tbuckley/cabot-search huggingface dataset:
Multicomponent domino reactions for the synthesis of biologically active natural products and drugs
Authors: Lutz F. Tietze, Andrea Modi
Journal: Medicinal Research Reviews (2000)

A main issue in modern synthetic organic chemistry, which deals with the preparation of natural products, pharmaceuticals, diagnostics, agrochemicals, and other important materials, is the improvement of efficiency, the avoidance of toxic reagents, the reduction of waste, and the responsible treatment of our resources. One of the ways to fulfill these goals is the development and use of domino processes, which consist of several bond-forming reactions and which allow the highly efficient synthesis of complex molecules starting from simple substrates. Herein, the combination of several catalytic bond-forming transformations is clearly most appropriate. The synthesis of the enantiopure alkaloid (−)-hirsutine 22, which has a strong inhibitorial effect on influenza A viruses, was accomplished using a biomimetic domino Knoevenagel-hetero-Diels Alder-solvolysis-hydrogenation process. In a similar way the alkaloids (+)-dihydrocorynantheine 23 and (−)-dihydroantirhine 24 as well as heterosteroids 62, D-homosteroids 65 and 68, and azasteroids 25 are prepared. In addition, novel steroid alkaloids 26 are accessible by a combination of the formation of an iminium salt, a hydride shift, and an alkylation. The anti-leukemic pentacyclic (−)-cephalotaxine 27 is obtained by a combination of two Pd-catalyzed reactions. © 2000 John Wiley & Sons, Inc. Med Res Rev, 20, No. 4, 304–322, 2000
BMI is not the driving factor in position dependent upper airway collapsibility in healthy subjects
Authors: Cedric Van Holsbeke, Wim Vos, Samir Vinchurkar, Jan De Backer, Oswald Peters, Nasser Nadjmi, Wilfried De Backer
Journal: European Respiratory Journal (2012)

Introduction 

In obstructive sleep apnea (OSA) patients, the minimal cross sectional area (CSA) of their upper airway (UA) correlates well with the severity of their pathology. However, since there is a correlation between body mass index (BMI) and severity of OSA in a population of OSA patients, it is not known if the minimal CSA is defined by the natural collapsibility of the UA or by the mass of the surrounding tissue. The objective of this study is to evaluate the influence of BMI on the position dependent changes in UA geometry assessed by CT imaging.

Materials and Methods 

A total of 20 normal subjects where 7 had a BMI 30 were included. 15 valid CBCT scans could be analyzed as the rotating gantry of the CBCT touched the shoulders of some subjects with a BMI>30, causing motion artifacts. The supine UA CT scans were performed using the GE VCT LightSpeed scanner and the upright CBCT scans were performed using the ISI i-CAT scanner.

Results 

BMI was not a predictor for difference between the minimal CSA in a supine and upright posture (R = 0.05, p = 0.86) as seen in the figure.

![Figure][1] 



Conclusions 

It can be concluded that in a healthy population, the BMI has no influence on the position dependent collapsibility of the airway. This means that collapse of the UA in healthy subjects is mostly defined by the natural collapsibility of the subject's airway.

 [1]: pending:yes
Evaluation of Polycyclic Aromatic Hydrocarbons Using Analytical Methods, Toxicology, and Risk Assessment Research: Seafood Safety after a Petroleum Spill as an Example
Authors: Jeffrey Wickliffe, Edward Overton, Scott Frickel, Jessi Howard, Mark Wilson, Bridget Simon, Stephen Echsner, Daniel Nguyen, David Gauthe, Diane Blake, Charles Miller, Cornelis Elferink, Shakeel Ansari, Harshica Fernando, Edward Trapido, Andrew Kane
Journal: Environmental Health Perspectives (2013)

