tbuckley/cabot-search huggingface dataset:
Sp1 Is Required for Transforming Growth Factor-β–Induced Mesenchymal Transition and Migration in Pancreatic Cancer Cells
Authors: Kerstin Jungert, Anita Buck, Götz von Wichert, Guido Adler, Alexander König, Malte Buchholz, Thomas M. Gress, Volker Ellenrieder
Journal: Cancer Research (2007)

Transition from a sessile epithelial phenotype to a migrating mesenchymal phenotype is a crucial step in transforming growth factor-beta (TGF-beta)-induced pancreatic cancer cell migration and invasion. These profound morphologic and functional alterations are associated with characteristic changes in TGF-beta-regulated gene expression, defined by rapid repression of epithelial markers and a strong and sustained transcriptional induction of mesenchymal markers such as the intermediate filament vimentin. In this study, we have analyzed the role of the transcription factor Sp1 in TGF-beta-induced and Smad-mediated gene regulation during epithelial to mesenchymal transition (EMT) and migration of pancreatic cancer cells. Here, we show that Sp1 is required for TGF-beta-induced EMT, and that this function is especially mediated through transcriptional induction of vimentin. Our results emphasize the functional relevance of vimentin in TGF-beta-induced EMT because prevention of its induction strongly reduces cell migration. Altogether, this study helps to better understand the role of Sp1 in TGF-beta-induced progression of pancreatic cancer. It suggests that Sp1, via transcriptional induction of vimentin, cooperates with activated Smad complexes in mesenchymal transition and migration of pancreatic cancer cells upon TGF-beta stimulation.
Severe skin reaction after leflunomide and etanercept in a patient with rheumatoid arthritis
Authors: F Soliotis
Journal: Annals of the Rheumatic Diseases (2002)

A 32 year old Pakistani woman developed a symmetrical polyarthritis, with a high erythrocyte sedimentation rate, in 1991. Within a few months, erosions developed and her rheumatoid factor became positive. The antinuclear antibodies were negative. Between 1991 and 1999 she was treated with sulfasalazine, sodium aurothiomalate, azathioprine, methotrexate, d-penicillamine, and hydroxychloroquine sequentially, but each drug had to be stopped either because of intolerance or leucopenia.

Her disease remained active and deformities developed. Her condition was maintained with 7.5 mg oral prednisolone and non-steroidal anti-inflammatory drugs. In April 2000 leflunomide was added. Three daily doses of 100 mg leflunomide were followed by 20 mg a day maintenance dose. Ten days later, she developed a vesicular rash over the trunk and the proximal parts of the arms and legs (fig 1). Leflunomide was discontinued and cholestyramine was introduced for wash out. A skin biopsy showed focal epidermal necrosis with partial lichenoid changes. …
A New pROM King for the MitoK <sub>ATP</sub> Dance
Authors: Amy K. Rines, Marina Bayeva, Hossein Ardehali
Journal: Circulation Research (2012)

I schemic heart disease remains the leading cause of death in the developed world, and mechanisms to reduce cardiac ischemic damage are being actively investigated.A potent protective mechanism for the heart is ischemic preconditioning (IPC), a phenomenon in which brief ischemic episodes protect the heart from tissue damage and cell death resulting from subsequent periods of ischemia and reperfusion. 1The precise molecular mechanisms at play during IPC are not known, but the opening of a mitochondrial ATP-sensitive potassium channel, mitoK ATP , is believed to be necessary for IPC-induced activation of several prosurvival pathways and processes.
Genome sequence of the necrotrophic plant pathogen Pythium ultimum reveals original pathogenicity mechanisms and effector repertoire
Authors: C André Lévesque, Henk Brouwer, Liliana Cano, John P Hamilton, Carson Holt, Edgar Huitema, Sylvain Raffaele, Gregg P Robideau, Marco Thines, Joe Win, Marcelo M Zerillo, Gordon W Beakes, Jeffrey L Boore, Dana Busam, Bernard Dumas, Steve Ferriera, Susan I Fuerstenberg, Claire MM Gachon, Elodie Gaulin, Francine Govers, Laura Grenville-Briggs, Neil Horner, Jessica Hostetler, Rays HY Jiang, Justin Johnson, Theerapong Krajaejun, Haining Lin, Harold JG Meijer, Barry Moore, Paul Morris, Vipaporn Phuntmart, Daniela Puiu, Jyoti Shetty, Jason E Stajich, Sucheta Tripathy, Stephan Wawra, Pieter van West, Brett R Whitty, Pedro M Coutinho, Bernard Henrissat, Frank Martin, Paul D Thomas, Brett M Tyler, Ronald P De Vries, Sophien Kamoun, Mark Yandell, Ned Tisserat, C Robin Buell
Journal: Genome biology (2010)

