tbuckley/cabot-search huggingface dataset:
Targeting the Pathophysiology of Diabetic Macular Edema
Authors: Pedro Romero-Aroca
Journal: Diabetes Care (2010)

Diabetic macular edema (DME) is the leading cause of blindness in the diabetic population, and its prevalence is variable. The Diabetes Control and Complications Trial (DCCT) reported that 27% of type 1 diabetic patients developed macular edema within 9 years of diabetes onset (1). Other studies indicate that in type 2 diabetic patients the prevalence increases from 3% within 5 years of diagnosis to 28% after 20 years duration (2). DME tends to be a chronic disease, although spontaneous recovery is not uncommon. It is important to recognize that ∼33–35% of patients with macular edema had spontaneous resolution after 6 months if untreated. To characterize the severity of macular edema and for treatment guidelines, the term clinically significant macular edema (CSME) as an equivalent of DME, defined by the Early Treatment of Diabetic Retinopathy Study (ETDRS), is used.

DME is a complex disease of multifactorial origin. The common pathway that results in DME is disruption of the blood-retinal barrier (BRB). The mechanism of BRB breakdown is multifactorial and secondary to changes in the tight junctions, pericyte loss, endothelial cell loss, retinal vessel leukostasis, upregulation of vesicular transport, and increased permeability of the surface membranes of retinal vessels and retinal pigment epithelium cells. The disruption of the BRB leads to abnormal inflow of fluid into the neurosensory retina that can exceed the outflow and cause residual accumulation of fluid in …
Circulating p53-Responsive MicroRNAs Are Predictive Indicators of Heart Failure After Acute Myocardial Infarction
Authors: Sen Matsumoto, Yasuhiko Sakata, Shinichiro Suna, Daisaku Nakatani, Masaya Usami, Masahiko Hara, Tetsuhisa Kitamura, Toshimitsu Hamasaki, Shinsuke Nanto, Yukio Kawahara, Issei Komuro
Journal: Circulation Research (2013)

Rationale: Despite a recent decline of in-hospital mortality attributable to acute myocardial infarction (AMI), the incidence of ischemic heart failure (HF) in post-AMI patients is increasing. Although various microRNAs have been proposed as diagnostic indicators for AMI, no microRNAs have been established as predictors of ischemic HF that develops after AMI. Objective: We attempted to identify circulating microRNAs that can serve as reliable predictors of ischemic HF in post-AMI patients. Methods and Results: Using sera collected a median of 18 days after AMI onset, we screened microRNAs in 21 patients who experienced development of HF within 1 year after AMI and in 65 matched controls without subsequent cardiovascular events after discharge. Among the 377 examined microRNAs, the serum level of only miR-192 was significantly upregulated in AMI patients with development of ischemic HF. Because miR-192 is reported to be p53-responsive, the serum levels of 2 other p53-responsive microRNAs, miR-194 and miR-34a, also were investigated. Interestingly, both microRNAs were coordinately increased with miR-192, particularly in exosomes, suggesting that these microRNAs function as circulating regulators of HF development via the p53 pathway. Furthermore, miR-194 and miR-34a expression levels were significantly correlated with left ventricular end-diastolic dimension 1 year after AMI. Conclusions: In the sera of post-AMI patients who experienced development of de-novo HF within 1 year of AMI onset, the levels of 3 p53-responsive microRNAs had been elevated by the early convalescent stage of AMI. Further investigations are warranted to confirm the usefulness of these circulating microRNAs for predicting the risk of development of ischemic HF after AMI.
The Expression of CD30 in Anaplastic Large Cell Lymphoma Is Regulated by Nucleophosmin-Anaplastic Lymphoma Kinase–Mediated JunB Level in a Cell Type–Specific Manner
Authors: Faye Yuan-Yi Hsu, Patrick B. Johnston, Kathleen A. Burke, Yi Zhao
Journal: Cancer Research (2006)

