tbuckley/cabot-search huggingface dataset:
Direct regulation of pituitary proopiomelanocortin by STAT3 provides a novel mechanism for immuno-neuroendocrine interfacing
Authors: Corinne Bousquet, Maria Chiara Zatelli, Shlomo Melmed
Journal: Journal of Clinical Investigation (2000)

Neuroendocrine ACTH secretion responds to peripheral inflammatory and stress signals. We previously demonstrated that the proinflammatory cytokine, leukemia inhibitory factor (LIF), affects the hypothalamo-pituitary-adrenal axis (HPA) by stimulating in vitro and in vivo pituitary proopiomelanocortin (POMC) gene expression and ACTH secretion and by potentiating the action of hypothalamic corticotropin releasing hormone (CRH). Whereas pathways shown thus far to regulate POMC expression exclusively involve cAMP or calcium, we here describe a direct and indirect STAT3-dependent regulation of POMC transcription by LIF. Using progressive 5′-deletions of POMC promoter, we identified a LIF-responsive –407/–301 region that contains two juxtaposed sequences within –399/–379 related to a STAT3 DNA-binding motif. Each sequence within –399/–379 separately corresponds to a low-affinity and direct binding site for STAT3, but, in combination, these sequences bind STAT3 cooperatively and with high affinity. Moreover, LIF-activated STAT3 indirectly mediates LIF corticotroph action by inducing and potentiating CRH-induced c-fos and JunB expression and binding to the POMC AP-1 element. We therefore conclude that both a direct and indirect route mediate LIF-induced STAT3 activation of POMC transcription. Demonstration of STAT3-dependent regulation of the POMC gene represents a powerful mechanism for immuno-neuroendocrine interfacing and implies a direct stimulation of ACTH secretion by inflammatory and stress-derived STAT3-inducing cytokines.
PLGA nanoparticles surface decorated with the sialic acid, N-acetylneuraminic acid
Authors: Lucia Bondioli, Luca Costantino, Antonio Ballestrazzi, Davide Lucchesi, Diana Boraschi, Federica Pellati, Stefania Benvenuti, Giovanni Tosi, Maria A. Vandelli
Journal: Biomaterials (2010)
<i>CUL3</i>and<i>NRF2</i>Mutations Confer an NRF2 Activation Phenotype in a Sporadic Form of Papillary Renal Cell Carcinoma
Authors: Aikseng Ooi, Karl Dykema, Asif Ansari, David Petillo, John Snider, Richard Kahnoski, John Anema, David Craig, John Carpten, Bin-Tean Teh, Kyle A. Furge
Journal: Cancer Research (2013)

Sustained activation of the stress-regulated transcription factor NRF2 (NFE2L2) is a prominent feature of many types of cancer, implying that mutations driving NRF2 may be important to tumor progression. In hereditary type 2 papillary renal cell carcinoma (PRCC2, also known as hereditary leiomyomatosis and renal cell cancer), NRF2 activation is a direct consequence of the accumulation of intracellular fumarate, a result of fumarate hydratase (FH) inactivation, but it is not clear how NRF2 may be activated in sporadic forms of PRCC2. Here we show that somatic mutations in NRF2, CUL3, and SIRT1 are responsible for driving the NRF2 activation phenotype in sporadic PRCC2. Transcriptome sequencing revealed the expression pattern of mutant alleles of NRF2, CUL3, and SIRT1 and also confirmed NRF2 activation in clinical specimens. Our results show a convergence in somatic mutations in sporadic PRCC2 with FH mutation in hereditary PRCC2.
Consolidation Therapy With Low-Dose Thalidomide and Prednisolone Prolongs the Survival of Multiple Myeloma Patients Undergoing a Single Autologous Stem-Cell Transplantation Procedure
Authors: Andrew Spencer, H. Miles Prince, Andrew W. Roberts, Ian W. Prosser, Kenneth F. Bradstock, Luke Coyle, Devinder S. Gill, Noemi Horvath, John Reynolds, Nola Kennedy
Journal: Journal of Clinical Oncology (2009)

