tbuckley/cabot-search huggingface dataset:
Raised levels of F2-isoprostanes and prostaglandin F2alpha in different rheumatic diseases
Authors: S Basu
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To evaluate oxidative injury and inflammatory status in various rheumatic diseases by measuring the levels of isoprostanes and prostaglandins in serum and synovial fluid. <h3>METHODS</h3> The concentrations of 8-iso-PGF<sub>2α</sub> (F<sub>2</sub>-isoprostane indicating oxidative injury) and 15-keto-dihydro-PGF<sub>2α</sub> (a major metabolite of prostaglandin F<sub>2α</sub>) were measured in both serum and synovial fluid aspirated from 26 patients with various arthritic diseases, including rheumatoid arthritis (RA), reactive arthritis (ReA), psoriatic arthritis (PsA), and osteoarthritis (OA). These prostaglandin derivatives were also measured in serum samples collected from 42 healthy control subjects. <h3>RESULTS</h3> Overall, serum levels of 8-iso-PGF<sub>2α</sub> and 15-keto-dihydro-PGF<sub>2α</sub> were much higher in patients with arthritic diseases than in the healthy control subjects. The levels of 8-iso-PGF<sub>2α</sub> and 15-keto-dihydro-PGF<sub>2α</sub> in synovial fluid aspirated from knee joints were also high and varied among various types of arthritic patients. Although the synovial fluid level of these prostaglandin derivatives was sometimes higher than in the corresponding serum sample, this was not a consistent finding. Overall, there was no correlation between serum and synovial fluid levels of 8-iso-PGF<sub>2α</sub>, or between serum and synovial fluid levels of 15-keto-dihydro-PGF<sub>2α</sub>. However, a strong relation was found between the levels of 8-iso-PGF<sub>2α</sub> and 15-keto-dihydro-PGF<sub>2α,</sub> in both serum (<i>r</i><sub>s</sub>=0.53, p&lt;0.001) and synovial fluid (<i>r</i><sub>s</sub>=0.62, p&lt;0.001). <h3>CONCLUSIONS</h3> These data suggest that both free radical mediated oxidative injury and cyclo-oxygenase dependent inflammatory responses are closely correlated in various types of arthritis.
[729] SERUM LEPTIN CONCENTRATIONS IN CHRONIC VIRAL HEPATITIS: A CLINICAL APPROACH
Authors: S. Manolakopoulos, S. Bethanis, C. Liapi, P. Sklavos, F. Stripeli, A. Margeli, A. Christidou, A. Katsanika, E. Vogiatzakis, D. Tzourmakliotis, S. Theocharis
Journal: Journal of Hepatology (2007)
An Integrated Risk Function for Estimating the Global Burden of Disease Attributable to Ambient Fine Particulate Matter Exposure
Authors: Richard T. Burnett, C. Arden Pope, Majid Ezzati, Casey Olives, Stephen S. Lim, Sumi Mehta, Hwashin H. Shin, Gitanjali Singh, Bryan Hubbell, Michael Brauer, H. Ross Anderson, Kirk R. Smith, John R. Balmes, Nigel G. Bruce, Haidong Kan, Francine Laden, Annette Prüss-Ustün, Michelle C. Turner, Susan M. Gapstur, W. Ryan Diver, Aaron Cohen
Journal: Environmental Health Perspectives (2014)

Estimating the burden of disease attributable to long-term exposure to fine particulate matter (PM2.5) in ambient air requires knowledge of both the shape and magnitude of the relative risk (RR) function. However, adequate direct evidence to identify the shape of the mortality RR functions at the high ambient concentrations observed in many places in the world is lacking.We developed RR functions over the entire global exposure range for causes of mortality in adults: ischemic heart disease (IHD), cerebrovascular disease (stroke), chronic obstructive pulmonary disease (COPD), and lung cancer (LC). We also developed RR functions for the incidence of acute lower respiratory infection (ALRI) that can be used to estimate mortality and lost-years of healthy life in children < 5 years of age.We fit an integrated exposure-response (IER) model by integrating available RR information from studies of ambient air pollution (AAP), second hand tobacco smoke, household solid cooking fuel, and active smoking (AS). AS exposures were converted to estimated annual PM2.5 exposure equivalents using inhaled doses of particle mass. We derived population attributable fractions (PAFs) for every country based on estimated worldwide ambient PM2.5 concentrations.The IER model was a superior predictor of RR compared with seven other forms previously used in burden assessments. The percent PAF attributable to AAP exposure varied among countries from 2 to 41 for IHD, 1 to 43 for stroke, < 1 to 21 for COPD, < 1 to 25 for LC, and < 1 to 38 for ALRI.We developed a fine particulate mass-based RR model that covered the global range of exposure by integrating RR information from different combustion types that generate emissions of particulate matter. The model can be updated as new RR information becomes available.
Comparative Analyses of H3K4 and H3K27 Trimethylations Between the Mouse Cerebrum and Testis
Authors: Peng Cui, Wanfei Liu, Yuhui Zhao, Qiang Lin, Daoyong Zhang, Feng Ding, Chengqi Xin, Zhang Zhang, Shuhui Song, Fanglin Sun, Jun Yu, Songnian Hu
Journal: Genomics Proteomics & Bioinformatics (2012)

