tbuckley/cabot-search huggingface dataset:
Effects of dietary sucrose on factors influencing cholesterol gall stone formation.
Authors: D Werner, P M Emmett, K W Heaton
Journal: Gut (1984)

Twelve subjects with radiolucent gall stones and bile supersaturated with cholesterol were studied after six weeks each on diets which contained 112 g and 16 g respectively of refined (fibre depleted) sucrose but which allowed free access to other foods. Energy intake was 24.5% higher on the high sugar diet and body weight ended 1.4 kg higher than on the low sugar diet. Biliary secretion rates of cholesterol, phospholipid and bile acid, measured by a perfusion technique, were similar on the two diets, as were the bile acid pool sizes measured by isotope dilution. Cholesterol saturation index of fasting 9gall bladder9 bile was 1.30 +/- 0.11 and 1.37 +/- 0.14 on high and low sugar respectively (NS). Plasma triglycerides were 36% higher and plasma high density lipoprotein cholesterol concentrations were 9% lower on the high sugar diet. These findings indicate that over a six week period refined sugar in normally consumed amounts does not adversely affect the lipid composition of bile.
EUREGIO MRSA-net Twente/Münsterland – a Dutch-German cross-border network for the prevention and control of infections caused by methicillin-resistant Staphylococcus aureus
Authors: A W Friedrich, I Daniels-Haardt, R Köck, F Verhoeven, A Mellmann, D Harmsen, J E van Gemert-Pijnen, K Becker, M  G R Hendrix
Journal: Eurosurveillance (2008)

Methicillin-resistant Staphylococcus aureus (MRSA) is associated with increased mortality and morbidity and a leading cause of hospital-acquired infections. Community-acquired (CA)-MRSA are a growing concern worldwide. In the last 10 years, an increase in the MRSA rate from 2% to approximately 23% has been observed in Germany, while a rate under 5% has been recorded for many years in the Netherlands and Scandinavia. In the Netherlands in particular, MRSA rates have become very low in stationary care due to a consistent 'search and destroy' policy. The main focus in Germany lies on hospital-acquired MRSA, whereas the Netherlands focus on the control of the importation of MRSA cases from abroad and on CA-MRSA. As MRSA in hospitals and in the community can be a problem in cross-border health care, the European Union-funded EUREGIO MRSA-net project was established in the bordering regions Twente/Achterhoek, the Netherlands and Münsterland, Germany. The main aim of the project is the creation of a network of the major health care providers in the EUREGIO and the surveillance and prevention of MRSA infections. A spa-typing network was established in order to understand the regional and cross-border dissemination of epidemic and potentially highly virulent MRSA genotypes. As the reduction of differences in health care quality is an important prerequisite for cross-border health care, a transborder quality group comprising hospitals, general practitioners, public health authorities, laboratories, and insurerance companies has been established since 2005 equalising the quality criteria for the control of MRSA on both sides of the border.
Glypican-1 modulates the angiogenic and metastatic potential of human and mouse cancer cells
Authors: Takuma Aikawa, Chery A. Whipple, Martha E. Lopez, Jason Gunn, Alison Young, Arthur D. Lander, Murray Korc
Journal: Journal of Clinical Investigation (2008)

Cells isolated from many types of human cancers express heparin-binding growth factors (HBGFs) that drive tumor growth, metastasis, and angiogenesis. The heparan sulfate proteoglycan glypican-1 (GPC1) is a coreceptor for HBGFs. Here we show that both cancer cell-derived and host-derived GPC1 are crucial for efficient growth, metastasis, and angiogenesis of human and mouse cancer cells. Thus downregulation of GPC1 in the human pancreatic cancer cell line PANC-1, using antisense approaches, resulted in prolonged doubling times and decreased anchorage-independent growth in vitro as well as attenuated tumor growth, angiogenesis, and metastasis when these cells were transplanted into athymic mice. Moreover, athymic mice that lacked GPC1 exhibited decreased tumor angiogenesis and metastasis following intrapancreatic implantation with either PANC-1 or T3M4 human pancreatic cancer cells and fewer pulmonary metastases following intravenous injection of murine B16-F10 melanoma cells. In addition, hepatic endothelial cells isolated from these mice exhibited an attenuated mitogenic response to VEGF-A. These data indicate that cancer cell- and host-derived GPC1 are crucial for full mitogenic, angiogenic, and metastatic potential of cancer cells. Thus targeting GPC1 might provide new avenues for cancer therapy and for the prevention of cancer metastasis.
Sef Downregulation by Ras Causes MEK1/2 to Become Aberrantly Nuclear Localized Leading to Polyploidy and Neoplastic Transformation
Authors: Stéphanie Duhamel, Josée Hébert, Louis Gaboury, Amélie Bouchard, Ronald Simon, Guido Sauter, Mark Basik, Sylvain Meloche
Journal: Cancer Research (2012)

