tbuckley/cabot-search huggingface dataset:
Nicholas Copernicus and the Inception of Bread-Buttering
Authors: Samuel B. Hand
Journal: JAMA (1970)

Historians have classically emphasized social, economic, and cultural factors as having the greatest impact upon the development of dietary habits. While their basic assumptions have doubtless been correct, they have unfortunately tended to ignore other significant factors. This essay will elaborate upon certain political and military circumstances and their relevance to the inception of buttered bread. During the first quarter of the 16th century, Ermland was the scene of frequent and terrible devastation. Bordering upon the Gulf of Danzig, Ermland was one of the four dioceses into which Prussia had been divided for purposes of ecclesiastical government. Its bishop, Fabian von Lossainen, was both temporal and spiritual ruler, and his secular responsibilities were the more burdensome. A vassal of the King of Poland, the Bishop was frequently engaged in conflict with the Order of Teutonic Knights. The Order had formerly ruled Ermland and periodically launched military expeditions to regain supremacy.
Effects of hydrogen peroxide on the metabolism of human rheumatoid and osteoarthritic synovial fibroblasts in vitro.
Authors: N Hutadilok, M M Smith, P Ghosh
Journal: Annals of the Rheumatic Diseases (1991)

The effects of hydrogen peroxide (H2O2) on the metabolism of cultured human synovial fibroblasts derived from joints of four patients with rheumatoid arthritis and three with osteoarthritis have been investigated. The exposure of rheumatoid cell cultures to this oxygen derived species at sublethal concentrations (1-100 mumol/l) induced a dose related inhibition of both hyaluronic acid (HA) and DNA synthesis. In contrast, in osteoarthritic cell lines a biphasic response was shown. At low concentrations of H2O2 (less than 10 mumol/l) a stimulatory effect on HA synthesis was noted, whereas in the presence of higher concentrations (greater than 10 mumol/l) a significant inhibition of synthesis occurred. These deleterious effects of H2O2 were partially reduced by the addition of catalase to the culture media. The finding that both HA and DNA synthesis were inhibited at concentrations of H2O2 less than those which caused loss of cell integrity (greater than 200 mumol/l) suggests oxidation of intracellular components, such as glyceraldehyde-3-phosphate dehydrogenase, and subsequent depletion of ATP concentrations.
The London Classification of gastrointestinal neuromuscular pathology: a little more flexibility would be wise...
Authors: G. Bassotti, V. Villanacci
Journal: Gut (2010)

We read with interest the recent article on the London Classification of gastrointestinal neuromuscular pathology,1 drafted by a panel of pathologists and a few clinicians trying to bring some order to a complex and often mined field. While we agree on the need for a classification of the neuromuscular disorders of the gastrointestinal tract, and we endorse the increasing use of immunohistochemical methods (too often underemployed) in addition to the classic, standard H&E, we found such a classification somewhat ‘rigid’, and would like to add some personal comments on it.

First we feel that, in the …
Analysis of expiratory tidal flow patterns as a diagnostic tool in airflow obstruction
Authors: MJ Morris, RG Madgwick, I Collyer, F Denby, DJ Lane
Journal: European Respiratory Journal (1998)

An index obtained from tidal expiration, the ratio of time to peak tidal expiratory flow (tPTEF) to expiratory time (tE), discriminates between groups with and without airflow obstruction in infants and children and correlates with other measurements of airflow obstruction in adults. The aim of this study was to determine whether the diagnosis of airflow obstruction could be made from an analysis of the later part of the expiratory tidal flow time curve, i.e beyond the maximum flow. One hundred and eighteen patients attending the lung function laboratory with a putative diagnosis of airflow obstruction were studied. From uncoached tidal breathing, measurements were made of the average time constant of the respiratory system (Trs) and extrapolated volume (EV). Forced expiratory spirometry and whole-body plethysmography were performed. In this cross-sectional study, Trs correlated with inspiratory airways resistance and forced expiratory volume in one second (FEV1), according to the linear regression equations, airway resistance (Raw)=3.03 Trs+1.2, r=0.65, p<0.001, and FEV1% predicted = 87.8-23.7 Trs, r=058, p<0.001. EV correlated positively with overinflation, functional residual capacity (FRC) % pred = 152 EV+103, r=0.68, p<0.001. This study shows that there is a relationship between these measurements made from analysis of tidal breathing and recognized measurements of airflow obstruction and overinflation.
Transmembrane glucose transport in skeletal muscle of patients with non-insulin-dependent diabetes.
Authors: R C Bonadonna, S Del Prato, M P Saccomani, E Bonora, G Gulli, E Ferrannini, D Bier, C Cobelli, R A DeFronzo
Journal: Journal of Clinical Investigation (1993)

