tbuckley/cabot-search huggingface dataset:
Lactobacillus acidophilus (strain LB) from the resident adult human gastrointestinal microflora exerts activity against brush border damage promoted by a diarrhoeagenic Escherichia coli in human enterocyte-like cells
Authors: V Lievin-Le Moal
Journal: Gut (2002)

<b>Background and aims:</b> The normal gastrointestinal microflora exerts a barrier effect against enteropathogens. The aim of this study was to examine whether lactobacilli, a minor genus of the resident gut microflora, exerts a protective effect against the cellular injuries promoted by the diarrhoeagenic Afa/Dr diffusely adhering <i>Escherichia coli</i> (Afa/Dr DAEC) C1845 strain in human intestinal cells. <b>Methods:</b> Cultured human intestinal fully differentiated enterocyte-like Caco-2/TC7 cells were used. Antibacterial activity was examined by measuring the viability of the adhering C1845 bacteria. The distribution of brush border associated cytoskeleton and functional proteins was examined by immunofluorescence labelling coupled to confocal laser scanning microscopy analysis. <b>Results:</b> The activity of <i>Lactobacillus acidophilus</i> strain LB isolated from the resident human gastrointestinal microflora was examined. A dose dependent decrease in viability of C1845 bacteria was observed after both direct contact in vitro between the spent culture supernatant (LB-SCS) and the bacteria, and when the bacteria were adherent on Caco-2/TC7 cells. Protection against the C1845 induced alterations in expression of F-actin, sucrase-isomaltase, dipeptidylpeptidase IV, alkaline phosphatase, and fructose transporter alterations was observed when the cells were exposed to LB-SCS. <b>Conclusion:</b><i>L acidophilus</i> strain isolated from the resident adult human gastrointestinal microflora, together with its antimicrobial activity, exerts a protective effect against the brush border lesions promoted by the diarrhoeagenic Afa/Dr DAEC strain C1845.
Inhibitors Targeting Mitosis: Tales of How Great Drugs against a Promising Target Were Brought Down by a Flawed Rationale
Authors: Edina Komlodi-Pasztor, Dan L. Sackett, Antonio Tito Fojo
Journal: Clinical Cancer Research (2012)

Abstract Although they have been advocated with an understandable enthusiasm, mitosis-specific agents such as inhibitors of mitotic kinases and kinesin spindle protein have not been successful clinically. These drugs were developed as agents that would build on the success of microtubule-targeting agents while avoiding the neurotoxicity that encumbers drugs such as taxanes and vinca alkaloids. The rationale for using mitosis-specific agents was based on the thesis that the clinical efficacy of microtubule-targeting agents could be ascribed to the induction of mitotic arrest. However, the latter concept, which has long been accepted as dogma, is likely important only in cell culture and rapidly growing preclinical models, and irrelevant in patient tumors, where interference with intracellular trafficking on microtubules is likely the principal mechanism of action. Here we review the preclinical and clinical data for a diverse group of inhibitors that target mitosis and identify the reasons why these highly specific, myelosuppressive compounds have failed to deliver on their promise. Clin Cancer Res; 18(1); 51–63. ©2012 AACR.
Intracellular signalling via the AKT axis and downstream effectors is active and prognostically significant in cancer of unknown primary (CUP): a study of 100 CUP cases
Authors: V. Golfinopoulos, G. Pentheroudakis, A. Goussia, V. Siozopoulou, M. Bobos, D. Krikelis, A. Cervantes, T. Ciuleanu, M. Marselos, G. Fountzilas, V. Malamou-Mitsi, N. Pavlidis
Journal: Annals of Oncology (2012)
Relationship Between Arterial Partial Oxygen Pressure After Resuscitation From Cardiac Arrest and Mortality in Children
Authors: Lee P. Ferguson, Andrew Durward, Shane M. Tibby
Journal: Circulation (2012)

