tbuckley/cabot-search huggingface dataset:
Abatacept modulates proinflammatory macrophage responses upon cytokine-activated T cell and Toll-like receptor ligand stimulation
Authors: M H Wenink, K C M Santegoets, A M Platt, W B van den Berg, P L C M van Riel, P Garside, T R D J Radstake, I B McInnes
Journal: Annals of the Rheumatic Diseases (2011)

Objectives We investigated whether Abatacept might reduce proinflammatory cytokine production by macrophages upon contact with cytokine activated T cells and/or stimulation with TLR ligands. Methods Macrophages and cytokine stimulated T cells (Tck) were added together in the presence of Abatacept or a control Ig, with or without TLR ligands. The production of cytokines was determined by luminex. Results Abatacept reduced Tck-induced production of TNFa by macrophages. Tck and TLR ligands synergistically induced the production of proinflammatory cytokines by macrophages, especially IL-12p70. The production of IL-12p70 coincided with the production of IFNg, which were both reduced in the presence of Abatacept. Conclusions Tck induce the production of TNFa by macrophages and facilitate the highly increased production of proinflammatory cytokines in the presence of TLR ligands. Abatacept was shown to potently suppress these pathways suggesting that its role may extend beyond antigen specific T cell mediated effector function.
Histological changes following Nd YAG laser photocoagulation of canine gastric mucosa.
Authors: D F Kelly, S G Bown, B M Calder, H Pearson, B M Weaver, C P Swain, P R Salmon
Journal: Gut (1983)

Tissue changes produced in the dog stomach by exposure to a Nd YAG laser varied from mild mucosal oedema to cell vaporisation. Intermediate degrees of damage caused a marked inflammatory response leading to extensive fibrosis in the submucosa and muscularis propria. The true extent of tissue damage was not apparent immediately, and treated mucosa that initially appeared intact sometimes sloughed several days later to leave an ulcer. The extent of damage and the rate of healing depended on the amount of laser energy used. With pulses at optimum laser power (75 w) and exposure time (0.4 sec), however, haemostasis was achieved in induced ulcers with total energy concentrations that did not produce full thickness tissue damage nor alter the healing rate from that observed in untreated ulcers. Thermal contraction was the primary haemostatic mechanism, thrombosis only occurring as a secondary effect.
Impact of early central venous catheter removal on outcome in patients with candidaemia
Authors: D. Rodriguez, B.J. Park, B. Almirante, M. Cuenca-Estrella, A.M. Planes, J. Mensa, M. Gimenez, P. Saballs, S.K. Fridkin, J.L. Rodriguez-Tudela, A. Pahissa
Journal: Clinical Microbiology and Infection (2007)
A Human Histocompatibility Leukocyte Antigen (HLA)-G–specific Receptor Expressed on All Natural Killer Cells
Authors: Sumati Rajagopalan, Eric O. Long
Journal: The Journal of Experimental Medicine (1999)

Human natural killer (NK) cells express several killer cell immunoglobulin (Ig)-like receptors (KIRs) that inhibit their cytotoxicity upon recognition of human histocompatibility leukocyte antigen (HLA) class I molecules on target cells. Additional members of the KIR family, including some that deliver activation signals, have unknown ligand specificity and function. One such KIR, denoted KIR2DL4, is structurally divergent from other KIRs in the configuration of its two extracellular Ig domains and of its transmembrane and cytoplasmic domains. Here we show that recombinant soluble KIR2DL4 binds to cells expressing HLA-G but not to cells expressing other HLA class I molecules. Unlike other HLA class I-specific KIRs, which are clonally distributed on NK cells, KIR2DL4 is expressed at the surface of all NK cells. Furthermore, functional transfer of KIR2DL4 into the cell line NK-92 resulted in inhibition of lysis of target cells that express HLA-G, but not target cells that express other class I molecules including HLA-E. Therefore, given that HLA-G expression is restricted to fetal trophoblast cells, KIR2DL4 may provide important signals to maternal NK decidual cells that interact with trophoblast cells at the maternal-fetal interface during pregnancy.
Marihuana: Deceptive Weed
Authors: Jean-Pierre Armand
Journal: JAMA (1973)