Polycyclic aromatic hydrocarbons (PAHs) are abundant and widespread environmental chemicals. They are produced naturally and through man-made processes, and they are common in organic media, including petroleum. Several PAHs are toxic, and a subset exhibit carcinogenic activity. PAHs represent a range of chemical structures based on two or more benzene rings and, depending on their source, can exhibit a variety of side modifications resulting from oxygenation, nitrogenation, and alkylation.Here we discuss the increasing ability of contemporary analytical methods to distinguish not only different chemical structures among PAHs but also their concentrations in environmental media. Using seafood contamination following the Deepwater Horizon accident as an example, we identify issues that are emerging in the PAH risk assessment process because of increasing analytical sensitivity for individual PAHs, and we describe the paucity of toxicological literature for many of these compounds.PAHs, including the large variety of chemically modified or substituted PAHs, are naturally occurring and may constitute health risks if human populations are exposed to hazardous levels. However, toxicity evaluations have not kept pace with modern analytic methods and their increased ability to detect substituted PAHs. Therefore, although it is possible to measure these compounds in seafood and other media, we do not have sufficient information on the potential toxicity of these compounds to incorporate them into human health risk assessments and characterizations.Future research efforts should strategically attempt to fill this toxicological knowledge gap so human health risk assessments of PAHs in environmental media or food can be better determined. This is especially important in the aftermath of petroleum spills.
Development of Health-Related Quality of Life Questionnaires for Children, Adolescents and Adults with Food Allergy: The Item Reduction.
Authors: B.M.J. de Blok, A. DunnGalvin, J.N.G. Oude Elberink, B.J. Vlieg-Boerstra, E.J. Duiverman, J.B. Hourihane, A.E.J. Dubois
Journal: Journal of Allergy and Clinical Immunology (2007)
Randomized Trial of Genotype-Guided Versus Standard Warfarin Dosing in Patients Initiating Oral Anticoagulation
Authors: Jeffrey L. Anderson, Benjamin D. Horne, Scott M. Stevens, Amanda S. Grove, Stephanie Barton, Zachery P. Nicholas, Samera F.S. Kahn, Heidi T. May, Kent M. Samuelson, Joseph B. Muhlestein, John F. Carlquist
Journal: Circulation (2007)

Background— Pharmacogenetic-guided dosing of warfarin is a promising application of “personalized medicine” but has not been adequately tested in randomized trials. Methods and Results— Consenting patients (n=206) being initiated on warfarin were randomized to pharmacogenetic-guided or standard dosing. Buccal swab DNA was genotyped for CYP2C9 *2 and CYP2C9 * 3 and VKORC1 C1173T with a rapid assay. Standard dosing followed an empirical protocol, whereas pharmacogenetic-guided dosing followed a regression equation including the 3 genetic variants and age, sex, and weight. Prothrombin time international normalized ratio (INR) was measured routinely on days 0, 3, 5, 8, 21, 60, and 90. A research pharmacist unblinded to treatment strategy managed dose adjustments. Patients were followed up for up to 3 months. Pharmacogenetic-guided predicted doses more accurately approximated stable doses ( P &lt;0.001), resulting in smaller ( P =0.002) and fewer ( P =0.03) dosing changes and INRs ( P =0.06). However, percent out-of-range INRs (pharmacogenetic=30.7%, standard=33.1%), the primary end point, did not differ significantly between arms. Despite this, when restricted to wild-type patients (who required larger doses; P =0.001) and multiple variant carriers (who required smaller doses; P &lt;0.001) in exploratory analyses, results (pharmacogenetic=29%, standard=39%) achieved nominal significance ( P =0.03). Multiple variant allele carriers were at increased risk of an INR of ≥4 ( P =0.03). Conclusions— An algorithm guided by pharmacogenetic and clinical factors improved the accuracy and efficiency of warfarin dose initiation. Despite this, the primary end point of a reduction in out-of-range INRs was not achieved. In subset analyses, pharmacogenetic guidance showed promise for wild-type and multiple variant genotypes.
Injury surveillance during a 2-day national female youth football tournament in Kenya
Authors: Marianne Lislevand, Thor Einar Andersen, Astrid Junge, Jiri Dvorak, Kathrin Steffen
Journal: British Journal of Sports Medicine (2013)

