tbuckley/cabot-search huggingface dataset:
P66 Histone deacetylase inhibitor CBHA attenuates the expression of plasminogen activator inhibitor-1 in human pleural mesothelial cells
Authors: C.-L. Chung, W.-L. Chen, Y.-W. Cheng, Y.-C. Chou, M.-J. Hsu, C.-J. Hsiao, J.-R. Sheu, G. Hsiao
Journal: Thorax (2010)

<h3>Background</h3> Plasminogen activator inhibitor-1 (PAI-1), primarily up-regulated by transforming growth factor (TGF)-β, is essential for development of fibrosis. Histone deacetylases (HDACs) have been shown to modulate gene expression and fibrogenesis in various tissues. However, the implications of HDAC in PAI-1 expression and pleural fibrosis remain unclear. We examined the effects of <i>m</i>-carboxycinnamic acid bis-hydroxamide (CBHA), a hybrid-polar HDAC inhibitor, on PAI-1 expression in a human pleural mesothelial cell line (MeT-5A). <h3>Methods</h3> MeT-5A cells were treated with TGF-β1 (10 ng/ml) in the presence or absence of CBHA (0.2–1 μM). The expression and stability of PAI-1 mRNA and protein, PAI-1 promoter activity, activation of Smad signaling, and protein–protein interactions of Smads with transcriptional cofactors Sp1 and coactivator p300 were assayed using the methods of Western blotting, reverse transcription-polymerase chain reaction, transient transfection and luciferase activity assay, immunoflurescence staining and immunoprecipitation, respectively. <h3>Results</h3> CBHA significantly inhibited TGF-β1-induced PAI-1 mRNA and protein expression, and attenuated PAI-1 promoter activity in MeT-5A cells. CBHA abrogated TGF-β1-induced Smad4 nuclear translocation, but not Smad2/3 activation. Furthermore, the TGF-β1-induced association of Smad4 with p300, but not with Sp1, was disrupted by CBHA. Alternatively, CBHA accelerated PAI-1 mRNA degradation, possibly through suppression of the mRNA stabilizing protein nucleolin (Abstract P66 Figure 1). <h3>Conclusion</h3> Our data suggests that inhibition of HDAC activity by CBHA may attenuate TGF-β1-induced PAI-1 expression in human pleural mesothelial cells through modulation of cellular signaling at multiple levels. HDAC inhibitors may be employed as potential therapeutic agents for pleural fibrosis.
Study of 500 patients with limb joint osteoarthritis. I. Analysis by age, sex, and distribution of symptomatic joint sites.
Authors: J Cushnaghan, P Dieppe
Journal: Annals of the Rheumatic Diseases (1991)

Five hundred subjects with symptomatic limb joint osteoarthritis, who had been referred to a rheumatologist, were enrolled into a continuing study. They comprised 342 women (mean age 65.3) and 158 men (mean age 59.7), with a mean symptom duration of 15.4 years at entry. Only 31 patients (6%) had symptomatic osteoarthritis of one joint alone; however, in a further 205 (41%) the disease was limited to one site. One hundred and eighty two (36.4%) had two sites affected and 82 (16.4%) three or more sites of symptomatic osteoarthritis. Of 847 affected joints the most commonly involved were 349 (41.2%) knees, 254 (30%) hands, and 161 (19%) hips. Hip disease stood out as a separate entity, often occurring alone, and having a stronger male preponderance and different associations than osteoarthritis at other joint sites. Knee and hand disease were significantly associated in women. Obesity, hypertension, and Heberden's nodes were common. The number of sites affected, as well as the distribution, was strongly related to age as well as sex, suggesting that polyarticular osteoarthritis arises from slow acquisition of new joint sites in a non-random distribution. 'Generalised' osteoarthritis did not emerge as a distinct entity.
Differential roles for ETS, CREB, and EGR binding sites in mediating VEGF receptor 1 expression in vivo
Authors: Enjing Jin, Ju Liu, Jun-ichi Suehiro, Lei Yuan, Yoshiaki Okada, Vesna Nikolova-Krstevski, Kiichiro Yano, Lauren Janes, David Beeler, Katherine C. Spokes, Dan Li, Erzsébet Regan, Shou-Ching Shih, Peter Oettgen, Takashi Minami, William C. Aird
Journal: Blood (2009)
1026. In Vivo Imaging for Evaluation of Adenoviral Capsid Modifications for Systemic Delivery in an Orthotopic Model of Locally Advanced Lung Cancer
Authors: Merja Särkioja, Anna Kanerva, Tanja Hakkarainen, Jarmo Salo, Lotta Kangasniemi, Mari Raki, Tuuli Ranki, Hongju Wu, David T. Curiel, Akseli Hemminki
Journal: Molecular Therapy (2005)