Abstract Background Pythium ultimum is a ubiquitous oomycete plant pathogen responsible for a variety of diseases on a broad range of crop and ornamental species. Results The P. ultimum genome (42.8 Mb) encodes 15,290 genes and has extensive sequence similarity and synteny with related Phytophthora species, including the potato blight pathogen Phytophthora infestans . Whole transcriptome sequencing revealed expression of 86% of genes, with detectable differential expression of suites of genes under abiotic stress and in the presence of a host. The predicted proteome includes a large repertoire of proteins involved in plant pathogen interactions, although, surprisingly, the P. ultimum genome does not encode any classical RXLR effectors and relatively few Crinkler genes in comparison to related phytopathogenic oomycetes. A lower number of enzymes involved in carbohydrate metabolism were present compared to Phytophthora species, with the notable absence of cutinases, suggesting a significant difference in virulence mechanisms between P. ultimum and more host-specific oomycete species. Although we observed a high degree of orthology with Phytophthora genomes, there were novel features of the P. ultimum proteome, including an expansion of genes involved in proteolysis and genes unique to Pythium . We identified a small gene family of cadherins, proteins involved in cell adhesion, the first report of these in a genome outside the metazoans. Conclusions Access to the P. ultimum genome has revealed not only core pathogenic mechanisms within the oomycetes but also lineage-specific genes associated with the alternative virulence and lifestyles found within the pythiaceous lineages compared to the Peronosporaceae.
Prognostic Value of Extracapsular Tumor Spread for Locoregional Control in Premenopausal Patients With Node-Positive Breast Cancer Treated With Classical Cyclophosphamide, Methotrexate, and Fluorouracil: Long-Term Observations From International Breast Cancer Study Group Trial VI
Authors: Günther Gruber, Marco Bonetti, M. Laura Nasi, Karen N. Price, Monica Castiglione-Gertsch, Carl-Magnus Rudenstam, Stig B. Holmberg, Jurij Lindtner, Rastko Golouh, John Collins, Diana Crivellari, Antonino Carbone, Beat Thürlimann, Edda Simoncini, Martin F. Fey, Richard D. Gelber, Alan S. Coates, Aron Goldhirsch
Journal: Journal of Clinical Oncology (2005)

