tbuckley/cabot-search huggingface dataset:
Endothelial NADPH oxidase 2: when does it matter in atherosclerosis?
Authors: J. Haendeler, A. Eckers, M. Lukosz, K. Unfried, J. Altschmied
Journal: Cardiovascular Research (2012)

This editorial refers to 'Endothelial-specific Nox2 overexpression increases vascular superoxide and macrophage recruitment in ApoE 2/2 mice' by G. Douglas et al., pp.20-29, this issue.Reactive oxygen species (ROS) act as a double-edged sword in numerous cardiovascular conditions.In addition to their known detrimental effects on all cellular macromolecules, referred to as oxidative stress, lower amounts of ROS also directly modify molecules and thereby modulate their functions -this process has been termed redox signalling.Both oxidative stress and redox signalling have been implicated in the process of atherosclerosis.The sources of cellular ROS include mitochondria, NADPH oxidases (Noxs), dysfunctional nitric oxide synthases, xanthine oxidase, and other oxygenases.Among these, the Noxs are unique, since their primary function is to produce ROS. 1 The Nox family comprises seven members, Nox1-5 and DUOX1-2, each based on a distinct core catalytic subunit. 1,2Nox1, 2, 4, and 5 are expressed in cardiovascular cells, although Nox5 is only found in humans and not in rodents. 3An involvement of Nox2 in atherosclerosis has been suspected.It was the first NADPH oxidase to be identified and is responsible for the phagocytic oxidative burst of neutrophils.It has subsequently been found to be expressed at lower levels in endothelial cells, cardiomyocytes, fibroblasts, vascular smooth muscle cells, monocytes, and macrophages, the latter two being central players in atherogenesis. 4 However, findings in mice with global Nox2 deficiency on an atherosclerosisprone ApoE 2/2 genetic background and fed a high-fat diet are contradictory.Kirk et al. 5 found no protection against atherosclerosis when examining aortic sinus sections, whereas Judkins et al. 6 demonstrated a 50% reduction in lesion area in the region between the aortic arch and iliac bifurcation.However, using global Nox2 deficiency, it is impossible to identify the cell types relevant for atherosclerosis.Thus, it is important to investigate the role of Nox2 in a cell-specific manner.Douglas et al. describe ApoE 2/2 mice with endothelial-targeted overexpression of human Nox2 (Nox2-Tg ApoE 2/2 ). 7The key findings of this study are that increased endothelial ROS production leads
Comparative studies of serum and synovial fluid C reactive protein concentrations.
Authors: I F Rowe, J Sheldon, P G Riches, A C Keat
Journal: Annals of the Rheumatic Diseases (1987)

The relation between serum and synovial fluid (SF) C reactive protein (CRP) concentrations was investigated in a variety of arthritides, including rheumatoid arthritis (RA), psoriatic arthritis, reactive arthritis, and osteoarthritis. SF CRP levels were significantly reduced compared with serum levels in the inflammatory arthritides, but there was good correlation between serum and SF values. SF CRP values were all at the lower limit of the detectable range in osteoarthritis. In patients with RA or psoriatic arthritis followed up serially through an exacerbation of arthritis, changes in SF CRP reflected closely changes in serum CRP. In patients with RA SF/serum ratios of proteins of different molecular weight were used to derive a regression equation between SF/serum ratio and molecular mass. SF/serum values for CRP were significantly less than predicted from its molecular weight, suggesting that CRP is either being selectively bound in synovium or specifically consumed in SF and may be playing an important part in the inflammatory process in RA.
Occlusion of Seminal Vesicles Increases Sexual Activity in a Mouse Model
Authors: Frédéric D. Birkhäuser, Celine Schumacher, Roland Seiler, Louis de Meuron, Pascal Zehnder, Beat Roth, Antoinette Wetterwald, George N. Thalmann, Marco G. Cecchini, Urs E. Studer
Journal: European Urology (2012)
Effect of Increased Dialysate Volume on Peritoneal Surface Area among Peritoneal Dialysis Patients
Authors: Avry Chagnac, Pearl Herskovitz, Yaacov Ori, Tali Weinstein, Judith Hirsh, Miriam Katz, Uzi Gafter
Journal: Journal of the American Society of Nephrology (2002)