ABSTRACT To the Editor.— The undersigned wish to state their disagreement with the opinions expressed by Dr. Liskow in his review of the book of Dr. Nahas, Marihuana: Deceptive Weed. They fully concur with Dr. Paton, Professor of Pharmacology at Oxford University, who wrote in the foreword:This is the first book to come from an author experienced in pharmacology as well as medicine. It is its realistic, medically responsible approach that gives this book such a freshness of outlook in a controversial field.Dr. Nahas has come to the conclusion, which I share, that the innocuousness of Cannabis is being overstated, and its dangers underestimated. The term deceptive weed is very apt, and reflects the unusual nature of the drug and its actions.... The reader will find, not only a general account of the plant and of the history of its use, but also the scientific and medical evidence so
Chloride transport by the rabbit cortical collecting duct
Authors: X Zhou, S L Xia, C S Wingo
Journal: Journal of the American Society of Nephrology (1998)

The rabbit cortical collecting duct (CCD) exhibits the capacity for active chloride absorption when basolateral Na-K-ATPase is inhibited by ouabain. The present studies examine the contribution of H,K-ATPase to this ouabain-insensitive Cl absorption and to related ion fluxes. Rabbits were fed a KCl-rich diet with no measurable Na for 4 to 13 d before isolation of the CCD for microperfusion. Application of peritubular ouabain (0.1 mM) significantly increased (P < 0.001) net luminal absorptive chloride flux (J(N)Cl) without an effect on lumen-to-bath isotopic 36Cl flux (J(lb)Cl). The H,K-ATPase inhibitor Sch 28080 (1 to 10 microM) abolished ouabain-insensitive J(N)Cl, but transepithelial voltage (V(T)) was not significantly affected. The contribution of H,K-ATPase activity on active Cl flux (J(A)Cl) and passive Cl flux (J(P)Cl) was also assessed. Ouabain significantly increased J(A)Cl and Sch 28080 inhibited J(A)Cl, but J(P)Cl was not affected by Sch 28080. To assess the contribution of changes in net bicarbonate flux (JtCO2) to changes in J(N)Cl, JtCO2 was measured under identical conditions as for J(N)Cl. Ouabain significantly increased JtCO2, and this ouabain-insensitive bicarbonate flux was inhibited by Sch 28080 without significantly affecting V(T). To assess the possibility that the CCD may possess mechanisms for neutral salt absorption, lumen-to-bath 86Rb efflux (K(Rb)), and 22Na efflux (K(Na)) were also measured. Ouabain significantly increased K(Rb), and Sch 28080 inhibited this ouabain-insensitive K(Rb). Furthermore, Sch 28080 and A80915a (a structurally distinct H,K-ATPase inhibitor) significantly inhibited K(Na) in the presence of 1 mM luminal amiloride. These observations suggest that, in addition to potassium, sodium can be transported via the H,K-ATPase. Although the CCD contains more than one cell population, the data could be fitted very well to the function of the B-type intercalated cell. A cell model is proposed for the hypothesis that ouabain-insensitive chloride absorption is mediated by the parallel operation of an apical H,K-ATPase with an apical Cl-HCO3 exchanger and that the H,K-ATPase can function, under certain conditions, as a mechanism of Na absorption.
Does early EBV infection protect against IgE sensitization?
Authors: Caroline Nilsson, Annika Linde, Scott M. Montgomery, Liselotte Gustafsson, Per Näsman, Marita Troye Blomberg, Gunnar Lilja
Journal: Journal of Allergy and Clinical Immunology (2005)

There is indirect evidence that an increased infectious burden is associated with a decreased prevalence of IgE-mediated allergy during childhood.To determine whether there is a relation between the serostatus of 13 different viruses and parentally reported infections and IgE sensitization in 2-year-old children. To investigate whether there is an interaction between cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in relation to IgE sensitization.A total of 246 infants were followed prospectively to 2 years of age with clinical examinations, skin prick test, and specific IgE analyses and through analysis of seropositivity against adenovirus, influenza, parainfluenza, respiratory syncytial virus, CMV, EBV, herpes simplex virus, human herpesvirus 6, and varicella-zoster virus.There was some evidence that IgE sensitization (24%) tended to be more common among children who were seropositive against few compared with children who were seropositive against many viruses, but this was not statistically significant, and there was no consistent trend across the groups. IgE sensitization was statistically significantly less prevalent at 2 years of age among infants who were seropositive against EBV but not other viruses (adjusted odds ratio, 0.34; 95% CI, 0.14-0.86). The interaction of seropositivity against both CMV and EBV antibodies indicated a further reduction in the risk for IgE sensitization (adjusted odds ratio for interaction, 0.10; 95% CI, 0.01-0.92), indicating effect modification associated with seropositivity against CMV.Our results indicate that acquisition of EBV infection during the first 2 years of life is associated with a reduced risk of IgE sensitization, and this effect is enhanced by CMV coinfection.
Management of Patients with Hereditary Hypercoagulable Disorders
Authors: C. Kearon, M. Crowther, J. Hirsh
Journal: Annual Review of Medicine (2000)

