tbuckley/cabot-search huggingface dataset:
AduPARE1A and gemcitabine combined treatment trigger synergistic antitumor effects in pancreatic cancer through NF-κB mediated uPAR activation
Authors: Maria Victoria Maliandi, Ana Mato-Berciano, Luciano Sobrevals, Gaël Roué, Anabel José, Cristina Fillat
Journal: Molecular Cancer (2015)

Combined treatment of oncolytic adenoviruses with chemotherapeutic agents is foreseen as a therapeutic option for cancer. Here we have investigated the potential to use gemcitabine in combination with the oncolytic adenovirus AduPARE1A to treat pancreatic cancer and evaluate the underlying mechanism.We treated pancreatic cancer cell lines BxPC-3 and PANC-1 with AduPARE1A and gemcitabine individually or in combination and analyzed cell viability, combination index, apoptosis and viral production. We also investigated the effects of the combination on tumor growth and mice survival in two xenograft models. Furthermore, we analyzed uPAR promoter activity from different uPAR-controlled adenovirus and studied NF-κB mediated effects.Synergistic cell killing from the combination AduPARE1A/Gemcitabine was observed in BxPC-3 and PANC-1 cells. Moreover, the combination treatment produced therapeutic benefits over either individual modality in two mouse models bearing orthotopic tumors, showing reduced tumor progression and significant prolonged mouse survival. Mechanistic studies showed that the synergistic cell death was not due to an increase in viral replication but occurred through an enhancement of apoptotic cell death. Gemcitabine stimulation increased the transcription of uPAR-controlled transgenes through the induction of NF-κB acting on the uPAR promoter. Interestingly, NF-κB gemcitabine-mediated induction of AduPAR adenoviruses interfered with the activation of NF-κB regulated genes, probably as a result of an intracellular competition for NF-κB DNA binding. Consequently, AduPARE1A infection sensitized cells to gemcitabine-induced apoptosis in the combined treatment.These data highlights the potential of the combination as a treatment modality for pancreatic cancer patients.
The Effect of Diuretics on Plasma Volume and Renal Function in Patients with Ascites.
Authors: Fred L. Lieberman
Journal: Annals of Internal Medicine (1964)

s1 October 1964The Effect of Diuretics on Plasma Volume and Renal Function in Patients with Ascites.Fred L. Lieberman, M.D.Fred L. Lieberman, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-61-4-815_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDiuretics are though to act by diminishing the plasma volume, thereby promoting the movement of ascites and edema fluid into the plasma to maintain equilibrium. Since renal function is dependent on renal blood flow, reduction in plasma volume during diuresis might compromise renal function. To determine if renal failure is a consequence of diuresis in cirrhosis, the plasma volume and endogenous creatinine clearance were measured before and after a large diuresis in 40 patients with alcoholic cirrhosis and ascites. The plasma volume was measured with radioactive serum albumin, and diuresis was induced by hydrochlorothiazide, ethacrynic acid, and spironolactone. Only 2... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Los Angeles, Calif. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1964Volume 61, Issue 4Page: 815-815KeywordsAscitesBlood plasmaCirrhosisCreatinineDiureticsEdemaPlasma volumeRenal circulationRenal failureSerum albumin Issue Published: 1 October 1964 PDF DownloadLoading ...
Activation of human liver sinusoidal endothelial cell by human platelets induces hepatocyte proliferation
Authors: Takuya Kawasaki, Soichiro Murata, Kazuhiro Takahashi, Reiji Nozaki, Yukio Ohshiro, Naoya Ikeda, Sugiru Pak, Andriy Myronovych, Katsuji Hisakura, Kiyoshi Fukunaga, Tatsuya Oda, Ryoko Sasaki, Nobuhiro Ohkohchi
Journal: Journal of Hepatology (2010)
Projecting Individualized Absolute Invasive Breast Cancer Risk in Asian and Pacific Islander American Women
Authors: Rayna K. Matsuno, Joseph P. Costantino, Regina G. Ziegler, Garnet L. Anderson, Huilin Li, David Pee, Mitchell H. Gail
Journal: JNCI Journal of the National Cancer Institute (2011)