Large dialysate volumes are often required to increase solute clearance for peritoneal dialysis patients. The resulting increase in solute clearance might be attributable to an increased plasma-to-dialysate concentration gradient and/or to an increased effective peritoneal surface area. One of the factors affecting the latter is the peritoneal surface area in contact with dialysate (PSA-CD). The aim of this study was to estimate the change in PSA-CD after a 50% increase in the instilled dialysate volume for patients undergoing peritoneal dialysis. PSA-CD was estimated by using a method applying stereologic techniques to computed tomographic (CT) scans of the peritoneal space. The peritoneal cavity of 10 peritoneal dialysis patients was filled with a solution containing dialysate, half-isotonic saline solution, and contrast medium. Peritoneal function tests and CT scanning of the abdomen were performed twice for each patient (with an interval of 1 wk), after instillation of a 2- or 3-L solution. Scanning of thin helical CT sections was performed, and 36 random sections of the abdomen were obtained after reconstruction. A grid was superimposed on the sections. The surface area was estimated by using stereologic methods. After instillation of the 2-L solution, the volume of the peritoneal solution at the time of CT scanning was 2.32 +/- 0.05 L. The PSA-CD was 0.57 +/- 0.03 m(2), ranging from 0.41 to 0.76 m(2). The use of the 3-L solution increased the peritoneal volume by 46 +/- 2%. PSA-CD increased by 18 +/- 2.3% to 0.67 +/- 0.04 m(2) (range, 0.49 to 0.84 m(2); P < 0.01). Creatinine mass transfer increased from 112 +/- 10 mg to 142 +/- 11 mg (P < 0.0001). The slope of the change of the plasma-to-dialysate creatinine concentration gradient with time decreased from -2.26 +/- 0.23 x 10(-2) to -1.97 +/- 0.16 x 10(-2) (P = 0.01). K(BD-0) (permeability-surface area product or mass area transfer coefficient at time 0 of the dwell) increased from 10.6 +/- 0.7 to 13.6 +/- 1.2 ml/min (P < 0.02). These data demonstrate that increasing the instilled dialysate volume by 50% for peritoneal dialysis patients results in significant increases in the PSA-CD and K(BD).
Spinal Cord Stimulation and Pain Relief in Painful Diabetic Peripheral Neuropathy: A Prospective Two-Center Randomized Controlled Trial
Authors: Rachel Slangen, Nicolaas C. Schaper, Catharina G. Faber, Elbert A. Joosten, Carmen D. Dirksen, Robert T. van Dongen, Alfons G. Kessels, Maarten van Kleef
Journal: Diabetes Care (2014)

OBJECTIVE Painful diabetic peripheral neuropathy (PDPN) is a common complication of diabetes mellitus. Unfortunately, pharmacological treatment is often partially effective or accompanied by unacceptable side effects, and new treatments are urgently needed. Small observational studies suggested that spinal cord stimulation (SCS) may have positive effects. RESEARCH DESIGN AND METHODS We performed a multicenter randomized clinical trial in 36 PDPN patients with severe lower limb pain not responding to conventional therapy. Twenty-two patients were randomly assigned to SCS in combination with the best medical treatment (BMT) (SCS group) and 14 to BMT only (BMT group). The SCS system was implanted only if trial stimulation was successful. Treatment success was defined as ≥50% pain relief during daytime or nighttime or “(very) much improved” for pain and sleep on the patient global impression of change (PGIC) scale at 6 months. RESULTS Trial stimulation was successful in 77% of the SCS patients. Treatment success was observed in 59% of the SCS and in 7% of the BMT patients (P &amp;lt; 0.01). Pain relief during daytime and during nighttime was reported by 41 and 36% in the SCS group and 0 and 7% in the BMT group, respectively (P &amp;lt; 0.05). Pain and sleep were “(very) much improved” in 55 and 36% in the SCS group, whereas no changes were seen in the BMT group, respectively (P &amp;lt; 0.001 and P &amp;lt; 0.05). One SCS patient died because of a subdural hematoma. CONCLUSIONS Treatment success was shown in 59% of patients with PDPN who were treated with SCS over a 6-month period, although this treatment is not without risks.
Effect of dietary fat on sympathetic nervous system activity in the rat.
Authors: J H Schwartz, J B Young, L Landsberg
Journal: Journal of Clinical Investigation (1983)