Background: Low or variable expression of the coxsackie and adenovirus receptor (CAR) has limited gene transfer efficacy to many types of cancer cells. To circumvent the problem, adenoviruses (Ads) have been modified by improving their ability to attach to heterologous receptors more regularly present on tumor cells. In the context of lung cancer, the most common cause of cancer associated mortality worldwide, targeting approaches have not been comprehensively evaluated. Our hypothesis was that we could use previously described targeting moieties for increasing gene transfer to NSCLC cells and clinical samples in vitro and in vivo. Ad5lucRGD is modified with an RGD-4C motif allowing binding to integrins. Ad5/3luc1 has a chimeric fiber protein featuring the knob domain derived from Ad3 and it uses the serotype 3 receptor for entry. One can also add a polylysine tail to the C-terminal end of the fiber. Polylysins bind to heparan sulfate proteoglygans (HSPGs). For improving tumor penetration and subsequent oncolysis, conditionally replicating adenoviruses (CRAds) have been constructed. In this study, we used CRAds with same targeting moieties as in the non-replicating Ads.
MUSTARD (YELLOW CROSS) BURNS
Authors: LEONARD D. FRESCOLN
Journal: JAMA (1918)

Recent attacks have shown that instead of the former  cloud offensives being employed, the so-called mustard gas shells have been used to play an important part in annoying the enemy. A burn of either the first or the second degree with some of the retained irritant is produced. The liquid may be splashed on the part or the vapor reach the skin sufficiently to produce a redness and some hemorrhage. The real burn may be suspected but not appear until twenty-four hours.  This irritant is called in German literature by several names, and yperite, or dichlor-ethyl-sulphid chemically. It vaporizes on the explosion of the shell and then does the damage to those exposed, but its effect is not much appreciated before four hours. Besides the skin manifestations there may be, after a day, vomiting, cough, hoarseness and pain. The eruption itself may appear as punctate, rose-red areas, simulating a
Influence of methylprednisolone of the sequential redistribution of cathepsin D and other lysosomal enzymes during myocardial ischemia in rabbits.
Authors: R S Decher, A R Poole, J T Dingle, K Wildenthal
Journal: Journal of Clinical Investigation (1978)

Occlusion of the circumflex coronary artery induced a profound redistribution in ischemic rabbit myocardium of several lysosomal acid hydrolases, including cathepsin D, B-acetylglycosaminidase, and acid phosphatase. 30-45 min after ligation non-sedimentable cathepsin D activity rose from 36% of the total activity to 42-48%, and in immunohistochemical preparations cathepsin D appeared to have diffused from lysosomes into the cytosol of injured cells. A pharmacologic dose of methylprednisolone (50mg/kg) significantly delayed the subcellular redistribution of cathepsin D and the other hydrolases in ischemic heart. Thus, in treated hearts the nonsedimentable activity of cathepsin D rose to only 38% after 30 min of ischemia and 42% after 45 min (P is less than 0.05 compared to untreated ischemia at each time). Similarly, unlike untreated hearts, noevidence of enzyme diffusion from lysosomes could be demonstrated immunohistochemically in corticosteroid-treated ischemic hearts for over 45 min. After 1-2 h of ischemia, however, steroid-protected myocytes deteriorated and the biochemical activity and anatomical distribution of cathepsin D were indistinguishable from untreated ischemic hearts. This study demonstrates that corticosteroid pretreatment does not prevent alterations in cardiac lysosomes during severe ischemia indefinitely, but does delay their development significantly.
Acute stress affects cytokines and nitric oxide production by alveolar macrophages differently.
Authors: J H Persoons, K Schornagel, J Brevé, F Berkenbosch, G Kraal
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The production of cytokines by alveolar macrophages was studied after exposure of rats to an acute stress paradigm (mild inescapable footshocks). When alveolar macrophages from nonstressed animals were isolated and cultured, they readily produced interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) after stimulation with lipopolysaccharides (LPS). For these cytokines the dose response relationship for LPS was clearly biphasic. Nitric oxide (NO) production could only be detected upon LPS stimulation and seemed to be monophasic. However, when the animals were exposed to the acute stress paradigm, isolated alveolar macrophages (AM) showed a marked increase of IL-1 beta and TNF-alpha secretion upon LPS stimulation in vitro, but no changes in the production of IL-6 were detected. In contrast, exposure to the stress paradigm resulted in a strong decrease in NO production. The results indicate that emotional stress can rapidly induce altered behavior of AM, which is discussed in view of the important role these cells play in the regulation of the local immune responses in the lungs and the possible contribution to asthma.
The headwaters of family medicine
Authors: D. Loxterkamp
Journal: BMJ (2008)

