tbuckley/cabot-search huggingface dataset:
Evaluation of the effects of prostate specific antigen (PSA) on prostate cancer bone metastasis
Authors: Janice S. Lai, Eva Corey, Lisha G. Brown, Ted S. Gross, Philippe Huber, Robert L. Vessella
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4371 

The establishment of metastatic prostate cancer (CaP) in bone and its tendency to elicit an osteoblastic bone response occurs via mechanisms not yet fully understood. Factors primarily or exclusively produced by CaP cells have been implicated in the bone osteoblastic response. Among these secreted factors are the human kallikrein proteins, including PSA. The objective of this study was to examine the potential roles of PSA in the development of the osteoblastic bone response elicited by metastatic CaP. Chinese hamster ovary cells were transfected to express PSA using the TET-on system (CHO/PSA). CHO/PSA cells treated with tetracycline had up to six-fold higher PSA levels compared to LNCaP cells (161.97±6.67 vs . 26.75±0.825 ng/ml/105 cells, P=0.0025). PSA expression did not alter the proliferation of CHO/PSA cells. PSA expression decreased osteoclast formation from RAW264.7 cells in co-culture experiments. Studies on the effects of PSA on osteoblast proliferation and differentiation are currently underway. To examine the effects of PSA expression in vivo, CHO/PSA cells were injected subcutaneously into intact male SCID mice and PSA expression was induced by the administration of doxycycline (Dox). High serum PSA levels were detected in the Dox induced animals. Four weeks post-injection, approximately half of the total serum PSA consisted of fPSA (fPSA=999±363 ng/ml, tPSA=1545±368 ng/ml), suggesting that the remainder of the total PSA consisted of enzymatically active PSA. PSA expression did not affect tumor growth in this model system. To evaluate the effects of PSA expression on bone, intact male SCID mice were intratibially injected with CHO/PSA cells. PSA expression was induced by the administration of Dox. High levels of serum PSA (1083±159 ng/ml) were measured in the Dox induced animals three weeks post-cell injection. Also, approximately half of the total serum PSA consisted of fPSA (fPSA=601±95 ng/ml), suggesting that the remainder of the total PSA was enzymatically active. Micro CT analysis of tumored tibiae showed that the periosteal and cortical bone volumes were decreased in the Dox- induced mice. Interestingly, endosteal bone volumes were also significantly decreased in comparison to untreated animals (0.48±0.03 vs. 0.67±0.08, P=0.05). In conclusion, our results suggest that PSA alone does not elicit an osteoblastic bone response. We are currently conducting bone histomorphometric analysis and additional animal studies to more clearly determine the role of PSA in the significant bone changes observed in vivo .
Gene–gene and gene–environment interactions on IgE production in prenatal stage
Authors: K. D. Yang, J.‐C. Chang, H. Chuang, H.‐M. Liang, H.‐C. Kuo, Y.‐S. Lee, T.‐Y. Hsu, C.‐Y. Ou
Journal: Allergy (2009)