We sought to determine retrospectively whether extracapsular spread (ECS) might identify a subgroup that could benefit from radiotherapy after mastectomy, especially patients with 1 to 3 positive lymph nodes (LN1-3+).We randomized 1,475 premenopausal women with node-positive breast cancer to three, six, or nine courses of "classical" CMF (cyclophosphamide, methotrexate, and fluorouracil). After a review of all pathology forms, 933 patients (63%) had information on the presence or absence of ECS. ECS was present in 49.5%. The median follow-up was 10 years.In univariate analyses, ECS was associated with worse disease-free survival (DFS) and overall survival (OS). In multivariate analyses adjusting for tumor size, vessel invasion, surgery type, and age group, ECS remained significant (DFS: hazard ratio, 1.61; 95% CI, 1.34 to 1.93; P < .0001; OS: 1.67; 95% CI, 1.34 to 2.08; P < .0001). However, ECS was not significant when the number of positive nodes was added. The locoregional failure rate +/- distant failure (LRF +/- distant failure) within 10 years was estimated at 19% (+/- 2%) without ECS, versus 27% (+/- 2%) with ECS. The difference was statistically significant in univariate analyses, but not after adjusting for the number of positive nodes. No independent effect of ECS on DFS, OS, or LRF could be confirmed within the subgroup of 382 patients with LN1-3+ treated with mastectomy without radiotherapy.Our results do not support an independent prognostic value of ECS, nor its use as an indication for irradiation in premenopausal patients with LN1-3+ treated with classical CMF. However, we could not examine whether extensive ECS is of prognostic importance.
Early Salvage Radiation Therapy Does Not Compromise Cancer Control in Patients with pT3N0 Prostate Cancer After Radical Prostatectomy: Results of a Match-controlled Multi-institutional Analysis
Authors: Alberto Briganti, Thomas Wiegel, Steven Joniau, Cesare Cozzarini, Marco Bianchi, Maxine Sun, Bertrand Tombal, Karin Haustermans, Tom Budiharto, Wolfgang Hinkelbein, Nadia Di Muzio, Pierre I. Karakiewicz, Francesco Montorsi, Hein Van Poppel
Journal: European Urology (2012)
Vascular capacitance and fluid shifts in dogs during prolonged hemorrhagic hypotension.
Authors: C F Rothe, J A Drees
Journal: Circulation Research (1976)

The mean circulatory pressure (Pmc) in dogs anesthetized with chloralose-urethane was estimated from 0.5 to 150 minutes after hemorrhages of 0, 17, or 34 ml/kg, or that volume giving an arterial pressure (Pa) of 40 mm Hg. The Pmc was determined by fibrillating the heart and then rapidly pumping blood from aorta to vena cava until Pa=venous pressure (Pv)=Pmc. Within about 10 seconds, the heart was defibrillated. Vascular compliance was estimated as the ratio of a test blood volume change (0, +/- 8.5, or 17 ml/kg) to the change in Pmc, determined 0.5 minute after the start of the test volume change. Erythrocyte and plasma volumes were measured by 51Cr-erythrocyte and 125I-albumin dilution. In response to prolonged hemorrhage: (1) the total vascular compliance apparently decreased; (2) most of the changes in capacity vessels occurred within 5 minutes, and indeed a large part of the response probably had occurred by the time of the first measurement at 30 seconds; (3) the progressive recovery in Pmc after 5 minutes was primarily from fluid shifting into the vasculature; (4) even after 2 hours of severe hemorrhagic hypotension, the venoconstriction was not lost; but (5) after an hour of severe hemorrhagic hypotension (arterial pressure of 40 mm Hg) there was water loss from the vasculature, because plasma protein and erythrocyte concentrations and plasma oncotic pressure increased.
Increased Risk of Recurrence After Hormone Replacement Therapy in Breast Cancer Survivors
Authors: L. Holmberg, O.-E. Iversen, C. M. Rudenstam, M. Hammar, E. Kumpulainen, J. Jaskiewicz, J. Jassem, D. Dobaczewska, H. E. Fjosne, O. Peralta, R. Arriagada, M. Holmqvist, J. Maenpa
Journal: JNCI Journal of the National Cancer Institute (2008)