The Breast Cancer Risk Assessment Tool (BCRAT) of the National Cancer Institute is widely used for estimating absolute risk of invasive breast cancer. However, the absolute risk estimates for Asian and Pacific Islander American (APA) women are based on data from white women. We developed a model for projecting absolute invasive breast cancer risk in APA women and compared its projections to those from BCRAT. Data from 589 women with breast cancer (case patients) and 952 women without breast cancer (control subjects) in the Asian American Breast Cancer Study were used to compute relative and attributable risks based on the age at menarche, number of affected mothers, sisters, and daughters, and number of previous benign biopsies. Absolute risks were obtained by combining this information with ethnicity-specific data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program and with US ethnicity-specific mortality data to create the Asian American Breast Cancer Study model (AABCS model). Independent data from APA women in the Women's Health Initiative (WHI) were used to check the calibration and discriminatory accuracy of the AABCS model. The AABCS model estimated absolute risk separately for Chinese, Japanese, Filipino, Hawaiian, Other Pacific Islander, and Other Asian women. Relative and attributable risks for APA women were comparable to those in BCRAT, but the AABCS model usually estimated lower-risk projections than BCRAT in Chinese and Filipino, but not in Hawaiian women, and not in every age and ethnic subgroup. The AABCS model underestimated absolute risk by 17% (95% confidence interval = 1% to 38%) in independent data from WHI, but APA women in the WHI had incidence rates approximately 18% higher than those estimated from the SEER program. The AABCS model was calibrated to ethnicity-specific incidence rates from the SEER program for projecting absolute invasive breast cancer risk and is preferable to BCRAT for counseling APA women.
Low bone mineral density is two to three times more prevalent in non-athletic premenopausal women than in elite athletes: a comprehensive controlled study
Authors: M K Torstveit, J Sundgot-Borgen
Journal: British Journal of Sports Medicine (2005)

Objective: To compare bone mineral density (BMD), investigate factors associated with BMD, and examine the prevalence of low BMD in athletes and non-athletic controls. Methods: The study included a questionnaire (part I), measurement of BMD (part II), and a clinical interview (part III). All Norwegian female athletes on national teams (n = 938) and an aged matched random sample of non-athletic controls (n = 900) were invited to participate. The questionnaire was completed by 88% of athletes and 70% of controls. A random sample of these athletes (n = 300) and controls (n = 300) was invited to participate in parts II and III. All parts were completed by 186 athletes (62%) and 145 controls (48%). Results: Mean (standard deviation) total body (TB) BMD was higher (p&lt;0.001) in athletes (1.21 (0.09) g/cm 2 ) than in controls (1.18 (0.08) g/cm 2 ), and higher (p&lt;0.001) in high impact (HI) sports athletes than in medium impact (MI) and low impact (LI) sports athletes. In athletes, body weight and impact loading sports were positively associated, and percent body fat and eating disorders were negatively associated with TB BMD. Body weight and weight bearing activities were positively associated and menstrual dysfunction was negatively associated with TB BMD in controls. A higher percentage of controls (28.3%) than athletes (10.7%) had low BMD (p&lt;0.001). Conclusion: Female elite athletes have 3–20% higher BMD than non-athletic controls and HI sports athletes have 3–22% higher BMD compared with MI and LI sports athletes. Low BMD is two to three times more common in non-athletic premenopausal women than in elite athletes.
Chromatin Structure and Gene Regulation in the Immune System
Authors: Stephen T. Smale, Amanda G. Fisher
Journal: Annual Review of Immunology (2002)

The development of the immune system and the host response to microbial infection rely on the activation and silencing of numerous, differentially expressed genes. Since the mid-1980s, a primary goal has been to identify transcription factors that regulate specific genes and specific immunological processes. More recently, there has been a growing appreciation of the role of chromatin structure in gene regulation. Before most activators of a gene access their binding sites, a transition from a condensed to a decondensed chromatin structure appears to take place. The activation of transcription is then accompanied by the remodeling of specific nucleosomes. Conversely, the acquisition of a more condensed chromatin structure is often associated with gene silencing. Chromatin structure is a particularly significant contributor to gene regulation because it is likely to be a major determinant of cell identity and cell memory. That is, the propagation of decondensed chromatin at specific loci through DNA replication and cell division helps a cell remember which genes are expressed constitutively in that cell type or are poised for expression upon exposure to a stimulus. Here we review recent progress toward understanding the role of chromatin in the immune system. The interleukin-4 gene serves as a primary model for exploring the events involved in the acquisition and heritable maintenance of a decondensed chromatin structure. Studies of the interleukin-12 p40 and interferon-beta genes are then reviewed for insight into the mechanisms by which the remodeling of specific nucleosomes in the vicinity of a promoter can contribute to rapid activation following cell stimulation. Finally, basic principles of gene silencing are discussed.
Trichofolliculoma: case report with immunohistochemical study of cytokeratins
Authors: I. Kurokawa, S. Nishijima, K. Kusumoto, H. Sensaki, N. Shikata, A. Tsubura
Journal: British Journal of Dermatology (2003)