Thalidomide is effective in the treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM). However, the role of thalidomide in the post-autologous stem cell transplantation (ASCT) context remains unclear. This study assessed whether the addition of thalidomide consolidation following ASCT would improve the durability of responses achieved and overall survival.Between January 2002 and March 2005, 269 patients with newly diagnosed MM who achieved disease stabilization or better with conventional induction chemotherapy received a single high-dose melphalan conditioned ASCT. Post-ASCT, 129 patients were randomly assigned to receive indefinite prednisolone maintenance therapy (control group) and 114 to receive the same in addition to 12 months of thalidomide consolidation (thalidomide group). The primary study end points were progression-free survival (PFS) and overall survival (OS). The secondary end point was tolerability.After a median follow-up of 3 years, the postrandomization 3-year PFS rates were 42% and 23% (P < .001; hazard ratio [HR], 0.5; 95% CI, 0.35 to 0.71) and the OS rates were 86% and 75% (P = .004; HR, 0.41; 95% CI, 0.22 to 0.76) in the thalidomide and control groups, respectively. There was no difference in survival between groups 12 months after disease progression (79% v 77%; P = .237). Neurological toxicities were more common in the thalidomide arm but there were no differences between arms for thromboembolic events.Consolidation therapy with 12 months of thalidomide combined with prednisolone prolongs survival when used after a single high-dose therapy supported ASCT in patients with newly diagnosed MM. Furthermore, thalidomide consolidation therapy did not adversely impact on survival in the subsequent salvage setting.
Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia
Authors: TingTing Hong, Huanghe Yang, Shan-Shan Zhang, Hee Cheol Cho, Mariya Kalashnikova, Baiming Sun, Hao Zhang, Anamika Bhargava, Michael Grabe, Jeffrey Olgin, Julia Gorelik, Eduardo Marbán, Lily Y Jan, Robin M Shaw
Journal: Nature Medicine (2014)
Pentoxifylline prevents indomethacin induced acute gastric mucosal damage in rats: role of tumour necrosis factor alpha.
Authors: L Santucci, S Fiorucci, M Giansanti, P M Brunori, F M Di Matteo, A Morelli
Journal: Gut (1994)

Neutrophil adherence within the gastric microcirculation is thought to be a major step in the pathogenesis of gastric mucosal damage induced by indomethacin. Pentoxifylline, a methylxanthine derivative, prevents leukocyte adherence to vascular endothelium and protects organs from shock by reducing tumour necrosis factor alpha (TNF alpha) concentrations. Rats were treated with 20 mg/kg oral indomethacin, pretreated with vehicle or with four different doses of pentoxifylline intraperitoneally, and killed after three hours. The gross gastric mucosal injury, neutrophil margination into the gastric microcirculation, mucosal concentrations of 6-keto-prostaglandin F1 alpha (PGF1 alpha), and PGE2 and serum TNF alpha values were measured. Whether the pentoxifylline induced protection involved nitric oxide mediated pathways or gastric acid secretion was evaluated. The data indicate that pentoxifylline reduces indomethacin induced mucosal damage and neutrophil margination in a dose dependent manner without exerting any effect on gastric mucosal prostaglandin concentrations. The maximally effective dose (200 mg/kg) of pentoxifylline reduced gastric damage by 90% and slightly stimulated acid secretion. The effect of pentoxifylline was not affected by pretreatment with the nitric oxide inhibitor. Pentoxifylline prevented the indomethacin induced increase in TNF alpha concentrations in a dose dependent fashion. Serum TNF alpha values were 30.5 (7.0) IU/ml (mean (SEM)) in rats treated with indomethacin alone and 5.0 (2.5) IU/ml (p < 0.01) in rats treated with indomethacin plus 200 mg/kg pentoxifylline. Pentoxifylline, therefore, prevents the acute gastric mucosal damage and neutrophil margination induced by indomethacin and reduces indomethacin induced release of TNF alpha.
<i>In vivo</i> Off-Resonance Saturation Magnetic Resonance Imaging of αvβ3-Targeted Superparamagnetic Nanoparticles
Authors: Chalermchai Khemtong, Chase W. Kessinger, Jimin Ren, Erik A. Bey, Su-Geun Yang, Jagadeesh Setti Guthi, David A. Boothman, A. Dean Sherry, Jinming Gao
Journal: Cancer Research (2009)