Abstract The global features of H3K4 and H3K27 trimethylations (H3K4me3 and H3K27me3) have been well studied in recent years, but most of these studies were performed in mammalian cell lines. In this work, we generated the genome-wide maps of H3K4me3 and H3K27me3 of mouse cerebrum and testis using ChIP-seq and their high-coverage transcriptomes using ribominus RNA-seq with SOLiD technology. We examined the global patterns of H3K4me3 and H3K27me3 in both tissues and found that modifications are closely-associated with tissue-specific expression, function and development. Moreover, we revealed that H3K4me3 and H3K27me3 rarely occur in silent genes, which contradicts the findings in previous studies. Finally, we observed that bivalent domains, with both H3K4me3 and H3K27me3, existed ubiquitously in both tissues and demonstrated an invariable preference for the regulation of developmentally-related genes. However, the bivalent domains tend towards a “winner-takes-all” approach to regulate the expression of associated genes. We also verified the above results in mouse ES cells. As expected, the results in ES cells are consistent with those in cerebrum and testis. In conclusion, we present two very important findings. One is that H3K4me3 and H3K27me3 rarely occur in silent genes. The other is that bivalent domains may adopt a “winner-takes-all” principle to regulate gene expression.
Tackling Ebola: new insights into prophylactic and therapeutic intervention strategies
Authors: Emmie de Wit, Heinz Feldmann, Vincent J Munster
Journal: Genome Medicine (2011)

Since its discovery in 1976, Ebolavirus has caused periodic outbreaks of viral hemorrhagic fever associated with severe and often fatal disease. Ebolavirus is endemic in Central Africa and the Philippines. Although there is currently no approved treatment available, the past 10 years has seen remarkable progress in our understanding of the pathogenicity of Ebolavirus and the development of prophylactic and post-exposure therapies against it. In vitro and in vivo experiments have shown that Ebolavirus pathogenicity is multifactorial, including viral and host determinants. Besides their function in the virus replication cycle, the viral glycoprotein, nucleoprotein, minor matrix protein and polymerase cofactor are viral determinants of pathogenicity, with evasion of the host innate and adaptive immune responses as the main mechanism. Although no licensed Ebolavirus vaccines are currently available, vaccine research in non-human primates, the 'gold standard' animal model for Ebolavirus, has produced several promising candidates. A combination of DNA vaccination and a recombinant adenovirus serotype 5 boost resulted in cross-protective immunity in non-human primates. A recombinant vesicular stomatitis vaccine vector protected non-human primates in pre- and post-exposure challenge studies. Several antiviral therapies are currently under investigation, but only a few of these have been tested in non-human primate models. Antisense therapies, in which oligonucleotides inhibit viral replication, have shown promising results in non-human primates following post-exposure treatment. In light of the severity of Ebolavirus disease and the observed increase in Ebolavirus outbreaks over the past decade, the expedited translation of potential candidate therapeutics and vaccines from bench to bedside is currently the most challenging task for the field. Here, we review the current state of Ebolavirus research, with emphasis on prophylactic and therapeutic intervention strategies.
The Secret(s) of Good Patient Care: Thoughts on Medicine in the 21st Century
Authors: Don Riesenberg
Journal: JAMA (1996)

Michel de Montaigne (1533-1592) is considered by many to be the father of the essay. Here's what he said: "If others examined themselves attentively, as I do, they would find themselves, as I do, full of inanity and nonsense." Sobering advice for those wishing to take the reader through medical practice with gun and camera. That task, which has been done supremely well by some, is more difficult than it first appears. When William Carlos Williams died we lost his genius for turning a clinical encounter into something universal. We will long await another Lewis Thomas, who lived at the right time and had a gift for framing medical life in terms of anthills and ancient rocks. Alas, few others are likely to make us wonder at the paradox of money in a physician's life the way David Hilfiker does. These exceptional talents give voice to what we experience in
Abstract 1071: DeltaEF1 promotes breast cancer cell proliferation through down-regulating p21 expression
Authors: Fen Hu, Chuan Wang, Tianhui Zhu, Shuang Yang
Journal: Cancer Research (2010)