Previous studies from our laboratory have demonstrated that dietary intake affects the sympathetic nervous system (SNS); carbohydrate intake, in particular, has been shown to stimulate sympathetic activity. The present studies were undertaken to characterize the effect of dietary fat on SNS activity in the rat. Sympathetic activity was assessed by measurement of norepinephrine (NE) turnover in heart, interscapular brown adipose tissue (IBAT), and pancreas and by excretion of NE in the urine. When fed a fat-enriched diet (50% chow, 50% lard), fractional NE turnover in heart (k) increased from 6.3 +/- 0.6% h in ad lib. fed controls to 14.7 +/- 1.3% h in the high-fat group (P less than 0.001); calculated NE turnover rate increased from 24.5 +/- 2.4 ng/heart per h to 36.8 +/- 3.5 (P less than 0.05). Urinary NE excretion more than doubled after 6 d of the same high fat diet (P less than 0.001). Ganglionic blockade produced a greater effect on NE turnover in fat-fed, as compared with chow-fed animals, consistent with increased sympathetic activity in the fat-fed group. When fat absorption was blocked with a bile acid binding resin (cholestyramine), the same high-fat diet did not increase cardiac NE turnover, indicating that fat absorption is required for the stimulatory effect on sympathetic activity. In another series of experiments, in which chow (and hence protein) intake was held constant, the effect of fat and isocaloric sucrose supplements on NE turnover was assessed in heart, IBAT, and pancreas. The caloric value of the supplements was 50, 100, and 335% of the chow in the different experiments. An effect of fat on NE turnover in heart and IBAT was demonstrable at the lowest level of fat supplement. Fat increased pancreatic NE turnover when added in amounts sufficient to double the caloric intake. The stimulatory effect of sucrose and fat on NE turnover in heart and IBAT was similar. These experiments demonstrate that fat increases SNS activity in the rat and that the magnitude of the effect is similar to that of sucrose. The results imply that fat may contribute to dietary thermogenesis in this species.
Emergence and Evolution of Modern Molecular Functions Inferred from Phylogenomic Analysis of Ontological Data
Authors: K. M. Kim, G. Caetano-Anolles
Journal: Molecular Biology and Evolution (2010)

The biological processes that characterize the phenotypes of a living system are embodied in the function of molecules and hold the key to evolutionary history, delimiting natural selection and change. These processes and functions provide direct insight into the emergence, development, and organization of cellular life. However, detailed molecular functions make up a network-like hierarchy of relationships that tells little of evolutionary links between structure and function in biology. For example, Gene Ontology terms represent widely-used vocabularies of processes and functions with evolutionary relationships that are implicit but not defined. Here, we uncover patterns of global evolutionary history in ontological terms associated with the sequence of 38 genomes. These patterns unfold the metabolic origins of modern molecular functions and major biological transitions in evolution toward complex life. Phylogenies reveal the primordial appearance of hydrolases and transferases, with ATPase, GTPase, and helicase activities being the most ancient. This indicates that ancient catalysts were crucial for binding and transport, the emergence of nucleic acids and protein biopolymers, and the communication of primordial cells with the environment. Finally, the history of biological processes showed that cellular biopolymer metabolic processes preceded biopolymer biosynthesis and essential processes related to macromolecular formation, directly challenging the existence of an RNA world. Phylogenomic systematization of biological function takes the structure and function paradigm to a completely new level of abstraction, demonstrating a "metabolic first" origin of life. The approach uncovers patterns in the morphing of function that are unprecedented and necessary for systematic views in biology.
Fully Biodegradable Airway Stents Using Amino Alcohol‐Based Poly(ester amide) Elastomers
Authors: Jane Wang, Kyle G. Boutin, Omar Abdulhadi, Lyndia D. Personnat, Tarek Shazly, Robert Langer, Colleen L. Channick, Jeffrey T. Borenstein
Journal: Advanced Healthcare Materials (2013)

Abstract Airway stents are often used to maintain patency of the tracheal and bronchial passages in patients suffering from central airway obstruction caused by malignant tumors, scarring, and injury. Like most conventional medical implants, they are designed to perform their functions for a limited period of time, after which surgical removal is often required. Two primary types of airway stents are in general use, metal mesh devices and elastomeric tubes; both are constructed using permanent materials, and must be removed when no longer needed, leading to potential complications. This paper describes the development of process technologies for bioresorbable prototype elastomeric airway stents that would dissolve completely after a predetermined period of time or by an enzymatic triggering mechanism. These airway stents are constructed from biodegradable elastomers with high mechanical strength, flexibility and optical transparency. This work combines microfabrication technology with bioresorbable polymers, with the ultimate goal of a fully biodegradable airway stent ultimately capable of improving patient safety and treatment outcomes.
A new computerized methodology to analyse tumour site in relation to phenotypic traits and epidemiological characteristics of cutaneous malignant melanoma
Authors: P. Gillgren, G. Brattstrom, E. Djureen Martensson, J. Frisell, J. Palmgren, U. Ringborg, J. Hansson
Journal: British Journal of Dermatology (2002)