Background— Observational studies in adults have shown a worse outcome associated with hyperoxia after resuscitation from cardiac arrest. Extrapolating from adult data, current pediatric resuscitation guidelines recommend avoiding hyperoxia. We investigated the relationship between arterial partial oxygen pressure and survival in patients admitted to the pediatric intensive care unit (PICU) after cardiac arrest. Methods and Results— We conducted a retrospective cohort study using the Pediatric Intensive Care Audit Network (PICANet) database between 2003 and 2010 (n=122 521). Patients aged &lt;16 years with documented cardiac arrest preceding PICU admission and arterial blood gas analysis taken within 1 hour of PICU admission were included. The primary outcome measure was death within the PICU. The relationship between postarrest oxygen status and outcome was modeled with logistic regression, with nonlinearities explored via multivariable fractional polynomials. Covariates included age, sex, ethnicity, congenital heart disease, out-of-hospital arrest, year, Pediatric Index of Mortality-2 (PIM2) mortality risk, and organ supportive therapies. Of 1875 patients, 735 (39%) died in PICU. Based on the first arterial gas, 207 patients (11%) had hyperoxia (Pa o 2 ≥300 mm Hg) and 448 (24%) had hypoxia (Pa o 2 &lt;60 mm Hg). We found a significant nonlinear relationship between Pa o 2 and PICU mortality. After covariate adjustment, risk of death increased sharply with increasing hypoxia (odds ratio, 1.92; 95% confidence interval, 1.80–2.21 at Pa o 2 of 23 mm Hg). There was also an association with increasing hyperoxia, although not as dramatic as that for hypoxia (odds ratio, 1.25; 95% confidence interval, 1.17–1.37 at 600 mm Hg). We observed an increasing mortality risk with advancing age, which was more pronounced in the presence of congenital heart disease. Conclusions— Both severe hypoxia and, to a lesser extent, hyperoxia are associated with an increased risk of death after PICU admission after cardiac arrest.
Lysophosphatidylcholine inhibits surface receptor-mediated intracellular signals in endothelial cells by a pathway involving protein kinase C activation.
Authors: K Kugiyama, M Ohgushi, S Sugiyama, T Murohara, K Fukunaga, E Miyamoto, H Yasue
Journal: Circulation Research (1992)

Lysophosphatidylcholine (lysoPC) transferred from oxidatively modified low density lipoprotein (Ox-LDL) to the endothelial surface membrane has been shown to produce a selective unresponsiveness to cell surface receptor-regulated endothelium-dependent relaxation (EDR) in the rabbit aorta. To determine its mechanism we examined the effects of lysoPC on endothelial surface receptor-mediated transmembrane signals. Incubation for 1 minute with palmitoyl lysoPC (5-10 microM) decreased thrombin (Th, 2 units/ml)- or histamine (His, 0.1 mM)-stimulated inositol 1,4,5-trisphosphate (IP3) production in primary cultures of human umbilical vein endothelial cells (HUVECs). LysoPC also decreased Th- or His-induced intracellular calcium ([Ca2+]i, fura 2) elevation. Pretreatment with protein kinase C (PKC) inhibitors staurosporine (100 nM) or H-7 (50 microM) prevented the inhibitory actions of lysoPC, but HA-1004 had no effect. Incubation for 5 minutes with phorbol 12-myristate 13-acetate (PMA, 100 nM) produced the inhibitory actions on the Th- or His-induced intracellular signals, which closely mimic those exhibited by lysoPC. However, the inhibitory effect of lysoPC was lost in cells that were depleted of PKC by pretreatment for 24 hours with 100 nM PMA. Furthermore, incubation of the cells for 1 minute with lysoPC stimulated PKC activity in the membrane fraction. In organ chamber experiments with porcine coronary artery rings, pretreatment with staurosporine (20 nM) attenuated lysoPC-induced impairment of EDR in response to Th. These results indicate that lysoPC, which accumulates in Ox-LDL and atherosclerotic arterial walls, inhibits the early transmembrane signaling pathway in endothelial cells, and PKC activation could at least partially be involved in the negative regulation by lysoPC.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine slows ischaemic metabolism in canine myocardium in vitro: relationship to ischaemic preconditioning
Authors: R. S V. Heide, K. A Reimer, R. B Jennings
Journal: Cardiovascular Research (1993)