Abstract Subcellular trafficking of key oncogenic signal pathway components is likely to be crucial for neoplastic transformation, but little is known about how such trafficking processes are spatially controlled. In this study, we show how Ras activation causes aberrant nuclear localization of phosphorylated mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK; MEK) MEK1/2 to drive neoplastic transformation. Phosphorylated MEK1/2 was aberrantly located within the nucleus of primary colorectal tumors and human colon cancer cells, and oncogenic activation of Ras was sufficient to induce nuclear accumulation of phosphorylated MEK1/2 and ERK1/2 in intestinal epithelial cells. Enforced nuclear localization of MEK1 in epithelial cells or fibroblasts was sufficient for hyperactivation of ERK1/2, thereby driving cell proliferation, chromosomal polyploidy, and tumorigenesis. Notably, Ras-induced nuclear accumulation of activated MEK1/2 was reliant on downregulation of the spatial regulator Sef, the reexpression of which was sufficient to restore normal MEK1/2 localization and a reversal of Ras-induced proliferation and tumorigenesis. Taken together, our findings indicate that Ras-induced downregulation of Sef is an early oncogenic event that contributes to genetic instability and tumor progression by sustaining nuclear ERK1/2 signaling. Cancer Res; 72(3); 626–35. ©2012 AACR.
Diverse Targets of β-Catenin during the Epithelial–Mesenchymal Transition Define Cancer Stem Cells and Predict Disease Relapse
Authors: Yi-Wen Chang, Ying-Jhen Su, Michael Hsiao, Kuo-Chen Wei, Wei-Hsin Lin, Chi-Jung Liang, Shin-Cheh Chen, Jia-Lin Lee
Journal: Cancer Research (2015)

Wnt signaling contributes to the reprogramming and maintenance of cancer stem cell (CSC) states that are activated by epithelial-mesenchymal transition (EMT). However, the mechanistic relationship between EMT and the Wnt pathway in CSC is not entirely clear. Chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) indicated that EMT induces a switch from the β-catenin/E-cadherin/Sox15 complex to the β-catenin/Twist1/TCF4 complex, the latter of which then binds to CSC-related gene promoters. Tandem coimmunoprecipitation and re-ChIP experiments with epithelial-type cells further revealed that Sox15 associates with the β-catenin/E-cadherin complex, which then binds to the proximal promoter region of CASP3. Through this mechanism, Twist1 cleavage is triggered to regulate a β-catenin-elicited promotion of the CSC phenotype. During EMT, we documented that Twist1 binding to β-catenin enhanced the transcriptional activity of the β-catenin/TCF4 complex, including by binding to the proximal promoter region of ABCG2, a CSC marker. In terms of clinical application, our definition of a five-gene CSC signature (nuclear β-catenin(High)/nuclear Twist1(High)/E-cadherin(Low)/Sox15(Low)/CD133(High)) may provide a useful prognostic marker for human lung cancer.
A long-term review of dermal grafts and bronchial reconstruction
Authors: I. Monk
Journal: Thorax (1973)

Between 1953 and 1962, 21 patients presented with bronchial strictures. Bronchial reconstruction was carried out on 15 of these while a dermal graft was employed in another six patients. The follow-up period, therefore, is between 10 and 20 years. Bronchial structures lend themselves to satisfactory reconstruction. This review, however, showed that late contraction of a dermal graft may occur even two years after operation.
Subclinical Late Cardiomyopathy After Doxorubicin Therapy for Lymphoma in Adults
Authors: O. Hequet, Q.H. Le, I. Moullet, E. Pauli, G. Salles, D. Espinouse, C. Dumontet, C. Thieblemont, P. Arnaud, D. Antal, F. Bouafia, B. Coiffier
Journal: Journal of Clinical Oncology (2004)