Abstract Background: Deregulation of the cell cycle and abnormal cell proliferation are involved in breast carcinogenesis. Recent evidence suggests that deltaEF1, a zinc finger-homeodomain transcription factor, is a potential regulatory factor at the crossroad between proliferation and differentiation. However, how deltaEF1 mediates its proliferative effects in tumorigenesis has not been recognized yet. Materials and Methods: Quantitative RT-PCR and immunoblotting were used to determine the expressions of deltaEF1, p21, p27, CDK2, CDK4, and CDK6 at the mRNA and the protein levels, respectively, in MCF-7, MDA-MB-231, T47D, and ZR-75-1 breast cancer cells, as well as in 22 breast cancer specimens. Cell proliferation and BrdU incorporation assays as well as flow cytometry were used to determine cell proliferation of MDA-MB-231 cells with deltaEF1-overexpression or deltaEF1 siRNA knockdown. Luciferase assay was used to determine deltaEF1-driven transcriptional activities of the wild-type and mutant human p21 promoters. Quantitative CHIP assay was used to detect the direct association of deltaEF1 with the wild-type human p21 proximal promoter. Results: We found that ectopic expression of deltaEF1 in MDA-MB-231 cells significantly promoted cell proliferation as indicated by an increase of cells in S phase of the cell cycle. As anticipated, deltaEF1 knockdown by RNA interference decreased the cells in S phase, suggesting a role of deltaEF1 in the G1-S transition of breast cancer cells. Importantly, we also demonstrated that deltaEF1 down-regulated p21 with up-regulation of CDK2 and CDK4. Furthermore, our studies revealed that deltaEF1 inhibited p21 transcription after recruited to the E2-box element on the p21 promoter. Depletion of endogenous deltaEF1 was sufficient to trigger p21 expression in MDA-MB-231 cells, resulting in the cell cycle arrest. In addition, an inverse correlation of deltaEF1 and p21 expression was detected in both breast cancer cell lines and clinical tumor specimens, further supporting the role of p21 down-regulation in the stimulatory effect of deltaEF1 on cell proliferation. Conclusions: We conclude that deltaEF1 plays a critical role in promoting cell proliferation in breast cancer. Given that higher expression level of deltaEF1 is associated with more progressive phenotype of breast cancer, our collective data suggest that deltaEF1 is a key regulatory factor at the crossroad between proliferation and differentiation, thus underscoring tumor progression and metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1071.
Utility of autofluorescence imaging videoendoscopy in screening for Barrett’s esophagus
Authors: D. Asaoka, A. Nagahara, M. Oguro, A. Kurosawa, T. Osada, M. Kawabe, M. Hojo, T. Yoshizawa, M. Otaka, T. Ogihara, S. Watanabe
Journal: Endoscopy (2009)

Barrett’s esophagus is a gastroesophageal reflux disease (GERD)-associated disorder and is considered a premalignant lesion for Barrett’s cancer. Therefore, diagnosis of Barrett’s esophagus is very important [1] [2]. However, advanced skills are required to diagnose Barrett’s esophagus using white light imaging (WLI) endoscopy. Recently, the AFI (autofluorescence imaging) videoendoscopy system (Olympus, Tokyo, Japan) has been developed for the diagnosis of hyperplasia and inflammation in the gastrointestinal tract.
Pneumococcal Pericarditis Treated with Intrapericardial Penicillin
Authors: Charles M. Grossman
Journal: New England Journal of Medicine (1945)

THE effectiveness of penicillin in the treatment of many varieties of pneumococcal infections is well established. Since it is believed that its effectiveness in a proved case of pneumococcal pericarditis is worth recording, the following case is presented.F. D., a 30-year-old shipyard office worker, was admitted to the Northern Permanente Foundation Hospital on April 8, 1945, complaining of severe knifelike chest pains and dyspnea. Four weeks prior to admission he developed pleuritis on the left side, associated with some coughing, which was relieved by heat and strapping. Three weeks prior to admission he developed substernal pain, which was made . . .
FDA warns about metal-on-metal hip replacements
Authors: J. H. Tanne
Journal: BMJ (2013)

The US Food and Drug Administration last week told healthcare professionals that it is updating safety information and recommendations on metal-on-metal hip replacements because of early failures in many cases.