Objective: Studies in rabbits suggest that the cardioprotective effects of adenosine against lethal cell injury may be related to production of adenosine and subsequent activation of adenosine A1, receptors. However, it is not known whether intracoronary adenosine therapy can mimic the metabolic sparing effects of preconditioning in rabbits or dogs. The purpose of this study was to determine the effect of intracoronary adenosine on ischaemic metabolism in totally ischaemic canine myocardium. Methods: Dog hearts (n=13) were excised and the coronary arteries were perfused with an oxygenated Krebs' buffer containing glucose. Adenosine was added to the buffer perfusing the circumflex (treated) region. Following perfusion, control and treated beds from each heart were subjected to 90 min total ischaemia at 37°C. Tissue levels of ATP and glycolytic intermediates were determined at several time points during the ischaemic incubation. Results: Adenosine significantly slowed the rate of ATP depletion, glycogen utilisation, and lactate accumulation during the first 20 minutes of total ischaemia. Conclusions: The results suggest that adenosine is capable of slowing ischaemic metabolism and they are consistent with the hypothesis that adenosine may mediate ischaemic preconditioning. Cardiovascular Research 1993;27:669-673
Association of the 6q23 region with the rate of joint destruction in rheumatoid arthritis
Authors: Hans Ulrich Scherer, Michael P M van der Linden, Fina A S Kurreeman, Gerrie Stoeken-Rijsbergen, Saskia le Cessie, Tom W J Huizinga, Annette H van der Helm-van Mil, René E M Toes
Journal: Annals of the Rheumatic Diseases (2009)

Background Two novel genetic polymorphisms on chromosome 6q23 are associated with susceptibility to rheumatoid arthritis (RA). Both polymorphisms (rs6920220 and rs10499194) reside in a region close to the gene encoding tumour necrosis factor α-induced protein 3 ( TNFAIP3 ). TNFAIP3 is a negative regulator of NF-κB and is involved in inhibiting TNF-receptor-mediated signalling effects. Interestingly, the initial associations were detected in patients with longstanding RA. However, no association was found for rs10499194 in a Swedish cohort with early arthritis. This might be caused by over-representation of patients with severe disease in cohorts with longstanding RA. Objective To analyse the effect of the 6q23 region on the rate of joint destruction. Methods Five single nucleotide polymorphisms in 6q23 were genotyped in 324 Dutch patients with early RA. Genotypes were correlated with progression of radiographic joint damage for a follow-up time of 5 years. Results Two polymorphisms (rs675520 and rs9376293) were associated with severity of radiographic joint damage in patients positive for anti-citrullinated protein/peptide antibodies (ACPA). Importantly, the effects were present after correction for confounding factors such as secular trends in treatment. Conclusions These data associate the 6q23 region with the rate of joint destruction in ACPA+ RA.
Association of Metformin, Elevated Homocysteine, and Methylmalonic Acid Levels and Clinically Worsened Diabetic Peripheral Neuropathy
Authors: Daryl J. Wile, Cory Toth
Journal: Diabetes Care (2009)