Harboyan syndrome (CDPD) consists of congenital corneal endothelial dystrophy and progressive perceptive deafness and is transmitted as an autosomal recessive trait. CDPD and autosomal recessive, non-syndromic congenital hereditary endothelial corneal dystrophy (CHED2) both map at overlapping loci at 20p13, and mutations of SLC4A11 were recently reported in CHED2. We here report genotype studies in six families with CDPD and one family with either CHED or CDPD, from various ethnic backgrounds (in the seventh families hearing loss could not be assessed because of the proband’s young age). We found novel SLC4A11 mutations in all patients. Why some mutations cause hearing loss in addition to corneal dystrophy is presently unclear. Our findings extend the implication of the SLC4A11 borate transporter beyond corneal dystrophy to perceptive deafness.
Successful treatment of lymphomatoid granulomatosis using cyclosporin-A after failure of intensive chemotherapy
Authors: Luis E. Raez, Jack D. Temple, Mario Saldana
Journal: American Journal of Hematology (1996)

We report the successful and maintained response of lymphomatoid granulomatosis using a new approach to therapy, cyclosporin-A, after failure of aggressive multiagent chemotherapy. © 1996 Wiley-Liss, Inc.
Noninvasive detection of coronary lesions using 16-detector multislice spiral computed tomography technology
Authors: Axel Kuettner, Tobias Trabold, Stephen Schroeder, Anja Feyer, Torsten Beck, Ariane Brueckner, Martin Heuschmid, Christof Burgstahler, Andreas F. Kopp, Claus D. Claussen
Journal: Journal of the American College of Cardiology (2004)
Effect of Th1 cytokines on acid secretion in pharmacologically characterised mouse gastric glands
Authors: I T Padol
Journal: Gut (2004)

Acid secretion plays an important role in the ecology of Helicobacter species and acid secretory status heralds patterns of gastritis. The presence of inflammatory cells and their products, in close proximity to parietal cells, questions the extent of the effect of cytokines on acid secretion.We adopted and extensively characterised the mouse gastric gland preparation and its secretory capacity, which was measured using (14)C-aminopyrine accumulation. Subsequently, we tested the secretory properties of a wide range of species specific cytokines, including those associated with Th1 and Th2 immune responses.(14)C-aminopyrine accumulation in mouse gastric glands was shown to be a very sensitive "in vitro" method of testing classical secretagogues and antisecretory compounds, and provided pharmacological data on acid secretion in the mouse. Only two mouse cytokines, interleukin 2 and interferon gamma, had a direct effect on acid secretion causing dose dependent inhibition.Both cytokines belong to the Th1 type immune response and consequently their inhibitory effect may play a role in the hyposecretion seen with H pylori infection and colonisation throughout the corpus of the stomach that potentially can lead to gastric atrophy and subsequently, in some cases, cancer.
Prostatic cancer and radionuclides Evidence implicates zinc-65
Authors: A Hilson
Journal: BMJ (1994)

Prostatic cancer and radionuclidesEvidence implicates zinc-65EDrroR,-In their paper on prostatic cancer in employees of the United Kingdom Atomic Energy Authority, Cleone Rooney and colleagues raise the possibility of localisation of zinc-65 in the prostate being an aetiological factor but state that "there are no reliable data on 65Zn uptake by the human prostate."'Prout et al showed in 1959 that 65Zn localises avidly in the prostate in human males, and especially in benign adenomas.2In 1956 Daniel et al showed that the ratio of the 65Zn concentration in normal prostates to that in blood was over 2-5:1; one patient had a ratio of 27:1.3The consensus of both groups was that neoplastic prostates concentrated less zinc.The uptake of zinc by the human prostate is so high that it is technically possible to image the prostate with ""9Zn."(Unfortunately, there are no isotopes of zinc suitable for routine imaging, so this approach has not found a place in routine nuclear medicine.)This avid uptake of zinc by the prostate must increase the probability of 65Zn being a relevant factor in carcinogenesis in this population.
OUTCOMES OF PCI IN PATIENTS UNDERGOING APPROPRIATE VERSUS UNCERTAIN PCI
Authors: Dechaboon Changsirivathanathamrong, Annapoorna Kini, Jason Kovacic, Michael Kim, Prakash Krishnan, Pedro Moreno, Javed Suleman, Choudhury Hasan, Samin Sharma
Journal: Journal of the American College of Cardiology (2013)
“Flatland: A romance of many dimensions”
Authors: Biswadip Hazarika, Barbara J. Bain
Journal: American Journal of Hematology (2012)