Purpose To assess the cardiac status of the long-term survivors and to estimate the incidence and the features of subclinical cardiotoxicity induced after conventional treatment with doxorubicin for non-Hodgkin's lymphoma or Hodgkin's lymphoma. Patients and Methods We analyzed a group of patients who previously received doxorubicin-based chemotherapy for lymphoma. Echocardiograms were performed at least 5 years after therapy with anthracyclines. Clinical cardiomyopathy was defined by the presence of clinical signs of congestive heart failure (CHF). Subclinical cardiomyopathy was defined by decrease of left ventricular fractional shortening (FS) without clinical signs of CHF. Cumulative dose of doxorubicin, male sex, older age, relapse, radiotherapy (mediastinal or total-body irradiation), autologous stem-cell transplantation, high-dose cyclophosphamide, and cardiovascular risk factors (hypertension, diabetes, hypercholesterolemia, familial history of cardiac disease, being overweight, and smoking history) were evaluated as potential risk factors for the development of cardiac dysfunction. Results Of 141 assessable patients (median age, 54 years; median cumulative dose of doxorubicin, 300 mg/m 2 ), only one developed CHF. Criteria of subclinical cardiomyopathy were found in 39 patients. In multivariate analysis, factors that contributed to decreased FS were male sex (P &lt; .01), older age (P &lt; .01), higher cumulative dose of doxorubicin or association with another anthracycline (P = .04), radiotherapy (P = .04), and being overweight (P = .04). Conclusion Cardiac abnormalities can occur in patients treated with doxorubicin for lymphoma in the absence of CHF, even in patients who received moderate anthracycline doses. Male sex, older age, higher dose of doxorubicin, radiotherapy, and being overweight were risk factors for the development of cardiomyopathy.
Book: Sports Medicine Handbook
Authors: V M K. Bhaskarabhatla
Journal: BMJ (1999)

Eds Roger G Hackney, Angus Wallace BMJ Books, £75, pp 505 ISBN 0 7279 1031 0 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> It is welcome news that more and more people seem to be taking up sporting activities, both leisure and competitive. Recently, when cyclist Lance Armstrong won the gruelling Tour de France after having survived cancer, the amazing news received wide media coverage. With this increased interest in sport, sports health care has … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Is auto-servoventilation unnecessary in patients with heart failure and apnoea?
Authors: Thibault Coppens, Olivier Rosant, Loïc Dégrugilliers, Cinthia Rames, Giuseppe Liistro, Grégory Reychler, Sam Bayat
Journal: European Respiratory Journal (2014)

Body: Rationale: Upper airway and nasal airflow resistance are significant in infancy, due to the fact that infants are nasal breathers in early life, and that obstructive nasal diseases are frequent at this age. Nasal flow resistance is closely determined by anatomy, which rapidly changes with growth. The goal of this study was to assess standardized measurements of the nasal cavity dimensions in the first 2 years of life. Methods: 34 head CT scans of infants aged 4.13±4.08 months (range: 0.07 to 19.4, 17 male, 17 female) available in the Amiens University Hospital Dept. of Radiology database were retrospectively analyzed. Infants with craniofacial deformities were excluded. Images were 3D reconstructed, axially oriented and the nasal cavity was segmented by density thresholding from nares to vocal cords. Surface areas of the piriform and choanal apertures were automatically computed in the coronal plane, in standardized positions based on bony reference points. Results:Piriform surface area measured (mean±SD): 54.3±13.8 mm2 (range: 29.1 - 83.9), and was significantly correlated to age (R=0.59, p<0.001), and height (R=0.57, p<0.001). Choanal aperture surface area: 81.3±28.1 mm2 (range: 38.0 – 164.7), and was significantly correlated to age (R=0.74, p<10-6), and height (R=0.71, p<10-5). Conclusions: These data suggest that the nasal cavity anterior and posterior apertures grow rapidly during the first 2 years of life, and that their dimensions are closely correlated to age and height. Further investigation will focus on how the anatomic growth of the nasal cavity in early life affects airflow resistance.
Methodologic Barriers to Addressing Critical Questions About Tobacco and Cancer Prognosis
Authors: Stephanie R. Land
Journal: Journal of Clinical Oncology (2012)

Cigarette smoking has been causally linked to cancer for decades, and we now know a great deal about its impact on primary cancer incidence in the lung and a growing list of other organ sites. However, the evidence regarding the effects of cigarette smoking and other tobacco use on subsequent prognosis is by no means complete. The article by Gillison et al that accompanies this editorial reports an increased risk of progression and death associated with cigarette smoking duration and intensity among patients with oropharyngeal cancer. This is important information to add to our growing understanding of smoking as a risk factor for clinical outcomes after diagnosis with cancer. The article also provides an opportunity to discuss several challenges—methodologic and otherwise—that are frequently barriers to capturing the data needed in studies of cigarette smoking and cancer prognosis.
Acetate intolerance is mediated by enhanced synthesis of nitric oxide by endothelial cells.
Authors: A Amore, P Cirina, S Mitola, L Peruzzi, R Bonaudo, B Gianoglio, R Coppo
Journal: Journal of the American Society of Nephrology (1997)