Magnetic resonance imaging is a powerful clinical imaging technique that allows for noninvasive tomographic visualization of anatomic structures with high spatial resolution and soft tissue contrast. However, its application in molecular imaging of cancer has been limited by the lack of sensitivity and detection accuracy in depicting the biochemical expression of these diseases. Here, we combine an ultrasensitive design of superparamagnetic polymeric micelles (SPPM) and an off-resonance saturation (ORS) method to enhance the imaging efficacy of tumor biomarkers in vivo. SPPM nanoparticles encoded with cyclic(RGDfK) were able to target the alpha(v)beta(3)-expressing microvasculature in A549 non-small cell lung tumor xenografts in mice. ORS greatly improved tumor detection accuracy over the conventional T(2)*-weighted method by its ability to turn "ON" the contrast of SPPM. This combination of ORS imaging with a tumor vasculature-targeted, ultrasensitive SPPM design offers new opportunities in molecular imaging of cancer.
OX40 (CD134) Controls Memory T Helper 2 Cells that Drive Lung Inflammation
Authors: Shahram Salek-Ardakani, Jianxun Song, Beth S. Halteman, Amha Gebre-Hiwot Jember, Hisaya Akiba, Hideo Yagita, Michael Croft
Journal: The Journal of Experimental Medicine (2003)

Asthma is caused by memory Th2 cells that often arise early in life and persist after repeated encounters with allergen. Although much is known regarding how Th2 cells develop, there is little information about the molecules that regulate memory Th2 cells after they have formed. Here we show that the costimulatory molecule OX40 is expressed on memory CD4 cells. In already sensitized animals, blocking OX40-OX40L interactions at the time of inhalation of aerosolized antigen suppressed memory effector accumulation in lung draining lymph nodes and lung, and prevented eosinophilia, airway hyperreactivity, mucus secretion, and Th2 cyto-kine production. Demonstrating that OX40 signals directly regulate memory T cells, antigen-experienced OX40-deficient T cells were found to divide initially but could not survive and accumulate in large numbers after antigen rechallenge. Thus, OX40-OX40L interactions are pivotal to the efficiency of recall responses regulated by memory Th2 cells.
Secondary gout in hemoglobinopathies: Report of two cases and review of the literature
Authors: Stanley Ballou, Muhammad A. Khan, Irving Kushner, John W. Harris
Journal: American Journal of Hematology (1977)

Abstract Although patients with hemolytic hemoglobinopathies characteristically are over‐producers of urate, and hyperuricemia is frequently recognized, clinical gout has rarely been reported in such patients. Our evaluation of 2 premenopausal women with gout led to the diagnosis of previously unrecognized hemoglobinopathies (SC disease and CC disease). Investigation of these 2 patients and review of the reported cases of gout in patients with hemoglobin S or C disorders suggest that relatively minor abnormalities of renal function in these patients may lead to early development of significant hyperuricemia. With increasing lifespan of patients with hemolytic hemoglobinopathies and the likelihood of increased occurrence of renal function abnormalities, it is anticipated that gout will more frequently be responsible for joint symptoms in such patients.
Experimentally induced acute hyperinsulinemia stimulates endogenous nitric oxide production in humans: Detection using urinary NO2−NO3− excretion
Authors: Hirokazu Tsukahara, Kiyoshi Kikuchi, Kumi Tsumura, Kouki Kimura, Ikue Hata, Masahiro Hiraoka, Masakatsu Sudo
Journal: Metabolism (1997)
Review of management and outcome in 65 patients with lentigo maligna
Authors: F. Al-Niaimi, C.S. Jury, S. McLaughlin, R.M. Herd
Journal: British Journal of Dermatology (2008)

Journal Article Review of management and outcome in 65 patients with lentigo maligna Get access F. Al‐Niaimi, F. Al‐Niaimi Department of Dermatology, Glasgow Royal Infirmary, Glasgow G4 0SF, U.K. Search for other works by this author on: Oxford Academic Google Scholar C.S. Jury, C.S. Jury Department of Dermatology, Glasgow Royal Infirmary, Glasgow G4 0SF, U.K. Search for other works by this author on: Oxford Academic Google Scholar S. McLaughlin, S. McLaughlin Department of Dermatology, Western Infirmary, Glasgow G11 6NT, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.M. Herd R.M. Herd Department of Dermatology, Western Infirmary, Glasgow G11 6NT, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 160, Issue 1, 1 January 2009, Pages 211–213, https://doi.org/10.1111/j.1365-2133.2008.08916.x Published: 01 January 2009
Adjuvant radiation therapy, local recurrence, and the need for salvage therapy in atypical meningioma
Authors: A. A. Aizer, N. D. Arvold, P. Catalano, E. B. Claus, A. J. Golby, M. D. Johnson, O. Al-Mefty, P. Y. Wen, D. A. Reardon, E. Q. Lee, L. Nayak, M. L. Rinne, R. Beroukhim, S. E. Weiss, S. H. Ramkissoon, M. Abedalthagafi, S. Santagata, I. F. Dunn, B. M. Alexander
Journal: Neuro-Oncology (2014)