The FDA also issued a proposed order that would require manufacturers of metal-on-metal hip replacements to submit premarket approval applications to prove the safety of the devices. At present the manufacturers have to show only that their devices are similar to ones on the market.

The FDA announcement said, …
Books of life, death---and what comes in between
Authors: R. Westcott
Journal: BMJ (2000)

I registered a death recently.

I had to make an appointment, which seemed a rather formal business. The registrar sat behind a computer. She stood up and we introduced ourselves. It would take about half an hour, she explained.

It was a surprisingly dignified occasion. She unfolded the death certificate from its familiar brown envelope, laid it out on her desk, and studied it carefully. I thought of the hundreds of certificates that I have quickly filled in and torn from that orange book in my desk drawer. We steadily worked our way through a series of questions on her computer. When that was done, she took out a fountain pen and recorded the details in her register, in black ink. Then she asked me how many copies I wanted.

I had …
A Question of Life: The Warnock Report on Human Fertilisation and Embryology
Authors: John C. Fletcher
Journal: JAMA (1986)

In 1978, the first healthy birth of a child after in vitro fertilization and embryo transfer (IVF-ET) opened a door to the treatment of infertility. New and profound ethical questions were quickly raised on the status of the human embryo in treatment and research, freezing embryos, and surrogate motherhood. In the new controversy, older issues in the treatment of infertility, such as artificial insemination by donor, were reexamined. Is society passive about such questions? LeRoy Walters of the Kennedy Institute of Ethics notes that 14 medical, religious, or governmental bodies have considered the ethical, legal, and social implications of IVF-ET, beginning with a 1979 report by a DHEW Ethics Advisory Board. Only one, the Catholic bishops of Australia, opposes the therapeutic use of IVF-ET to treat infertility. Much more controversy exists about the window of opportunity for embryo research opened by IVF and the link to surrogate motherhood. In 1982,
Elective Circulatory Arrest During Neurosurgery for Basilar Artery Aneurysms
Authors: Aaron J. Gissen
Journal: JAMA (1969)

The results of surgical treatment of basilar artery aneurysms have been poor compared to those after treatment of intracranial aneurysms in other locations. In order to facilitate the neurosurgical approach to this lesion, moderate hypothermia has been combined with circulatory arrest. Arrest was induced by open-chest ventricular fibrillation in five patients. Repeated intermittent cardiac massage for one minute following three to four minutes of arrest maintained tissue nutrition while still providing the neurosurgeon with good operating conditions. Careful monitoring of the patients' vital functions together with accurate correction of the blood pH changes resulted in rapid cardiovascular recovery following anesthesia and surgery.
Abstract 4475: Discovery and characterization of PI3K isoform-selective inhibitors
Authors: Angela Virone-Oddos, Franck Halley, Victor Certal, Jean-Christophe Carry, Fabienne Thompson, Laurent Schio, Laurent Debussche, Helene Bonnevaux, Jean-Paul Nicolas, Cécile Delorme, Andreas Karlsson, Renaud Morales, Pierre-Yves Abecassis, Pascale Lejeune, Tsiala Benard, Nadine Michot, Paul Foster, Joerg Bussenius, Chris Jaeger, Torsten Trowe, Oliver Raeber, Jing Wang, Lam Nguyen, Ron Aoyama, Ken Rice, David Matthews, Christoph Lengauer
Journal: Cancer Research (2010)