▪ Abstract The inherited hypercoagulable states can be divided into those that are common and associated with a modest risk of thrombosis (i.e. factor V Leiden and G20210A prothrombin gene) and those that are uncommon but asssociated with a high risk of thrombosis. There is no convincing evidence that, independent of other clinical factors, the presence of factor V Leiden or the prothrombin gene mutation should influence the use of primary prophylaxis or the duration of anticoagulant therapy following an episode of thrombosis. Indrect evidence sugests that the presence of antithrombin, protein C deficiency, or protein S deficiency justifies avoiding additional risk factors for thrombosis, such as estrogen therapy, and justifies use of more aggressive primary prophylaxis when additional risk factors cannot readily be avoided (e.g. pregnancy). The presence of one of these three abnormalities also favors more prolonged anticoagulant therapy following venous thrombosis. However, their presence or absence appears to have less influence on the risk of recurrent venous thromboembolism than whether thrombosis was provoked by a major reversible risk factor, such as surgery.
Imaging Ca <sup>2+</sup> Nanosparks in Heart With a New Targeted Biosensor
Authors: Wei Shang, Fujian Lu, Tao Sun, Jiejia Xu, Lin-Lin Li, Yanru Wang, Gang Wang, Liangyi Chen, Xianhua Wang, Mark B. Cannell, Shi-Qiang Wang, Heping Cheng
Journal: Circulation Research (2013)

Rationale: In cardiac dyads, junctional Ca 2+ directly controls the gating of the ryanodine receptors (RyRs), and is itself dominated by RyR-mediated Ca 2+ release from the sarcoplasmic reticulum. Existing probes do not report such local Ca 2+ signals because of probe diffusion, so a junction-targeted Ca 2+ sensor should reveal new information on cardiac excitation–contraction coupling and its modification in disease states. Objective: To investigate Ca 2+ signaling in the nanoscopic space of cardiac dyads by targeting a new sensitive Ca 2+ biosensor (GCaMP6f) to the junctional space. Methods and Results: By fusing GCaMP6f to the N terminus of triadin 1 or junctin, GCaMP6f-triadin 1/junctin was targeted to dyadic junctions, where it colocalized with t-tubules and RyRs after adenovirus-mediated gene transfer. This membrane protein-tagged biosensor displayed ≈4× faster kinetics than native GCaMP6f. Confocal imaging revealed junctional Ca 2+ transients (Ca 2+ nanosparks) that were ≈50× smaller in volume than conventional Ca 2+ sparks (measured with diffusible indicators). The presence of the biosensor did not disrupt normal Ca 2+ signaling. Because no indicator diffusion occurred, the amplitude and timing of release measurements were improved, despite the small recording volume. We could also visualize coactivation of subclusters of RyRs within a single junctional region, as well as quarky Ca 2+ release events. Conclusions: This new, targeted biosensor allows selective visualization and measurement of nanodomain Ca 2+ dynamics in intact cells and can be used to give mechanistic insights into dyad RyR operation in health and in disease states such as when RyRs become orphaned.
Intraocular degradation behavior of crosslinked and linear poly(trimethylene carbonate) and poly(d,l-lactic acid)
Authors: Janine Jansen, Steven A. Koopmans, Leonoor I. Los, Roelofje J. van der Worp, Johanna G. Podt, Johanna M.M. Hooymans, Jan Feijen, Dirk W. Grijpma
Journal: Biomaterials (2011)
Barriers to Physical Activity Among Patients With Type 1 Diabetes
Authors: Anne-Sophie Brazeau, Rémi Rabasa-Lhoret, Irene Strychar, Hortensia Mircescu
Journal: Diabetes Care (2008)

To determine, in an adult population with type 1 diabetes, barriers to regular physical activity using a diabetes-specific barriers measure (the Barriers to Physical Activity in Diabetes [type 1] [BAPAD1] scale) and factors associated with these barriers.One hundred adults with type 1 diabetes answered a questionnaire assessing perceived barriers to physical activity and related factors. A1C was obtained from the medical chart of each individual.Fear of hypoglycemia was identified as being the strongest barrier to physical activity. Greater knowledge about insulin pharmacokinetics and using appropriate approaches to minimize exercise-induced hypoglycemia were factors associated with fewer perceived barriers. Greater barriers were positively correlated with A1C levels (r = 0.203; P = 0.042) and negatively with well-being (r = -0.45; P < 0.001).Fear of hypoglycemia is the strongest barrier to regular physical activity in adults with type 1 diabetes, who should therefore be informed and supported in hypoglycemia management.
New developments in natural products‐based anti‐AIDS research
Authors: Donglei Yu, Susan L. Morris‐Natschke, Kuo‐Hsiung Lee
Journal: Medicinal Research Reviews (2006)