Journal Article Trichofolliculoma: case report with immunohistochemical study of cytokeratins Get access I. Kurokawa, I. Kurokawa Department of Dermatology, Hyogo Prefectural Tsukaguchi Hospital, 6‐8‐17 Minamitsukaguchi‐cho, Amagasaki, Hyogo 661‐0012, Japan Search for other works by this author on: Oxford Academic Google Scholar S. Nishijima, S. Nishijima Department of Dermatology, Kori Branch Hospital Search for other works by this author on: Oxford Academic Google Scholar K. Kusumoto, K. Kusumoto Department of Plastic and Reconstructive Surgery Search for other works by this author on: Oxford Academic Google Scholar H. Sensaki, H. Sensaki Department of Pathology, Kansai Medical University, Japan E‐mail: ikuro@alles.or.jp Search for other works by this author on: Oxford Academic Google Scholar N. Shikata, N. Shikata Department of Pathology, Kansai Medical University, Japan E‐mail: ikuro@alles.or.jp Search for other works by this author on: Oxford Academic Google Scholar A. Tsubura A. Tsubura Department of Pathology, Kansai Medical University, Japan E‐mail: ikuro@alles.or.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 148, Issue 3, 1 March 2003, Pages 597–598, https://doi.org/10.1046/j.1365-2133.2003.05209_6.x Published: 01 March 2003
Imaging and characterization of acute myocardial infarction in vivo by gated nuclear magnetic resonance.
Authors: G Wesbey, C B Higgins, P Lanzer, E Botvinick, M J Lipton
Journal: Circulation (1984)

Imaging by nuclear magnetic resonance (NMR) techniques has been shown to provide high-contrast resolution between soft tissues and characterization of normal and pathologic tissues by differences in magnetic relaxation times. The current study was designed to determine whether electrocardiogram (ECG)-gated NMR imaging of the canine heart in vivo could distinguish normal from infarcted myocardium without the use of intravenous paramagnetic contrast agents. Seven dogs were studied by ECG-gated NMR imaging in vivo (spin-echo technique) with a 0.35 Tesla superconducting magnet at 2 to 7 days after ligation of the left anterior descending coronary artery. In six of the seven dogs, signal intensity was increased in the anterior wall compared with the remainder of the left ventricle; this region of high signal intensity corresponded to the area of myocardial infarction demonstrated at postmortem examination. The signal intensity of the infarcted region was 66 +/- 27% greater than that of normal myocardium (p less than .01). The T2 (spin-spin) relaxation time was 69 +/- 3% longer in the infarcted myocardium as compared with normal myocardium (p less than .01). The NMR images from the seventh dog had uniform signal intensity throughout the myocardium of the left ventricle. An infarct was not evident on postmortem examination in this dog. Thus gated NMR imaging in vivo by the spin-echo technique displays acute myocardial infarctions as regions of high signal intensity without the use of contrast media. The infarct is characterized by a prolonged T2 relaxation time.
Cystatin C Associates with Arterial Stiffness in Older Adults
Authors: Magdalena Madero, Christina L. Wassel, Carmen A. Peralta, Samer S. Najjar, Kim Sutton-Tyrrell, Linda Fried, Robert Canada, Anne Newman, Michael G. Shlipak, Mark J. Sarnak
Journal: Journal of the American Society of Nephrology (2009)

Large arteries commonly become stiff in kidney failure, but few studies have investigated arterial stiffness in earlier stages of kidney disease. We evaluated the association between kidney function and aortic pulse wave velocity (aPWV) and its potential modification by race, diabetes, or coronary heart disease in older adults. We measured aPWV in 2468 participants in the Health Aging and Body Composition (Health ABC) study; mean age was 73.7 yr, 40% were black, and 24% had diabetes. After categorizing kidney function into three groups on the basis of cystatin C level, multivariable analysis revealed that the medium and high cystatin C groups associated with a 5.3% (95% confidence interval 0.8 to 10.0%) and 8.0% (95% confidence interval 2.2 to 14.1%) higher aPWV than the low cystatin C group; however, chronic kidney disease, as defined by estimated GFR &lt;60 ml/min per 1.73 m<sup>2</sup>, did not significantly associate with aPWV. We did not identify interactions between cystatin C and race, diabetes, or coronary heart disease. In conclusion, stiffness of large arteries, a major risk factor for cardiovascular disease, may partially mediate the association between cystatin C and cardiovascular risk in older adults.
Effects of small airway dysfunction on the clinical expression of asthma: a focus on asthma symptoms and bronchial hyper-responsiveness
Authors: E. van der Wiel, D. S. Postma, T. van der Molen, L. Schiphof-Godart, N. H. T. ten Hacken, M. van den Berge
Journal: Allergy (2014)