Abstract Abnormal PI3K pathway activation plays a major role in cancer, as a result of either RTK activation or somatic mutations of major components of the pathway, including activating point mutations and amplification of the PIK3CA gene as well as loss of negative regulatory proteins such as PTEN. Most of the ATP-competitive PI3K inhibitors currently in clinical development inhibit all class I PI3K isoforms: however, several recent reports support the development of isoform-specific inhibitors. In particular, while PI3Kα specific inhibitors are predicted to inhibit growth of tumors with PIK3CA mutations, PTEN-deficient tumors have been shown to depend on PI3Kβ. In addition, isoform specific PI3K inhibitors may exhibit better safety profiles compared to pan-selective PI3K inhibitors, and thus may be easier to combine with other targeted or cytotoxic therapies. Here we report the discovery of ATP-competitive inhibitors with selectivity for PI3Kα, PI3Kα/mTOR, or PI3Kβ, which were identified and optimized by means of high-throughput screening and medicinal chemistry. These inhibitors exhibit biochemical IC50 values below 100 nM and good selectivity over other PI3K isoforms and a diverse panel of protein kinases. Cellular assays demonstrate that PI3Kα or PI3Kα/mTOR compounds inhibit phosphorylation of targets downstream of PI3K (Akt) and mTOR (S6 and p70S6 kinase) in the PI3Kα-activated MCF7 cell line, and that effects on PI3K pathway readouts are less pronounced in PC3 cells lacking PTEN. In contrast, PI3Kβ compounds potently inhibit phosphorylation of AKT (cellular IC50s &amp;lt; 200 nM) in the PTEN-deficient PC3 tumor cell line, and the most PI3Kβ-selective inhibitors are inactive on AKT phosphorylation in PI3Kα-activated H460 cells. In vivo pharmacodynamic analyses following oral administration of these isoform-selective inhibitors to mice bearing xenografted tumors demonstrate dose-dependent inhibition of phosphorylation of PI3K and mTOR effectors at well-tolerated doses. These results strongly argue for the development of isoform-selective PI3K inhibitors for the treatment of cancer patients harboring tumors with PTEN- deficient or PI3Kα-activated specific genotypes. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4475.
Continued Fevers in Egypt
Authors: W. H. MacNamara
Journal: BMJ (1886)

got ready.A change had also taken place in the family occupyin the lower roonus of the station, a new inspector having come, and brought with him hi8 newly married wife, a strong, hea[thy.lookingyoung woman from Essex.On November 28th, 1885, this yoing woman was taken ill with diphtheria, and had a moderately severe attack wbich lasted till December 13th.On examining tho walls of the two rooms on the ground floor, occupied as kitchen and sitting-room by her and herhusband, I fouind them danml for a con- siderable distance from the floor, varying from one to two feet, along the outer wall of the house.No furniture could be left standing .imminstthis wall without becoming damp.Even in the kitchen, wlhere a fire was constantly burhing, and gas very often aliglht, as it was rather a dark room, the wall was constantly damp; and the floor.(loth covering the kitchen floor, on being turned up, was found to be (lamp and mouldy.I advised the authorities that these rooms were
R-roscovitine (CYC202) alleviates renal cell proliferation in nephritis without aggravating podocyte injury
Authors: Maja Milovanceva-Popovska, Uta Kunter, Tammo Ostendorf, Arndt Petermann, Song Rong, Frank Eitner, Dontscho Kerjaschki, Anna Barnett, Jürgen Floege
Journal: Kidney International (2005)
The quack doctor of Serpukhov.
Authors: M Ryan
Journal: BMJ (1981)

poor, and although this improved considerably he developed symmetrical gangrene of the fingers and necrosis of the chest wall overlying the cephalic vein. It was thought that the gangrene on the chest was secondary to septic thrombophlebitis of the cephalic system following the original infection. Intensive care and treatment were continued, but his condition deteriorated and he developed a pseudomonas peritonitis and died 12 days after the initial injury. No streptococci were isolated after penicillin treatment was started, and necropsy examination showed only the complications of disseminated intravascular coagulation. Cases 3 and 4?The two further cases were association with predisposing conditions?hypophysectomy for pituitary adenoma in one and aplastic anaemia and renal failure in the other. Both patients died within 24 hours of the onset of symptoms. In the first case the infection was thought to have begun with a pricked finger, and gangrene of the arms and legs developed over a few hours. The responsible organisms were a group A streptococcus T/M type 1/1 in the first case and a group G streptococcus in the second. Comment
Infant Psychiatry: A New Synthesis
Authors: Leon Tec
Journal: JAMA (1976)

This volume consists of 22 reprinted articles exploring a multitude of aspects of infant development. Many outstanding child psychiatrists have contributed. The following findings are among the highlights: Korner and Grobstein emphasize the individual differences at birth, and although the observations were derived from single children, future field data will help test statistically how generally true these relationships are. Blank focuses on the mother's role in infant development, emphasizing immediate effects of care-taking practices as opposed to their possible long-term consequences. Wolff concentrates in Piaget's sensorimotor theory of intelligence. Anthony picks up an extremely important topic of how children cope in families with a psychotic parent. Caplan et al focus their attention on perinatal stress, cognitive organization, and ego function in prematurely born children. The editors indicate why the reprinted papers were selected: (1) they were regarded as a classic and often quoted, (2) each represents a pioneering effort, which