Objective To analyse the incidence, characteristics and circumstances of injuries during a female youth amateur football tournament in Kenya. Design 14 injury recorders prospectively registered and classified all injuries during all matches. Four physiotherapists and two doctors supported the injury recorders. Setting A 2-day Mathare Youth Sports Association (MYSA) inter-provincial football tournament for female players in Nairobi, Kenya. The tournament is organised by a non-governmental organisation (NGO). Participants 938 females divided into three age groups (under 13 years (U13), under 16 years (U16) and over 16 years (O16)). Main outcome measurements Overall injury incidence. Results 123 injuries occurred in 106 matches. The incidence of all injuries was 93.3 injuries/1000 h. Players in the U13 (relative risk (RR)=2.16, 95% CI 1.3 to 3.5; p=0.002) and U16 (RR=2.17, 95% CI 1.3 to 3.5; p=0.002) age groups had an increased risk of injury compared to the O16 group. Most injuries allowed the players to continue to play (n=98 of 121; 81%). For 15 (12%) of the injuries the player did not continue to play but was expected to fully participate in the following match, and eight of the injuries (6.1 injuries/1000 h) were expected to result in the player's absence from play for 1–7 days. The injuries most commonly affected the lower limb (n=100; 82%); contusions to the ankle (n=15; 12%) and foot/toe (n=15; 12%) were the most common specific injury types. Most acute injuries (89 of 113, 79%) were caused by player contact. Conclusions The incidence of injuries among female youth football players in a national tournament in Kenya was high, but time-loss injuries were rare. Playing football in a tournament organised by an NGO at the inter-provincial level was safe.
Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls
Authors: Srdan Verstovsek, Hagop M. Kantarjian, Zeev Estrov, Jorge E. Cortes, Deborah A. Thomas, Tapan Kadia, Sherry Pierce, Elias Jabbour, Gautham Borthakur, Elisa Rumi, Ester Pungolino, Enrica Morra, Domenica Caramazza, Mario Cazzola, Francesco Passamonti
Journal: Blood (2012)
Mechanism of Salt-Sensitive Hypertension
Authors: Toshiro Fujita
Journal: Journal of the American Society of Nephrology (2014)

A central role for the kidney among the systems contributing to BP regulation and the development of hypertension has been proposed. Both the aldosterone/mineralocorticoid receptor pathway and the renal sympathetic nervous system have important roles in the regulation of renal excretory function and BP control, but the mechanisms underlying these processes have remained unclear. However, recent studies revealed the activation of two pathways in salt-sensitive hypertension. Notably, Rac1, a member of the Rho-family of small GTP binding proteins, was identified as a novel ligand-independent modulator of mineralocorticoid receptor activity. Furthermore, these studies point to crucial roles for the Rac1–mineralocorticoid receptor–NCC/ENaC and the renal β-adrenergic stimulant–glucocorticoid receptor–WNK4-NCC pathways in certain rodent models of salt-sensitive hypertension. The nuclear mineralocorticoid and glucocorticoid receptors may contribute to impaired renal excretory function and the resulting salt-sensitive hypertension by increasing sodium reabsorption at different tubular segments. This review provides an in-depth discussion of the evidence supporting these conclusions and considers the significance with regard to treating salt-sensitive hypertension and salt-induced cardiorenal injury.
Functional heterogeneity of L3T4+ T cells in MRL-lpr/lpr mice. L3T4+ T cells suppress major histocompatibility complex-self-restricted L3T4+ T helper cell function in association with autoimmunity.
Authors: C S Via, G M Shearer
Journal: The Journal of Experimental Medicine (1988)

The present study demonstrates in MRl-lpr/lpr autoimmune mice an age-dependent loss of MHC-self-restricted function by L3T4+ Th. This defect is not present in age-matched, congenic MRL-+/+ spleen cells and appears to be due to the presence of suppressor cells that are selective for L3T4+ Th and not for Lyt-2+ Th. Surprisingly, the suppressor cells are also L3T4+ T cells and can suppress the IL-2 production of congenic MRL/+ L3T4+ Th to MHC-self-restricted antigens. These data support the idea of functional specialization within the L3T4+ population of T cells. Because L3T4+ suppressor cells are detected late in the course of autoimmunity, we interpret their presence not as a primary initiating event in the development of autoimmunity, but rather as a compensatory mechanism. Additionally, similar suppression of L3T4+ Th function has also been reported in a murine graft-vs.-host model of autoimmunity, suggesting that the suppressor cells represent an immunoregulatory mechanism that is a common feature of autoimmunity. Since excessive class II-restricted Th activity for B cells has been reported for both models of autoimmunity, L3T4+ suppressor cells may represent an attempt to down regulate such excessive Th activity. These findings may be relevant to human autoimmune diseases, such as systemic lupus erythematosus, in which B cell hyperactivity is also associated with reduced IL-2 production by Th.
Increased Risk of Allergy Associated with the Use of Kerosene Fuel in the Home
Authors: ANDREA J. VENN, HAILE YEMANEBERHAN, ZEGEYE BEKELE, SARAH A. LEWIS, ELDRYD PARRY, JOHN BRITTON
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Allergic diseases are becoming increasingly prevalent in developing countries, consistent with an environmental etiology associated with affluence or urbanization. We have tested the hypothesis that the risk of allergy is increased by the use of non-biomass fuels (kerosene, gas or electricity) in the home, using data from a survey of the urban population of Jimma, Ethiopia. Questionnaire data on allergic symptoms, domestic fuel use and lifestyle factors were collected from 9844 adults and children, and allergen skin sensitization measured in a subsample of 2372. Use of any non-biomass fuel was reported by 959 individuals (10%), usually in combination with biomass fuel, and was significantly associated with an increased risk of allergic sensitization (age, sex and socio-economic status adjusted odds ratio (95% confidence interval) = 1.78 [1.06 to 2.97]) and wheeze (1.56 [1.07 to 2.26]), rhinitis (2.06 [1.46 to 2.91]) and eczema (2.82 [1.61 to 4.96]) relative to use of biomass fuel only. These effects were predominantly due to kerosene, which was significantly related to all outcomes, and gas, which was strongly related to allergic sensitization. Our findings suggest that domestic combustion of refined fossil fuels increases the risk of allergic sensitization and symptoms, and may have contributed to the increasing prevalence of allergic disease.
Are inflammatory cells increased in painful human tendinopathy? A systematic review
Authors: Benjamin John Floyd Dean, Peter Gettings, Stephanie Georgina Dakin, Andrew Jonathan Carr
Journal: British Journal of Sports Medicine (2015)

