tbuckley/cabot-search huggingface dataset:
Advanced Glycation End Products in Nondiabetic Patients With Coronary Artery Disease
Authors: Masao Kanauchi, Nobuhiro Tsujimoto, Toshio Hashimoto
Journal: Diabetes Care (2001)

To investigate whether advanced glycation end products (AGEs) participate in the development of coronary artery disease (CAD) in nondiabetic and diabetic subjects.Serum concentrations of AGEs were measured using a newly established enzyme-linked immunosorbent assay in 48 nondiabetic patients (normal glucose tolerance, n = 20; impaired glucose tolerance, n = 28) who received coronary angiography for the study of chest pain or suspected CAD. Insulin sensitivity was examined by the euglycemic-hyperinsulinemic glucose clamp technique and was estimated as the mean glucose infusion rate during the last 30 min of clamp time (M value).Patients were classified into four groups based on the number of significantly stenosed vessels, defined as 0-, 1-, 2-, or 3-vessel disease. Serum concentrations of AGEs were significantly higher in nondiabetic subjects with CAD than in control subjects (2.42 +/- 0.65 vs. 1.96 +/- 0.40 mU/ml, P < 0.01) and significantly correlated with the number of significantly stenosed vessels (r = 0.678, P < 0.001). M values significantly inversely correlated with serum concentrations of AGEs (r = -0.490, P < 0.05). In multiple regression analysis, with the number of significantly stenosed vessels as the dependent variable, serum concentrations of AGEs, 2-h plasma glucose, and areas under the plasma glucose response curve were independently associated.This pilot study indicates the relation between AGEs and the severity of CAD in nondiabetic patients. The measurement of serum AGE concentrations may be predictive of vascular damage.
Bevacizumab for Advanced Breast Cancer: All Tied Up With a RIBBON?
Authors: Harold J. Burstein
Journal: Journal of Clinical Oncology (2011)

biomarkers that can predict response means a commitment to conducting correlative studies in large clinical trials.It is likely that novel drugs for cancer coming to market will continue to have stratospheric price tags. 10It is also likely that novel agents will achieve, at best, incremental improvements in PFS that often will not translate into improvements in overall survival.We will serve our patients best by designing trials that permit us to identify which patients have the highest likelihood of deriving a meaningful survival benefit from a novel agent.Correlative science for effective patient selection may be the key to cost-effective treatment of cancer in the biologic therapy era.
Segregation is good for patients with cystic fibrosis
Authors: Steven Conway
Journal: Journal of the Royal Society of Medicine (2008)

It is bewildering, in the face of so much evidence for the potential for cross-infection between patients – cross-infection that may have devastating consequences – that we continue to debate the advantages (numerous and important) and disadvantages (few and largely irrelevant) of keeping patients separated. Amazingly, to my mind, there has been no resolution of the conflicting points of view since Professor Geddes and I first argued this issue in a cystic fibrosis (CF) conference in 2001. Some CF centres have a strict patient segregation policy, some centres have no policy at all, and many centres follow management protocols that fall at varied points between these two extremes. In this paper I will provide evidence which I believe supports a strict segregation policy as practised in the Leeds CF centres. An interesting and quizzical starting point might be to ask this question: Why does the international CF community readily accept separation of patients with Burkholderia cepacia complex (Bcc) infection from all other patients but does not universally accept separation of all patients from each other? It is instructive to consider this. We treat patients with Bcc infection separately because we know that Bcc is a potentially virulent pathogen, that it can cause an accelerated or catastrophic clinical deterioration, that it is difficult to treat and almost impossible to eradicate, that it may preclude acceptance onto a lung transplant programme, but most of all because Bcc infection is transmitted from patient to patient. We have known all these facts for some time. In 1987, Tablan et al. reported that patients with Bcc infection and moderate or advanced CF were hospitalized for longer and died sooner than controls with similar levels of disease severity. These early data suggested a possible nosocomial source of Bcc infection, consistent with a report as far back as 1986 that an introduction of infection control measures resulted in a sharp decline in the incidence of Bcc infection. In 1995, Whiteford et al. reported a Bcc outbreak in children with CF and, importantly, a concurrent ‘dramatic decrease in the number of newly colonized patients’ after the introduction of segregation measures. In 1998, Ledson et al. reported cross infection with different Bcc strains between patients with Bcc infection who were already separated from other patients but not from each other, advising that further subsegregation of patients within the Bcc infected group might be necessary. By 1999, the UK CF Trust confidently stated that
Prolymphocytic transformation of chronic lymphocytic leukemia: A case report of lengthy survival after intensive chemotherapy
Authors: John D. Roberts, Barbara H. Tindle, Bruce R. Macpherson
Journal: American Journal of Hematology (1989)