Prevalence of allergic diseases in children has increased worldwide over the past decades. Allergy sensitization may occur in fetal life. This study investigated whether gene-gene and gene-environment interactions affected cord blood IgE (CBIgE) levels.A total of 575 cord blood DNA samples were subjected to a multiplex microarray for 384 single nucleotide polymorphisms (SNPs) in 159 allergy candidate genes. Genetic association was initially assessed by univariate and multivariate analyses. Multifactor dimensionality reduction (MDR) was used to identify gene-gene and gene-environment interactions. Environmental factors for analysis included maternal atopy, paternal atopy, parental smoking, gender, and prematurity.Twenty-one SNPs in 14 genes were associated with CBIgE elevation (>or =0.5 KU/l) in univariate analysis. Multivariate analysis identified eleven genes (IL13, IL17A, IL2RA, CCL17, CXCL1, PDGFRA, FGF1, HAVCR1, GNAQ, C11orf72, and ADAM33) which were significantly associated with CBIgE elevation. MDR analyses of gene-gene interactions identified IL13 interacted with IL17A and/or redox genes on CBIgE elevation with the prediction accuracy of 62.52%. Analyses of gene-environment interactions identified that maternal atopy combined with IL13, rs1800925 and CCL22, rs170359 SNPs had the highest prediction accuracy of 67.15%. All the high and low risk classifications on gene-gene and gene-environment interactions by MDR analyses could be validated by Chi-square test.Gene-gene (e.g. immune and redox genes) and gene-environment (e.g. maternal atopy and FGF1or redox genes) interactions on IgE production begin in prenatal stage, suggesting that prevention of IgE-mediated diseases may be made possible by control of maternal atopy and redox responses in prenatal stage.
Androgen deprivation therapy plus docetaxel and estramustine versus androgen deprivation therapy alone for high-risk localised prostate cancer (GETUG 12): a phase 3 randomised controlled trial
Authors: Karim Fizazi, Laura Faivre, François Lesaunier, Remy Delva, Gwenaëlle Gravis, Frédéric Rolland, Frank Priou, Jean-Marc Ferrero, Nadine Houede, Loïc Mourey, Christine Theodore, Ivan Krakowski, Jean-François Berdah, Marjorie Baciuchka, Brigitte Laguerre, Aude Fléchon, Alain Ravaud, Isabelle Cojean-Zelek, Stéphane Oudard, Jean-Luc Labourey, Paule Chinet-Charrot, Eric Legouffe, Jean-Léon Lagrange, Claude Linassier, Gaël Deplanque, Philippe Beuzeboc, Jean-Louis Davin, Anne-Laure Martin, Muriel Habibian, Agnès Laplanche, Stéphane Culine
Journal: The Lancet Oncology (2015)
Markers of autoreactivity, coagulation and angiogenesis in patients with nonallergic asthma
Authors: R. Asero, A. Tedeschi, M. Cugno
Journal: Allergy (2011)

Patients with nonallergic asthma frequently show autoreactivity as do subjects with chronic urticaria (CU). Activation of the coagulation cascade and hyper-expression of vascular endothelial growth factor (VEGF) were recently found in CU, and there is sparse evidence that the same may occur in asthma.To investigate autoreactivity, activation of the coagulation cascade, and expression of VEGF in patients with nonallergic asthma.Twenty-one adults with nonallergic asthma underwent autologous plasma skin test (APST) and the measurement of plasma levels of the prothrombin fragment F1+2, D-dimer, VEGF, and the inflammatory marker C-reactive protein (CRP). Twenty-one healthy sex- and age-matched subjects served as normal controls.The APST scored positive in 19 of 21 (90%) patients vs 0 controls. Mean fragment F1+2 plasma levels were significantly higher in patients with asthma (267 ± 243 pM) than in controls (150 ± 51 pM; P = 0.0001). Similarly, plasma levels of both D-dimer and VEGF were significantly higher in patients than in controls (D-dimer: 2364 ± 1467 vs 1301 ± 525 pM; P = 0.0001; VEGF: 1721 ± 2566 vs 76 ± 375 fM; P = 0.0001). A trend toward increased levels of F1+2, D-dimer, VEGF, and CRP was found in patients with a more severe disease according to GINA classification.Nonallergic asthma is characterized by autoreactivity as well as increased coagulation and angiogenesis markers, which are known to enhance vascular permeability. The presence of circulating vasoactive factors may be relevant to understand the disease pathophysiology and to detect novel therapeutic strategies in nonallergic asthma.
Effect of Hormones on Growth and Neoplastic Development of Transplanted Hyperplastic Alveolar Nodules of the Mammary Gland of C3H/Crgl Mice &lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Satyabrata Nandi, Howard A. Bern, K. B. Deome
Journal: JNCI Journal of the National Cancer Institute (1960)

