-type and cathepsin-B-deficient animals with phorbol-12-myristate-13-acetate (PMA)-activated neutrophils and macrophages, caerulein or TNFα, and activities of trypsin, cathepsin-B and caspase-3 were measured, as well as necrosis using fluorogenic substrates. TNFα was inhibited with monospecific antibodies. <h3>Results</h3> Deletion of CD18 prevented transmigration of leucocytes into the pancreas during pancreatitis, greatly reduced disease severity and abolished digestive protease activation. Depletion of neutrophils and macrophages equally reduced premature trypsinogen activation and disease severity. In vitro activated neutrophils and macrophages directly induced premature protease activation and cell death in pancreatic acini and stimulation of acini with TNFα induced caspase-3 activation and necrosis via a cathepsin-B and calcium-dependent mechanism. Neutralising antibodies against TNFα and genetic deletion of TNFα prevented leucocyte-induced trypsin activity and necrosis in isolated acini. <h3>Conclusions</h3> The soluble inflammatory cell mediator TNFα directly induces premature protease activation and necrosis in pancreatic acinar cells. This activation depends on calcium and cathepsin-B activity. The findings from the present work further suggest that targeting TNFα, for which pharmaceutical agents are readily available, could be an effective treatment strategy that directly addresses the cellular causes of pancreatitis.
Assigning an '18' rating to movies with tobacco imagery is essential to reduce youth smoking
Authors: C. Millett, S. A. Glantz
Journal: Thorax (2010)

Exposure to smoking in movies is a potent stimulus for youth smoking.1–4 In this issue of Thorax , ( see page 417 ) McNeil et al document the occurrence of tobacco in the most commercially successful films released in the UK from 1989 to 2008.5 While there is a decrease in the mean rate of tobacco episodes (which includes tobacco use, tobacco paraphernalia, inferred tobacco use, brand appearances) over time, 70% of the films had one or more tobacco episodes. Tobacco or tobacco-related products appeared in 68% of all youth-rated films (British Board of Film Classification (BBFC) rating ‘15’ and below). More important, of the films from 2004 to 2008 that contained tobacco, 97% were rated BBFC 15 and lower and 73% were deemed suitable for those <15 years of age.

This continuing high level of exposure to smoking in films rated suitable for youth undermines efforts to reduce smoking among children and adolescents, not only in Britain but globally. Approximately one in five young teenagers (13–15 years) worldwide is a regular smoker with 80–100 000 children taking up the habit every day.6 7 One in six 15-year-old girls in England (17%) and Scotland (16%) were regular smokers in 2008, and the prevalence of smoking among 15-year-old boys in Scotland actually increased from 12% in 2006 to 14% in 2008.8 9 Smoking prevalence and usage are highest among youth living in deprived areas. For example, 29% of 15-year-old regular smokers living in the most deprived areas in Scotland reported smoking more than 70 cigarettes a week compared with only 12% in the most affluent areas.9

Concern about the impact of exposure …
Analysis of polymorphonuclear neutrophil (PMN) phenotype and function at the onset of collagen-induced arthritis
Authors: E Rath, R Byrne, A Savitskaya, B Niederreiter, M Bonelli, J S Smolen, C Scheinecker
Journal: Annals of the Rheumatic Diseases (2010)

Background Polymorphonuclear neutrophils (PMNs) participate in the initiation of rheumatoid arthritis (RA), but their precise role at the earliest stages of the synovial infl ammatory response is only partially understood.We therefore analysed the initial steps of synovial infl ammation in the mouse model of collagen-induced arthritis (CIA) with regard to the role of PMN. Materials and Methods CIA was induced in C57/BL6 mice.Mice were tested for anti-CII serum antibodies by ELISA.Mice were killed on days 10 and 20 after the fi rst immunisation before clinical signs of arthritis occurred and at various time points after the onset of arthritis.Hind and front paws were collected and non-decalcifying cryostat sections as well as conventional paraffi n sections were prepared.Joint sections were analysed after immunohistochemistry (haematoxylin and eosin, tartrate-resistant acid phosphatase (TRAP), on August 10, 2023 by guest.
Health Literacy and Pregnancy Preparedness in Pregestational Diabetes
Authors: Loraine K. Endres, Lisa K. Sharp, Elaine Haney, Sharon L. Dooley
Journal: Diabetes Care (2004)

