tbuckley/cabot-search huggingface dataset:
PMO-126 The role of vascular-adhesion-protein 1 (vap-1) in mediating monocyte migration across inflamed hepatic sinusoidal endothelium
Authors: H Zimmermann, C J Weston, S M Curbishley, D H Adams
Journal: Gut (2012)

<h3>Introduction</h3> There is compelling evidence that accumulating monocyte-derived macrophages are pivotally involved in driving liver fibrogenesis. It remains unclear which molecules mediate transmigration of these cells across hepatic sinusoidal endothelial cells (HSEC). VAP-1 is an atypical adhesion molecule with enzymatic monoamine oxidase activity that is predominantly expressed in the liver microvasculature. It possesses key function in the recruitment of various lymphocyte subsets. The aim of this study was to decipher VAP-1 contribution to monocytic transendothelial transmigration. <h3>Methods</h3> Primary human HSEC were isolated from explanted and grown to confluence in flow chambers. After activation with TNF-α/IFN-γ for 24h HSEC were treated with VAP-1 antibody and enzyme inhibitors. Monocytes were enriched from peripheral blood by using OptiPrep gradient. Monocyte subsets (CD14<sup>++</sup>CD16<sup>−</sup>, CD14<sup>++</sup>CD16<sup>+</sup>, CD14<sup>+</sup>CD16<sup>++</sup>) were isolated by FACS-sorting. Isolated monocytes were perfused over HSEC monolayers under constant flow simulating physiological shear stress (0.05 Pa). Adhesion and transmigration was studied using phase contrast microscopy. Transwell assays were used to study the phenotype of transmigrated monocytes by flowcytometry. <h3>Results</h3> HSEC pretreatment with VAP-1 antibody (TK8-14) or enzyme inhibitor Semicarbizide equally reduced monocyte transmigration by ∼50%. VCAM-1 blockade had a similar but redundant effect whereas CLEVER-1-antibody or LOX-inhibitor (β-APN) did not alter monocyte transmigration. VAP-1 antibody acted in a time-dependent manner with influence on monocyte adhesion only after short-term application (15 min). Inhibiting VAP-1 led to profound reduction of proinflammatory <i>nonclassical</i> CD14<sup>+</sup>CD16<sup>++</sup> monocyte transmigration but also affected <i>classical</i> CD14<sup>++</sup>CD16<sup>−</sup> whereas the <i>intermediate</i> CD14<sup>++</sup>CD16<sup>+</sup> subtype was not affected. Under static conditions VAP-1 enzymatic or antibody inhibition was significantly blunted suggesting flow to be a mandatory prerequisite for the biological function of VAP-1 on monocytes. Increased expression of HLA-DR and the M2 macrophage marker CD206 on monocyte subsets after endothelial transmigration was not altered by VAP-1 inhibition. <h3>Conclusion</h3> Endothelial VAP-1 differentially modulates monocyte recruitment under flow conditions in a time-dependent fashion and .favours transmigration of a proinflammatory monocyte subset. The critical role of VAP-1 enzyme function renders small molecules as a promising therapeutic approach in combating liver inflammation and subsequent fibrosis. <h3>Competing interests</h3> None declared.
Is increased ammonia liberation after bleeding in the digestive tract the consequence of complete absence of isoleucine in hemoglobin? A study in pigs
Authors: Charles L. H. van Berlo, Anton E. J. M. van de Bogaard, Marion A. H. van der Heijden, Hans M. H. van Eijk, Mieke A. Janssen, May C. F. Bost, Peter B. Soeters
Journal: Hepatology (1989)