Abstract A case of prolymphocytic transformation of chronic lymphocytic leukemia (CLL) is presented in which complete peripheral morphometric remission and lengthy survival were observed after intensive chemotherapy. The case is discussed within the context of the reported therapeutic experience.
Influence of definition based versus pragmatic birth registration on international comparisons of perinatal and infant mortality: population based retrospective study
Authors: K. S. Joseph, S. Liu, J. Rouleau, S. Lisonkova, J. A. Hutcheon, R. Sauve, A. C. Allen, M. S. Kramer
Journal: BMJ (2012)

<b>Objectives</b> To examine variations in the registration of extremely low birthweight and early gestation births and to assess their effect on perinatal and infant mortality rankings of industrialised countries. <b>Design</b> Retrospective population based study. <b>Setting </b>Australia, Canada, European countries, and the United States for 2004; Australia, Canada, and New Zealand for 2007. <b>Population</b> National data on live births and on fetal, neonatal, and infant deaths. <b>Main outcome measures</b> Reported proportions of live births with birth weight/gestational age of less than 500 g, less than 1000 g, less than 24 weeks, and less than 28 weeks; crude rates of fetal, neonatal, and infant mortality; mortality rates calculated after exclusion of births under 500 g, under 1000 g, less than 24 weeks, and less than 28 weeks. <b>Results</b> The proportion of live births under 500 g varied widely from less than 1 per 10 000 live births in Belgium and Ireland to 10.8 per 10 000 live births in Canada and 16.9 in the United States. Neonatal deaths under 500 g, as a proportion of all neonatal deaths, also ranged from less than 1% in countries such as Luxembourg and Malta to 29.6% in Canada and 31.1% in the United States. Rankings of countries based on crude fetal, neonatal, and infant mortality rates differed substantially from rankings based on rates calculated after exclusion of births with a birth weight of less than 1000 g or a gestational age of less than 28 weeks. <b>Conclusions</b> International differences in reported rates of extremely low birthweight and very early gestation births probably reflect variations in registration of births and compromise the validity of international rankings of perinatal and infant mortality.
Role of NF- B and PPAR- in lung inflammation induced by monocyte-derived microparticles
Authors: T. Neri, C. Armani, A. Pegoli, C. Cordazzo, Y. Carmazzi, S. Brunelleschi, C. Bardelli, M.C. Breschi, P. Paggiaro, A. Celi
Journal: European Respiratory Journal (2010)

Microparticles (MP) are phospholipid vesicles shed by cells upon activation or apoptosis. Monocyte-derived MP upregulate the synthesis of proinflammatory mediators by lung epithelial cells; the molecular bases of such activity are unknown. Peroxisome proliferator-activated receptors (PPAR) have been demonstrated to be involved in the modulation of nuclear factor (NF)-κB transcriptional activity and inflammation. We investigated whether the upregulation of the synthesis of proinflammatory cytokines by human lung epithelial cells induced by monocyte/macrophage-derived MP involves NF-κB activation and is modulated by PPAR-γ. MP were generated by stimulation of human monocytes/macrophages with the calcium ionophore, A23187. MP were incubated with human lung epithelial cells. NF-κB translocation was assessed by electrophoretic mobility shift assay. Interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1 synthesis was assessed by ELISA and RT-PCR. Stimulation of A549 alveolar cells with monocyte/macrophage-derived MP caused an increase in NF-κB activation and IL-8 and MCP-1 synthesis that was inhibited by pre-incubation with the PPAR-γ agonists, rosiglitazone and 15-deoxy-Δ 12,14 -prostaglandin-J 2 . Parallel experiments with normal human bronchial epithelial cells largely confirmed the results. The effects of PPAR-γ agonists were reversed by the specific antagonist, GW9662. Upregulation of the synthesis of proinflammatory mediators by human lung epithelial cells induced by monocyte/macrophage-derived MP is mediated by NF-κB activation through a PPAR-γ dependent pathway.
Pathogenesis of posttransfusion viral hepatitis in children with β-thalassemia
Authors: Mark Feitelson, Laura Lega, Juanhui Guo, Massimo Resti, Maria E. Rossi, Chiara Azzari, Baruch S. Blumberg, Alberto Vierucci
Journal: Hepatology (1994)