Insulin resistance for glucose metabolism in skeletal muscle is a key feature in non-insulin-dependent diabetes mellitus (NIDDM). Which cellular effectors of glucose metabolism are involved is still unknown. We investigated whether transmembrane glucose transport in vivo is impaired in skeletal muscle in nonobese NIDDM patients. We performed euglycemic insulin clamp studies in combination with the forearm balance technique (brachial artery and deep forearm vein catheterization) in six nonobese NIDDM patients and five age- and weight-matched controls. Unlabeled D-mannitol (a nontransportable molecule) and radioactive 3-O-methyl-D-glucose (the reference molecular probe to assess glucose transport activity) were simultaneously injected into the brachial artery, and the washout curves were measured in the deep venous effluent blood. In vivo transmembrane transport of 3-O-methyl-D-glucose in forearm muscle was determined by computerized analysis of the washout curves. At similar steady-state plasma concentrations of insulin (approximately 500 pmol/liter) and glucose (approximately 5.15 mmol/liter), transmembrane inward transport of 3-O-methyl-D-glucose in skeletal muscle was markedly reduced in the NIDDM patients (6.5 x 10(-2) +/- 0.56 x 10(-2).min-1) compared with controls (12.5 x 10(-2) +/- 1.5 x 10(-2).min-1, P < 0.005). Mean glucose uptake was also reduced in the diabetics both at the whole body level (9.25 +/- 1.84 vs. 28.3 +/- 2.44 mumol/min per kg, P < 0.02) and in the forearm tissues (5.84 +/- 1.51 vs. 37.5 +/- 7.95 mumol/min per kg, P < 0.02). When the latter rates were extrapolated to the whole body level, skeletal muscle accounted for approximately 80% of the defect in insulin action seen in NIDDM patients. We conclude that transmembrane glucose transport, when assessed in vivo in skeletal muscle, is insensitive to insulin in nonobese NIDDM patients, and plays a major role in determining whole body insulin resistance.
Leptin Interferes with the Effects of the Antiestrogen ICI 182,780 in MCF-7 Breast Cancer Cells
Authors: Cecilia Garofalo, Diego Sisci, Eva Surmacz
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Obesity is a risk factor for breast cancer development in postmenopausal women and correlates with shorter disease-free and overall survival in breast cancer patients, regardless of menopausal status. Adipose tissue is a major source of leptin, a cytokine regulating energy balance and controlling different processes in peripheral tissues, including breast cancer cell growth. Here, we investigated whether leptin can counteract antitumorigenic activities of the antiestrogen ICI 182,780 in breast cancer cells. Experimental Design: Mitogenic response to leptin and the effects of leptin on ICI 182,780-dependent growth inhibition were studied in MCF-7 estrogen receptor α-positive breast cancer cells. The expression of leptin receptor and the activation of signaling pathways were studied by Western immunoblotting. The interference of leptin with ICI 182,780-induced estrogen receptor α degradation was probed by Western immunoblotting, fluorescence microscopy, and pulse-chase experiments. Leptin effects on estrogen receptor α–dependent transcription in the presence and absence of ICI 182,780 were studied by luciferase reporter assays and chromatin immunoprecipitation. Results: MCF-7 cells were found to express the leptin receptor and respond to leptin with cell growth and activation the signal transducers and activators of transcription 3, extracellular signal-regulated kinase-1/2, and Akt/GSK3/pRb pathways. The exposure of cells to 10 nmol/L ICI 182,780 blocked cell proliferation, induced rapid estrogen receptor α degradation, inhibited nuclear estrogen receptor α expression, and reduced estrogen receptor α–dependent transcription from estrogen response element–containing promoters. All of these effects of ICI 182,780 were significantly attenuated by simultaneous treatment of cells with 100 ng/mL leptin. Conclusions: Leptin interferes with the effects of ICI 182,780 on estrogen receptor α in breast cancer cells. Thus, high leptin levels in obese breast cancer patients might contribute to the development of antiestrogen resistance.
Inhibition of Mammalian Target of Rapamycin Is Required for Optimal Antitumor Effect of HER2 Inhibitors against HER2-Overexpressing Cancer Cells
Authors: Todd W. Miller, James T. Forbes, Chirayu Shah, Shelby K. Wyatt, H. Charles Manning, Maria G. Olivares, Violeta Sanchez, Teresa C. Dugger, Nara de Matos Granja, Archana Narasanna, Rebecca S. Cook, J. Phillip Kennedy, Craig W. Lindsley, Carlos L. Arteaga
Journal: Clinical Cancer Research (2009)