We investigated the association between functional health literacy and markers of pregnancy preparedness in women with pregestational diabetes.English- and Spanish-speaking pregnant women with pregestational diabetes were recruited. Women completed the Test of Functional Health Literacy in Adults (TOFHLA) short form and a questionnaire. A TOFHLA score of < or =30 was defined as low functional health literacy.Of 74 women participating in the study, 16 (22%) were classified as having low functional health literacy. Compared with women with adequate health literacy, those with low health literacy were significantly more likely to have an unplanned pregnancy (P = 0.02) and significantly less likely to have either discussed pregnancy ahead of time with an endocrinologist or obstetrician (P = 0.01) or taken folic acid (P = 0.001).The results of this study suggest that low functional health literacy among women with pregestational diabetes is associated with several factors that may adversely impact birth outcomes.
Diastolic vibration improves systolic function in cases of incomplete relaxation.
Authors: T Takagi, Y Koiwa, J Kikuchi, H Honda, N Hoshi, J P Butler, T Takishima
Journal: Circulation (1992)

Incomplete relaxation of the left ventricle (LV) affects LV filling, but the subsequent effect on LV systolic function remains unclear. We attempted to improve relaxation by applying oscillatory mechanical perturbation during diastole (diastolic vibration) and examined the extent to which systolic function improved.Using 10 open-chest canine preparations, pacing tachycardia and administration of propranolol were imposed to induce various levels of incomplete relaxation. Myocardial length perturbation was induced with an oscillator attached to the LV surface (50 Hz, 1-mm amplitude) and was restricted to the period from the beginning of isovolumic relaxation to end diastole. At resting heart rates, diastolic vibration caused an immediate decrease in the time constant (T) of LV pressure fall without any influence on heart rate, LV peak systolic pressure (peak LVP), stroke volume (SV), LV peak positive dP/dt, and total systemic vascular resistance. With pacing tachycardia, diastolic vibration increased both peak LVP and SV at 160 beats per minute (before) and 120 beats per minute (after propranolol), simultaneously decreasing both T and LV diastolic pressures and increasing end-diastolic segment length. The increase in peak LVP and SV caused by diastolic vibration correlated with the T/diastolic interval (r = 0.82), the assumed index of severity of incomplete relaxation.These results suggest that diastolic vibration accelerates the LV relaxation rate and that this increased relaxation improves systolic function through the Frank-Starling mechanism.
The Yeast Protein Interaction Network Evolves Rapidly and Contains Few Redundant Duplicate Genes
Authors: A Wagner
Journal: Molecular Biology and Evolution (2001)

In this paper, the structure and evolution of the protein interaction network of the yeast Saccharomyces cerevisiae is analyzed. The network is viewed as a graph whose nodes correspond to proteins. Two proteins are connected by an edge if they interact. The network resembles a random graph in that it consists of many small subnets (groups of proteins that interact with each other but do not interact with any other protein) and one large connected subnet comprising more than half of all interacting proteins. The number of interactions per protein appears to follow a power law distribution. Within approximately 200 Myr after a duplication, the products of duplicate genes become almost equally likely to (1) have common protein interaction partners and (2) be part of the same subnetwork as two proteins chosen at random from within the network. This indicates that the persistence of redundant interaction partners is the exception rather than the rule. After gene duplication, the likelihood that an interaction gets lost exceeds 2.2 x 10(-3)/Myr. New interactions are estimated to evolve at a rate that is approximately three orders of magnitude smaller. Every 300 Myr, as many as half of all interactions may be replaced by new interactions.
Migration of Dendritic Cell Subsets and their Precursors
Authors: Gwendalyn J. Randolph, Jordi Ochando, Santiago Partida-Sánchez
Journal: Annual Review of Immunology (2007)

The ability of dendritic cells (DCs) to initiate and orchestrate immune responses is a consequence of their localization within tissues and their specialized capacity for mobilization. The migration of a given DC subset is typified by a restricted capacity for recirculation, contrasting markedly with T cells. Routes of DC migration into lymph nodes differ notably for distinct DC subsets. Here, we compare the distinct migratory patterns of plasmacytoid DCs (pDCs), CD8alpha(+) DCs, Langerhans cells, and conventional myeloid DCs and discuss how the highly regulated patterns of DC migration in vivo may affect their roles in immunity. Finally, to gain a more molecular appreciation of the specialized migratory properties of DCs, we review the signaling cascades that govern the process of DC migration.
Visceral fat accumulation is an independent risk factor for hepatocellular carcinoma recurrence after curative treatment in patients with suspected NASH
Authors: T Ohki, R Tateishi, S Shiina, E Goto, T Sato, H Nakagawa, R Masuzaki, T Goto, K Hamamura, F Kanai, H Yoshida, T Kawabe, M Omata
Journal: Gut (2009)