The pathogenesis of posttransfusion hepatitis was determined in 14 children with β-thalassemia. All had blood samples obtained in 1980 or 1981, were vaccinated against hepatitis B virus in 1983 and had another serum sample collected in 1989. Seven children had detectable antibodies against hepatitis C virus before vaccination, and all were positive in 1989. With specific solid-phase enzyme immunoassays, all children had antibodies against hepatitis B virus, X and polymerase antigens in 1981, and six had one or both antibodies in 1989. Hepatitis B virus infection was confirmed by means of polymerase chain reaction, which demonstrated virus DNA in 13 of the 14 children. The amplification products spanning the X/precore region were smaller than expected, suggesting mutations in this region. Cloning and sequencing of these products revealed deletions spanning part or all of the X gene. The results show that these children were infected with hepatitis B virus even without other markers in serum, that hepatitis B persists years after vaccination and that such infections are associated with the presence of X deletion mutants. Coinfection with hepatitis B and C viruses, the former containing a new class of variants, is common in children with β-thalassemia. (Hepatology 1994;19:558-568).
B cells from hyper-IgM patients carrying <i>UNG</i> mutations lack ability to remove uracil from ssDNA and have elevated genomic uracil
Authors: Bodil Kavli, Sonja Andersen, Marit Otterlei, Nina B. Liabakk, Kohsuke Imai, Alain Fischer, Anne Durandy, Hans E. Krokan, Geir Slupphaug
Journal: The Journal of Experimental Medicine (2005)

The generation of high-affinity antibodies requires somatic hypermutation (SHM) and class switch recombination (CSR) at the immunoglobulin (Ig) locus. Both processes are triggered by activation-induced cytidine deaminase (AID) and require UNG-encoded uracil-DNA glycosylase. AID has been suggested to function as an mRNA editing deaminase or as a single-strand DNA deaminase. In the latter model, SHM may result from replicative incorporation of dAMP opposite U or from error-prone repair of U, whereas CSR may be triggered by strand breaks at abasic sites. Here, we demonstrate that extracts of UNG-proficient human B cell lines efficiently remove U from single-stranded DNA. In B cell lines from hyper-IgM patients carrying UNG mutations, the single-strand–specific uracil-DNA glycosylase, SMUG1, cannot complement this function. Moreover, the UNG mutations lead to increased accumulation of genomic uracil. One mutation results in an F251S substitution in the UNG catalytic domain. Although this UNG form was fully active and stable when expressed in Escherichia coli, it was mistargeted to mitochondria and degraded in mammalian cells. Our results may explain why SMUG1 cannot compensate the UNG2 deficiency in human B cells, and are fully consistent with the DNA deamination model that requires active nuclear UNG2. Based on our findings and recent information in the literature, we present an integrated model for the initiating steps in CSR.
N-3 Fatty Acids
Authors: Scott M. Grundy
Journal: Circulation (2003)

large body of data points to potential benefits of N-3 polyunsaturated fatty acids in reducing the risk of cardiovascular disease (CVD). 1 Available data suggest that higher intakes of N-3 fatty acids will reduce various forms of CVD, especially sudden cardiovascular death.These data derive from laboratory animal studies, epidemiological data, metabolic studies, and smaller clinical trials.The literature also contains other evidence that N-3 fatty acids may help to prevent or treat several non-cardiovascular diseases.This editorial nonetheless will limit itself to the cardiovascular system.
Mechanisms of cell death induced by suicide genes encoding purine nucleoside phosphorylase and thymidine kinase in human hepatocellular carcinoma cells in vitro
Authors: Tim U. Krohne, Srinivas Shankara, Michael Geissler, Bruce L. Roberts, Jack R. Wands, Hubert E. Blum, Leonhard Mohr
Journal: Hepatology (2001)