Abstract This review discusses anti‐HIV natural products from several compound classes, including terpenoids, coumarins, alkaloids, polyphenols, tannins, and flavonoids. Natural products can provide novel anti‐AIDS chemotherapeutic leads that are structurally unique or have new mechanisms of action. The drug discovery and development process proceeds from bioactivity‐directed isolation and identification of a promising lead natural product, followed by rational design‐based structural modification and structure–activity relationship analyses to optimize the lead compound as a drug candidate. This process is notably exemplified by the discovery of the modified betulinic acid derivative, DSB [PA‐457], which is currently in Phase II clinical trial and is the first‐in‐class HIV maturation inhibitor (MI). © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 1, 108–132, 2007
Epidural steroid injections compared with gabapentin for lumbosacral radicular pain: multicenter randomized double blind comparative efficacy study
Authors: S. P. Cohen, S. Hanling, M. C. Bicket, R. L. White, E. Veizi, C. Kurihara, Z. Zhao, S. Hayek, K. B. Guthmiller, S. R. Griffith, V. Gordin, M. A. White, Y. Vorobeychik, P. F. Pasquina
Journal: BMJ (2015)

<b>Objective</b> To evaluate whether an epidural steroid injection or gabapentin is a better treatment for lumbosacral radiculopathy. <b>Design</b> A multicenter randomized study conducted between 2011 and 2014. Computer generated randomization was stratified by site. Patients and evaluating physicians were blinded to treatment outcomes. <b>Settings</b> Eight military, Veterans Administration, and civilian hospitals. <b>Participants</b> 145 people with lumbosacral radicular pain secondary to herniated disc or spinal stenosis for less than four years in duration and in whom leg pain is as severe or more severe than back pain. <b>Interventions</b> Participants received either epidural steroid injection plus placebo pills or sham injection plus gabapentin. <b>Main outcome measures</b> Average leg pain one and three months after the injection on a 0-10 numerical rating scale. A positive outcome was defined as a ≥2 point decrease in leg pain coupled with a positive global perceived effect. All patients had one month follow-up visits; patients whose condition improved remained blinded for their three month visit. <b>Results</b> There were no significant differences for the primary outcome measure at one month (mean pain score 3.3 (SD 2.6) and mean change from baseline −2.2 (SD 2.4) in epidural steroid injection group versus 3.7 (SD 2.6) and −1.7 (SD 2.6) in gabapentin group; adjusted difference 0.4, 95% confidence interval −0.3 to 1.2; P=0.25) and three months (mean pain score 3.4 (SD 2.7) and mean change from baseline −2.0 (SD 2.6) versus 3.7 (SD 2.8) and −1.6 (SD 2.7), respectively; adjusted difference 0.3, −0.5 to 1.2; P=0.43). Among secondary outcomes, one month after treatment those who received epidural steroid injection had greater reductions in worst leg pain (−3.0, SD 2.8) than those treated with gabapentin (−2.0, SD 2.9; P=0.04) and were more likely to experience a positive successful outcome (66% <i>v</i> 46%; number needed to treat=5.0, 95% confidence interval 2.8 to 27.0; P=0.02). At three months, there were no significant differences between treatments. <b>Conclusions</b> Although epidural steroid injection might provide greater benefit than gabapentin for some outcome measures, the differences are modest and are transient for most people. <b>Trial registration</b> ClinicalTrials.gov Identifier: NCT01495923.
Concomitant Activation of the JAK/STAT, PI3K/AKT, and ERK Signaling Is Involved in Leptin-Mediated Promotion of Invasion and Migration of Hepatocellular Carcinoma Cells
Authors: Neeraj K. Saxena, Dipali Sharma, Xiaokun Ding, Songbai Lin, Fabio Marra, Didier Merlin, Frank A. Anania
Journal: Cancer Research (2007)