Hormone replacement therapy (HT) is known to increase the risk of breast cancer in healthy women, but its effect on breast cancer risk in breast cancer survivors is less clear. The randomized HABITS study, which compared HT for menopausal symptoms with best management without hormones among women with previously treated breast cancer, was stopped early due to suspicions of an increased risk of new breast cancer events following HT. We present results after extended follow-up. HABITS was a randomized, non–placebo-controlled noninferiority trial that aimed to be at a power of 80% to detect a 36% increase in the hazard ratio (HR) for a new breast cancer event following HT. Cox models were used to estimate relative risks of a breast cancer event, the maximum likelihood method was used to calculate 95% confidence intervals (CIs), and χ 2 tests were used to assess statistical significance, with all P values based on two-sided tests. The absolute risk of a new breast cancer event was estimated with the cumulative incidence function. Most patients who received HT were prescribed continuous combined or sequential estradiol hemihydrate and norethisterone. Of the 447 women randomly assigned, 442 could be followed for a median of 4 years. Thirty-nine of the 221 women in the HT arm and 17 of the 221 women in the control arm experienced a new breast cancer event (HR = 2.4, 95% CI = 1.3 to 4.2). Cumulative incidences at 5 years were 22.2% in the HT arm and 8.0% in the control arm. By the end of follow-up, six women in the HT arm had died of breast cancer and six were alive with distant metastases. In the control arm, five women had died of breast cancer and four had metastatic breast cancer ( P = .51, log-rank test). After extended follow-up, there was a clinically and statistically significant increased risk of a new breast cancer event in survivors who took HT.
Quality of Life and Satisfaction with Outcome among Prostate-Cancer Survivors
Authors: Martin G. Sanda, Rodney L. Dunn, Jeff Michalski, Howard M. Sandler, Laurel Northouse, Larry Hembroff, Xihong Lin, Thomas K. Greenfield, Mark S. Litwin, Christopher S. Saigal, Arul Mahadevan, Eric Klein, Adam Kibel, Louis L. Pisters, Deborah Kuban, Irving Kaplan, David Wood, Jay P. Ciezki, Nikhil Shah, John T. Wei
Journal: New England Journal of Medicine (2008)

We sought to identify determinants of health-related quality of life after primary treatment of prostate cancer and to measure the effects of such determinants on satisfaction with the outcome of treatment in patients and their spouses or partners.
Pneumococcal Meningitis in an Infant
Authors: E. M. Metcalfe
Journal: BMJ (1948)

The following are the results of further investigations.Feb. 19:-Blood count: red cells, 4,380,000 per c.mm.; haemoglobin, 87%; white cells 5,200 per c.mm. Agglutinations: negative in dilutions of 1: 25 and 1: 50 against Br.abortus; positive in dilutions of 1:125, 1:250, and 1:1,250.April 16:-Blood count:
Refining the changes. Or, how to modify the shape, not the spirit
Authors: A. T. Dinh-Xuan, V. Brusasco
Journal: European Respiratory Journal (2009)

In the January issue of the European Respiratory Journal ( ERJ ) we outlined some of the issues that we felt to be important in the peer-review process 1, and hoped that the changes we were about to implement would reduce the reviewing turnaround time. Six months on, we are proud to announce that the median length of time it takes for authors to be notified with a first decision about their manuscript has reduced from 32 to 20 days. As we believe a further reduction in this turnaround time to be an unrealistic aim, we are starting to explore new ways in which to reshape the Journal without changing its core content and spirit. One such possibility would be to strengthen …
Lymphoma in a patient with rheumatoid arthritis receiving methotrexate treatment: successful treatment with rituximab
Authors: M Stewart, V Malkovska, J Krishnan, L Lessin, W Barth
Journal: Annals of the Rheumatic Diseases (2001)

A 55 year old man with chronic lymphocytic leukaemia (CLL) and rheumatoid arthritis (RA), treated for four years with methotrexate (MTX), who developed a B cell non-Hodgkin's lymphoma (B-NHL), is described. The tumour was localised to the shoulder and axillary lymph nodes, and positive for Epstein-Barr viral antigens. After failure of radiation and chemotherapy, a complete remission was achieved with a combination of antibody treatment (rituximab) and EPOCH. The development of a second malignancy in a patient with RA receiving MTX has not been described before. The summation of T cell deficiencies induced by MTX, CLL, and RA may all have contributed to the development of the B-NHL.
THE ETIOLOGY OF BERI-BERI
Authors: W. G. Ellis
Journal: BMJ (1903)