Abstract Chromosomal translocation t(2;5) and the resulting fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) are detected in 50% to 70% of anaplastic large cell lymphoma (ALCL), which is a T/null cell non–Hodgkin's lymphoma showing anaplastic morphology with cell surface expression of CD30. Because aberrant CD30 expression was also observed in the T-cell lymphoma derived from lineage-specific NPM-ALK transgenic mice, we tested the hypothesis that there might be a functional relationship between the two neoplastic-related proteins: NPM-ALK and CD30. In this study, we used the RNA interference method to modulate NPM-ALK protein expression in ALCL-derived, t(2;5)-positive Karpas 299 cells. We observed decreased CD30 expression when NPM-ALK was repressed. Further analysis suggested that JunB functioned as the mediator of NPM-ALK-derived CD30 transcriptional regulation. The NPM-ALK-repressed cells, which had low CD30 expression, were characterized with lower cell proliferation compared with cells in the control group, suggesting that altered CD30 expression may correlate to NPM-ALK-mediated tumor cell growth inhibition. Combination of NPM-ALK repression and CD30 ligand leads to significantly increased tumor cell growth inhibition compared with one method alone, suggesting its potential application for ALCL-specific cancer treatment. (Cancer Res 2006; 66(18): 9002-8)
Depletion of Cd4+ T Cells Causes Reactivation of Murine Persistent Tuberculosis despite Continued Expression of Interferon γ and Nitric Oxide Synthase 2
Authors: Charles A. Scanga, V.P. Mohan, Keming Yu, Heather Joseph, Kathryn Tanaka, John Chan, JoAnne L. Flynn
Journal: The Journal of Experimental Medicine (2000)

Tuberculosis is a major cause of death in much of the world. Current estimates are that one-third of the world's population is infected with Mycobacterium tuberculosis. Most infected persons control the infection but in many cases may not eliminate the organism. Reactivation of this clinically latent infection is responsible for a large proportion of active tuberculosis cases. A major risk factor for reactivation of latent tuberculosis is HIV infection, suggesting a role for the CD4+ T cell subset in maintaining the latent persistent infection. In this study, we tested the requirement for CD4+ T cells in preventing reactivation in a murine model of latent tuberculosis. Antibody-mediated depletion of CD4+ T cells resulted in rapid reactivation of a persistent infection, with dramatically increased bacterial numbers in the organs, increased pathology in the lungs, and decreased survival. Although CD4+ T cells are believed to be a major source of interferon (IFN)-γ, expression of the gene for IFN-γ in the lungs of CD4+ T cell–depleted mice was similar to that in control mice. In addition, inducible nitric oxide synthase production and activity was unimpaired after CD4+ T cell depletion, indicating that macrophage activation was present even during CD4+ T cell deficiency. These data indicate that CD4+ T cells are necessary to prevent reactivation but may have roles in addition to IFN-γ production and macrophage activation in controlling a persistent tuberculous infection.
Diagnostic accuracy of routine antenatal determination of fetal RHD status across gestation: population based cohort study
Authors: L. S. Chitty, K. Finning, A. Wade, P. Soothill, B. Martin, K. Oxenford, G. Daniels, E. Massey
Journal: BMJ (2014)

<b>Objectives</b> To assess the accuracy of fetal <i>RHD</i> genotyping using cell-free fetal DNA in maternal plasma at different gestational ages. <b>Design</b> A prospective multicentre cohort study. <b>Setting</b> Seven maternity units in England. <b>Participants</b> RhD negative pregnant women who booked for antenatal care before 24 weeks' gestation. <b>Interventions</b> Women who gave consent for fetal <i>RHD</i> genotyping had blood taken at the time of booking for antenatal care and, when possible, at other routine visits such as for Down's syndrome screening between 11 and 21 weeks' gestation, at the anomaly scan at 18-21 weeks, and in the third trimester when blood was taken for the routine antibody check. The results of cord blood analysis, done routinely in RhD negative pregnancies, were also obtained to confirm the fetal <i>RHD</i> genotyping.<b></b> <b>Main outcome measures</b> The accuracy of fetal <i>RHD</i> genotyping compared with RhD status predicted by cord blood serology. <b>Results</b> Up to four analyses per woman were performed in 2288 women, generating 4913 assessable fetal results. Sensitivity for detection of fetal <i>RHD</i> positivity was 96.85% (94.95% to 98.05%), 99.83% (99.06% to 99.97%), 99.67% (98.17% to 99.94%), 99.82% (98.96% to 99.97%), and 100% (99.59% to 100%) at &lt;11, 11-13, 14-17, 18-23, and &gt;23 completed weeks' gestation, respectively. Before 11 weeks' gestation 16/865 (1.85%) babies tested were falsely predicted as <i>RHD</i> negative. <b>Conclusions</b> Mass throughput fetal <i>RHD</i> genotyping is sufficiently accurate for the prediction of RhD type if it is performed from 11 weeks' gestation. Testing before this time could result in a small but significant number of babies being incorrectly classified as <i>RHD</i> negative. These mothers would not receive anti-RhD immunoglobulin, and there would be a risk of haemolytic disease of the newborn in subsequent pregnancies.
Antibody to the receptor for polymerized human serum albumin in acute and persistent infection with hepatitis B virus
Authors: Hiroaki Okamoto, Sadakazu Usuda, Mitsunobu Imai, Katsumi Tachibana, Eiji Tanaka, Tomoko Kumakura, Masako Itabashi, Emiko Takai, Fumio Tsuda, Tetsuo Nakamura, Yuzo Miyakawa, Makoto Mayumi
Journal: Hepatology (1986)