A variable protein-induced toxicity has been reported in liver disease. The aim of this study was to establish the cause of increased ammonia liberation in the gut after intraluminal bleeding. Therefore, blood was sampled from catheterized piglets [20 ± 0.8 kg (means ± S.E.); n = 10] to determine ammonia, urea and amino acid levels before and 1, 2, 3 and 6 hr after a standard pig meal (750 gm, 12% protein). After 1 week, this procedure was repeated after ingestion of an isonitro-genous amount of bovine whole blood (400 ml). In a second series of experiments, the same procedures were performed after ingestion of plasma, whole blood, eryth-rocytes and feed. Electromagnetically measured total intestinal, small and large bowel flow was not significantly influenced by the type of meal ingested. Portal ammonia release was significantly increased 2-fold after a blood meal, whereas intestinal glutamine utilization did not increase. Plasma urea levels were increased 200 to 300% after whole blood and erythro-cytes, whereas after ingestion of plasma, urea levels were similar to values in controls. Glutamine utilization was not different among the various groups and occurred predominantly in the small bowel. In the fasted state, small bowel glutamine utilization paralleled ammonia production. In the fed state, this equimolar relationship could not be assessed because luminal glutamine utilization could not be determined. Isoleucine levels decreased to 25% of fasting levels. Analysis of blood constituents revealed a complete lack of isoleucine in the hemoglobin molecule. Net total α-amino-nitrogen absorption was doubled after a blood meal. The highest absorption was found in the small bowel. These findings lead us to hypothesize that, due to complete lack of isoleucine in hemoglobin, ingestion of blood into the gut presents the organism with protein of low biological value, leading to decreased protein synthesis and to net protein degradation, which in turn may result in increased ammonia- and ureagenesis.
Intramural Delivery of Agent via a Novel Drug-Delivery Sleeve
Authors: Alvaro Moura, Jules Y.T. Lam, Daniel Hébert, James R. Kermode, Gordon W. Grant, Danielle Robitaille, Enrique J. Klein, Paul G. Yock, John B. Simpson, Aaron V. Kaplan
Journal: Circulation (1995)

Background The infusion sleeve is a novel drug-delivery catheter system designed to deliver an agent under controlled conditions into the arterial wall at the site of angioplasty. The purpose of the present study was to characterize the delivery agent via the infusion sleeve in ex vivo and in vivo models. Methods and Results The delivery of horseradish peroxidase via the infusion sleeve was studied in a porcine explanted heart model. Under physiological conditions, arteries underwent balloon injury (≈10% overstretch), after which horseradish peroxidase (2.5 mL) was delivered at specific pressures. Cross-sectional analysis demonstrated greater staining when the agent was delivered at increasing pressures. The infusion sleeve was evaluated in an in vivo canine coronary model. With an infusion sleeve loaded over a standard dilatation catheter through a 9F guide, overstretch balloon injury was performed, after which fluoresceinated heparin was delivered. Animals were killed 2 hours after delivery. Fluoresceinated heparin–treated segments demonstrated high fluorescence signals, localizing with smooth muscle cell nuclei with less activity in the interstitium. The functional significance of intramural heparin delivery was studied in a porcine carotid model. In the presence of 111 In-labeled platelets, arteries underwent overstretch injury followed by delivery of heparin (50 or 100 units/kg) or vehicle. Platelet deposition was reduced at 30 minutes (57%, P &lt;.01) and 12 hours (39%, P =.06) compared with saline controls. Conclusions Agent delivery via the infusion sleeve is pressure dependent; transmural delivery is possible with minimal disruption of arterial wall architecture; the infusion sleeve is compatible with standard angioplasty equipment; and heparin delivery at the site of balloon injury significantly reduces platelet deposition in a porcine model for a minimum of 12 hours.
A Case of Tracheal Metastasis in Colon Cancer
Authors: Minkyung Lee, Yu Kyung Lee, Tae Joo Jeon, Seung-Kook Sohn, Young Hoon Ryu
Journal: Clinical Nuclear Medicine (2014)

A 44-year-old female patient received proctocolectomy and chemotherapy for a diagnosis of colon cancer 10 years previously and presented here with new onset of cough for 2 months and a progressive increase of her serum CA19-9 level. 18F-FDG PET/CT imaging revealed a hypermetabolic lesion within the trachea. Immunostaining confirmed that this lesion was a metastatic adenocarcinoma that originated from the patient’s initial colon cancer. 18F-FDG PET/CT enabled localization of unusual endotracheal metastasis and facilitated the development of an appropriate treatment plan.
Fluorine and Dental Health
Authors: Jan Lieben
Journal: New England Journal of Medicine (1944)

standable language makes it readable also for the health officer, sanitary engineer, or sanitarian who may rather suddenly encounter the problems accompanying the issuance of a reactor construction permit by the Atomic Energy Commission. The six chapters-Radiation Detection and Measurement,  Exposure Control, Permissible Levels of Radiation,  Exposure Incidents, Radioactive Material Transport, and Radioactive Waste Disposal-are a mixture of operating procedures for reactor personnel and basic concepts in radiological health. The booklet will give a detailed insight into the health problems connected with reactor operation, radiation exposure control, laundering of contaminated clothing, shipment of isotopes, and waste disposal. It deals rather extensively with the regulations of the Atomic Energy Commission but tells the reader nothing of the laws and regulations which have been adopted so far by 28 states. The book, which states in the introduction that it has been prepared for as wide an audience as possible, is misleading with its broad title, Radiation Protection. The title should read Radiation Protection at a Major Nuclear Installation. About 65 per cent of the material, while very interesting, will be of little immediate value for the average holder of an isotope license or the user of x-ray machines. JAN LIEBEN
Listening to the Patient
Authors: MANFRED S. ROTHSTEIN
Journal: Annals of Internal Medicine (1984)