The small airways are an important site of inflammation in asthma. However, the relation between small airway dysfunction and clinical expression of asthma has hardly been studied.To investigate the association of small and large airway dysfunction with asthma symptoms and bronchial hyper-responsiveness (BHR).Fifty-eight patients with asthma were characterized with spirometry, body plethysmography, impulse oscillometry, alveolar and bronchial exhaled nitric oxide, and a methacholine provocation. Symptoms of nocturnal asthma, exercise-related symptoms, BHR symptoms, and respiratory symptoms were assessed with the Asthma Control Questionnaire and Bronchial Hyper-responsiveness Questionnaire. Perception of dyspnea was rated with the Borg score during the provocation test.Small and large airway dysfunction did not associate with higher scores for nocturnal, exercise-related, or BHR symptoms. Only higher scores on wheezing were significantly associated with higher values of difference between R5 and R20 (R5-R20) (r = 0.367, P < 0.01) and AX (r = 0.354, P < 0.01). Lower FEF25-75% (P = 0.024) and higher R5-R20 (P = 0.003) values were independently associated with more severe BHR to methacholine, but not FEV1 or R20 values. The increase in dyspnea during the methacholine provocation was strongly and independently correlated with the decrease in FEV1 and reactance of the respiratory system at 5 Hertz.Small and large airway dysfunction poorly associate with asthma symptoms in our patients. However, deteriorations in small airway dysfunction are strongly related to an increase in dyspnea during bronchial provocation with methacholine. Small airway dysfunction contributes also independently to the clinical expression of asthma, as reflected by the severity of BHR.
A double-blind, delayed-start trial of rasagiline in Parkinson's disease (the ADAGIO study): prespecified and post-hoc analyses of the need for additional therapies, changes in UPDRS scores, and non-motor outcomes
Authors: Olivier Rascol, Cheryl J Fitzer-Attas, Robert Hauser, Joseph Jankovic, Anthony Lang, J William Langston, Eldad Melamed, Werner Poewe, Fabrizio Stocchi, Eduardo Tolosa, Eli Eyal, Yoni M Weiss, C Warren Olanow
Journal: The Lancet Neurology (2011)
Early versus Late Parenteral Nutrition in Critically Ill Adults
Authors: Michael P. Casaer, Dieter Mesotten, Greet Hermans, Pieter J. Wouters, Miet Schetz, Geert Meyfroidt, Sophie Van Cromphaut, Catherine Ingels, Philippe Meersseman, Jan Muller, Dirk Vlasselaers, Yves Debaveye, Lars Desmet, Jasperina Dubois, Aime Van Assche, Simon Vanderheyden, Alexander Wilmer, Greet Van den Berghe
Journal: New England Journal of Medicine (2011)

Controversy exists about the timing of the initiation of parenteral nutrition in critically ill adults in whom caloric targets cannot be met by enteral nutrition alone.In this randomized, multicenter trial, we compared early initiation of parenteral nutrition (European guidelines) with late initiation (American and Canadian guidelines) in adults in the intensive care unit (ICU) to supplement insufficient enteral nutrition. In 2312 patients, parenteral nutrition was initiated within 48 hours after ICU admission (early-initiation group), whereas in 2328 patients, parenteral nutrition was not initiated before day 8 (late-initiation group). A protocol for the early initiation of enteral nutrition was applied to both groups, and insulin was infused to achieve normoglycemia.Patients in the late-initiation group had a relative increase of 6.3% in the likelihood of being discharged alive earlier from the ICU (hazard ratio, 1.06; 95% confidence interval [CI], 1.00 to 1.13; P=0.04) and from the hospital (hazard ratio, 1.06; 95% CI, 1.00 to 1.13; P=0.04), without evidence of decreased functional status at hospital discharge. Rates of death in the ICU and in the hospital and rates of survival at 90 days were similar in the two groups. Patients in the late-initiation group, as compared with the early-initiation group, had fewer ICU infections (22.8% vs. 26.2%, P=0.008) and a lower incidence of cholestasis (P<0.001). The late-initiation group had a relative reduction of 9.7% in the proportion of patients requiring more than 2 days of mechanical ventilation (P=0.006), a median reduction of 3 days in the duration of renal-replacement therapy (P=0.008), and a mean reduction in health care costs of €1,110 (about $1,600) (P=0.04).Late initiation of parenteral nutrition was associated with faster recovery and fewer complications, as compared with early initiation. (Funded by the Methusalem program of the Flemish government and others; EPaNIC ClinicalTrials.gov number, NCT00512122.).
PTU-010 Percutaneous Endoscopic Gastrostomy (peg) Care And Prevention Of Buried Bumper Syndrome (bbs)
Authors: M Nagari, C Morgan-Edwards, S Henson, CL Ch’ng
Journal: Gut (2014)