OBJECTIVE The severity of peripheral neuropathy in diabetic patients varies for unclear reasons. Long-term use of metformin is associated with malabsorption of vitamin B12 (cobalamin [Cbl]) and elevated homocysteine (Hcy) and methylmalonic acid (MMA) levels, which may have deleterious effects on peripheral nerves. The intent of this study was to clarify the relationship among metformin exposure, levels of Cbl, Hcy, and MMA, and severity of peripheral neuropathy in diabetic patients. We hypothesized that metformin exposure would be associated with lower Cbl levels, elevated Hcy and MMA levels, and more severe peripheral neuropathy. RESEARCH DESIGN AND METHODS This was a prospective case-control study of patients with type 2 diabetes and concurrent symptomatic peripheral neuropathy, comparing those who had received &amp;gt;6 months of metformin therapy (n = 59) with those without metformin exposure (n = 63). Comparisons were made using clinical (Toronto Clinical Scoring System and Neuropathy Impairment Score), laboratory (serum Cbl, fasting Hcy, and fasting MMA), and electrophysiological measures (nerve conduction studies). RESULTS Metformin-treated patients had depressed Cbl levels and elevated fasting MMA and Hcy levels. Clinical and electrophysiological measures identified more severe peripheral neuropathy in these patients; the cumulative metformin dose correlated strongly with these clinical and paraclinical group differences. CONCLUSIONS Metformin exposure may be an iatrogenic cause for exacerbation of peripheral neuropathy in patients with type 2 diabetes. Interval screening for Cbl deficiency and systemic Cbl therapy should be considered upon initiation of, as well as during, metformin therapy to detect potential secondary causes of worsening peripheral neuropathy.
Increased angiogenesis and blood vessel maturation in acellular collagen–heparin scaffolds containing both FGF2 and VEGF
Authors: Suzan T.M. Nillesen, Paul J. Geutjes, Ronnie Wismans, Joost Schalkwijk, Willeke F. Daamen, Toin H. van Kuppevelt
Journal: Biomaterials (2006)
From cystic pulmonary airway malformation, to bronchioloalveolar carcinoma and adenocarcinoma of the lung
Authors: O. C. Ioachimescu, A. C. Mehta
Journal: European Respiratory Journal (2005)