Hyperplastic alveolar nodules and normal lobules were transplanted into mammary gland-free fat pads of C3H/Crgl female mice. The effects on these transplants of the removal of various endocrine glands and of various hormone treatments were studied. The pituitary and the ovary are necessary for the maintenance and growth of normal lobule transplants. No tumors developed from any lobule transplants. The pituitary is necessary for the maintenance and growth of nodule transplants, but unless the pituitary and either the ovaries or the adrenals were present, no tumors developed from these nodules. Growth and neoplastic development of transplanted nodules in hypophysectomized-ovariectomized mice occurred after treatment with estradiol-17β (E) plus progesterone (P) plus somatotropin (STH), E plus deoxycorticosterone acetate (DCA) plus STH, DCA plus STH, and DCA plus mammotropin (MH). Cortisol, in the doses used, with STH or MH induced lactation and did not support the neoplastic transformation of nodules. It is suggested that the same hormones required for the development of normal lobules and of hyperplastic alveolar nodules are also involved in mammary tumorigenesis. In the virgin female C3H/Crgl mouse, these hormones are probably estrogen plus corticosteroids plus somatotropin.
Transmission off Mammary Tumor Virus by the GR Mouse Strain. I. Role of the Virus in the Production of Lesions2
Authors: S. Nandi, Cheryl Helmich
Journal: JNCI Journal of the National Cancer Institute (1974)

Mammary lesions in susceptible, but mammary tumor virus (MTV)-free, BALB/c mice (C−) and in their progeny were analyzed after attempts were made to infect these mice with GR MTV. Ovaries of C− and GR females were transplanted into the ovarian capsules of (C− × GR)F1 mice, and these hybrids were mated with I or C− males. The C− progeny born of ovary transplants were judged MTV-free because of the failure of forced-bred females to develop mammary lesions or of the males to transmit virus to their progeny. These results indicate that the germ cells of C− females, even after prolonged exposure to a GR MTV-containing environment, fail to become infected with this virus. Of ≥3-week-old C− females inoculated with GR blood cells and forced-bred, 80% developed nodules and pregnancy-independent tumors. None of these mice developed plaques. Unfiltered plasma from GR donors inoculated into similar mice induced mammary adenocarcinoma in 31% of the mice, none of which, however, developed either nodules or plaques. Filtered plasma from the GR donors inoculated into mice induced no mammary lesions. Of the C− females mated with GR males 2–6 times, 47% contained nodules. Nodules resulting from blood cell inoculation and male transmission (semen) were transplanted into mammary-gland-free fat pads of 3-week-old C− females, which were subsequently forced-bred. These hosts developed only nodules and pregnancy-independent tumors, but their female progeny developed all 3 types of lesions including plaques. The results indicate that both blood cells and semen from GR mice contain MTV information for the development of both nodules and plaques. The nature of the lesions induced seems to depend on the age at which the host receives GR MTV.
Abstract P202: Association of Masked Hypertension and Prehypertension with Subclinical Cardiovascular Disease in the Jackson Heart Study
Authors: Nicole Redmond, John N Booth, Rikki M Tanner, Keith M Diaz, Marwah Abdalla, Mario Sims, Paul M Muntner, Daichi Shimbo
Journal: Circulation (2015)

