tbuckley/cabot-search huggingface dataset:
Modulation of Murine Breast Tumor Vascularity, Hypoxia, and Chemotherapeutic Response by Exercise
Authors: Allison S. Betof, Christopher D. Lascola, Douglas Weitzel, Chelsea Landon, Peter M. Scarbrough, Gayathri R. Devi, Gregory Palmer, Lee W. Jones, Mark W. Dewhirst
Journal: JNCI Journal of the National Cancer Institute (2015)

Exercise has been shown to improve postischemia perfusion of normal tissues; we investigated whether these effects extend to solid tumors. Estrogen receptor–negative (ER-, 4T1) and ER+ (E0771) tumor cells were implanted orthotopically into syngeneic mice (BALB/c, N = 11–12 per group) randomly assigned to exercise or sedentary control. Tumor growth, perfusion, hypoxia, and components of the angiogenic and apoptotic cascades were assessed by MRI, immunohistochemistry, western blotting, and quantitative polymerase chain reaction and analyzed with one-way and repeated measures analysis of variance and linear regression. All statistical tests were two-sided. Exercise statistically significantly reduced tumor growth and was associated with a 1.4-fold increase in apoptosis (sedentary vs exercise: 1544 cells/mm2, 95% CI = 1223 to 1865 vs 2168 cells/mm2, 95% CI = 1620 to 2717; P = .048), increased microvessel density (P = .004), vessel maturity (P = .006) and perfusion, and reduced intratumoral hypoxia (P = .012), compared with sedentary controls. We also tested whether exercise could improve chemotherapy (cyclophosphamide) efficacy. Exercise plus chemotherapy prolonged growth delay compared with chemotherapy alone (P < .001) in the orthotopic 4T1 model (n = 17 per group). Exercise is a potential novel adjuvant treatment of breast cancer.
Acid lysosomal hydrolases in systemic sclerosis and other connective tissue diseases
Authors: K. HERRMANN, U.-F. HAUSTEIN, H.-J. BÖHME, I. LOHRISCH
Journal: British Journal of Dermatology (1982)

The activities of five lysosomal hydrolases were determined fluorometrically in the serum of patients with systemic sclerosis (PSS), systemic lupus erythematosus (SLE), dermatomyositis (DM), rheumatoid arthritis (RA), or Raynaud's disease (RD). In PSS the beta-galactosidase activity was significantly increased compared with controls and the other connective tissue diseases. The beta-N-acetyl-glucosaminidase was significantly increased in PSS, SLE and DM. In PSS both enzymes were more active in the early stage of the disease than later. These changes of enzyme pattern seem to be a relatively reliable marker for the differential diagnosis of PSS compared to other connective tissue diseases, especially for RD, in which the beta-galactosidase activity was significantly decreased. Further work is required to determine whether these polysaccharide-degrading acid hydrolases play a role in the pathogenesis of PSS.
Downregulation of CD1 Marks Acquisition of Functional Maturation of Human Thymocytes and Defines a Control Point in Late Stages of Human T Cell Development
Authors: Pieter Res, Bianca Blom, Toshiyuki Hori, Kees Weijer, Hergen Spits
Journal: The Journal of Experimental Medicine (1997)

We have investigated whether in the human thymus transition of CD4+CD8+ double positive (DP) to CD4+ or CD8+ single positive (SP) cells is sufficient for generation of functional immunocompetent T cells. Using the capacity of thymocytes to expand in vitro in response to PHA and IL-2 as a criterion for functional maturity, we found that functional maturity of both SP and DP thymocytes correlates with downregulation of CD1a. CD1a− cells with a persistent DP phenotype were also found in neonatal cord blood, suggesting that at least a proportion of mature DP cells can emigrate from the thymus. The requirements for generating functional T cells were investigated in a hybrid human/mouse fetal thymic organ culture. MHC class II– positive, but not MHC class II–negative, mouse thymic microenvironments support differentiation of human progenitors into TCRαβ+CD4+ SP cells, indicating that mouse MHC class II can positively select TCRαβ+CD4+ SP human cells. Strikingly, these SP are arrested in the CD1a+ stage and could not be expanded in vitro with PHA and IL-2. CD1a+CD4+ SP thymocytes do not represent an end stage population because purified CD1a+CD4+ SP thymocytes differentiate to expandable CD1a− cells upon cocultivation with human thymic stromal cells. Taken together these data indicate that when CD1a+ DP TCRαβlow cells mature, these cells interact with MHC, but that an additional, apparently species-specific, signal is required for downregulation of CD1a to generate functional mature TCRαβ+ cells.
Stress and oesophageal motility in normal subjects and patients with irritable bowel syndrome.
Authors: R C Ayres, D A Robertson, K Naylor, C L Smith
Journal: Gut (1989)