For gene therapy of hepatocellular carcinoma (HCC), the Escherichia coli purine nucleoside phosphorylase (PNP)/fludarabine suicide gene system may be more useful than the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system as a result of a stronger bystander effect. To analyze the molecular mechanisms involved in PNP/fludarabine-mediated cell death in human HCC cells in comparison with HSV-tk/GCV, we transduced human HCC cells of the cell lines, HepG2 and Hep3B, with PNP or HSV-tk using adenoviral vectors, followed by prodrug incubation. Both systems predominantly induced apoptosis in HepG2 and Hep3B cells. PNP/fludarabine induced strong p53 accumulation and a more rapid onset of apoptosis in p53-positive HepG2 cells as compared with p53-negative Hep3B cells, but efficiency of tumor cell killing was similar in both cell lines. In contrast, HSV-tk/GCV-induced apoptosis was reduced in p53-negative Hep3B cells as compared with p53-positive HepG2 cells. HSV-tk/GCV, but not PNP/fludarabine, caused up-regulation of Fas in p53-positive HepG2 cells and of Fas ligand (FasL) in both HCC cell lines. These results demonstrate cell line-specific differences in response to treatment with PNP/fludarabine and HSV-tk/GCV, respectively, and indicate that PNP/fludarabine may be superior to HSV-tk/GCV for the treatment of human HCC because of its independence from p53 and the Fas/FasL system. (Hepatology 2001;34:511-518.)
Thrombospondin-1 Activation of Signal-Regulatory Protein-α Stimulates Reactive Oxygen Species Production and Promotes Renal Ischemia Reperfusion Injury
Authors: Mingyi Yao, Natasha M. Rogers, Gábor Csányi, Andres I. Rodriguez, Mark A. Ross, Claudette St. Croix, Heather Knupp, Enrico M. Novelli, Angus W. Thomson, Patrick J. Pagano, Jeffrey S. Isenberg
Journal: Journal of the American Society of Nephrology (2014)

Ischemia reperfusion injury (IRI) causes tissue and organ injury, in part, through alterations in tissue blood flow and the production of reactive oxygen species. The cell surface receptor signal-regulatory protein-α (SIRP-α) is expressed on inflammatory cells and suppresses phagocytosis, but the function of SIRP-α in IRI has not been determined. We reported previously that the matricellular protein thrombospondin-1 is upregulated in IRI. Here, we report a novel interaction between thrombospondin-1 and SIRP-α on nonphagocytic cells. In cell-free experiments, thrombospondin-1 bound SIRP-α. In vascular smooth muscle cells and renal tubular epithelial cells, treatment with thrombospondin-1 led to phosphorylation of SIRP-α and downstream activation of Src homology domain 2-containing phosphatase-1. Thrombospondin-1 also stimulated phosphorylation of p47(phox) (an organizer subunit for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1/2) and increased production of superoxide, both of which were abrogated by knockdown or antibody blockade of SIRP-α. In rodent aortic rings, treatment with thrombospondin-1 increased the production of superoxide and inhibited nitric oxide-mediated vasodilation in a SIRP-α-dependent manner. Renal IRI upregulated the thrombospondin-1-SIRP-α signaling axis and was associated with increased superoxide production and cell death. A SIRP-α antibody that blocks thrombospondin-1 activation of SIRP-α mitigated the effects of renal IRI, increasing blood flow, suppressing production of reactive oxygen species, and preserving cellular architecture. A role for CD47 in SIRP-α activation in these pathways is also described. Overall, these results suggest that thrombospondin-1 binding to SIRP-α on nonphagocytic cells activates NADPH oxidase, limits vasodilation, and promotes renal IRI.
Tumor-Infiltrating Lymphocytes and Response to Platinum in Triple-Negative Breast Cancer
Authors: Nadine M. Tung, Eric P. Winer
Journal: Journal of Clinical Oncology (2015)

OS. 12-14 In the BIG (Breast International Group) 2-98 trial, for patients with TNBC and 50% TILs, 5-year DFS and OS rates were 92%, representing a significantly decreased risk for both relapse (hazard ratio, 0.3; 95% CI, 0.11 to 0.81) and death (hazard ratio, 0.3; 95% CI, 0.09 to 0.92) compared with patients with lower levels of TILs. 14 Higher pCR rates are also seen after neoadjuvant anthracycline and taxane-based chemotherapy in TN and HER2-positive breast cancer with higher levels of TILs. 15-17 Limited data exist regarding the prognosticvalueofTILsintheabsenceofchemotherapy;afewstudieshave reported that an increase in expression of immune markers in breast cancer is associated with decreased risk of relapse. 18
Colon cancer stem cells
Authors: L Ricci-Vitiani, A Pagliuca, E Palio, A Zeuner, R De Maria
Journal: Gut (2007)