Summary Background While sunlight is important in the aetiology of cutaneous malignant melanoma (CMM), the relationship between skin areas receiving intermittent or chronic sun exposure and the development of CMM has not been fully explored. There is a requirement for an improved method for more detailed site mapping and for analysis of tumour density in different areas of the skin in relation to the type of sun exposure, phenotypic traits and prognosis of patients with CMM. Objectives To describe and demonstrate the use of EssDoll©, a new computerized method to map and analyse tumour sites. Methods We have used the new software to analyse data on 2517 patients with 2608 primary CMMs. Results The results obtained were consistent with previous data on the distribution of CMM in men and women. The distribution of CMM on the back was uneven, with the density on the upper back being twice that on the lower back. Conclusions The new methodology allows a more accurate mapping and analysis of skin tumour site, including determination of tumour density. This improves the possibility of analysing tumour site in relation to aetiological, phenotypic and prognostic parameters.
Oxygen delivery to tissues
Authors: RW Samsel, PT Schumacker
Journal: European Respiratory Journal (1991)

For health, well perfused tissues, oxygen uptake is determined primarily by metabolic need rather than by oxygen supply. Tissue hypoxia supervenes when tissue oxygen tension (PO2) falls below a critical point, and the point where this occurs can be predicted from the systemic oxygen delivery or extraction ratio. A growing body of evidence suggest that tissue oxygen extraction may be impaired in adult respiratory distress syndrome (ARDS) and sepsis. In these syndromes the minimum oxygen delivery needed to maintain a normal oxygen uptake appears to be increased, as tissues become hypoxic despite high levels of delivery. However, controversy surrounds every phase of this observation, from its experimental basis, to potential causes, to its implications for patient care. In this review, we discuss the physiology of oxygen transport, the determinants of tissue oxygenation in normal and pathological states, and the therapeutic implications of oxygen transport.
High-Throughput Analysis of Genome-Wide Receptor Tyrosine Kinase Expression in Human Cancers Identifies Potential Novel Drug Targets
Authors: Carsten Müller-Tidow, Joachim Schwäble, Björn Steffen, Nicola Tidow, Burkhardt Brandt, Kerstin Becker, Eric Schulze-Bahr, Hartmut Halfter, Ulf Vogt, Ralf Metzger, Paul M. Schneider, Thomas Büchner, Christian Brandts, Wolfgang E. Berdel, Hubert Serve
Journal: Clinical Cancer Research (2004)

Abstract Novel high-throughput analyses in molecular biology allow sensitive and rapid identification of disease-related genes and drug targets. We have used quantitative real-time reverse transcription-PCR reactions (n = 23,000) to analyze expression of all human receptor tyrosine kinases (n = 56) in malignant tumors (n = 313) of different origins and normal control samples (n = 58). The different tumor types expressed very different numbers of receptor tyrosine kinases: whereas brain tumors and testicular cancer expressed 50 receptor tyrosine kinases, acute myeloid leukemia (AML) samples expressed only 20 different ones. Specimens of similar tumor origin exhibited characteristic receptor tyrosine kinase expression patterns and were grouped together in hierarchical cluster analyses. When we focused on specific tumor entities, receptor tyrosine kinases were identified that were disease and/or stage specific. Leukemic blasts from AML bone marrow samples differed significantly in receptor tyrosine kinase expression compared with normal bone marrow and purified CD34+ cells. Among the differentially expressed receptor tyrosine kinases, we found FLT3, c-kit, CSF1 receptor, EPHB6, leukocyte tyrosine kinase, and ptk7 to be highly overexpressed in AML samples. Whereas expression changes of some of these were associated with altered differentiation patterns (e.g., CSF1 receptor), others, such as FLT3, were genuinely overexpressed in leukemic blasts. These data and the associated database (http://medweb.uni-muenster.de/institute/meda/research/) provide a comprehensive view of receptor tyrosine kinase expression in human cancer. This information can assist in the definition of novel drug targets.
Toward a Defined Anti-<i>Leishmania</i> Vaccine Targeting Vector Antigens
Authors: Jesus G. Valenzuela, Yasmine Belkaid, Mark K. Garfield, Susana Mendez, Shaden Kamhawi, Edgar D. Rowton, David L. Sacks, José M.C. Ribeiro
Journal: The Journal of Experimental Medicine (2001)