In 1884 Edwin Abbott, an English novelist, wrote a popular novel “Flatland: A Romance of Many Dimensions”. It was a reflection of great scientific imagination of a land which was of only two dimensions unlike our world of three dimensions. Naturally, the inhabitants of that “Flat land” were triangles, rectangles and circles. The book was illustrated by the author (himself a square) [1]. The world we observe in microscopic screening of blood or bone marrow films is also a flat land – a world of two dimensions. Though the creatures of this land, white cells, red cells, platelets and their precursors are originally three dimensional structures in their homeland of blood or bone marrow, they are flattened into two dimensional structures when films are made on glass slides. In this process the cytoplasmic materials overlying the nuclei slide over to the periphery to give the conventional morphological pictures of the observable cytoplasmic constituents, such as granules and vacuoles, surrounding the nucleus. Sometimes, these cytoplasmic elements still overlie the nucleus. This can be difficult to appreciate with routine hematological staining but a cytochemical stain, with a counterstain, can help to visualize them. This myeloperoxidase stain (substrate 3, 3′ DAB with a counterstain of diluted Giemsa in phosphate buffer, pH 6.8 [2]) from a patient with acute myeloid leukemia shows cytoplasmic constituents, including granules, surrounding the nucleus but several Auer rods have been left, stranded on top of the nucleus. Our flatland can be as entrancing as that described by Abbott in 1884.
Met 358 to Arg mutation of alpha 1-antitrypsin associated with protein C deficiency in a patient with mild bleeding tendency.
Authors: D Vidaud, J Emmerich, M Alhenc-Gelas, J Yvart, J N Fiessinger, M Aiach
Journal: Journal of Clinical Investigation (1992)

The molecular defect responsible for a dramatic prolongation of all standard clotting tests discovered in a 15-yr-old boy has been identified. Initial investigations revealed the presence of an activated Factor X (Factor Xa) and thrombin inhibitor which copurified with alpha 1-antitrypsin (alpha 1-AT), thereby suggesting the occurrence of an alpha 1-AT variant similar to alpha 1-AT Pittsburgh. This was confirmed by dot-blot analysis and direct sequencing after amplification by the polymerase chain reaction. A G to T transition at nucleotide 10038 results in the substitution of Met to an Arg, converting alpha 1-AT into an Arg-Ser protease inhibitor (serpin) that inhibited thrombin and Factor Xa more effectively than antithrombin III. Surprisingly, there was no bleeding history in the proband. The common mutation Z, which may explain a reduced expression of the allele bearing the Arg 358 Met mutation, was not observed in the propositus' DNA. To exclude the presence of another mutation, the coding regions and intron/exon junctions were sequenced. No other mutation was found. Recently, the patient experienced his first hemorrhagic episode at the age of 17. The level of the abnormal inhibitor had increased twofold 2 mo before. The large decrease in protein C concentration may account for the mild bleeding tendency in this case, despite the presence of the alpha 1-AT Pittsburgh mutation. An abnormal protein C pattern was observed in patient's plasma, suggesting that the circulating deficiency might be due to a deleterious effect of the abnormal inhibitor on both intracellular processing and catabolism of protein C.
Release of Gelatinase from a Novel Secretory Compartment of Human Neutrophils
Authors: Beatrice Dewald, Ursula Bretz, Marco Baggiolini
Journal: Journal of Clinical Investigation (1982)