Patterns of oesophageal motility were recorded in 17 healthy volunteers and 12 patients with the irritable bowel syndrome. Recordings were taken at rest and under stress by hyperventilation, a dichotic hearing challenge and a cold pressor test. In healthy volunteers the dichotic hearing challenge was associated with a significant increase in the mean amplitude of oesophageal peristalsis from 69.9 mmHg to 82.4 mmHg (p less than 0.01) and in the percentage of simultaneous waves from 9.7% to 24.5% (p less than 0.01). The cold pressor test increased the peristaltic amplitude from 69.9 mmHg to 87.1 mmHg (p less than 0.001) and the percentage of simultaneous waves from 9.7% to 34.4% (p less than 0.01). Both manoeuvres were associated with increases in pulse and blood pressure. In patients with irritable bowel syndrome, the resting mean oesophageal peristaltic amplitude was higher than that seen in normal volunteers (95.9 mmHg v 69.9 mmHg p less than 0.05). Changes in oesophageal motility during stress were similar in these patients to those seen in normal subjects although the changes were not significant. This study refutes the hypothesis that symptoms of irritable bowel syndrome and their association with stress are attributable to increased sensitivity of oesophageal motility to disruption by stressful stimuli.
Drug use in children: cohort study in three European countries
Authors: M. C J M Sturkenboom, K. M C Verhamme, A. Nicolosi, M. L Murray, A. Neubert, D. Caudri, G. Picelli, E. F. Sen, C. Giaquinto, L. Cantarutti, P. Baiardi, M.-G. Felisi, A. Ceci, I. C K Wong
Journal: BMJ (2008)

<b>Objective</b> To provide an overview of drug use in children in three European countries. <b>Design</b> Retrospective cohort study, 2000-5. <b>Setting</b> Primary care research databases in the Netherlands (IPCI), United Kingdom (IMS-DA), and Italy (Pedianet). <b>Participants</b> 675 868 children aged up to 14 (Italy) or 18 (UK and Netherlands). <b>Main outcome measure</b> Prevalence of use per year calculated by drug class (anatomical and therapeutic). Prevalence of “recurrent/chronic” use (three or more prescriptions a year) and “non-recurrent” or “acute” use (less than three prescriptions a year) within each therapeutic class. Descriptions of the top five most commonly used drugs evaluated for off label status within each anatomical class. <b>Results</b> Three levels of drug use could be distinguished in the study population: high (&gt;10/100 children per year), moderate (1-10/100 children per year), and low (&lt;1/100 children per year). For all age categories, anti-infective, dermatological, and respiratory drugs were in the high use group, whereas cardiovascular and antineoplastic drugs were always in the low use group. Emollients, topical steroids, and asthma drugs had the highest prevalence of recurrent use, but relative use of low prevalence drugs was more often recurrent than acute. In the top five highest prevalence drugs topical inhaled and systemic steroids, oral contraceptives, and topical or systemic antifungal drugs were most commonly used off label. <b>Conclusion</b> This overview of outpatient paediatric prescription patterns in a large European population could provide information to prioritise paediatric therapeutic research needs.
Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity
Authors: Lesley E. Smythies, Marty Sellers, Ronald H. Clements, Meg Mosteller-Barnum, Gang Meng, William H. Benjamin, Jan M. Orenstein, Phillip D. Smith
Journal: Journal of Clinical Investigation (2005)

Intestinal macrophages, which are thought to orchestrate mucosal inflammatory responses, have received little investigative attention compared with macrophages from other tissues. Here we show that human intestinal macrophages do not express innate response receptors, including the receptors for LPS (CD14), Fcalpha (CD89), Fcgamma (CD64, CD32, CD16), CR3 (CD11b/CD18), and CR4 (CD11c/CD18); the growth factor receptors IL-2 (CD25) and IL-3 (CD123); and the integrin LFA-1 (CD11a/CD18). Moreover, resident intestinal macrophages also do not produce proinflammatory cytokines, including IL-1, IL-6, IL-10, IL-12, RANTES, TGF-beta, and TNF-alpha, in response to an array of inflammatory stimuli but retain avid phagocytic and bacteriocidal activity. Thus, intestinal macrophages are markedly distinct in phenotype and function from blood monocytes, although intestinal macrophages are derived from blood monocytes. To explain this paradox, we show that intestinal stromal cell-derived products downregulate both monocyte receptor expression and, via TGF-beta, cytokine production but not phagocytic or bacteriocidal activity, eliciting the phenotype and functional profile of intestinal macrophages. These findings indicate a mechanism in which blood monocytes recruited to the intestinal mucosa retain avid scavenger and host defense functions but acquire profound "inflammatory anergy," thereby promoting the absence of inflammation characteristic of normal intestinal mucosa despite the close proximity of immunostimulatory bacteria.
Guideline for 5-α-Reductase Inhibitors in the Prevention of Prostate Cancer Is Premature
Authors: Paul H. Frankel, Przemyslaw Twardowski
Journal: Journal of Clinical Oncology (2009)