Various epidemiologic studies have shown that obesity is associated with hepatocellular carcinoma. Leptin, the key player in the regulation of energy balance and body weight control, also acts as a growth factor on certain organs in both normal and disease states. It is plausible that leptin acts to promote hepatocellular carcinogenesis directly affecting malignant properties of liver cancer cells. However, a direct role for leptin in hepatocellular carcinoma has not been shown. In this study, we analyzed the role of leptin and the mechanism(s) underlying its action in hepatocellular carcinoma cells, which express both short and long isoforms of leptin receptors. Treatment with leptin resulted in increased proliferation of both HepG2 and Huh7 cells and involves activation of signal transducers and activators of transcription 3 (STAT3), AKT, and extracellular signal-regulated kinase (ERK) signaling pathways. Leptin-induced phosphorylation of ERK and AKT was dependent on Janus-activated kinase (JAK)/STAT activation. Intriguingly, we also found that leptin potently induces invasion of hepatocellular carcinoma cells in Matrigel invasion and electric cell-substrate impedance-sensing assays. Leptin-stimulated invasion was effectively blocked by pharmacologic inhibitors of JAK/STAT and, to a lesser extent, by ERK and phosphatidylinositol 3-kinase (PI3K) inhibition. Importantly, leptin also induced the migration of both HepG2 and Huh7 cells on fibronectin matrix. Inhibition of JAK/STAT, ERK, and PI3K activation using pharmacologic inhibitors effectively blocked leptin-induced migration of HepG2 and Huh7 cells. Taken together, these data indicate that leptin promotes hepatocellular carcinoma growth, invasiveness, and migration and implicate the JAK/STAT pathway as a critical mediator of leptin action. Our findings have potential clinical implications for hepatocellular carcinoma progression in obese patients.
Sclerodermalike Esophageal Disease in Children of Mothers With Silicone Breast Implants
Authors: Garry S. Brody
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The Editorial by Dr Flick<sup>1</sup>commenting on breast-feeding and silicone implants presents an intriguing example of how accurate reporting of information can be misconstrued when diluted by repetition and presented out of context. Flick questions: "Should US physicians join their European colleagues in recommending that mothers with silicone implants refrain from nursing their infants?" He references Yoshida et al.<sup>2</sup>Yoshida et al<sup>2(p11)</sup>wrote without reference: "A potentially larger and more clinically significant problem would be the possibility of silicone-induced disease in children of mothers who nursed with silicone implants. This problem has not been addressed in the US;<i>in Europe nursing is not recommended for mothers with implants"</i>[emphasis added]. This seemed inconsistent when all but one of the European countries permit unrestricted use of this device. On questioning, representatives of European implant manufacturers knew nothing of this ban nor did the chairman of
Effects of Dietary Treatment Alone or Diet With Voglibose or Glyburide on Abdominal Adipose Tissue and Metabolic Abnormalities in Patients With Newly Diagnosed Type 2 Diabetes
Authors: Kazuhisa Takami, Noriyuki Takeda, Kazuya Nakashima, Rieko Takami, Makoto Hayashi, Shigehiko Ozeki, Akiko Yamada, Yoshiaki Kokubo, Mayumi Sato, Shin-ichi Kawachi, Akihiko Sasaki, Keigo Yasuda
Journal: Diabetes Care (2002)

OBJECTIVE—To examine the effects of diet and diet with voglibose or glyburide on abdominal adiposity and metabolic abnormalities in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 36 Japanese patients with newly diagnosed type 2 diabetes (50.8 ± 8.6 years of age, BMI 24.5 ± 3.5 kg/m2) and 273 normal control subjects were studied. The patients were treated for 3 months with diet alone (30 kcal/kg per day) (n = 15), diet with voglibose (n = 12), or diet with glyburide (n = 9). They underwent 75-g oral glucose tolerance testing, assessment of insulin sensitivity (SI), and acute insulin response (AIR) with intravenous glucose tolerance testing based on the minimal model, and measurement of abdominal visceral adipose tissue area (VAT) and subcutaneous adipose tissue area (SAT) by computed tomography before and after treatment. RESULTS—The diabetic patients had comparable SAT but larger VAT than the control subjects. With a mean weight loss of 2–3 kg, VAT and SAT were decreased similarly in all treatment groups. The VAT-to-SAT ratio was decreased only in the voglibose group. Glycemic control and serum lipid profiles were improved in all groups. Changes in glycemic control after diet were closely correlated with changes in VAT but not with changes in SAT. SI and AIR were unchanged in the diet group but were improved in the voglibose and glyburide groups. CONCLUSIONS—In Japanese patients with newly diagnosed type 2 diabetes who were relatively lean but had excess VAT, diet with or without voglibose or glyburide effectively reduced VAT. Decrease in VAT was closely associated with improvement of glycemic control with diet. Additional use of voglibose or low-dose glyburide had no detrimental effects on abdominal adiposity and had beneficial effects on SI and AIR.