Visceral fat accumulation reportedly increases the risk of hepatocellular carcinoma (HCC) development in patients with chronic liver disease. However, it has not been fully elucidated whether visceral fat accumulation increases the risk of HCC recurrence after curative treatment in patients with suspected non-alcoholic steatohepatitis (NASH). Therefore this was investigated in the current study.62 patients with naive HCC with suspected NASH were enrolled. All were curatively treated with percutaneous radiofrequency ablation between 1999 and 2006. The visceral fat area (VFA) was determined in each patient from CT images, taken at the time of HCC diagnosis. Patients were divided into two groups based on VFA: the high VFA group (>130 cm(2) in males, >90 cm(2) in females, n = 27) and the others (n = 35). The effects of VFA on HCC recurrence were analysed together with other factors including patients' background, tumour-related factors and liver function-related factors.The cumulative recurrence rates differed significantly between the two groups; 15.9, 56.5 and 75.1% at 1, 2 and 3 years, respectively, in the high VFA group, and 9.7, 31.1 and 43.1%, respectively, in the controls (p = 0.018). Multivariate analysis indicated visceral fat accumulation (risk ratio 1.08, per 10 cm(2), p = 0.046) and older age (risk ratio 1.06 per 1 year, p = 0.04) as independent risk factors of HCC recurrence.Visceral fat accumulation is an independent risk factor of HCC recurrence after curative treatment in patients with suspected NASH.
Identification of Hodgkin and Reed-Sternberg cell-specific genes by gene expression profiling
Authors: Ralf Küppers, Ulf Klein, Ines Schwering, Verena Distler, Andreas Bräuninger, Giorgio Cattoretti, Yuhai Tu, Gustavo A. Stolovitzky, Andrea Califano, Martin-Leo Hansmann, Riccardo Dalla-Favera
Journal: Journal of Clinical Investigation (2003)

Hodgkin lymphoma (HL) is a malignancy of unknown pathogenesis. The malignant Hodgkin and Reed/Sternberg (HRS) cells derive from germinal center B cells (or rarely, T cells) but have a heterogeneous and largely uncharacterized phenotype. Using microarrays, we compared the gene expression profile of four HL cell lines with profiles of the main B cell subsets and B cell non-HLs to find out whether HRS cells, despite their described heterogeneity, show a distinct gene expression, to study their relationship to other normal and malignant B cells, and to identify genes aberrantly or overexpressed by HRS cells. The HL lines indeed clustered as a distinct entity, irrespective of their B or T cell derivation, and their gene expression was most similar to that of EBV-transformed B cells and cell lines derived from diffuse large cell lymphomas showing features of in vitro-activated B cells. Twenty-seven genes, most of which were previously unknown to be expressed by HRS cells, showed aberrant expression specifically in these cells, e.g., the transcription factors GATA-3, ABF1, EAR3, and Nrf3. For five genes, expression in primary HRS cells was confirmed. The newly identified HL-specific genes may play important roles in the pathogenesis of HL, potentially represent novel diagnostic markers, and can be considered for therapeutic targeting.
Receptor-induced death in human natural killer cells: involvement of CD16.
Authors: J R Ortaldo, A T Mason, J J O'Shea
Journal: The Journal of Experimental Medicine (1995)