V. H. 2t.F. 43.0 6.6 4.8 39.4 6.2 0.0 J. H. 10 M. 17-4 7.0 4.4 63.8 6.2 1.2 M. 2 M. 35.8 10.3 6.i 42.9 4.8 o.6 M. 4 M. 39.6 9 0 3.6 43.0 4.6 0 2 J. 14 F F. 5r-4 7.2 2.6 34.4 4.2 0.2 P. I12 F F. 33.2 7.6 4-4 50.0 4.2 0.6 W. 3 F. 31.2 8.2 6.4 50.2 3.8 0.2 M. I 4 F. 33.2 23.2 6.2 43.6 3.6 0.2 B. 7 F. 44.8 6.9 4-3 40.4 3.6 0.0 S. 6 F, 41.8 4.2 6.2 44.4 3.0 0.4 'V. 4 M, 34.6 Io.8 3 2 48.8 2.6 0.0 CR. 2 F. 46.2 7.8 6.2 38.2 1.4 0.2 A. P. I8 M. 23.8 2.1 73.0 I.I 0.0 A. P.* -23.0 4.2 71.8 0.4 o.6 * Second examination.more than 6-tlhat is, a distinct increase-while 36 per cent..are less than 4 per cent.In less than half the cases, there- fore, is any indication of diagnostic importance found in the blood examination.Indeed, it maybe that the number of .positiveresults should be considered to be lower even than this, since an eosinophilia may occur in children without any apparent cause.Zappert2 was the first to call attention to this point, and for normal children gives 46 blood counts where the numbers of eosinophiles as a whole far exceed those recorded here, reaching in one instance the remarkable figure of I9 per cent.Zappert does not, however, exclude or take into consideration the question of worms, and it is at least not improbable that some, at any rate, of his children were infected with parasites.The experience of other ob- servers has not confirmed the very high figures given by Xappert, though the fact that sporadic eosinophilias do occur in children has been confirmed.Table II.gives the per- centage of eosinophiles in io consecutive cases of normal and (as far as could be ascertained) wormless children: TABLE II.
Clues Emerge on How HIV Increases Lymphoma Risk
Authors: Vicki Brower
Journal: JNCI Journal of the National Cancer Institute (2010)

Two recent studies provide new clues to why people infected with human immunodeficiency virus (HIV) are at high risk — sometimes very high risk--for lymphoma. One of the studies adds new data linking macrophages in HIV patients with the development of AIDS-related lymphoma (ARL). The other suggests that AIDS patients who develop lymphoma have higher levels of certain cytokines as early as 2 years before their diagnosis. The fi ndings could lead to new prevention and treatment strategies not only for ARL but also for other types of lymphoma, according to the researchers, who presented their fi ndings in April at the annual meeting of the American
Modulation of Signal Transducers and Activators of Transcription 1 and 3 Signaling in Melanoma by High-Dose IFNα2b
Authors: Wenjun Wang, Howard D. Edington, Uma N.M. Rao, Drazen M. Jukic, Stephanie R. Land, Soldano Ferrone, John M. Kirkwood
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The Janus-activated kinase/signal transducers and activators of transcription (STAT) pathway of IFN signaling is important to immunoregulation and tumor progression. STAT1 plays a prominent role in the effector immune response, whereas STAT3 is implicated in tumor progression and down-regulation of the response to type I IFNs. The goal of this study was to understand the effects of high-dose IFNα2b (HDI) in relation to the balance of pSTAT1 and pSTAT3. Experimental Design: We evaluated STAT1 and STAT3 jointly as mediators of IFNα effects in the setting of a prospective neoadjuvant trial of HDI, in which tissue samples were obtained before and after 20 doses of HDI therapy. Double immunohistochemistry for pSTAT1 and pSTAT3 was done on paired fixed (9 patients) or frozen (12 patients) biopsies. Results: HDI was found to up-regulate pSTAT1, whereas it down-regulates pSTAT3 and total STAT3 levels in both tumor cells and lymphocytes. Higher pSTAT1/pSTAT3 ratios in tumor cells pretreatment were associated with longer overall survival (P = 0.032). The pSTAT1/pSTAT3 ratios were augmented by HDI both in melanoma cells (P = 0.005) and in lymphocytes (P = 0.022). Of the immunologic mediators and markers tested, TAP2 was augmented by HDI (but not TAP1 and MHC class I/II). Conclusion: IFNα2b significantly modulates the balance of STAT1/STAT3 in tumor cells and host lymphocytes, leading to up-regulation of TAP2 and augmented host antitumor response. The pSTAT1/pSTAT3 ratio in tumor cells at baseline may serve as a useful predictor of clinical outcome in cutaneous melanoma; the modulation of this ratio may serve as a predictor of therapeutic effect.
Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings.
Authors: G E Reiber, L Vileikyte, E J Boyko, M del Aguila, D G Smith, L A Lavery, A J Boulton
Journal: Diabetes Care (1999)