The antibody against the receptor for polymerized human serum albumin was determined by radioimmunoassay. The method involved the inhibition by the test serum, absorbed with HBsAg particles without the receptor, on the binding of polymerized human serum albumin to HBsAg particles with the receptor fixed on a solid support. The amount of polymerized human serum albumin captured by the receptor on HBsAg was then determined by the radiolabeled monoclonal antibody directed to an epitope specific for polymerized human serum albumin. In acute infection, the antibody to the receptor for polymerized human serum albumin appeared in the early recovery phase while HBs antigenemia and elevated transaminase levels were still present, preceding the antibody to HBsAg (anti-HBs). The antibody was detected in 4 (1%) of 358 sera from asymptomatic carriers of HBsAg containing antibody to HBeAg, and in none of 67 sera containing HBeAg. Although the antibody was found in as many as 111 (74%) of 150 sera from blood donors who had presumably acquired anti-HBs after natural infection, it was not detected in any sera from 77 recipients of hepatitis B vaccine who had seroconverted for anti-HBs. On the basis of these observations, the determination of antibody to the receptor for polymerized human serum albumin helps in further understanding the immunity to hepatitis B virus.
The business of injury prevention in circus performance
Authors: E Lamme
Journal: British Journal of Sports Medicine (2011)

Background Cirque du Soleil (CDS) is an acrobatic circus company with 1500 acrobatic and non-acrobatic performers for its current 20 touring and resident shows. Although published data analysis revealed that injuries at CDS are generally minor (80% requiring seven treatments or less), injury prevention and rehabilitation have and continue to be a high priority. The company considers injury surveillance an essential tool in evaluating the effect of policy changes on artists' health. Objective To describe an example of how CDS uses injury surveillance to improve injury prevention. Design Pre-post study. Setting and Participants Circus artists. Intervention A new touring concept directed for a pilot change in performance schedule where there was a need for artists to travel between cities on ‘non-performance days’, and to perform in more than one city per week. Main outcome measurements Injury rate and frequency of treatments. Results The previously new and unknown performance concept increased CDS' usual injury rate 1.8-fold and the number of treatments increased 2.4-fold in the two months following the change in tour-schedule. Additional analyses ruled out other changes over time including changes in cast size, and changes in locations. Based on these analyses, CDS did not continue with the pilot policy changes in performance scheduling. Conclusion Injury surveillance can be a useful tool to help sport and artistic businesses minimise injury rates and as such maximise the longevity of their athletes and artists.
Deoxyribonucleic acid damage in human lymphocytes after percutaneous transluminal coronary angioplasty
Authors: Maria Grazia Andreassi, Nicoletta Botto, Antonio Rizza, Maria Giovanna Colombo, Cataldo Palmieri, Sergio Berti, Samantha Manfredi, Serena Masetti, Aldo Clerico, Andrea Biagini
Journal: Journal of the American College of Cardiology (2002)
Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin
Authors: Genevieve Nguyen, Françoise Delarue, Céline Burcklé, Latifa Bouzhir, Thomas Giller, Jean-Daniel Sraer
Journal: Journal of Clinical Investigation (2002)

Renin is an aspartyl protease essential for the control of blood pressure and was long suspected to have cellular receptors. We report the expression cloning of the human renin receptor complementary DNA encoding a 350-amino acid protein with a single transmembrane domain and no homology with any known membrane protein. Transfected cells stably expressing the receptor showed renin- and prorenin-specific binding. The binding of renin induced a fourfold increase of the catalytic efficiency of angiotensinogen conversion to angiotensin I and induced an intracellular signal with phosphorylation of serine and tyrosine residues associated to an activation of MAP kinases ERK1 and ERK2. High levels of the receptor mRNA are detected in the heart, brain, placenta, and lower levels in the kidney and liver. By confocal microscopy the receptor is localized in the mesangium of glomeruli and in the subendothelium of coronary and kidney artery, associated to smooth muscle cells and colocalized with renin. The renin receptor is the first described for an aspartyl protease. This discovery emphasizes the role of the cell surface in angiotensin II generation and opens new perspectives on the tissue renin-angiotensin system and on renin effects independent of angiotensin II.
Myofibrillar Mass in Rat and Rabbit Heart Muscle: CORRELATION OF MICROCHEMICAL AND STEREOLOGICAL MEASUREMENTS IN NORMAL AND HYPERTROPHIC HEARTS
Authors: ERNEST PAGE, PHILIP I. POLIMENI, RADOVAN ZAK, JUDY EARLEY, MARGARET JOHNSON
Journal: Circulation Research (1972)