THE EDITOR: It is well-recognized that researchers can examine the same data and yet have divergent opinions. 1In our view, the evidence-based guideline 2 for use of 5-␣-reductase inhibitors (5-ARIs) in the prevention of prostate cancer should more clearly recommend against use of 5-ARIs in otherwise healthy men at this time.There is no evidence that healthy men live longer with use of 5-ARIs, nor is there any evidence of improved quality of life, the two measures that are most relevant for healthy individuals.In fact, the guideline states that studies have reported higher all-cause mortality in patients receiving finasteride when compared with control groups, as well as "a consistently higher frequency of adverse events."Aside from the empirical observation of more deaths among patients receiving finasteride than in the placebo group in the PCPT (Prostate Cancer Prevention Trial) study, 3 the guideline reports that the upper 95% CI for relative risk of death from any cause is 1.18, suggesting that the evidence to date cannot rule out an 18% increase in risk of death resulting from finasteride.In addition, the prostatespecific benefit is quite small, requiring 1,000 men treated for 7 years to prevent just 15 cases of prostate cancer.The guideline notes the possibility of an increase of three cases of high-grade prostate cancer in those 1,000 men.In more general terms, the prostate-specific mortality rates for finasteride and placebo were identical.When considering a healthy person, one should not focus on a single gland, single disease, or even single potential cause of death.The trend of specialization in medicine exemplified by organ-centric analysis sometimes obscures the consideration of overall health of the individual.From that perspective, the recommendation that healthy, asymptomatic men with low PSA values "may benefit from a discussion" 2 about use of 5-ARIs may be interpreted as an implicit endorsement of a drug for prostate cancer prevention, which we believe is, at this point, premature.
Analysis of Genetic Variants in Never-Smokers with Lung Cancer Facilitated by an Internet-Based Blood Collection Protocol: A Preliminary Report
Authors: Nicolas Girard, Emil Lou, Christopher G. Azzoli, Rekha Reddy, Mark Robson, Megan Harlan, Irene Orlow, Yasushi Yatabe, Khedoudja Nafa, Marc Ladanyi, Agnes Viale, Mark G. Kris, Gregory Riely, Vincent Miller, Robert J. Klein, Keitaro Matsuo, William Pao
Journal: Clinical Cancer Research (2010)

Germ line polymorphisms may confer susceptibility to lung cancer in never smokers, but studies in the United States have been limited by the low number of cases seen at single institutions. We hypothesized that we could use the Internet to bolster the accrual of appropriate patients.We established an Internet-based protocol to collect blood and information from patients throughout the United States. To illustrate the power of this approach, we used these samples, plus additional cases and age-matched controls from the Memorial Sloan-Kettering Cancer Center (New York, NY) and the Aichi Cancer Center (Nagoya, Japan), to analyze germ line DNA for genetic variants reportedly associated with lung cancer susceptibility. The genotypes for the polymorphisms rs763317 (intron 1) and T790M (exon 20) in the EGFR gene were determined by direct sequencing, and CHRNA3 nicotinic acetylcholine receptor single nucleotide polymorphisms (rs8034191 and rs1051730) were genotyped as part of a pilot genome-wide association study.We successfully analyzed germ line DNA from 369 cases, including 45 obtained via the Internet, and 342 controls. A germ line EGFR T790M variant was identified in 2 of the 369 cases (0.54%; 95% confidence interval, 0.21-1.29%), and in none of the 292 controls (P = 0.21). No difference was observed in EGFR rs763317 frequency between cases and controls. Similarly, neither CHRNA3 rs8034191 nor rs1051730 were associated with lung cancer risk.The Internet provides a way to recruit patients throughout the country for minimal risk studies. This approach could be used to facilitate studies of germ line polymorphisms in specific groups of patients with cancer.
Detection of Cancer DNA in Plasma of Patients with Early-Stage Breast Cancer
Authors: Julia A. Beaver, Danijela Jelovac, Sasidharan Balukrishna, Rory L. Cochran, Sarah Croessmann, Daniel J. Zabransky, Hong Yuen Wong, Patricia Valda Toro, Justin Cidado, Brian G. Blair, David Chu, Timothy Burns, Michaela J. Higgins, Vered Stearns, Lisa Jacobs, Mehran Habibi, Julie Lange, Paula J. Hurley, Josh Lauring, Dustin A. VanDenBerg, Jill Kessler, Stacie Jeter, Michael L. Samuels, Dianna Maar, Leslie Cope, Ashley Cimino-Mathews, Pedram Argani, Antonio C. Wolff, Ben Ho Park
Journal: Clinical Cancer Research (2014)