Background:  Masked hypertension (MHT), defined as non-elevated clinic blood pressure (CBP) and elevated blood pressure on ambulatory blood pressure (ABP) monitoring (ABPM), and prehypertension (PHT) are individually associated with increased cardiovascular disease (CVD) risk. The degree of diagnostic overlap between PHT and MHT and their associations with subclinical CVD including left ventricular mass index (LVMI) or common carotid intima-media thickness (CCIMT) is poorly characterized among African-Americans (AAs).   Methods:  In the Jackson Heart Study (JHS), a large community-based cohort of AAs in Jackson, MS, CBP measurements and 24-hour ABPM were obtained at baseline (2000-2004) using standardized protocols. Analyses were restricted to 391 participants who were not taking antihypertensive medications with complete data for CBP, ABPM, LVMI measured with 2D echocardiography, and CCIMT taken from carotid ultrasound. Clinic hypertension (HTN) was defined as ≥140/90 mmHg. Non-elevated CBP was defined as    Results:  Of the 391 participants, 74 (18.9%) had HTN. Among the 317 participants with non-elevated CBP, 185 (58.4%) had PHT and 68 (21.5%) had MHT; 68 (21.5%) had MHT (59 in those with PHT, and 9 in those with normal CBP). In a fully-adjusted model (see Table), compared to participants with both PHT and MHT, LVMI and CCIMT was less among participants with non-elevated CBP (including those with normal CBP and PHT) and without MHT. There was no difference in LVMI and CCIMT in individuals with PHT and MHT vs. those with normal CBP and MHT.   Conclusions:  For AAs with non-elevated CBP, LVMI and CCIMT were the highest among individuals with MHT, regardless of whether PHT was present. This finding supports using ABPM to detect MHT among AAs with non-elevated CBP.
Aberrant DNA methylation associated with<i>MTHFR</i>C677T genetic polymorphism in cutaneous squamous cell carcinoma in renal transplant patients
Authors: M.E. Laing, R. Cummins, A. O’Grady, P. O’Kelly, E.W. Kay, G.M. Murphy
Journal: British Journal of Dermatology (2010)

Background Changes in genomic DNA methylation associated with cancer include global DNA hypomethylation and gene‐specific hyper‐ or hypomethylation. We have previously identified a genetic variant in the MTHFR gene involved in the methylation pathway which confers risk for the development of squamous cell carcinoma (SCC) in renal transplant patients. This genetic variant has also been discovered to confer SCC risk in nontransplant patients with low folate status. Objectives To explore the methylation profile of SCC compared with adjacent non‐neoplastic skin using pyrosequencing, and to elucidate whether the MTHFR polymorphism impacts upon the methylation patterns in SCC. Methods We used pyrosequencing to evaluate global (using long interspersed nuclear element 1) and gene‐specific (p16 and MGMT) methylation status in 47 SCCs and 40 adjacent autologous non‐neoplastic skin samples in those with (n = 16) and without (n = 17) the MTHFR polymorphism. Results Pyrosequencing methylation analysis revealed that SCC was hypomethylated compared with adjacent non‐neoplastic skin (P < 0·04). Patients with the MTHFR polymorphism had higher levels of global methylation in tumours and non‐neoplastic skin compared with those without the MTHFR polymorphism (P < 0·002). There was no association between levels of methylation in tumour and non‐neoplastic skin for the genes MGMT and p16. Conclusions Global hypomethylation appears to be a feature of SCC. Aberrant methylation of DNA appears related to polymorphisms of MTHFR. Such findings suggest that intervention in the form of demethylating agents or folate supplementation might be beneficial in the treatment or prevention of SCC.
Abstract 687: Cardiac Imaging with Multi-Slice Computed Tomography and Echocardiography to Guide Left Ventricular Lead Placement in Resynchronization Therapy. The CAMERA Trial
Authors: Ronan Curtin, Richard A Grimm, Giuseppe Saracino, Jeff Hsing, Tingfei Hu, Stacey Kuzmiak, Larry J Mulligan, Bruce Wilkoff
Journal: Circulation (2008)