The impact of adjuvant radiation in patients with atypical meningioma remains poorly defined. We sought to determine the impact of adjuvant radiation therapy in this population.We identified 91 patients with World Health Organization grade II (atypical) meningioma managed at Dana-Farber/Brigham and Women's Cancer Center between 1997 and 2011. A propensity score model incorporating age at diagnosis, gender, Karnofsky performance status, tumor location, tumor size, reason for diagnosis, and era of treatment was constructed using logistic regression for the outcome of receipt versus nonreceipt of radiation therapy. Propensity scores were then used as continuous covariates in a Cox proportional hazards model to determine the adjusted impact of adjuvant radiation therapy on both local recurrence and the combined endpoint of use of salvage therapy and death due to progressive meningioma.The median follow-up in patients without recurrent disease was 4.9 years. After adjustment for pertinent confounding variables, radiation therapy was associated with decreased local recurrence in those undergoing gross total resection (hazard ratio, 0.25; 95% CI, 0.07-0.96; P = .04). No differences in overall survival were seen in patients who did and did not receive radiation therapy.Patients who have had a gross total resection of an atypical meningioma should be considered for adjuvant radiation therapy given the improvement in local control. Multicenter, prospective trials are required to definitively evaluate the potential impact of radiation therapy on survival in patients with atypical meningioma.
David Sackett and the birth of Evidence Based Medicine: How to Practice and Teach EBM
Authors: P. E. H. Richardson
Journal: BMJ (2015)

Smith has written a most interesting obituary of Dave Sackett, whom I first met in 1995 at his office at the John Radcliffe Hospital in Oxford.1 I was publishing director for Churchill Livingstone and had made the appointment directly with him by email, of which he was a prolific and early user.

Sackett sat at a very large screen, talking to …
Late computed tomography scan response improvement and gallium scintigraphy evaluation as on-treatment prognostic parameters to tailor treatment intensity in patients with Hodgkin's lymphoma. A prospective phase II study
Authors: A. Re, S. Ferrari, P. Frata, C. Pizzocaro, C. Crippa, A. Tucci, F. Facchetti, L. Grazioli, S.M. Magrini, G. Rossi
Journal: Annals of Oncology (2008)
Evolution and operant behavior, metaphor or theory?
Authors: Frances K. McSweeney, Kenjiro Aoyama
Journal: Behavioral and Brain Sciences (2001)

The idea that similar selective processes operate in gene-based evolution, immunology, and operant psychology provides an intuitively appealing metaphor. This idea also isolates questions that operant psychologists should ask and makes some empirical predictions. However, the idea currently lacks the detail needed to precisely separate it from some plausible alternatives. This sort of thinking is the kind that operant psychologists should do if operant theorizing is to survive the competition among ideas.
Selective Identification of Secreted and Transmembrane Breast Cancer Markers using <i>Escherichia coli</i> Ampicillin Secretion Trap
Authors: Deborah A. Ferguson, Matthew R. Muenster, Qun Zang, Jeffrey A. Spencer, Jeoffrey J. Schageman, Yun Lian, Harold R. Garner, Richard B. Gaynor, J. Warren Huff, Alexander Pertsemlidis, Raheela Ashfaq, John Schorge, Carlos Becerra, Noelle S. Williams, Jonathan M. Graff
Journal: Cancer Research (2005)