A sequestered fraction of myofibrillar magnesium presumably bound to thin filaments during polymerization of actin was used to determine myofibrillar mass in rat left ventricles and rabbit hearts. Myofibrillar volume was also determined by stereological measurements on electron micrographs of rat ventricles. Myofibrillar Mg (1.11 mmoles/kg dry ventricle) can be determined in glycerinated ventricle either by measuring 28 Mg-inexchangeable Mg or Mg remaining after extraction with EDTA, KCl, and a nonionic detergent. These measurements, combined with the Mg content of myofibrillar suspensions similarly extracted (3.2 mmoles/kg protein), indicated that myofibrillar mass was 347 g myofibrillar protein/kg dry ventricle. In rabbit hearts, increases in myofibrillar Mg per unit dry weight were as follows: auricular appendage &lt; right ventricle &lt; left ventricle ⋍ interventricular septum. After production of left ventricular hypertrophy in rats by constriction of the ascending aorta, both myofibrillar Mg and volume increased within 24 hours. After 10 or more days, myofibrillar Mg and myofibrillar volume increased proportionately more than tissue dry mass and cell volume, and the ratio of mitochondrial volume to cell volume decreased.
Granulocyte/macrophage colony-stimulating factor stimulates the expression of the 5-lipoxygenase-activating protein (FLAP) in human neutrophils.
Authors: M Pouliot, P P McDonald, P Borgeat, S R McColl
Journal: The Journal of Experimental Medicine (1994)

The synthesis of leukotrienes in human blood neutrophils chiefly relies on the activity of two enzymes, phospholipase A2 and 5-lipoxygenase (5-LO). In turn, the activation of the 5-LO requires the participation of a recently characterized membrane-bound protein, the 5-LO-activating protein (FLAP). In this study, we have investigated conditions under which FLAP expression in neutrophils may be modulated. Of several cytokines tested, only granulocyte/macrophage colony-stimulating factor (GM-CSF) (and to a lesser extent tumor necrosis factor alpha) significantly increased expression of FLAP. GM-CSF increased FLAP mRNA steady-state levels in a time- and dose-dependent manner. The stimulatory effect of GM-CSF on FLAP mRNA was inhibited by prior treatment of the cells with the transcription inhibitor, actinomycin D, and pretreatment of the cells with the protein synthesis inhibitor, cycloheximide, failed to prevent the increase in FLAP mRNA induced by GM-CSF. The accumulation of newly synthesized FLAP, as determined by immunoprecipitation after incorporation of 35S-labeled amino acids, was also increased after incubation of neutrophils with GM-CSF. In addition, the total level of FLAP protein was increased in GM-CSF-treated neutrophils, as determined by two-dimensional gel electrophoresis, followed by Western blot. GM-CSF did not alter the stability of the FLAP protein, indicating that the effect of GM-CSF on FLAP accumulation was the consequence of increased de novo synthesis as opposed to decreased degradation of FLAP. Finally, incubation of neutrophils with the synthetic glucocorticoid dexamethasone directly stimulated the upregulation of FLAP mRNA and protein, and enhanced the effect of GM-CSF. Taken together, these data demonstrate that FLAP expression may be upmodulated after appropriate stimulation of neutrophils. The increase in FLAP expression induced by GM-CSF in inflammatory conditions could confer upon neutrophils a prolonged capacity to synthesize leukotrienes.
Association of transdermal nitroglycerin to vasopressin infusion in the treatment of variceal hemorrhage: A placebo-controlled clinical trial
Authors: Jaime Bosch, Roberto J. Groszmann, Joan C. García-Pagán, Josep Terés, Guadalupe García-Tsao, Miquel Navasa, Antoni Mas, Joan Rodés
Journal: Hepatology (1989)