Letters and Corrections1 September 1984Listening to the PatientMANFRED S. ROTHSTEIN, M.D.MANFRED S. ROTHSTEIN, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-101-3-406_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Understanding what patients are trying to tell us(1) is a critical aspect of the art of medicine and is better learned by listening to a patient than by reading a text.The story is told at Duke University Medical Center of the woman who presented with a chief complaint of "falling out spells." Only after an extensive and completely unremarkable neurologic examination did anyone discover that the patient was suffering from a prolapse of the uterus. Other common terms in this area of the nation are "high blood" for hypertension, "bad blood" for syphilis, "risin'" for a...Reference1. BURNUM J. Dialect is diagnostic. Ann Intern Med. 1984;100:899-901. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: MANFRED S. ROTHSTEIN, M.D.Affiliations: Fayetteville Dermatology Clinic 1308 Medical Drive; Fayetteville, NC 28304 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDriving Miss Evers' Boys to the Historical Tuskegee Study of Untreated Syphilis 1 September 1984Volume 101, Issue 3Page: 406-406KeywordsBloodHypertensionSyphilisUterus ePublished: 1 December 2008 Issue Published: 1 September 1984 PDF downloadLoading ...
Quantitative Copy Number Analysis of Onco- and Tumor Suppressor Genes in Invasive Breast Cancer by Dedicated Multiplex Ligation-Dependent Probe Amplification.
Authors: P. van Diest, C. Moelans, H. Monsuur, R. de Weger
Journal: Cancer Research (2009)

Abstract Several genes have been shown to be implicated in the development, progression and response to therapy of invasive breast cancer. The phenotypic uniqueness (and thus the heterogeneity of clinical behavior) among patients' tumors may be traceable to the underlying variation in DNA copy number. In the present work, we sought to obtain a more complete view of copy numbers of breast cancer related genes by multiplex ligation-dependent probe amplification (MLPA) in 104 invasive breast cancers, and to assess phenotypic correlations.There was a significant correlation between the number of amplifications on the one hand and histological grade and mitotic index on the other. MLPA revealed the following frequent amplifications: MYC in 48%, PRDM14 in 34%, TOP2A in 32%, ADAM9 in 32%, HER2 in 28%, CCND1 in 26%, EMSY in 25%, IKBKB in 21%, AURKA in 17%, FGFR1 in 17%, ESR1 in 16%, CCNE1 in 12% and EGFR in 9%. Amplifications of EGFR, CCNE1 and HER2 were negatively associated with ER while FGFR1, ADAM9, IKBKB and TOP2A were positively associated with ER. Amplifications of ESR1, PRDM14, MYC and HER2 were associated with a higher mitotic index and PRDM14 and HER2 amplifications with higher grade. MYC amplification was more frequent in ductal tumors and high level MYC amplifications were significantly associated with larger tumor size. HER2-MYC, HER2-CCNE1 and EGFR-MYC co-amplified tumors were significantly larger than tumors with either of both amplifications. CDH1 (20%) and FGFR1 (10%) were the most frequently lost genes.In conclusion, gene copy number analysis with this “breast cancer MLPA kit” allowed to simultaneously assess copy numbers of 20 important breast cancer genes, providing an overview of the most frequent (co)amplifications as well as interesting phenotypic correlations, and thereby data on the potential importance of these genes in breast carcinogenesis and progression. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5168.
Scleritis and associated disease.
Authors: S M Lachmann, B L Hazleman, P G Watson
Journal: BMJ (1978)