Background The role of inflammation in tendinopathy has historically been a subject of significant controversy. Our primary aim was to determine whether inflammatory cell numbers were increased in painful human tendinopathy versus healthy control tendons. Our secondary aim was to assess whether the inflammatory cells had been linked with symptoms or disease stage. Methods We conducted a systematic review of the scientific literature using the PRISMA and Cochrane guidelines of the Medline database using specific search criteria. Only studies measuring inflammatory cells using specific markers in tissue from human patients with the clinical diagnosis of tendinopathy were included. Inclusion was agreed on by 2 independent researchers on review of abstracts or full-text using specific predetermined criteria. The search yielded 5 articles in total. Results There were increased numbers of macrophages (4 studies) and mast cells (3 studies) in tendinopathic versus healthy control tissues. One study demonstrated increased numbers of T cells in tendinopathic tissue versus healthy control tendons. There were reduced numbers of T cells (1 study), macrophages (2 studies) and mast cells (2 studies) in torn tendon versus intact tendinopathic tissue. Conclusions The existing evidence supports the hypothesis that increased numbers of inflammatory cells are present in pathological tendons. The lack of high-quality quantitative studies in this area demonstrates a clear need for future research to better understand the role of inflammation in tendinopathy.
Sympathetic Control of Pulmonary Vascular Impedance in Anesthetized Dogs
Authors: John B. Pace
Journal: Circulation Research (1971)

The effects of left stellate ganglion stimulation on pulmonary hydraulic input impedance was evaluated in 21 experiments on open-chest dogs anesthetized with chloralose. The stellate ganglion was stimulated at 1, 2, 5, 10, and 20 cps, and impedance spectra were generated at each frequency. Control spectra were characterized by frequency-dependent oscillations in impedance magnitude. Generally, impedance minimums occurred between 2 and 3 cps and maximums between 4 and 6 cps. Stellate ganglion stimulation caused elevations in impedance magnitude and shifted the impedance curve upward. The average control impedance magnitude at the minimum was 4780 dyne sec cm -5 kg ± 262 SE and was increased to 82.80 ± 452 during stimulation at 20 cps, while the frequency of the first harmonic in the control averaged 2.50 ± 0.08 SE cps and was 3.10 ± 0.08 during stimulation at 20 cps. Maximum activation of sympathetic outflows (10-20 cps) caused the impedance curve to flatten, attenuating frequency dependent oscillations characteristic of control spectra. The administration of propranolol attenuated cardiogenic increases in pulmonary pressure and flow during stellate ganglion stimulation, but elevations in pulmonary vascular impedance still occurred, indicating that this was not dependent on changes in harmonic content of the flow pulse that attended changes in heart rate and stroke volume. Frequency dependent oscillations in impedance magnitude were usually enhanced during left stellate ganglion stimulation following propranolol. The results indicate that sympathetic nerve stimulation increases the opposition to pulsatile flow; since pulmonary vascular resistance was relatively less affected, the input impedance becomes a greater fraction of the total opposition that must be overcome in moving blcod through the lungs.
Conditioning with 8-Gy total body irradiation and fludarabine for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia
Authors: Matthias Stelljes, Martin Bornhauser, Matthias Kroger, Joerg Beyer, Maria C. Sauerland, Achim Heinecke, Bjorna Berning, Christian Scheffold, Gerda Silling, Thomas Buchner, Andreas Neubauer, Axel A. Fauser, Gerhard Ehninger, Wolfgang E. Berdel, Joachim Kienast
Journal: Blood (2005)
Gene Silencing of Human Neuronal Cells for Drug Addiction Therapy using Anisotropic Nanocrystals
Authors: Wing-Cheung Law, Supriya D. Mahajan, Atcha Kopwitthaya, Jessica L. Reynolds, Maixian Liu, Xin Liu, Guanying Chen, Folarin Erogbogbo, Lisa Vathy, Ravikumar Aalinkeel, Stanley A. Schwartz, Ken-Tye Yong, Paras N. Prasad
Journal: Theranostics (2012)

