tbuckley/cabot-search huggingface dataset:
966 ASSOCIATION OF MANNOSE-BINDING-LECTIN-2-GENE POLYMORPHISM TO THE DEVELOPMENT OF HEPATITIS-C-INDUCED HEPATOCELLULAR CARCINOMA
Authors: P. Eurich, S. Boas-Knoop, R. Neuhaus, R. Somasunsaram, M. Ruehl, U.P. Neumann, P. Neuhaus, M. Bahra, D. Seehofer
Journal: Journal of Hepatology (2011)
Regulation of Fibroblast Growth Factor-2 Activity by Human Ovarian Cancer Tumor Endothelium
Authors: Melissa K. Whitworth, Alison C. Backen, Andrew R. Clamp, Godfrey Wilson, Rhona McVey, Andreas Friedl, Alan C. Rapraeger, Guido David, Alan McGown, Richard J. Slade, John T. Gallagher, Gordon C. Jayson
Journal: Clinical Cancer Research (2005)

Abstract Fibroblast growth factor-2 (FGF-2) is a potent angiogenic cytokine that is dependent on heparan sulfate for its biological activity. We have investigated the relationship among heparan sulfate, FGF-2, and the signal-transducing receptors in human, advanced-stage, serous ovarian adenocarcinoma. Using a unique molecular probe, FR1c-Ap, which consisted of a soluble FGF receptor 1 isoform lllc covalently linked to an alkaline phosphatase moiety, the distribution of heparan sulfate that had the ability to support the formation of a heparan sulfate/FGF-2/FGFR1 isoform IIIc alkaline phosphatase heparan sulfate construct complex was determined. This may be taken as a surrogate marker for the distribution of biologically active heparan sulfate and was distributed predominantly in endothelial cells and stroma but was absent from adenocarcinoma cells. In situ hybridization revealed the expression of FGFR1 mRNA in the endothelium and reverse transcription-PCR confirmed the presence of FGFR1 isoform IIIc but not isoform IIIb. The presence of FGF-2 around tumor endothelium was detected through immunohistochemistry. Double-staining techniques showed that heparan sulfate was found predominantly at the basal aspect of the endothelium and suggested that syndecan-3 might function as one of the proteoglycans involved in FGF-2 signaling in the endothelium. The data suggest that the entire extracellular signaling apparatus, consisting of FGF-2, biologically active heparan sulfate, and FGFRs capable of responding to FGF-2, is present in ovarian cancer endothelium, thereby highlighting the cytokine and its cognate receptor as potential targets for the antiangiogenic treatment of this disease.
Somatostatin, gastrointestinal peptides, and the carcinoid syndrome.
Authors: R G Long, J R Peters, S R Bloom, M R Brown, W Vale, J E Rivier, D G Grahame-Smith
Journal: Gut (1981)

During a control infusion noradrenaline and alcohol each provoked carcinoid flushing in four of five patients and pentagastrin in two of five patients. When tetradecapeptide somatostatin was infused on another day no patient flushed at any time, even when 16 microgram of either noradrenaline or pentagastrin were administered. Carcinoid flushing was not associated with release of gastrin or any of the other vasoactive or postprandially released gut regulatory peptides measured. In a sixth patient with severe prolonged carcinoid flushing, subcutaneous Des AA1, 2, 4, 5, 12D Trp8 somatostatin markedly reduced the incidence and severity of flushing for two days. Somatostatin is thus a potent inhibitor of carcinoid flushing, but no evidence has been found for the gut hormones measured to be mediators of flushing.
Lyn Is Essential for Fcγ Receptor III–Mediated Systemic Anaphylaxis but Not for the Arthus Reaction
Authors: Takae Yuasa, Masao Ono, Takeshi Watanabe, Toshiyuki Takai
Journal: The Journal of Experimental Medicine (2001)

The Src family kinase Lyn initiates intracellular signal transduction by associating with a variety of immune receptors such as antigen receptor on B cells and high-affinity Fc receptor (FcR) for immunoglobulin Ig(E) (FcεRI) on mast cells. Involvement of Lyn in the IgE-mediated immediate-type hypersensitivity is well documented, but the physiological significance of Lyn in IgG-dependent, type III low-affinity FcR for IgG (FcγRIII)-mediated responses is largely unknown. In this study, we generated a double-mutant mouse strain deficient in both type II FcR for IgG (FcγRIIB) and Lyn to exclude any involvement of inhibitory signaling by FcγRIIB, which otherwise downregulates FcγRIII-mediated cellular responses. FcγRIIB-deficient but Lyn-sufficient mice served as controls. The Lyn deficiency attenuated IgG-mediated systemic anaphylaxis in vivo, and significantly reduced calcium mobilization and degranulation responses of bone marrow–derived mast cells (BMMCs) in vitro. However, we found that either interleukin 4 or tumor necrosis factor α release by BMMCs was comparable to that from Lyn-deficient and control mice, and the reverse-passive Arthus reaction was equally induced in both mutant mice, indicating that Lyn is not involved in the onset of the IgG-mediated, FcγRIII-dependent late phase responses of mast cells. These findings provide us with insight into distinct signaling mechanisms in mast cells underlying the development of diverse pathologies as well as a therapeutic potential for selective treatment of allergic disorders.
The MD and MS degrees in Britain.
Authors: I. C. McManus
Journal: BMJ (1988)