One hundred patients (66 women and 34 men) who presented consecutively to Moorfields Eye Hospital with scleral disease underwent medical examination. Thirteen were found to have seropositive rheumatoid arthritis and another 16 also had rheumatoid factor present (Rheumaton test). Autoantibodies were present in 35% of patients, being most common in the elderly and most frequent in cases of necrotising and diffuse scleritis. Although scleral disease is uncommon, it is associated with connective-tissue disorders. Scleritis may be severe and destructive locally, and one series showed that 27% of patients who develop necrotising scleritis are dead from systemic complications within five years. It is therefore important for it to be correctly diagnosed and effectively treated at an early stage.
586. Novel Lipidic Vectors for Targeted Delivery of Functional Oligonucleotides to Pulmonary Endothelium
Authors: Annette S. Wilson, Stephen J. Kennel, Leaf Huang, Bruce R. Pitt, Song Li
Journal: Molecular Therapy (2005)

Top of pageAbstract
Targeted delivery of functional oligonucleotides to pulmonary endothelium shows promise both as a novel therapeutics for the treatment of pulmonary diseases and as a research tool to study gene function in pulmonary endothelium. To this end, we have developed a novel lipidic vector that is highly efficient in targeted delivery to pulmonary endothelium of functional oligonucleotides including antisense ODN, siRNA and synthetic minigenes. This is based on a method that utilizes an ionizable aminolipid (1,2-dioleoyl-3-dimethylammonium propane, DODAP) and an ethanol-containing buffer system for encapsulating large quantities of polyanionic ODN in lipid vesicles. An endothelium-specific antibody (34A) is incorporated into the lipid vesicles via a distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG) spacer. These vesicles are around 100-200 nm in diameter with an ODN entrapment efficiency of 60-80%. 34A antibody mediated efficient delivery of ODN to mouse lung endothelial cells in vitro and in intact mice. Furthermore, this formulation is associated with minimal proinflammatory cytokine response and other hematological toxicities. These results provide a basis for lipid-mediated delivery of ODN for the treatment of pulmonary diseases. They also suggest the utility of this approach as a research tool to characterize the function of genes in the pulmonary endothelium.
The G(-248)A polymorphism in the promoter region of the Bax gene does not correlate with prognostic markers or overall survival in chronic lymphocytic leukemia
Authors: Å Skogsberg, G Tobin, A Kröber, D Kienle, U Thunberg, A Åleskog, K Karlsson, A Laurell, M Merup, J Vilpo, C Sundström, G Roos, H Jernberg-Wiklund, H Döhner, K Nilsson, S Stilgenbauer, R Rosenquist
Journal: Leukemia (2005)
Phylogenetic Signals in DNA Composition: Limitations and Prospects
Authors: J. Mrazek
Journal: Molecular Biology and Evolution (2009)

The concept of genome signature allows sequence comparisons without alignment. It relies on the premise that oligonucleotide compositions of DNA segments from the same or closely related genomes tend to be more similar than those from distantly related genomes. This concept has been used in detection of lateral gene transfer, phylogenetic classification of metagenome sequences (binning), and in studies of evolution of viruses and plasmids. The goal of this work is to explore limitations of genome signature in phylogenetic classification of DNA sequences and to identify formal representations of genome signature that expose best the phylogenetic relationships among prokaryotes. We found that genome signatures that best represent phylogenetic relationships are those normalized to factor out differences in G + C content and utilizing the standard A-C-G-T alphabet or the degenerate R-Y (purine-pyrimidine) alphabet. The main limitation of all genome signature representations tested is lack of divergence among some distantly related species. "Crowding" of the genome signature space and absence of molecular clock likely contribute to this phenomenon. We introduce "periodicity signatures"--formal representations of periodic sequence patterns related to DNA curvature--which can discriminate between bacterial and archaeal DNA sequences. Interestingly, archaea of the order Halobacteriaceae have periodic signatures similar to bacteria, possibly due to their early divergence from other archaea, extensive lateral gene transfer, or due to their adaptation to high salt environments. Our results have practical implications for development and application of genome signature-based methods for analysis and classification of DNA sequences.
Long term comparison of azapropazone with allopurinol in control of chronic gout and hyperuricaemia
Authors: J. S. Templeton
Journal: Annals of the Rheumatic Diseases (1983)

modifications,2 to fibrinopeptide f3, (FpB,81-42)3 with modifications2 and to ,8-thromboglobulin (,ITG)4 with tnodifications.2Serum cholesterol and triglycerides were measured direct5 while high density lipoprotein cholesterol (HDLC) was estimated-by precipitation of 13-and prebeta-lipoproteins and measurement of cholesterol in the a-lipoprotein.'Data from these patients were compared with data from age-matched controls (Table 1).No significant differences between patients with gout pnd controls were found.Spearman rank correlation coefficients were calculated between FpA, FpB,81-42 and BTG and lipid concentrations, alcohol consumption, and weight as the data on alcohol and weight tend not to be distributed normally.There were only two significant correlations--that is, cholesterol in mmol/l with FpA in pmolll and HDLC in mmol/l with
Mediating ERK1/2 signaling rescues congenital heart defects in a mouse model of Noonan syndrome
Authors: Tomoki Nakamura, Melissa Colbert, Maike Krenz, Jeffery D. Molkentin, Harvey S. Hahn, Gerald W. Dorn, Jeffrey Robbins
Journal: Journal of Clinical Investigation (2007)