Abstract Purpose: A significant fraction of HER2-overexpressing breast cancers exhibit resistance to the HER2 antibody trastuzumab. Hyperactivity of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway confers trastuzumab resistance, and mammalian target of rapamycin (mTOR) is a major downstream effector of PI3K/AKT. Therefore, we examined whether mTOR inhibitors synergize with trastuzumab. Experimental Design: Immunocompetent mice bearing HER2+ mammary tumors were treated with trastuzumab, the mTOR inhibitor rapamycin, or the combination. Mice were imaged for tumor cell death using an optical Annexin-V probe and with [18F]FDG positron emission tomography. The signaling and growth effects of the mTOR inhibitor RAD001 on HER2+ cells treated with trastuzumab or lapatinib were evaluated. Results: Treatment of mice with trastuzumab plus rapamycin was more effective than single-agent treatments, inducing complete regression of 26 of 26 tumors. The combination induced tumor cell death (Annexin-V binding) and inhibited FDG uptake. Rapamycin inhibited mTOR and tumor cell proliferation as determined by phosphorylated S6 and Ki-67 immunohistochemistry, respectively. In culture, the combination of RAD001 plus trastuzumab inhibited cell growth more effectively than either drug alone. Trastuzumab partially decreased PI3K but not mTOR activity. Knockdown of TSC2 resulted in HER2-independent activation of mTOR and dampened the response to trastuzumab and lapatinib. Treatment with the HER2 inhibitor lapatinib decreased phosphorylated S6 and growth in TSC2-expressing cells but not in TSC2-knockdown cells. Conclusions: Inhibition of PI3K and mTOR are required for the growth-inhibitory effect of HER2 antagonists. These findings collectively support the combined use of trastuzumab and mTOR inhibitors for the treatment of HER2+ breast cancer. (Clin Cancer Res 2009;15(23):7266–76)
Imaging of haemodialysis-associated amyloidosis with 123I-serum amyloid P component
Authors: S.R Nelson, P.N Hawkins, Suzanne Richardson, M.B Pepys, J.P Lavender, D Sethi, P.E Gower, C.W Pugh, C.G Winearls, D.O Oliver
Journal: The Lancet (1991)
Walking versus Cycling
Authors: Véronique Pepin, Didier Saey, Francçois Whittom, Pierre LeBlanc, Francçois Maltais
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

There is no consensus regarding which exercise test to use to evaluate the functional impact of bronchodilators in patients with chronic obstructive pulmonary disease.Bronchodilator-induced changes in endurance time were evaluated during cycling and walking in 17 patients with chronic obstructive pulmonary disease who completed two cycle endurance tests and two endurance shuttle walks at 80% of peak capacity. Each endurance test was preceded by the nebulization of a placebo or 500 microg of ipratropium bromide using a randomized, double-blind, crossover design. Quadriceps twitch force was measured with magnetic stimulation of the femoral nerve before and after each endurance test.Cycling endurance time did not improve significantly after bronchodilation despite a significant increase in FEV1 (delta endurance time ipratropium bromide - placebo: 51 +/- 255 s, p = 0.42). A similar change in FEV1 was associated with a significant improvement in walking endurance time (delta endurance time ipratropium bromide - placebo: 164 +/- 177 s, p < 0.01). A 22 +/- 17% fall in quadriceps twitch force was observed after cycling, whereas no significant change was seen after walking.The endurance shuttle walk is a sensitive test to detect changes in exercise tolerance after bronchodilation. Differences in the occurrence of quadriceps muscle fatigue may explain, in part, the different responsiveness to change between cycling and walking.
Reading the Chest Radiograph: A Physiologic Approach
Journal: Thorax (1993)

Book notices ally thousands of exercise tests on normal subjects and patients, especially humbling.The book also highlights how far respiratory physiologists are willing to risk their lives and personal comfort in the interest of science.In particular, a new species has been named-the CARP (completely apnoeic respiratory physiologist).The book needs a chapter that brings together all the ideas into a general overview.The symposium seems to have highlighted not only how far we have advanced in our understanding of breathlessness, but also how far we were away from the answer 25 years ago.This book is certainly not for the casual reader, and does not make easy bedtime reading.However, for anybody who is intending to work in respiratory failure, respiratory muscles, or measurement of sensations and functional capacity in breathless patients, it is essential reading and an excellent source of references.All in all, this book makes a fitting tribute to the illustrious career of Moran Campbell.
Horizontal Gene Transfer in the Molecular Evolution of Mannose PTS Transporters
Authors: Manuel Zuniga, Iñaqui Comas, Raquel Linaje, Vicente Monedero, María-Jesus Yebra, Carlos David Esteban, Josef J. Deutscher, Gaspar Perez-Martinez, Fernando Gonzáles-Candelas
Journal: Molecular Biology and Evolution (2005)

The phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) represents hitherto the only example of group translocation transport systems. PTS transporters are exclusively found in bacteria and can be grouped on the basis of sequence and structure into six classes. We have analyzed the evolution of mannose-class PTS transporters. These transporters have a limited distribution among bacteria being mostly harbored by species associated to animals. The results obtained indicate that these genes have undergone a complex evolutionary history, including extensive horizontal gene transfer events, duplications, and nonorthologous displacements. The phylogenetic analysis revealed an early diversification to specialize in different transport capabilities, but these events have also occurred relatively recently. In addition, these transporters can be further divided into seven groups and this division correlates with their transport capabilities. Finally, the consideration of the genomic context allowed us to propose putative functional roles for some uncharacterized PTS transporters. The functional role and distribution of mannose-class PTS transporters suggest that their expansion may have played a significant role in the establishment of symbiotic relationships between animals and some bacteria.
Mechanisms Underlying Selective Neuronal Tracking of Attended Speech at a “Cocktail Party”
Authors: Elana M. Zion Golumbic, Nai Ding, Stephan Bickel, Peter Lakatos, Catherine A. Schevon, Guy M. McKhann, Robert R. Goodman, Ronald Emerson, Ashesh D. Mehta, Jonathan Z. Simon, David Poeppel, Charles E. Schroeder
Journal: Neuron (2013)
Antiangiogenic and Proapoptotic Effects of Dietary Restriction on Experimental Mouse and Human Brain Tumors
Authors: Purna Mukherjee, Laura E. Abate, Thomas N. Seyfried
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The antiangiogenic and proapoptotic mechanisms of dietary caloric restriction (DR) are unknown. In this study, we evaluated the effects of moderate (40%) DR on the orthotopic growth of mouse and human brain tumors that differ in cell origin, angiogenicity, host environment, and biochemical composition. Experimental Design: A malignant mouse astrocytoma (CT-2A) and a human glioma (U87-MG) were highly angiogenic and fast growing, whereas a mouse ependymoblastoma was less vascularized and slower growing. The tumors were evaluated for growth, cell proliferation, microvessel density, and apoptosis under DR and ad libitum feeding. Serum vascular endothelial growth factor and insulin-like growth factor I levels were examined as angiogenic biomarkers. Results: DR significantly decreased vascularity (factor VIII) and increased apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling) in all tumors. These effects were associated with enhanced caspase-3 and poly(ADP-ribose) polymerase cleavage in the CT-2A and ependymoblastoma tumors, but not in the U87-MG tumor. DR also caused reductions of serum insulin-like growth factor I and glucose levels. Conclusions: DR had significant antiangiogenic and proapoptotic effects in the three distinct brain tumor models. DR, however, had differential effects on cell proliferation, biomarkers of angiogenesis, and apoptosis, suggesting multiple mechanisms of action. Because extensive angiogenesis and resistance to apoptosis are hallmarks of gliomas, this study provides new insight into the molecular basis of the DR-induced inhibition of brain tumor growth.
The incidence, predictors, and outcomes of early reinfarction after primary angioplasty for acute myocardial infarction
Authors: Steven J Kernis, Kishore J Harjai, Gregg W Stone, Lorelei L Grines, Judith A Boura, Michael W Yerkey, William O’Neill, Cindy L Grines
Journal: Journal of the American College of Cardiology (2003)
Perchlorate and the Thyroid Gland
Authors: J. Wolff
Journal: Pharmacological Reviews (1998)