Bronchioloalveolar carcinoma (BAC) of the lungs is a known morphological subtype of nonsmall cell cancer. The current study presents several carcinogenetic theories of BAC and the possible relationship with atypical adenomatous hyperplasia and congenital pulmonary airway malformation (CPAM). The authors present an unusual case of BAC developed in an area of CPAM, with subsequent progression to metastatic adenocarcinoma (AC). The case is unique due to the combination of: early age of presentation; neoplastic transformation of a CPAM; unaltered course over 15 yrs; and its particular pattern of slow morphogenesis and degeneration into an invasive AC of the lung. The case also presents the unique features of a long-standing, unaltered natural course of paediatric BAC towards invasive and metastatic AC, illustrating that lack of growth over many years cannot be entirely trusted as a criterion of benignity. In conclusion, clinicians and pathologists need to be aware of the fact that congenital pulmonary airway malformation so far represents the only known pre-invasive lesion for mucinous bronchioloalveolar carcinoma.
Histopathologic Examination of Failed Grafts in Descemet's Stripping with Automated Endothelial Keratoplasty
Authors: Leejee H. Suh, Daniel G. Dawson, Lejla Mutapcic, Steven I. Rosenfeld, William W. Culbertson, Sonia H. Yoo, Terrence P. O'Brien, Sander R. Dubovy
Journal: Ophthalmology (2009)
Type I interferons are involved in the development of ultraviolet B-induced inflammatory skin lesions in systemic lupus erythaematosus patients
Authors: E Reefman, H Kuiper, P C Limburg, C G M Kallenberg, M Bijl
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To investigate the involvement of type I interferons and endothelial cell adhesion molecules in the development of ultraviolet B (UVB)-induced systemic lupus erythaematosus (SLE) skin lesions <h3>Methods:</h3> A total of 19 SLE patients and 13 controls were irradiated with two minimal erythaemal doses (MED) of UVB. Subsequently, skin biopsies were analysed (immuno)histologically over 10 days, for expression of IFNα-induced MxA, numbers of plasmacytoid dendritic cells (pDC), and expression of endothelial cell adhesion molecules, namely E-selectin, ICAM-1, and L-selectin ligand. Additionally, MxA expression was compared to its expression in nine established cutaneous lupus erythaematosus (CLE) lesions of SLE patients. <h3>Results:</h3> Before irradiation IFNα-induced MxA was expressed at significantly higher levels in non-lesional skin of SLE patients compared to healthy controls. In patients developing infiltrates upon UVB irradiation, MxA expression increased further, reaching expression levels similar to or exceeding levels in CLE-skin lesions. In these patients, MxA expression was sustained up to day 10, in contrast to patients not developing infiltrates in whom expression decreased. No noteworthy numbers of plasmacytoid dendritic cells (pDC) were detected in non-irradiated skin or at any time after UVB exposure in SLE patients or controls. MxA expression correlated with influx of T-cells and monocytes/macrophages, and with expression of E-selectin and ICAM-1. <h3>Conclusion:</h3> Development of UVB-induced SLE skin lesions involves a skewing towards production of Th1-associated cytokines, such as IFNα. In turn, this may lead to up-regulation of E-selectin and ICAM-1 resulting in recruitment of T-cells and macrophages.
271 EFFICACY AND SAFETY OF PERCUTANEOUS MICROWAVE ABLATION FOR HCC &gt; 3 cm. A SINGLE-CENTER EXPERIENCE
Authors: M. Russello, R. Benigno, V. Magnano, S. Lio, A. Bellia, C. Cocuzza, R. Faulisi, A. Digiacomo, P. Bellissima, A. Davi, G. Scifo
Journal: Journal of Hepatology (2013)
High dose chemotherapy and autologous stem cell transplantation as adjuvant therapy for primary breast cancer patients with four or more lymph nodes involved: long-term results of an international randomised trial
Authors: R.C. Coombes, A. Howell, M. Emson, C. Peckitt, C. Gallagher, C. Bengala, A. Tres, R. Welch, P. Lawton, R. Rubens, E. Woods, J. Haviland, D. Vigushin, E. Kanfer, J.M. Bliss
Journal: Annals of Oncology (2005)
Genetic variability in the IL1RN gene and the balance between IL1-Ra and IL-1β in IPF
Authors: Nicole Barlo, Coline van Moorsel, Nicoline Korthagen, Michiel Heron, Ger Rijkers, Henk Ruven, Jules van den Bosch, Jan Grutters
Journal: European Respiratory Journal (2011)

Introduction:  Idiopathic pulmonary fibrosis (IPF) is a rapidly progressive interstitial lung disease of unknown etiology. Interleukin (IL) -1β plays an important role in inflammation and has been associated with fibrotic remodelling. We investigated the balance between IL-1β and interleukin-1 receptor antagonist (IL-1Ra) in bronchoalveolar lavage fluid (BALf) and serum as well as the influence of genetic variability in the IL1B and IL1RN gene on disease susceptibility and cytokine levels.   Materials and methods:  In 77 IPF patients and 349 healthy controls, single nucleotide polymorphisms (SNPs) in the IL1RN and IL1B gene were determined. Serum and BALf IL-1Ra and IL-1β levels were measured using a multiplex suspension bead array system and were correlated with genotypes.   Results:  Both in serum and BALf a significantly decreased IL-1Ra/ IL-1β ratio was found in IPF patients compared to healthy controls. In the IL1RN gene, one SNP was associated with both the susceptibility to IPF and reduced IL-1Ra/IL-1β ratios in BALf.   Conclusion:  Our results show that genetic variability in the IL1RN gene plays a role in the pathogenesis of IPF and that this role may be more important than until recently thought. IPF patients appear to have a relative shortage of IL-1Ra, which might contribute to a pro-inflammatory and pro-fibrotic environment in their lungs.
METABOLIC ENGINEERING WITH RECOMBINANT ADENOVIRUSES
Authors: Peter A. Antinozzi, Hal K. Berman, Robert M. O'Doherty, Christopher B. Newgard
Journal: Annual Review of Nutrition (1999)