Propriocidal regulation of T cells refers to apoptosis induced by interleukin 2 (IL-2) activation with subsequent antigen receptor stimulation. We examined whether natural killer (NK) cells exhibited cytokine- and ligand-induced death similar to activated T cells. Peripheral NK cells were examined for ligand-induced death using antibodies to surface moieties (CD2, CD3, CD8, CD16, CD56), with and without prior activation of IL-2. Only those NK cells stimulated first with IL-2 and then with CD16 exhibited ligand-induced death; none of the other antibody stimuli induced this phenomenon. Next we examined various cytokines (IL-2, IL-4, IL-6, IL-7, IL-12, IL-13, interferon alpha and gamma) that can activate NK cells and determined if CD16-induced killing occurred. Only IL-2 and IL-12 induced NK cell death after occupancy of this receptor by aggregated immunoglobulin or by cross-linking with antireceptor antibody. The CD16-induced death was inhibited by herbimycin A, indicating that cell death was dependent upon protein tyrosine kinases. Identical to T cells, the form of cell death for NK cells was demonstrated to be receptor-induced apoptosis. Overall these data indicate that highly activated NK cells mediate ligand-induced apoptosis via signaling molecules like CD16. Whereas the propriocidal regulation of T cells is antigen specific, this is not the case for NK cells due to the nature of the receptor. The clinical implications of this finding are considered.
Fractionated doses of gemtuzumab ozogamicin with escalated doses of daunorubicin and cytarabine as first acute myeloid leukemia salvage in patients aged 50–70‐year old: A phase 1/2 study of the acute leukemia French association
Authors: Hassan Farhat, Oumedaly Reman, Emmanuel Raffoux, Celine Berthon, Cécile Pautas, Leila Kammoun, Sylvain Chantepie, Claude Gardin, Philippe Rousselot, Sylvie Chevret, Hervé Dombret, Sylvie Castaigne
Journal: American Journal of Hematology (2011)

This Phase 1/2 study aimed to determine optimal doses of daunorubicin (DNR; mg/m(2)) and cytarabine (mg/m(2)) to be combined with fractionated doses of gemtuzumab ozogamicin (GO, Mylotarg(®); 3 mg/m(2) on day 1, 4, and 7) satisfying safety requirements. Three dose levels of DNR/AraC were investigated namely (45, 100), (60, 100), and (60, 200). Patients included were acute myeloid leukemia in first relapse, aged 50-70 years. Hematological recovery was 31 days for neutrophil and 32 days for platelet counts. A documented infectious episode > Grade 2 occurred in 11/20 patients (55%). None of the 20 patients had signs of veno-occlusive disease. Overall, eleven patients reached complete remission (CR), two CR with incomplete platelets recovery. The results showed that combination of fractionated GO doses with DNR at 60 mg/m(2)/d for 3 days and cytarabine at 200 mg/m(2)/d for 7 days is tolerable and could be further investigated in the front-line therapy.
Pericardial Adipose Tissue, Atherosclerosis, and Cardiovascular Disease Risk Factors
Authors: Jiankang Liu, Caroline S. Fox, DeMarc Hickson, Daniel Sarpong, Lynette Ekunwe, Warren D. May, Gregory W. Hundley, J. Jeffery Carr, Herman A. Taylor
Journal: Diabetes Care (2010)

OBJECTIVE Pericardial adipose tissue (PAT), a regional fat depot that surrounds the heart, is associated with an unfavorable cardiometabolic risk factor profile. The associations among PAT, cardiometabolic risk factors, and coronary artery calcification (CAC) and abdominal aortic artery calcification (AAC) in African American populations have not been explored. RESEARCH DESIGN AND METHODS A total of 1,414 African Americans (35% men; mean ± SD age 58 ± 11 years) drawn from the Jackson Heart Study (JHS) underwent multidetector computed tomography assessment of abdominal visceral adipose tissue (VAT) and PAT between 2007 and 2009. Cardiometabolic risk factors, CAC, and AAC were examined in relation to increments of PAT and VAT. RESULTS PAT was significantly correlated with BMI, waist circumference, and VAT (r = 0.35, 0.46, and 0.69; all P &amp;lt; 0.0001). PAT (per 1-SD increase) was associated with elevated levels of systolic blood pressure (P &amp;lt; 0.04), fasting glucose, triglycerides, and C-reactive protein and lower levels of HDL (all P values&amp;lt;0.0001). PAT was also associated with metabolic syndrome (odds ratio [OR] 1.89; P &amp;lt; 0.0001), hypertension (1.48; P &amp;lt; 0.0006), and diabetes (1.40; P &amp;lt; 0.04); all associations were diminished after further adjustment for VAT (most P &amp;gt; 0.05). However, the association of PAT with CAC but not with AAC remained significant (OR 1.34 [95% CI 1.10–1.64]; P &amp;lt; 0.004) after multivariable and VAT adjustment. CONCLUSIONS PAT is significantly correlated with most cardiometabolic risk factors and CAC in the JHS cohort. The results suggest that PAT is an important VAT depot that may exert a local effect on the coronary vasculature.