The aim of this study was to evaluate, using a double-blind technique, the efficacy of the association of transdermal nitroglycerin to vasopressin infusion for the treatment of variceal bleeding. Sixty-nine cirrhotic patients with active variceal bleeding were randomly allocated to receive vasopressin (0.4 to 0.8 unit per min until variceal bleeding has been controlled for 12 hr) associated with nitroglycerin administered transdermically in a slow-release preparation (10 mg in 24 hr) or placebo. An initial control of variceal hemorrhage was achieved in 83% of the patients receiving vasopressin-nitroglycerin and in 74% in the vasopressin-placebo group. Owing to a lower frequency of recurrent bleeding during therapy (18 vs. 42%, p = 0.11), vasopressin-nitroglycerin achieved a definitive control of bleeding in a higher proportion of patients than vasopressin-placebo (73 vs. 54%, p = 0.13). The group treated with the drug combination showed favorable results in relation to transfusion requirements (2.9 +/- 0.4 vs. 4.2 +/- 0.5 units, p = 0.05), total dose of vasopressin required (453 +/- 47 vs. 587 +/- 50 units, p less than 0.05), need of balloon tamponade (6 vs. 15, p less than 0.05) and requirement for emergency surgery (0 vs. 4, p = 0.07). There were no significant differences in the undesirable effects associated with treatment, observed in 37 and 49% of cases, respectively. Hospital mortality was similar (33 vs. 25%). This study demonstrates that transdermal nitroglycerin improves the effectiveness of vasopressin for controlling variceal hemorrhage.
Alveolar Cell Senescence in Patients with Pulmonary Emphysema
Authors: Takao Tsuji, Kazutetsu Aoshiba, Atsushi Nagai
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

The prevalence of chronic obstructive pulmonary disease (COPD) is age-dependent, suggesting an intimate relationship between the pathogenesis of COPD and aging. In this study we investigated whether the senescence of alveolar epithelial and endothelial cells is accelerated in emphysematous lungs.Samples of lung tissue were obtained from patients with emphysema, asymptomatic smokers, and asymptomatic nonsmokers. Paraffin-embedded lung tissue sections were evaluated for cellular senescence by quantitative fluorescence in situ hybridization to assess telomere shortening, and by immunohistochemistry to assess the expression of senescence-associated cyclin-dependent kinase inhibitors. Tissue sections were also immunostained for proliferating cell nuclear antigen (PCNA), surfactant protein A, and CD31.The patients with emphysema had significantly higher percentages of type II cells positive for p16INK4a and p21CIP1/WAF1/Sdi1 than the asymptomatic smokers and nonsmokers. They had also significantly higher percentages of endothelial cells positive for p16INK4a than the asymptomatic smokers and nonsmokers, and higher percentages of endothelial cells positive for p21CIP1/WAF1/Sdi1 than the asymptomatic nonsmokers. Telomere length in alveolar type II cells and endothelial cells was significantly shorter in the patients with emphysema than in the asymptomatic nonsmokers. The level of p16INK4a expression was negatively correlated with the level of PCNA expression. The level of alveolar cell senescence was positively correlated with airflow limitation.These results suggest that the senescence of alveolar epithelial and endothelial cells is accelerated in patients with emphysema. Cellular senescence may explain the abnormal cell turnover that promotes the loss of alveolar cells in emphysematous lungs.
Campaigners fear that Russia's new tobacco law won't work
Authors: K. Danishevski
Journal: BMJ (2002)

Russia has introduced its first law in more than 20 years that limits the use of tobacco. The law, signed by President Putin last July, came into force last month.

It is the first to be enacted since the 1970s, when smoking in trains and by doctors when working with patients was banned.

The new law prohibits almost all forms of tobacco advertising, including on television, radio, and billboards, and …
Clinical and laboratory diagnosis of von Willebrand disease: A synopsis of the 2008 NHLBI/NIH guidelines
Authors: William L. Nichols, Margaret E. Rick, Thomas L. Ortel, Robert R. Montgomery, J. Evan Sadler, Barbara P. Yawn, Andra H. James, Mae B. Hultin, Marilyn J. Manco‐Johnson, Mark Weinstein
Journal: American Journal of Hematology (2009)

Von Willebrand factor (VWF) mediates blood platelet adhesion and accumulation at sites of blood vessel injury, and also carries coagulation factor VIII (FVIII) that is important for generating procoagulant activity. Von Willebrand disease (VWD), the most common inherited bleeding disorder, affects males and females, and reflects deficiency or defects of VWF that may also cause decreased FVIII. It may also occur less commonly as an acquired disorder (acquired von Willebrand syndrome). This article briefly summarizes selected features of the March 2008 evidence-based clinical and laboratory diagnostic recommendations from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel for assessment for VWD or other bleeding disorders or risks. Management of VWD is also addressed in the NHLBI guidelines, but is not summarized here. The VWD guidelines are available at the NHLBI Web site (http://www.nhlbi.nih.gov/guidelines/vwd).