OBJECTIVE: To determine the frequency and constellations of anatomic, pathophysiologic, and environmental factors involved in the development of incident diabetic foot ulcers in patients with diabetes and no history of foot ulcers from Manchester, U.K., and Seattle, Washington, research settings. RESEARCH DESIGN AND METHODS: The Rothman model of causation was applied to the diabetic foot ulcer condition. The presence of structural deformities, peripheral neuropathy, ischemia, infection, edema, and callus formation was determined for diabetic individuals with incident foot ulcers in Manchester and Seattle. Demographic, health, diabetes, and ulcer data were ascertained for each patient. A multidisciplinary group of foot specialists blinded to patient identity independently reviewed detailed abstracts to determine component and sufficient causes present and contributing to the development of each patient's foot ulcer. A modified Delphi process assisted the group in reaching consensus on component causes for each patient. Estimates of the proportion of ulcers that could be ascribed to each component cause were computed. RESULTS: From among 92 study patients from Manchester and 56 from Seattle, 32 unique causal pathways were identified. A critical triad (neuropathy, minor foot trauma, foot deformity) was present in &amp;gt; 63% of patient's causal pathways to foot ulcers. The components edema and ischemia contributed to the development of 37 and 35% of foot ulcers, respectively. Callus formation was associated with ulcer development in 30% of the pathways. Two unitary causes of ulcer were identified, with trauma and edema accounting for 6 and &amp;lt; 1% of ulcers, respectively. The majority of the lesions were on the plantar toes, forefoot, and midfoot. CONCLUSIONS: The most frequent component causes for lower-extremity ulcers were trauma, neuropathy, and deformity, which were present in a majority of patients. Clinicians are encouraged to use proven strategies to prevent and decrease the impact of modifiable conditions leading to foot ulcers in patients with diabetes.
Emerging roles of Notch signaling in liver disease
Authors: Fabian Geisler, Mario Strazzabosco
Journal: Hepatology (2014)

This review critically discusses the most recent advances in the role of Notch signaling in liver development, homeostasis, and disease. It is now clear that the significance of Notch in determining mammalian cell fates and functions extends beyond development, and Notch is a major regular of organ homeostasis. Moreover, Notch signaling is reactivated upon injury and regulates the complex interactions between the distinct liver cell types involved in the repair process. Notch is also involved in the regulation of liver metabolism, inflammation, and cancer. The net effects of Notch signaling are highly variable and finely regulated at multiple levels, but also depend on the specific cellular context in which Notch is activated. Persistent activation of Notch signaling is associated with liver malignancies, such as hepatocellular carcinoma with stem cell features and intrahepatic cholangiocarcinoma. The complexity of the pathway provides several possible targets for agents able to inhibit Notch. However, further cell- and context-specific in-depth understanding of Notch signaling in liver homeostasis and disease will be essential to translate these concepts into clinical practice and be able to predict benefits and risks of evolving therapies.
ARE CORONARY ARTERY CALCIUM SCORE AND/OR CT ANGIOGRAPHY APPROPRIATE FOR ASYMPTOMATIC PATIENTS WITH DIABETES MELLITUS?
Authors: Makoto Kondo, Takeshi Kondo, Fujimoto Shinichiro, Kazuhisa Takamura, Hiroshi Arai, Tadaaki Orihara, Junichi Sugiyama, Akira Endo, Hiroshi Fukazawa, Hideki Nagaoka, Akitsugu Oida
Journal: Journal of the American College of Cardiology (2013)