Leishmania parasites are transmitted to their vertebrate hosts by infected phlebotomine sand fly bites. Sand fly saliva is known to enhance Leishmania infection, while immunity to the saliva protects against infection as determined by coinoculation of parasites with vector salivary gland homogenates (SGHs) or by infected sand fly bites (Kamhawi, S., Y. Belkaid, G. Modi, E. Rowton, and D. Sacks. 2000. Science. 290:1351–1354). We have now characterized nine salivary proteins of Phlebotomus papatasi, the vector of Leishmania major. One of these salivary proteins, extracted from SDS gels and having an apparent mol wt of 15 kD, was able to protect vaccinated mice challenged with parasites plus SGH. A DNA vaccine containing the cDNA for the predominant 15-kD protein (named SP15) provided this same protection. Protection lasted at least 3 mo after immunization. The vaccine produced both intense humoral and delayed-type hypersensitivity (DTH) reactions. B cell–deficient mice immunized with the SP15 plasmid vaccine successfully controlled Leishmania infection when injected with Leishmania plus SGH. These results indicate that DTH response against saliva provides most or all of the protective effects of this vaccine and that salivary gland proteins or their cDNAs are viable vaccine targets against leishmaniasis.
Benefit of adjuvant trastuzumab-based chemotherapy in T1ab node-negative HER2-overexpressing breast carcinomas: a multicenter retrospective series
Authors: M.J. Rodrigues, J. Peron, J.-S. Frénel, Y.-A. Vano, J. Wassermann, M. Debled, F. Picaud, L. Albiges, A. Vincent-Salomon, P.H. Cottu
Journal: Annals of Oncology (2012)
ACC/AHA/ASNC Guidelines for the Clinical Use of Cardiac Radionuclide Imaging—Executive Summary
Authors: Francis J Klocke, Michael G Baird, Beverly H Lorell, Timothy M Bateman, Joseph V Messer, Daniel S Berman, Patrick T O’Gara, Blase A Carabello, Richard O Russell, Manuel D Cerqueira, Martin G St. John Sutton, Anthony N DeMaria, James E Udelson, J.Ward Kennedy, Mario S Verani, Kim Allan Williams, Elliott M Antman, Sidney C Smith, Joseph S Alpert, Gabriel Gregoratos, Jeffrey L Anderson, Loren F Hiratzka, David P Faxon, Sharon Ann Hunt, Valentin Fuster, Alice K Jacobs, Raymond J Gibbons, Richard O Russell
Journal: Journal of the American College of Cardiology (2003)
<i>Drosophila split ends</i> Homologue <i>SHARP</i> Functions as a Positive Regulator of Wnt/β-Catenin/T-Cell Factor Signaling in Neoplastic Transformation
Authors: Ying Feng, Guido T. Bommer, Yali Zhai, Aytekin Akyol, Takao Hinoi, Ira Winer, Hua V. Lin, Ken M. Cadigan, Kathleen R. Cho, Eric R. Fearon
Journal: Cancer Research (2007)

Abstract Wnt ligands have pleiotropic and context-specific roles in embryogenesis and adult tissues. Among other effects, certain Wnts stabilize the β-catenin protein, leading to the ability of β-catenin to activate T-cell factor (TCF)-mediated transcription. Mutations resulting in constitutive β-catenin stabilization underlie development of several human cancers. Genetic studies in Drosophila highlighted the split ends (spen) gene as a positive regulator of Wnt-dependent signaling. We have assessed the role of SHARP, a human homologue of spen, in Wnt/β-catenin/TCF function in mammalian cells. We found that SHARP gene and protein expression is elevated in human colon and ovarian endometrioid adenocarcinomas and mouse colon adenomas and carcinomas carrying gene defects leading to β-catenin dysregulation. When ectopically expressed, the silencing mediator for retinoid and thyroid receptors/histone deacetylase 1-associated repressor protein (SHARP) protein potently enhanced β-catenin/TCF transcription of a model reporter gene and cellular target genes. Inhibition of endogenous SHARP function via RNA inhibitory (RNAi) approaches antagonized β-catenin/TCF-mediated activation of target genes. The effect of SHARP on β-catenin/TCF-regulated genes was mediated via a functional interaction between SHARP and TCF. β-Catenin–dependent neoplastic transformation of RK3E cells was enhanced by ectopic expression of SHARP, and RNAi-mediated inhibition of endogenous SHARP in colon cancer cells inhibited their transformed growth. In toto, our findings implicate SHARP as an important positive regulator of Wnt signaling in cancers with β-catenin dysregulation. [Cancer Res 2007;67(2):482–91]