Perchlorate competitively blocks iodide from entering the thyroid by an effect on the Na+/I- symporter thus preventing the further synthesis of thyroid hormone but has no effect on the iodination process itself. It is concentrated by thyroid tissue in a manner similar to iodide but is not significantly metabolized in the gland or peripherally. What is not settled is whether there are additional perchlorate effects on iodide transport. Perchlorate has a fast turnover in the body and requires frequent daily doses for therapy of thyrotoxicosis. Perchlorate appears to be substantially more effective against large iodide loads than the thionamides, and, with long-term iodide contamination, combined therapy of perchlorate (with < or = 1 g/day) and thionamides is recommended for the more severe cases of thyrotoxicosis that may result from excess iodide or iodide-generating organic compounds, as for example with amiodarone. After approximately 30 days, the perchlorate dosage can be tapered or stopped, continuing with thionamides alone. This markedly increases its safe use. Despite serious side effects during its early use, lower dosages and shorter treatment periods appear to have prevented such reactions in its recent reintroduction, mostly for amiodarone-induced thyroid dysfunction. Perchlorate can also protect against inhibition of thyroid function and the resulting hypothyroidism caused by excess iodide, presumably by reducing the formation of an iodinated inhibitor. The reduction of the iodide pool by perchlorate thus has dual effects--reduction of excess hormone synthesis and hyperthyroidism, on the one hand, and reduction of thyroid inhibitor synthesis and hypothyroidism on the other. Perchlorate remains very useful also as a single dose application in tests measuring the discharge of radioiodide accumulated in the thyroid as a result of many different disruptions in the further metabolism of iodide in the thyroid gland.
Sildenafil Has No Effect on Portal Pressure but Lowers Arterial Pressure in Patients With Compensated Cirrhosis
Authors: Puneeta Tandon, Irteza Inayat, Michael Tal, Marcelo Spector, Martha Shea, Roberto J. Groszmann, Guadalupe Garcia–Tsao
Journal: Clinical Gastroenterology and Hepatology (2010)
Surgery of the Colon and Rectum
Authors: R GRACE
Journal: Gut (1998)

Surgery of the Colon and Rectum. Nicholls J, Dozios R R, eds. (Pp 1300; £185.00.) Edinburgh: Churchill Livingstone, 1997. ISBN 0-443-05565-3.

This latest volume on colorectal disease represents an attempt to bridge the Atlantic gap by bringing together the expertise of authors from both sides of the water, emphasising this by appointing distinguished joint editors from the UK and the USA. The publishers thereby have attempted to widen their potential audience. The place of such a textbook needs to be …
Safety and Tumor Responses with Lambrolizumab (Anti–PD-1) in Melanoma
Authors: Omid Hamid, Caroline Robert, Adil Daud, F. Stephen Hodi, Wen-Jen Hwu, Richard Kefford, Jedd D. Wolchok, Peter Hersey, Richard W. Joseph, Jeffrey S. Weber, Roxana Dronca, Tara C. Gangadhar, Amita Patnaik, Hassane Zarour, Anthony M. Joshua, Kevin Gergich, Jeroen Elassaiss-Schaap, Alain Algazi, Christine Mateus, Peter Boasberg, Paul C. Tumeh, Bartosz Chmielowski, Scot W. Ebbinghaus, Xiaoyun Nicole Li, S. Peter Kang, Antoni Ribas
Journal: New England Journal of Medicine (2013)

The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. We tested the anti–PD-1 antibody lambrolizumab (previously known as MK-3475) in patients with advanced melanoma.
Bronchoscopy and bronchoalveolar lavage findings in cross-country skiers with and without "ski asthma"
Authors: M Sue-Chu, L Larsson, T Moen, SI Rennard, L Bjermer
Journal: European Respiratory Journal (1999)

Bronchial hyperresponsiveness to methacholine with asthma-like symptoms ("ski asthma") is frequent in elite cross-country skiers. To further the understanding of "ski asthma", 10 nonasthmatic, nonatopic controls and 30 adolescent elite skiers were investigated by bronchoscopy and bronchoalveolar lavage (BAL). Nine skiers were atopic without allergy symptoms. Compared with controls, the macroscopic inflammatory index in the proximal airways in skiers was three-fold greater (median (interquartile range) 3.0 (2.0-5.0) versus 1.0 (0.8-2.3), p=0.008). In the BAL fluid, skiers had significantly greater total cell (p<0.05) and percentage lymphocyte (p<0.01) and mast cell counts (p<0.05). Neutrophil and eosinophil counts were not significantly different and eosinophil cationic protein was not detected. Tumour necrosis factor-alpha and myeloperoxidase were detected in 12 (40%) and six (20%) skiers, respectively. In skiers with ski asthma, the inflammatory index was greater than in nonasthmatic skiers. Lymphocyte subtypes and activation markers, and concentration of albumin, fibronectin and hyaluronan were not different from those in controls. Cross-country skiers have a minor to moderate degree of macroscopic inflammation in the proximal airways at bronchoscopy and a bronchoalveolar lavage fluid profile which differs in several respects from healthy controls. Skiers with ski asthma tend to show even higher degrees of bronchial inflammation.