Higher medical degrees--MD and MS--have been awarded at an increased rate since 1980, owing partly to increased numbers of medical graduates and partly to greater career competition. The pass rate has not changed since 1965. Regulations at various universities show substantial differences, particularly in the use of viva voce examinations for failed candidates, in permissible subject matter, and in allowing the submission of previously published papers. As these degrees are important for careers, and are registrable by the General Medical Council, it is suggested that it should issue minimal standards to be observed by all universities.
Ultrasonic<i>versus</i>jet nebulization of iloprost in severe pulmonary hypertension
Authors: T. Gessler, T. Schmehl, M.M. Hoeper, F. Rose, H.A. Ghofrani, H. Olschewski, F. Grimminger, W. Seeger
Journal: European Respiratory Journal (2001)

Inhalation of iloprost, a stable prostacyclin analogue, is a promising perspective in the treatment of pulmonary hypertension. In initial clinical studies, a conventional jet nebulizer system was successfully used to decrease pulmonary vascular resistance and pressure, requiring however, up to twelve inhalations of 12–15 min per day. The aim of this study was to investigate if the application of an equal dose of iloprost at a drastically reduced duration of inhalation with the use of a more efficient ultrasonic nebulizer, leads to comparable haemodynamic effects, without escalation of side effects. The physical features of the jet nebulizer system (Ilo-Neb TM ) and the ultrasonic nebulizer (Multisonic Compact TM ) were characterized by laser diffractometry and a Tc 99m -tracer technique. Mass median aerodynamic diameters were 3.2 µm for the jet and 3.9 µm for the ultrasonic nebulizer. Total output (mean±sd) was 60±7 µL·min −1 (jet) and 163±15 µL·min −1 (ultrasonic), and efficiency of the devices was 39±3% (jet) and 86±5% (ultrasonic). Based on these data, a total inhalative dose of 2.8 µg iloprost was delivered by jet nebulization within 12 min and by ultrasonic nebulization within 4 min, in 18 patients with severe primary and secondary pulmonary hypertension (New York Heart Association class III and IV), in a randomized crossover design. Haemodynamics were assessed by right heart catheterization. Inhalation with the ultrasonic device and jet nebulizer, reduced mean±sem pulmonary artery pressure from 54.3±2.1 to 47.1±2.0 and from 53.5±2.2 to 47.0±2.2 mmHg, respectively, and mean±sem pulmonary vascular resistance from 1073±109 to 804±87 and from 1069±125 to 810±83 dyn·s·cm −5 , respectively. Both modes of aerosolization were well tolerated. In conclusion, due to the markedly higher efficiency and output of the ultrasonic device, wastage of drug is largely avoided and the duration of inhalation can be shortened to one-third, with comparable haemodynamic effects and without enforcing side effects.
LSC 2013 abstract - Functional modulation of bone marrow-derived dendritic cells depends on polystyrene particles size
Authors: Emilie Seydoux, Fabian Blank, Alke Fink, Barbara Rothen-Rutishauser, Christophe Von Garnier
Journal: European Respiratory Journal (2013)

The respiratory tract may represent an ideal target organ for immunotherapy, given a vast surface where interaction between antigen-presenting cells (APC) such as dendritic cells (DC) and novel nano-sized immunomodulatory compounds may occur. To date, immune responses to a specific size, shape or chemical surface of a given synthetic nano-sized particle are still largely unknown. To investigate the effect of size on interactions between particles and APC, bone marrow-derived DC (BMDC) were exposed in vitro to 20nm or 1000nm polystyrene (PS) particles. Changes in surface phenotype, activation, the capacity of BMDC to take up and process antigen, as well as antigen-specific stimulation of CD4+T cells, were analysed by flow cytometry and confocal microscopy. With 20nm particles we observed higher frequencies (69.1%) of particle positive BMDC already at the early (10 minutes) time-point, compared to larger 1000nm particles (35.8%, p =0.0004). PS-particles did not significantly affect surface phenotype or expression of activation markers, such as CD40, CD86 or MHCII. Though particle treatment did not alter antigen uptake, 20nm-sized particles decreased the capacity of BMDC to process antigen, without affecting the ability to stimulate antigen-specific CD4+T cells. These data showed that micro-sized (1000nm) PS particles did not significantly affect DC phenotype and function, while nano-sized (20nm) particles decreased antigen processing in DC. Therefore, particle size may represent a relevant parameter determining DC function and down-stream immune responses to particles.
Evaluation of Neurologic Function in Gulf War Veterans&lt;subtitle&gt;A Blinded Case-Control Study&lt;/subtitle&gt;
Authors: Robert W. Haley
Journal: JAMA (1997)