Abstract Secreted and cell surface proteins play important roles in cancer and are potential drug targets and tumor markers. Here, we describe a large-scale analysis of the genes encoding secreted and cell surface proteins in breast cancer. To identify these genes, we developed a novel signal sequence trap method called Escherichia coli ampicillin secretion trap (CAST). For CAST, we constructed a plasmid in which the signal sequence of β-lactamase was deleted such that it does not confer ampicillin resistance. Eukaryotic cDNA libraries cloned into pCAST produced tens of thousands of ampicillin-resistant clones, 80% of which contained cDNA fragments encoding secreted and membrane spanning proteins. We identified 2,708 unique sequences from cDNA libraries made from surgical breast cancer specimens. We analyzed the expression of 1,287 of the 2,708 genes and found that 166 were overexpressed in breast cancers relative to normal breast tissues. Eighty-five percent of these genes had not been previously identified as markers of breast cancer. Twenty-three of the 166 genes (14%) were relatively tissue restricted, suggesting use as cancer-specific targets. We also identified several new markers of ovarian cancer. Our results indicate that CAST is a robust, rapid, and low cost method to identify cell surface and secreted proteins and is applicable to a variety of relevant biological questions.
Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, active comparator study
Authors: Luis Miguel Ruilope, Andrej Dukat, Michael Böhm, Yves Lacourcière, Jianjian Gong, Martin P Lefkowitz
Journal: The Lancet (2010)
Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque
Authors: Margalida Rotger, Judith Dalmau, Andri Rauch, Paul McLaren, Steven E. Bosinger, Raquel Martinez, Netanya G. Sandler, Annelys Roque, Julia Liebner, Manuel Battegay, Enos Bernasconi, Patrick Descombes, Itziar Erkizia, Jacques Fellay, Bernard Hirschel, Jose M. Miró, Eduard Palou, Matthias Hoffmann, Marta Massanella, Julià Blanco, Matthew Woods, Huldrych F. Günthard, Paul de Bakker, Daniel C. Douek, Guido Silvestri, Javier Martinez-Picado, Amalio Telenti
Journal: Journal of Clinical Investigation (2011)

High levels of HIV-1 replication during the chronic phase of infection usually correlate with rapid progression to severe immunodeficiency. However, a minority of highly viremic individuals remains asymptomatic and maintains high CD4+ T cell counts. This tolerant profile is poorly understood and reminiscent of the widely studied nonprogressive disease model of SIV infection in natural hosts. Here, we identify transcriptome differences between rapid progressors (RPs) and viremic nonprogressors (VNPs) and highlight several genes relevant for the understanding of HIV-1–induced immunosuppression. RPs were characterized by a specific transcriptome profile of CD4+ and CD8+ T cells similar to that observed in pathogenic SIV-infected rhesus macaques. In contrast, VNPs exhibited lower expression of interferon-stimulated genes and shared a common gene regulation profile with nonpathogenic SIV-infected sooty mangabeys. A short list of genes associated with VNP, including CASP1, CD38, LAG3, TNFSF13B, SOCS1, and EEF1D, showed significant correlation with time to disease progression when evaluated in an independent set of CD4+ T cell expression data. This work characterizes 2 minimally studied clinical patterns of progression to AIDS, whose analysis may inform our understanding of HIV pathogenesis.
p53: How a Tumor Suppressor Works
Authors: E. Blume
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article p53: How a Tumor Suppressor Works Get access Elaine Blume Elaine Blume Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 3, 6 February 1991, Pages 158–160, https://doi.org/10.1093/jnci/83.3.158 Published: 06 February 1991
Dietary fish oil in renal transplant recipients treated with cyclosporin-A
Authors: M F Kooijmans-Coutinho, J Rischen-Vos, J Hermans, J W Arndt, F J van der Woude
Journal: Journal of the American Society of Nephrology (1996)

This study aimed to determine whether dietary supplementation with fish oil has a beneficial effect on graft function and the incidence of rejection in renal allograft recipients treated with cyclosporin A (CsA). Renal function, blood pressure, the incidence of acute rejection episodes, graft survival, and renal histology and immunochemistry were investigated. In a randomized, placebo-controlled, double-blind trial, groups of 25 recipients of primary cadaveric renal allografts who had been treated with CsA took fish oil (30% C20:5 omega-3 and 20% C22:6 omega-3) or coconut oil (63% C8:0 and 36% C10:0) at 6 g/day for 3 months. There were no differences between the two patient groups with regard to HLA matching, panel-reactive antibody titers, or the demographic characteristics of donors or recipients. The GFR and effective RPF were determined at 1, 3, and 12 months after transplantation by simultaneous measurement of (125I-)iothalamate and (131I-)hippuran clearances. At 1 yr after transplantation, patients treated with fish oil showed better renal function than did the control patients, but this difference was not statistically significant. Blood pressure and antihypertensive drug use were similar in both groups. The number of rejection episodes was also similar, and renal histopathological and immunohistochemical studies showed no significant differences between the fish-oil group and the control patients. It is concluded that fish oil, at a dose of 6 g/day, has no beneficial effect after renal transplantation within the time scale of the study.