The clinical picture of acetate intolerance strictly mimics the nitric oxide (NO) effect, including smooth muscle relaxation and extreme vasodilation. Because acetate induces production of cAMP, which is a powerful stimulus of NO synthase (NOS), we evaluated the effect of different dialysate solutions with and without acetate on NOS activity in endothelial cells (EC). NOS activity of EC, evaluated as H3-citrulline produced from H3-arginine, was modulated by the dialysate composition (e.g., 38 mmol/L acetate produced an increase of 3.2 +/- 0.39-fold compared with basal values (P < 0.0005), and the small amount of acetate (4 mmol/L) in 35 mmol/L bicarbonate solution increased the NOS activity by 2 +/- 0.49-fold (P < 0.05). Conversely, the acetate-free solution produced no effect on NOS activity. The mRNA encoding for inducible NOS was highly expressed in EC incubated with acetate buffer and also with acetate in bicarbonate dialysis buffer. The EC proliferative index was depressed by acetate (P < 0.0005), and tumor necrosis factor synthesis was increased (P < 0.0005) compared with acetate-free buffer. This study suggests that dialytic "acetate intolerance" can be induced by the activation, through cAMP and tumor necrosis factor release, of NOS. The small amount of acetate in bicarbonate dialysate, although capable of inducing in vitro NOS activation, is likely to be rapidly metabolized, whereas the large amounts of this anion in acetate fluids overwhelm metabolism by the liver. Acetate-free dialysate is the only solution that provides an acceptable level of biocompatibility both in vivo and in vitro.
Clinical Development of Immunostimulatory Monoclonal Antibodies and Opportunities for Combination
Authors: Ignacio Melero, Antonio M. Grimaldi, Jose L. Perez-Gracia, Paolo A. Ascierto
Journal: Clinical Cancer Research (2013)

Immune system responses are under the control of extracellular biomolecules, which express functions in receptors present on the surface of cells of the immune system, and thus are amenable to be functionally modulated by monoclonal antibodies. Some of these mechanisms are activating and dictate whether the response ensues, while others play the role of powerful repressors. Antagonist antibodies acting on such repressors result in enhanced immune responses, a goal that is also achieved with agonist antibodies acting on the activating receptors. With these simple logics, a series of therapeutic agents are under clinical development and one of them directed at the CTL-associated antigen 4 (CTLA-4) inhibitory receptor (ipilimumab) has been approved for the treatment of metastatic melanoma. The list of antagonist agents acting on repressors under development includes anti-CTLA-4, anti-PD-1, anti-PD-L1 (B7-H1), anti-KIR, and anti-TGF-β. Agonist antibodies currently being investigated in clinical trials target CD40, CD137 (4-1BB), CD134 (OX40), and glucocorticoid-induced TNF receptor (GITR). A blossoming preclinical pipeline suggests that other active targets will also be tested in patients in the near future. All of these antibodies are being developed as conventional monoclonal immunoglobulins, but other engineered antibody formats or RNA aptamers are under preclinical scrutiny. The "dark side" of these immune interventions is that they elicit autoimmune/inflammatory reactions that can be severe in some patients. A critical and, largely, pending subject is to identify reliable predictive biomarkers both for efficacy and immune toxicity. Preclinical and early clinical studies indicate a tremendous potential to further improve efficacy, using combinations from among these new agents that frequently act in a synergistic fashion. Combinations with other more conventional means of treatment such as radiotherapy, chemotherapy, or cancer vaccines also hold much promise.
Phase II Study of Intraperitoneal Paclitaxel Plus Cisplatin and Intravenous Paclitaxel Plus Bevacizumab As Adjuvant Treatment of Optimal Stage II/III Epithelial Ovarian Cancer
Authors: Jason A. Konner, Diana M. Grabon, Scott R. Gerst, Alexia Iasonos, Howard Thaler, Sandra D. Pezzulli, Paul J. Sabbatini, Katherine M. Bell-McGuinn, William P. Tew, Martee L. Hensley, David R. Spriggs, Carol A. Aghajanian
Journal: Journal of Clinical Oncology (2011)

Intraperitoneal (IP) cisplatin and intravenous (IV) or IP paclitaxel constitute a standard therapy for optimally debulked ovarian cancer. Bevacizumab prolongs progression-free survival (PFS) when included in first-line IV chemotherapy. In this study, the safety and feasibility of adding bevacizumab to a first-line IP regimen were assessed.
Synchronous Coexpression of Epidermal Growth Factor Receptor and Cyclooxygenase-2 in Carcinomas of the Uterine Cervix
Authors: Gwi Eon Kim, Yong Bae Kim, Nam Hoon Cho, Hyun-Cheol Chung, Hong Ryull Pyo, Jong Doo Lee, Tchan Kyu Park, Woong Sub Koom, Mison Chun, Chang Ok Suh
Journal: Clinical Cancer Research (2004)