Detecting circulating plasma tumor DNA (ptDNA) in patients with early-stage cancer has the potential to change how oncologists recommend systemic therapies for solid tumors after surgery. Droplet digital polymerase chain reaction (ddPCR) is a novel sensitive and specific platform for mutation detection.In this prospective study, primary breast tumors and matched pre- and postsurgery blood samples were collected from patients with early-stage breast cancer (n = 29). Tumors (n = 30) were analyzed by Sanger sequencing for common PIK3CA mutations, and DNA from these tumors and matched plasma were then analyzed for PIK3CA mutations using ddPCR.Sequencing of tumors identified seven PIK3CA exon 20 mutations (H1047R) and three exon 9 mutations (E545K). Analysis of tumors by ddPCR confirmed these mutations and identified five additional mutations. Presurgery plasma samples (n = 29) were then analyzed for PIK3CA mutations using ddPCR. Of the 15 PIK3CA mutations detected in tumors by ddPCR, 14 of the corresponding mutations were detected in presurgical ptDNA, whereas no mutations were found in plasma from patients with PIK3CA wild-type tumors (sensitivity 93.3%, specificity 100%). Ten patients with mutation-positive ptDNA presurgery had ddPCR analysis of postsurgery plasma, with five patients having detectable ptDNA postsurgery.This prospective study demonstrates accurate mutation detection in tumor tissues using ddPCR, and that ptDNA can be detected in blood before and after surgery in patients with early-stage breast cancer. Future studies can now address whether ptDNA detected after surgery identifies patients at risk for recurrence, which could guide chemotherapy decisions for individual patients.
Immunomodulatory synergy by combination of atorvastatin and glatiramer acetate in treatment of CNS autoimmunity
Authors: O. Stuve
Journal: Journal of Clinical Investigation (2006)

One approach to improving efficacy in MS therapy is to identify medications that provide additive or synergistic benefit in combination. Orally administered cholesterol-lowering HMG-CoA reductase inhibitors (known as statins), which exhibit immunomodulatory properties and are effective in treatment of the MS model EAE, are being tested in MS. As atorvastatin can enhance protective Th2 responses and has a different mechanism of action than glatiramer acetate (GA), a parenterally administered immunomodulatory agent approved for MS treatment, we tested whether the combination of these agents could be beneficial in EAE. Combination therapy using suboptimal doses of atorvastatin and GA prevented or reversed clinical and histologic EAE. Secretion of proinflammatory Th1 cytokines was reduced — and conversely Th2 cytokine secretion was increased — in these mice, but not in mice treated with each drug alone at the same doses. Monocytes treated with the combination of suboptimal doses of atorvastatin and GA secreted an antiinflammatory type II cytokine pattern and, when used as APCs, promoted Th2 differentiation of naive myelin-specific T cells. Our results demonstrate that agents with different mechanisms of immune modulation can combine in a synergistic manner for the treatment of CNS autoimmunity and provide rationale for testing the combination of atorvastatin and GA in MS.
A nutritional study of Irish athletes
Authors: A. Barry, T. Cantwell, F. Doherty, Jean C. Folan, M. Ingoldsby, J. P. Kevany, J. D. O'Broin, H. O'Connor, B. O'Shea, B. A. Ryan, J. Vaughan
Journal: British Journal of Sports Medicine (1981)

The aims of this study were (1) to carry out a nutritional assessment of selected Irish athletes and (2) to provide individual results and specific advice to each athlete on how to achieve an optimum diet. Dietary intakes were measured by a three-day weighed dietary record technique designed to evaluate each athlete's usual eating habits. The results were evaluated against a set of dietary standards in order to determine adequacy. Nutritional status was also assessed in a limited form by selected anthropometric and biochemical measurements. A total of 148 subjects took part in the assessment which began in May, 1979 and continued until April, 1980. The sports involved included: canoeing, cycling, rowing, swimming, hockey, squash and track and field events. The results indicated a range of sub-optimal dietary patterns relating in particular to abnormal intakes of folate, iron, pyridoxine and calcium. The significance and applications of these findings are discussed.
ABC Transporter Genes and Risk of Type 2 Diabetes
Authors: Jesper Schou, Anne Tybjærg-Hansen, Holger J. Møller, Børge G. Nordestgaard, Ruth Frikke-Schmidt
Journal: Diabetes Care (2012)