Gelatinase is a metallo-proteinase that acts specifically on denatured collagen. In human neutrophils, this enzyme is localized in small, morphologically still unidentified storage organelles that are resolved from the specific and the azurophil granules upon subcellular fractionation by differential sedimentation. When neutrophils isolated from freshly drawn blood are exposed to soluble stimuli such as N-formyl-methionyl-leucyl-phenylalanine, zymosan-activated serum, phorbol myristate acetate, or the calcium ionophore A 23187, or are induced to phagocytose opsonized zymosan, they rapidly release gelatinase in large amounts (30-70% of the cellular content in 10 min). When neutrophils from donor blood, which had been stored for 24 h at 4°C are used, extensive release even occurs without added stimuli by simply warming to 37°C.
Increased innate immune responses by interleukin-22 contributes to the inflammatory process in rheumatoid arthritis
Authors: Renoud J Marijnissen, Marije I Koenders, Cheryl Nickerson-Nutter, Shahla Abdollahi-Roodsaz, Annemieke M H Boots, Leo A B Joosten, Wim B van den Berg
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> IL-22 is a mediator in antimicrobial responses and inflammatory autoimmune diseases. It can be produced by innate and adaptive haematopoietic immune cells, but the expression of the receptor (IL-22R) seems to be restricted to non-haematopoietic tissue cells. Although both IL-22 and the IL-22R have been identified in the synovium of RA patients, the contribution to disease pathogenicity remains to be established. <h3>Materials and methods</h3> The authors first investigated the expression and origin of IL-22 and the IL-22R in the inflamed joints of IL-1Ra-/- mice. Furthermore, the mice were treated with neutralising anti-IL-22 antibodies. Subsequently, the authors analysed the IL-22R expressing cells in human RA synovium by immunohistochemistry (IHC) and flow cytometry. Eventually, the authors stimulated RA synovial biopsies, RA human fibroblast-like cells (RAFLS) and endothelial (HUVEC) cells with IL-22 and analysed the production of inflammatory mediators. <h3>Results</h3> In the arthritic joints of IL-1Ra-/- mice, IL-22 is mainly produced by T cells that co-expressed IL-17. Anti-IL-22 treatment of IL-1Ra-/- mice significantly reduced inflammation and bone erosion, suggesting an important role of IL-22 in joint destruction. The authors subsequently analysed the effects of IL-22 on human RA synovium. Exposure to IL-22 increased the expression of TNFα, IL-6 and IL-8. Compared to IL-17, stimulation with IL-22 induced higher levels of IL-8, and combination of the two cytokines resulted in an additional response. IHC identified endothelial cells and synovial fibroblast-like cells as the main IL-22 receptor expressing cells. Surprisingly, stimulation of RA human fibroblast-like cells and endothelial (HUVEC) cells did not result in a clear increase in the innate immune response. This in contrast to the synovial tissue, which is heavily infiltrated with inflammatory cells. <h3>Conclusions</h3> Our data support the dual role of IL-22 in pathological inflammation, showing that the functional importance of IL-22 is context dependent. Current SCID studies with neutralising IL-22 antibodies will have to prove the therapeutic potential of IL-22 in RA.
Is shock-wave lithotripsy the solution for gallstones in this, the year of the boom?
Authors: Leslie J. Schoenfield
Journal: Hepatology (1986)

We treated nine patients with functioning gallbladders containing one to three symptomatic radiolucent stones not larger than 25 mm in diameter, as well as five patients with stones in the common bile duct that were not removable by endoscopic procedures, by means of extracorporeally generated shock waves during general anesthesia. The patients with gallbladder stones received adjuvant treatment with a combination of ursodeoxycholic acid and chenodeoxycholic acid. All gallbladder stones were disintegrated into sludge or fragments with diameters of no more than 8 mm. In six of the nine patients the fragments disappeared completely within 1 to 25 weeks. No adverse effects were detected during a follow-up period of 10 to 34 weeks, except transient biliary pain in two patients, with mild pancreatitis in one. In four of the five patients with common-bile-duct stones, shock-wave treatment permitted stone disintegration and successful endoscopic extraction or spontaneous passage of fragments. We conclude that gallstone disease may be treated successfully and without serious adverse effects by extracorporeally generated shock waves in selected patients.
N‐terminal pro brain natriuretic peptide in the management of patients in the medical emergency department (PROMPT): correlation with disease severity, utilization of hospital resources, and prognosis in a large, prospective, randomized multicentre trial
Authors: Andreas Luchner, Martin Möckel, Eberhard Spanuth, Joachim Möcks, Dirk Peetz, Hannsjörg Baum, Christoph Spes, Christian E. Wrede, Jörn Vollert, Reinhold Müller, Hugo Katus, Evangelos Giannitsis
Journal: European Journal of Heart Failure (2012)
IMPACT OF DIABETES MELLITUS INIODINE-123 META-IODOBENZYLGUANIDINE (I123MIBG) CARDIAC UPTAKE IN PATIENTS WITH HEART FAILURE
Authors: Gennaro Pagano, Dario Leosco, Stefania Paolillo, Emilio Attena, Grazia Daniela Femminella, Claudio de Lucia, Teresa Pellegrino, Alberto Cuocolo, Nicola Ferrara, Pasquale Perrone-Filardi, Antonio Rapacciuolo, Giuseppe Rengo
Journal: Journal of the American College of Cardiology (2013)