<h3>Introduction</h3> PEG tube insertion is useful in an appropriately indicated patient but there are some complications to it. Buried Bumper Syndrome is usually a late and rare complication which is normally avoidable but occurs when the stomach lining grows over the internal bumper of a PEG feeding tube and it can lead to infection, inability to administer feeds/medications, peritonitis and admission to hospital. Our literature search of large studies shows the overall incidence of BBS to be 2–4.5%. <h3>Aim</h3> The aim was to conduct an audit to ascertain the incidence of BBS in our Hospital Trust (ABMU) and to develop tools to try and reduce the incidence as well as re-audit our practice to assess the improvement. <h3>Methods</h3> It was a retrospective data collection to ascertain the incidence followed by development of tools which predominantly consisted of daily PEG care and an action plan. Daily PEG Care mainly included hand hygiene before and after every use, cleaning techniques and pushing the tube approximately 5cm into the stomach and rotating 360˚ before securing it back. Action plan included training in Nursing Homes, increased number of visits and spot checks, completion of VA1 (POVA) where necessary and regular meetings with Nurse Assessors and Commissioners. Re-auditing was carried out after educating the people who are involved in PEG care thereby completing the audit cycle. <h3>Results</h3> The incidence in our trust before the implementation of Daily PEG care and the action plan was around 13%. We are pleased to report that since then there have been no new cases of BBS diagnosed during 2013. The training sessions are continuing and audit of PEG care will be carried out annually, with written feedback to each nursing home. <h3>Conclusion</h3> Daily PEG care and reinforcement of training the staff and relatives involved will help in the prevention of a serious complication of PEG tube. <h3>References</h3> Young and Leedham An audit of incidence and treatment of buried iInternal gastrostomy fixators. <i>Gut</i> 2011;60: A100–A101 Kejariwal D <i>et al.</i> Buried bumper syndrome. <i>Nutr Clin Pract</i> Jun-July; 2008;23(3):322-4 <h3>Disclosure of Interest</h3> None Declared.
Overexpression of <i>Eg5</i> Causes Genomic Instability and Tumor Formation in Mice
Authors: Andrew Castillo, Herbert C. Morse, Virginia L. Godfrey, Rizwan Naeem, Monica J. Justice
Journal: Cancer Research (2007)

Abstract Proper chromosome segregation in eukaryotes is driven by a complex superstructure called the mitotic spindle. Assembly, maintenance, and function of the spindle depend on centrosome migration, organization of microtubule arrays, and force generation by microtubule motors. Spindle pole migration and elongation are controlled by the unique balance of forces generated by antagonistic molecular motors that act upon microtubules of the mitotic spindle. Defects in components of this complex structure have been shown to lead to chromosome missegregation and genomic instability. Here, we show that overexpression of Eg5, a member of the Bim-C class of kinesin-related proteins, leads to disruption of normal spindle development, as we observe both monopolar and multipolar spindles in Eg5 transgenic mice. Our findings show that perturbation of the mitotic spindle leads to chromosomal missegregation and the accumulation of tetraploid cells. Aging of these mice revealed a higher incidence of tumor formation with a mixed array of tumor types appearing in mice ages 3 to 30 months with the mean age of 20 months. Analysis of the tumors revealed widespread aneuploidy and genetic instability, both hallmarks of nearly all solid tumors. Together with previous findings, our results indicate that Eg5 overexpression disrupts the unique balance of forces associated with normal spindle assembly and function, and thereby leads to the development of spindle defects, genetic instability, and tumors. [Cancer Res 2007;67(21):1–10] [Cancer Res 2007;67(21):10138–47]