Noonan syndrome (NS) is an autosomal dominant disorder characterized by a wide spectrum of defects, which most frequently include proportionate short stature, craniofacial anomalies, and congenital heart disease (CHD). NS is the most common nonchromosomal cause of CHD, and 80%-90% of NS patients have cardiac involvement. Mutations within the protein tyrosine phosphatase Src homology region 2, phosphatase 2 (SHP2) are responsible for approximately 50% of the cases of NS with cardiac involvement. To understand the developmental stage- and cell type-specific consequences of the NS SHP2 gain-of-function mutation, Q79R, we generated transgenic mice in which the mutated protein was expressed during gestation or following birth in cardiomyocytes. Q79R SHP2 embryonic hearts showed altered cardiomyocyte cell cycling, ventricular noncompaction, and ventricular septal defects, while, in the postnatal cardiomyocyte, Q79R SHP2 expression was completely benign. Fetal expression of Q79R led to the specific activation of the ERK1/2 pathway, and breeding of the Q79R transgenics into ERK1/2-null backgrounds confirmed the pathway's necessity and sufficiency in mediating mutant SHP2's effects. Our data establish the developmental stage-specific effects of Q79R cardiac expression in NS; show that ablation of subsequent ERK1/2 activation prevents the development of cardiac abnormalities; and suggest that ERK1/2 modulation could have important implications for developing therapeutic strategies in CHD.
Fifty-seven Cases of Diaphragmatic Hernia and Eventration
Authors: C. J. Evans, J. A. Simpson
Journal: Thorax (1950)

During the last 20 years great advances have been made in the recognition of diaphragmatic hernia, and many series of cases reported by numerous authors have helped to place the diagnosis and treatment on a sound surgical basis (Dunhill, 1935; Barrett and Wheaton, 1934; Donovan. 1945; Morton, 1939; Harrington, 1940; Gross, 1946).More recently progress in thoracic surgery and anaesthesia has given a more direct approach to the lesion itself and has placed the treatment of diaphragmatic hernia on a basis comparable with the treatment of other types of herniation of the abdominal organs (Sweet, 1948;Truesdale, 1945 ;Allison, 1946).Since 1937, 46 cases of diaphragmatic hernia have been admitted to this unit.These are reviewed, and three additional cases, treated by Mr. G. A. Mason at the Nottingham General Hospital, have been included in the series.They are classified as (1) traumatic hernia (a) due to non-penetrating injuries; (b) due to penetrating injuries.(c) post-operative; and (2) non-traumatic herniae: (a) oesophageal hiatus hernia with normal oesophagus; (b) oesophageal hiatus hernia with patho- logical changes in the oesophagus; and (c) hernia through defects in the muscular and tendinous portions of the diaphragm.The subdivision of oesophageal hiatus hernia into those with and those without pathological changes in the oesophagus is necessary in view of the different problems of diagnosis and treatment involved.No attempt has been made to classify the cases into congenital and acquired types ; accurate differentiation is not always possible and is of academic interest only.Eight cases of eventration of the diaphragm seen over the same period are also reviewed.TRAUMATIC HERNIA DUE TO NON-PENETRATING INJURIES (7 Cases).-Severecrushing injuries to the abdomen accounted for five cases, and four of these also sustained a fractured pelvis.In none did coincident rupture of any abdominal viscera occur, although in one patient a laparotomy had been performed elsewhere with this suspected diagnosis.Only one sustained bruising of the chest wall and none had fractured ribs, which suggests that the mechanism of injury to the diaphragm is in the nature of an explosive rupture due to sudden increase in intra-abdominal pressure.Case I (No. 5307).-Awoman aged 39 was involved in a car accident and thrown Aiolently forwards against the driver's seat.She was seven and a half months pregnant on July 13, 2023 by guest.