OBJECTIVE Alterations of pancreatic β-cell cholesterol content may contribute to β-cell dysfunction. Two important determinants of intracellular cholesterol content are the ATP-binding cassette (ABC) transporters A1 (ABCA1) and -G1 (ABCG1). Whether genetic variation in ABCA1 and ABCG1 predicts risk of type 2 diabetes in the general population is unknown. RESEARCH DESIGN AND METHODS We tested whether genetic variation in the promoter and coding regions of ABCA1 and ABCG1 predicted risk of type 2 diabetes in the general population. Twenty-seven variants, identified by previous resequencing of both genes, were genotyped in the Copenhagen City Heart Study (CCHS) (n = 10,185). Two loss-of-function mutations (ABCA1 N1800H and ABCG1 g.-376C&amp;gt;T) (n = 322) and a common variant (ABCG1 g.-530A&amp;gt;G) were further genotyped in the Copenhagen General Population Study (CGPS) (n = 30,415). RESULTS Only one of the variants examined, ABCG1 g.-530A&amp;gt;G, predicted a decreased risk of type 2 diabetes in the CCHS (P for trend = 0.05). Furthermore, when validated in the CGPS or in the CCHS and CGPS combined (n = 40,600), neither the two loss-of-function mutations (ABCA1 N1800H, ABCG1 g.-376C&amp;gt;T) nor ABCG1 g.-530A&amp;gt;G were associated with type 2 diabetes (P values &amp;gt;0.57 and &amp;gt;0.30, respectively). CONCLUSIONS Genetic variations in ABCA1 and ABCG1 were not associated with increased risk of type 2 diabetes in the general population. These data were obtained in general population samples harboring the largest number of heterozygotes for loss-of-function mutations in ABCA1 and ABCG1.
Complex regulation of autophagy in cancer – Integrated approaches to discover the networks that hold a double-edged sword
Authors: János Kubisch, Dénes Türei, László Földvári-Nagy, Zsuzsanna A. Dunai, Lilian Zsákai, Máté Varga, Tibor Vellai, Péter Csermely, Tamás Korcsmáros
Journal: Seminars in Cancer Biology (2013)
Determination of Regional Cerebral Blood Flow by Inhalation of 133-Xenon
Authors: WALTER D. OBRIST, HOWARD K. THOMPSON, HERSCHEL KING, HSIOH SHAN WANG
Journal: Circulation Research (1967)

A method for estimating regional cerebral blood flow is described in which tracer amounts of 133 Xe are inhaled for 2 min and monitored extracranially over the next 45 to 60 min. A three-compartment model used to analyze the resulting clearance curves provided separate blood flows for "gray" and "white" matter, plus a decay constant for a slow third component, believed to arise from extracerebral tissue. The analysis included a correction for recirculation of all three components, based on radioisotope concentration of the expired air or arterial blood. Results from the analysis were compared with those obtained by the more traditional two-compartment approach, using data from 15 healthy young males. Whereas the three-compartment method yielded measurements comparable with those obtained by established techniques (average CBF = 54.7 ml/100 g/min), the two-compartment analysis gave consistently lower values (average CBF = 30.2). Comparison of results based on expired air and arterial sampling suggested that end-expiratory air is a reasonable substitute for arterial blood. Although the 133 Xe inhalation method is technically simpler and less traumatic than other methods, complex analytic treatment of the data is necessitated by the presence of appreciable recirculation and extracerebral contamination.
The different shades of mammalian pluripotent stem cells
Authors: E. W. Kuijk, S. M. Chuva de Sousa Lopes, N. Geijsen, N. Macklon, B. A. J. Roelen
Journal: Human Reproduction Update (2010)

BACKGROUNDPluripotent stem cells have been derived from a variety of sources such as from the inner cell mass of preimplantation embryos, from primordial germ cells, from teratocarcinomas and from male germ cells. The recent development of induced pluripotent stem cells demonstrates that somatic cells can be reprogrammed to a pluripotent state in vitro.
Aspirin and Clopidogrel Drug Response in Patients Undergoing Percutaneous Coronary Intervention
Authors: Eli I. Lev, Rajnikant T. Patel, Kelly J. Maresh, Sasidhar Guthikonda, Juan Granada, Timothy DeLao, Paul F. Bray, Neal S. Kleiman
Journal: Journal of the American College of Cardiology (2005)