▪ Abstract Fuel homeostasis in mammals is accomplished by the interplay between tissues and organs with distinct metabolic roles. These regulatory mechanisms are disrupted in obesity and diabetes, leading to a renewed emphasis on discovery of molecular and pharmacologic methods for reversing metabolic disorders. In this chapter, we review the use of recombinant adenoviral vectors as tools for delivering metabolic regulatory genes to cells in culture and to tissues of intact animals. Included are studies on the use of these vectors for gaining insights into the biochemical mechanisms that regulate glucose-stimulated insulin secretion from pancreatic islet β-cells. We also highlight their use for understanding the function of newly discovered genes that regulate glycogen metabolism in liver and other tissues, and for evaluating “candidate” genes such as glucose-6-phosphatase, which may contribute to development of metabolic dysfunction in pancreatic islets and liver. Finally, we discuss the use of adenoviral and related vectors for causing chronic increases in the levels of circulating hormones. These examples serve to highlight the power of viral gene transfer vectors as tools for understanding metabolic regulatory mechanisms.
Increase in Number of Splenic Transplantable Colony-Forming Units in the SJL/J Mice After Infection With Rauscher Leukemia Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: James P. OKunewick, Eleanore L. Phillips, Penny Erhard
Journal: JNCI Journal of the National Cancer Institute (1972)

Previous experiments demonstrated that mice infected with Rauscher leukemia virus (RLV) possessed a significant resistance to the lethal effects of radiation. The present experiments were designed to determine whether changes in either the number of hematopoietic colony-forming units (CFU) or in the number of peripheral white cells might correlate with this resistance. The number of transplantable CFU in the spleens of SJL/J mice 14 days after they received an injection of RLV was measured relative to CFUs in the spleens of uninfected control mice. It was found that as a result of RLV infection the total number of transplantable splenic CFUs increased in the RLV-infected mice in proportion to the increase in spleen size. Conversely, no change was noted in either the total white blood cells or the lymphoid/myeloid ratio at 14 days after RLV injection, even though the leukemia could be demonstrated in the peripheral blood at later times.—J Natl Cancer Inst 49: 1101–1106, 1972.
Development of Inflammatory Angiogenesis by Local Stimulation of Fas In Vivo
Authors: Luigi Biancone, Antonella De Martino, Viviana Orlandi, Pier Giulio Conaldi, Antonio Toniolo, Giovanni Camussi
Journal: The Journal of Experimental Medicine (1997)

Fas–Fas ligand interaction is thought to be a crucial mechanism in controlling lymphocyte expansion by inducing lymphocyte apoptosis. However, Fas is also broadly expressed on nonlymphoid cells, where its function in vivo remains to be determined. In this study, we describe the development of inflammatory angiogenesis induced by agonistic anti-Fas mAb Jo2 in a murine model where Matrigel is used as a vehicle for the delivery of mediators. The subcutaneous implants in mice of Matrigel containing mAb Jo2 became rapidly infiltrated by endothelial cells and by scattered monocytes and macrophages. After formation and canalization of new vessels, marked intravascular accumulation and extravasation of neutrophils were observed. Several mast cells were also detected in the inflammatory infiltrate. The phenomenon was dose and time dependent and required the presence of heparin. The dependency on activation of Fas is suggested by the observation that the inflammatory angiogenesis was restricted to the agonistic anti-Fas mAb and it was absent in lpr Fas-mutant mice. Apoptotic cells were not detectable at any time inside the implant or in the surrounding tissue, suggesting that angiogenesis and cell infiltration did not result from recruitment of phagocytes by apoptotic cells but rather by a stimulatory signal through Fas-engagement. These findings suggest a role for Fas–Fas ligand interaction in promoting local angiogenesis and inflammation.