Theranostic platform integrating diagnostic imaging and therapeutic function into a single system has become a new direction of nanoparticle research. In the process of treatment, therapeutic efficacy is monitored. The use of theranostic nanoparticle can add an additional "layer" to keep track on the therapeutic agent such as the pharmacokinetics and biodistribution. In this report, we have developed quantum rod (QR) based formulations for the delivery of small interfering RNAs (siRNAs) to human neuronal cells. PEGlyated QRs with different surface functional groups (amine and maleimide) were designed for selectively down-regulating the dopaminergic signaling pathway which is associated with the drug abuse behavior. We have demonstrated that the DARPP-32 siRNAs were successfully delivered to dopaminergic neuronal (DAN) cells which led to drastic knockdown of specific gene expression by both the electrostatic and covalent bond conjugation regimes. The PEGlyated surface offered high biocompatibilities and negligible cytotoxicities to the QR formulations that may facilitate the in vivo applications of these nanoparticles.
Selective Recruitment of Immature and Mature Dendritic Cells by Distinct Chemokines Expressed in Different Anatomic Sites
Authors: Marie-Caroline Dieu, Béatrice Vanbervliet, Alain Vicari, Jean-Michel Bridon, Elisabeth Oldham, Smina Aït-Yahia, Francine Brière, Albert Zlotnik, Serge Lebecque, Christophe Caux
Journal: The Journal of Experimental Medicine (1998)

DCs (dendritic cells) function as sentinels of the immune system. They traffic from the blood to the tissues where, while immature, they capture antigens. They then leave the tissues and move to the draining lymphoid organs where, converted into mature DC, they prime naive T cells. This suggestive link between DC traffic pattern and functions led us to investigate the chemokine responsiveness of DCs during their development and maturation. DCs were differentiated either from CD34+ hematopoietic progenitor cells (HPCs) cultured with granulocyte/macrophage colony–stimulating factor (GM-CSF) plus tumor necrosis factor (TNF)-α or from monocytes cultured with GM-CSF plus interleukin 4. Immature DCs derived from CD34+ HPCs migrate most vigorously in response to macrophage inflammatory protein (MIP)-3α, but also to MIP-1α and RANTES (regulated on activation, normal T cell expressed and secreted). Upon maturation, induced by either TNF-α, lipopolysaccharide, or CD40L, DCs lose their response to these three chemokines when they acquire a sustained responsiveness to a single other chemokine, MIP-3β. CC chemokine receptor (CCR)6 and CCR7 are the only known receptors for MIP-3α and MIP-3β, respectively. The observation that CCR6 mRNA expression decreases progressively as DCs mature, whereas CCR7 mRNA expression is sharply upregulated, provides a likely explanation for the changes in chemokine responsiveness. Similarly, MIP-3β responsiveness and CCR7 expression are induced upon maturation of monocyte- derived DCs. Furthermore, the chemotactic response to MIP-3β is also acquired by CD11c+ DCs isolated from blood after spontaneous maturation. Finally, detection by in situ hybridization of MIP-3α mRNA only within inflamed epithelial crypts of tonsils, and of MIP-3β mRNA specifically in T cell–rich areas, suggests a role for MIP-3α/CCR6 in recruitment of immature DCs at site of injury and for MIP-3β/CCR7 in accumulation of antigen-loaded mature DCs in T cell–rich areas.