Cardiac resynchronization (CRT) is associated with reverse ventricular remodeling and improved clinical outcomes, but is not successful in all patients. We looked at the feasibility of combined non-invasive imaging of the coronary veins and assessment of left ventricular dyssynchrony prior to pacemaker implantation and whether this combination would improve procedural success and patient outcome. Heart failure patients with standard indications for CRT were randomized to cardiac Multi-Detector CT (MDCT) plus Doppler echocardiographic assessment of left ventricular dyssynchrony versus conventional management prior to CRT. Co-registration of MDCT and tissue synchronization imaging data using a novel software program was performed and the results were used to optimize left ventricular lead placement for patients in the non-invasive imaging arm. 21 patients were enrolled with 9 patients randomized to the contemporary non-invasive imaging strategy and 12 patients randomized to the control group. MDCT correctly identified 19 of 24 (79%) coronary venous branches ≥ 2 mm in diameter when compared to invasive coronary venography. Patients in the non-invasive imaging group had a significant improvement in the 6 minute walk time on 6 month follow up (76.1 ± 48.4 meters vs 20.0 ± 64.8 meters, p = 0.04). Improvements in NYHA functional class and LV remodeling at 6 months were not significantly different in the non-invasive imaging and control arms. Left ventricular lead placement was successful in all patients, however more patients in the non-invasive imaging arm demonstrated LV lead placement in the most delayed or adjacent myocardial segment (8 of 9 vs 6 of 12, p = 0.09). Those patients with “optimal” lead placement showed a trend towards improved 6 minute walk times and improvement in left ventricular function 6 months after biventricular pacing. An imaging-guided strategy with coregistration of MDCT coronary venous anatomy and delayed myocardial segments by tissue Doppler echocardiography prior to CRT is feasible and may improve patient outcomes by facilitating optimal LV lead placement.
Abstract 11007: Decreased Serum Brain-Derived Neurotrophic Factor Levels are Associated With Exercise Intolerance in Patients With Heart Failure
Authors: Shingo Takada, Shintaro Kinugawa, Arata Fukushima, Tsuneaki Homma, Yoshihiro Masaki, Takaaki Furihata, Ryoichi Katsuyama, Takashi Yokota, Shouji Matsushima, Takahiro Abe, Tadashi Suga, Tomoyasu Kadoguchi, Koichi Okita, Hiroyuki Tsutsui
Journal: Circulation (2013)
Press: An end to health scares?
Authors: A. Ferriman
Journal: BMJ (1999)

At last, something is going to be done about health scares Irresponsible, biased medical journalists are going to be taken in hand and forced to abide by a code of conduct which will be drawn up a by a working party of the great and the good, according to last week's edition of GP magazine.

The working party is being set up as the result of a recommendation from the House of Commons Select Committee on Science and Technology. In the committee's report on genetically modified food, published in May, the committee recommended that “media coverage of scientific matters should be governed by a Code of Practice, which stipulates that scientific stories should be factually accurate. Breaches of the Code of Practice should be referred to the Press Complaints Commission.” The readers of GP magazine must have breathed a collective sigh of relief.

But wait a moment. Which guardians of the public good are going to set up this powerful working party? Two organisations are involved apparently: the Royal Institution of Great Britain in London and …
Global response to non-communicable disease
Authors: Maria Teresa Cerqueira, Alejandro Cravioto, Nancy Dianis, Hassen Ghannem, Naomi Levitt, Lijing L Yan, Sylvester Kimaiyo, Tracey Koehlmoos, Jaime Miranda, Louis Niessen, Dorairaj Prabhakaran, Manuel Ramirez-Zea, Adolfo Rubinstein, Yangfeng Wu, Denis Xavier, Richard Smith
Journal: BMJ (2011)

The forthcoming UN meeting on non-communicable diseases is an important opportunity for promoting global action on conditions that have been neglected. A network of researchers from low and middle income countries describes what is needed
Abstract 4881: Depletion of the Endothelial Nitric Oxide Synthase (eNOS) Substrate NADPH Triggers Endothelial Dysfunction in the Post-Ischemic Heart: Role of Glucose 6 Phosphate Dehydrogenase (G6PD)
Authors: Levy A Reyes, Cristian Dumitrescu, Lawrence Druhan, Jay L Zweier
Journal: Circulation (2009)