Colorectal cancer (CRC) is the third most common form of cancer and the second cause of cancer-related death in the Western world, leading to 655,000 deaths worldwide per year (Jemal et al. in CA Cancer J Clin 56:106–130, 2006). Despite the emergence of new targeted agents and the use of various therapeutic combinations, none of the treatment options available is curative in patients with advanced cancer. A growing body of evidence is increasingly supporting the idea that human cancers can be considered as a stem cell disease. According to the cancer stem cell model, malignancies originate from a small fraction of cancer cells that show self-renewal and pluripotency and are capable of initiating and sustaining tumor growth (Boman and Wicha in J Clin Oncol 26:2795–2799, 2008). The cancer-initiating cells or “cancer stem cells” were first identified in hematologic malignancies and most recently in several solid tumors, including CRC. The hypothesis of stem cell-driven tumorigenesis in colon cancer raises questions as to whether current treatments are able to efficiently target the tumorigenic cell population that is responsible for tumor growth and maintenance. This review will focus on the different aspects of stem cell biology in the context of CRC, which might help to understand the mechanisms that give rise to tumor development and resistance to therapy. First, we will briefly revise the knowledge available on normal intestinal stem cells and recent advances in understanding crypt biology, which have led to new theory on the origins of colon adenomas and cancers. Then, we will summarize the evidence and current status on colon cancer stem cells, focusing on their relevance and promises for the treatment of colorectal carcinoma.
Rho and Rho Kinase Mediate Thrombin-Stimulated Vascular Smooth Muscle Cell DNA Synthesis and Migration
Authors: Tammy M. Seasholtz, Mousumi Majumdar, Daniel D. Kaplan, Joan Heller Brown
Journal: Circulation Research (1999)

Abstract —Aberrant regulation of smooth muscle cell proliferation and migration is associated with the pathophysiology of vascular disorders such as hypertension, atherosclerosis, restenosis, and graft rejection. To elucidate molecular mechanisms that regulate proliferation and migration of vascular smooth muscle cells, we determined whether signaling through the small G protein Rho is involved in thrombin- and phenylephrine-stimulated proliferation and migration of rat aortic smooth muscle cells (RASMCs). Thrombin and the thrombin peptide SFLLRNP stimulated DNA synthesis of RASMCs as measured by [ 3 H]thymidine incorporation. Both ligands also increased cell migration as measured by the Boyden chamber method. l -Phenylephrine failed to induce either of these responses but increased inositol phosphate accumulation and mitogen-activated protein kinase activation in these cells, which indicated that the cells were responsive to α 1 -adrenergic stimulation. The C3 exoenzyme, which ADP-ribosylates and inactivates Rho, fully inhibited both thrombin-stimulated proliferation and migration but had no effect on inositol phosphate accumulation. In addition, Y-27632, an inhibitor of the Rho effector p160ROCK/Rho kinase, decreased thrombin-stimulated DNA synthesis and migration. To directly examine Rho activation, Rho-[ 35 S]GTPγS binding was measured. The addition of the thrombin peptide SFLLRNP, but not phenylephrine, to RASMC lysates resulted in a significant increase in Rho-[ 35 S]GTPγS binding. Thrombin and SFLLRNP, but not phenylephrine, also increased membrane-associated Rho in intact RASMCs, consistent with selective activation of Rho by thrombin. These results indicate that thrombin activates Rho in RASMCs and establish Rho as a critical mediator of thrombin receptor effects on DNA synthesis and cell migration in these cells.
Gastric polypoid lesion at the antrum
Authors: C-J Chen, C-W Chang, H-L Chen, Y-J Chan, M-J Chen
Journal: Gut (2009)

A 79-year-old man underwent upper endoscopy 5 months ago because of dyspepsia and anaemia, with haemoglobin of 7.2 g/dl. Upper endoscopy revealed an ulcer 12 mm in diameter at the antrum (fig 1A) and biopsies showed benign ulceration and were …