To evaluate the potential of the new prognostic information gained by analyzing the coexpression of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in cervical cancer patients.Sixty-eight patients with International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix, who underwent concurrent chemoradiotherapy between 1993 and 1996, were divided into the following four groups according to their immunoreactivities for EGFR and COX-2 in paraffin-embedded sections: (a). the EGFR-negative/COX-2-negative group (n = 11); (b). the EGFR-negative/COX-2-positive group (n = 8); (c). the EGFR-positive/COX-2-negative group (n = 27); and (d). the EGFR-positive/COX-2-positive group (n = 22). The clinical features, patterns of treatment failure, and survival data in the four groups were compared.Positive immunoreactivity for EGFR and COX-2 was observed in 49 of 68 (72%) and 19 of 68 (28%), respectively. However, no strong correlation was found between the levels of EGFR and COX-2 immunopositivity (R(2) = 0.05, P = 0.07). Patients in the EGFR-positive/COX-2-positive group had a higher likelihood of locoregional recurrence than those in the other three groups (P = 0.02). Of the patients in the four groups, patients positive for both oncoproteins were found to have the worst prognosis with an overall 5-year disease-free survival rate of 55% compared with 91% for the EGFR-negative/COX-2-negative patients, 88% for the EGFR-negative/COX-2-positive patients, and 69% for the EGFR-positive/COX-2-negative patients (P = 0.05, log-rank test). In addition, the synchronous coexpression of the EGFR and COX-2 oncoproteins was found to be an independent prognostic factor by univariate and multivariate analyses (relative risk = 4.0, P = 0.03).Given these observations, we conclude that the coexpression of EGFR and COX-2 immunoreactivity may be used as a potent molecular risk factor for predicting the poor survival of patients with the International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix.
Antibacterial honey for the prevention of peritoneal-dialysis-related infections (HONEYPOT): a randomised trial
Authors: David W Johnson, Sunil V Badve, Elaine M Pascoe, Elaine Beller, Alan Cass, Carolyn Clark, Janak de Zoysa, Nicole M Isbel, Steven McTaggart, Alicia T Morrish, E Geoffrey Playford, Anish Scaria, Paul Snelling, Liza A Vergara, Carmel M Hawley
Journal: The Lancet Infectious Diseases (2013)
Serum Cardiac Troponins and N-Terminal Pro-Brain Natriuretic Peptide: A Staging System for Primary Systemic Amyloidosis
Authors: Angela Dispenzieri, Morie A. Gertz, Robert A. Kyle, Martha Q. Lacy, Mary F. Burritt, Terry M. Therneau, Philip R. Greipp, Thomas E. Witzig, John A. Lust, S. Vincent Rajkumar, Rafael Fonseca, Steven R. Zeldenrust, Christopher G.A. McGregor, Allan S. Jaffe
Journal: Journal of Clinical Oncology (2004)

Primary systemic amyloidosis (AL) is a multisystemic disorder resulting from an underlying plasma cell dyscrasia. There is no formal staging system for AL, making comparisons between studies and treatment centers difficult. Our group previously identified elevated serum cardiac troponin T (cTnT) as the most powerful predictor of overall survival. Others have reported that N-terminal pro-brain natriuretic peptide (NT-proBNP) is a valuable prognostic marker. We sought to develop a staging system for patients with AL.Two hundred forty-two patients with newly diagnosed AL who were seen at the Mayo Clinic between April 1979 and November 2000, and who had echocardiograms and stored serum samples at presentation were eligible for this retrospective review. NT-proBNP measurements were performed on 242 patients in whom cTnT and cardiac troponin I (cTnI) had been previously run. Two prognostic models were designed using threshold values of NT-proBNP and either cTnT or cTnI (NT-proBNP < 332 ng/L, cTnT < 0.035 microg/L, and cTnI < 0.1 microg/L). Depending on whether NT-proBNP and troponin levels were both low, were high for only one level, or were both high, patients were classified as stage I, II, or III, respectively.Using the cTnT+NT-proBNP model 33%, 30%, and 37% of patients were stages I, II, and III, respectively, with median survivals of 26.4, 10.5, and 3.5 months, respectively. The alternate cTnI+NT-proBNP model predicted median survivals of 27.2, 11.1, and 4.1 months, respectively.Stratification of AL patients into three stages is possible with two readily available and reproducible tests setting the stage for more consistent and reliable cross comparisons of therapeutic outcomes.