Reperfusion injury causes dysfunction in the coronary vascular endothelium; however, current understanding of this process is incomplete. Delineation of the mechanisms involved is critical for advancing treatment of myocardial infarction. Previously, we showed that endothelial dysfunction is triggered by loss of the eNOS cofactor, tetrahydrobiopterin (BH 4 ), and BH 4 repletion partially restored endothelial-dependent vasodilation. We hypothesize that the oxidative stress induced by ischemia/reperfusion (I/R) injury may also result in loss of the essential eNOS substrate NADPH, which is also utilized for BH 4 resynthesis, thus impairing eNOS function. We observe in the isolated rat heart that NADPH declines by ~70% after 30 min I and 30 min R (from 0.41±0.02 to 0.13±0.04 μ M/gram tissue, by HPLC, n=4, p&lt;0.01). The importance of this NADPH depletion was demonstrated by the marked rescue of coronary flow, with 80.0±4.0% increase, following NADPH repletion (175 μ M liposomal formulation infused for 10 min) in hearts subjected to 30 min of I and R. Further studies were performed to understand the mechanism of NADPH depletion. In the presence of oxidative stress, NADPH is rapidly oxidized and glucose 6 phosphate dehydrogenase (G6PD), is required for its regeneration. We observe that myocardial G6PD activity was decreased ~43% during ischemia (Table ), but this activity partially recovered after 30 min R. Interestingly, with addition of excess exogenous glucose-6-phosphate (G6P) the activity did not significantly change from control levels after 30 min of I and after 30 min R only a modest 20% fall was seen (Table ). Thus, the ability of G6PD to resynthesize NADPH remained largely intact but was limited by lack of its substrate G6P. In conclusion, we found that repletion of NADPH post ischemia results in a near total restoration of endothelial dependent coronary flow, and that ischemic depletion of G6P may be partially responsible for the limited bioavailability of NADPH. Glucose-6-Phosphate Dehydrogenase Enzyme Activity
The importance of parenting in child health
Authors: M. Hoghughi
Journal: BMJ (1998)

Parenting is probably the most important public health issue facing our society. It is the single largest variable implicated in childhood illnesses and accidents; teenage pregnancy and substance misuse; truancy, school disruption, and underachievement; child abuse; unemployability; juvenile crime; and mental illness. These are serious in themselves but are even more important as precursors of problems in adulthood and the next generation.1 This is why British and other governments are giving parenting high priority (such as, in Britain, the cross departmental committee chaired by the Minister for Public Health and the prime minister's social exclusion unit).

The importance of parenting arises from its role as a buffer against adversity (such as poverty or delinquent influences) or mediator of damage (as in child abuse). Parenting usually involves biological parents but is …
Abstract 3261: Characterization of Onset Scenarios of Paroxysmal Atrial Fibrillation in Patients without Pacemaker Indication
Authors: Franziska Kunz, Jasmin Ortak, Frank Bode, Frank Eberhardt, Uwe K Wiegand, Hendrik Bonnemeier
Journal: Circulation (2006)

Atrial-based pacing has recently gained prominence as a new concept for prevention of paroxysmal atrial fibrillation (pAF) by suppressing atrial ectopy and eliminating bradycardia. Data on type and...
P0121 : Angiotensin II inhibition to treat severe liver fibrosis: A double-blind randomized trial (ANRS HC19)
Authors: P. Cales, Y. Bacq, C. Bonny, J.L. Payen, D. Guyader, A. Tran, D. Larrey, C. Silvain, M.C. Rousselet, M. Simony, F. Oberti, F. Carrat
Journal: Journal of Hepatology (2015)
Mutations in the gene encoding ɛ-sarcoglycan cause myoclonus–dystonia syndrome
Authors: Alexander Zimprich, Monika Grabowski, Friedrich Asmus, Markus Naumann, Daniela Berg, Markus Bertram, Karl Scheidtmann, Peter Kern, Juliane Winkelmann, Bertram Müller-Myhsok, Leonhard Riedel, Matthias Bauer, Tanja Müller, Mirna Castro, Thomas Meitinger, Tim M. Strom, Thomas Gasser
Journal: Nature Genetics (2001)