To determine whether Gulf War-related illnesses are associated with central or peripheral nervous system dysfunction.Nested case-control study.Twenty-three veterans with factor analysis-derived syndromes (the cases), 10 well veterans deployed to the Gulf War (the deployed controls), and 10 well veterans not deployed to the Gulf War (the nondeployed controls).With investigators blinded to group identities, participants underwent objective neurophysiological, audiovestibular, neuroradiological, neuropsychological, and blood tests.Evidence of neurologic dysfunction.Compared with the 20 controls, the 23 cases had significantly more neuropsychological evidence of brain dysfunction on the Halstead Impairment Index (P=.01), greater interside asymmetry of the wave I to wave III interpeak latency of brain stem auditory evoked potentials (P=.02), greater interocular asymmetry of nystagmic velocity on rotational testing, increased asymmetry of saccadic velocity (P=.04), more prolonged interpeak latency of the lumbar-to-cerebral peaks on posterior tibial somatosensory evoked potentials (on right side, P=.03, and on the left side, P=.005), and diminished nystagmic velocity after caloric stimulation bilaterally (P values range from .02 to .04). Cases (n=5) with syndrome 1 ("impaired cognition") were the most impaired on brain stem auditory evoked potentials (P=.005); those (n=13) with syndrome 2 ("confusion-ataxia") were the most impaired on the Halstead Impairment Index (P=.006), rotational testing (P=.01), asymmetry of saccadic velocity (P=.03), and somatosensory evoked potentials (P< or =.01); and those (n=5) with syndrome 3 ("arthro-myo-neuropathy") were the most impaired on caloric stimulation (P< or =.01).The 3 factor-derived syndromes identified among Gulf War veterans appear to represent variants of a generalized injury to the nervous system.
Physiological changes seen after six weeks sequence training.
Authors: R. P. Macdonald
Journal: British Journal of Sports Medicine (1983)

Changes in body fat, cardiovascular endurance, muscular endurance, flexibility and strength were assessed in 22 women and 16 men after 6 weeks sequence training. It was found that two training sessions per week were sufficient to cause a significant increase in the majority of measurements made. The extent of the improvement in women was inversely related to the starting value, with most measurements, whereas this was not found in men. The measurements in this small group were comparable to those found in a large series in Canada, with the exception of the proportion of body fat which was lower in this UK series.
High prevalence of Mycobacterium avium subspecies paratuberculosis IS900 DNA in gut tissues from individuals with Crohn's disease
Authors: F Autschbach
Journal: Gut (2005)

<b>Background and aims:</b> Conflicting results exist about the presence of <i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> (MAP) specific IS<i>900</i> DNA in Crohn's disease (CD) tissues. Therefore, we examined IS<i>900</i> in a large number of gut samples from patients with CD (n = 100) and ulcerative colitis (UC, n = 100), and in non-inflamed control tissues (nIBD, n = 100). We hypothesised that IS<i>900</i> DNA detection might be associated with distinct clinical phenotypic characteristics in CD. <b>Methods:</b> The prevalence of MAP DNA in surgically resected tissues was examined using a mechanical-enzymatic disruption technique and nested IS<i>900</i> specific polymerase chain reaction (PCR). CD patients were stratified according to the criteria of the Vienna classification and other clinical characteristics. <b>Results:</b> IS<i>900</i> PCR detection rate was significantly higher in CD tissue samples (52%) than in UC (2%) or nIBD (5%) specimens (p&lt;0.0001). In CD patients, IS<i>900</i> DNA was detected in samples from both diseased small bowel (47%) as well as from the colon (61%). No firm association between MAP specific IS<i>900</i> detection rates and clinical phenotypic characteristics in CD could be established. However, corticosteroid medication constituted a factor which tended to have a negative influence on IS<i>900</i> DNA detection rates in CD (p&lt;0.01). <b>Conclusions:</b> The presence of MAP specific IS<i>900</i> DNA is a predominant feature of CD. Therapeutic intervention against MAP might represent a potential target for disease mitigation in Crohn's disease.
975. Immunization with an Adenovirus Vector Expressing a P. aeruginosa OprF Epitope in the Capsid Enables Boosting of Anti-Epitope Immune Responses and Protects Against Pulmonary Infection with P. aeruginosa
Authors: Stefan Worgall, JianPing Qiu, Anja Krause, Kyung-Hee Kim, Peter W. Roelvink, Joseph T. Bruder, Thomas J. Wickham, Imre Kovesdi, Ronald G. Crystal
Journal: Molecular Therapy (2005)

Top of pageAbstract
Pseudomonas aeruginosa causes chronic infections of the respiratory tract, particularly in cystic fibrosis (CF). The outer membrane protein F (OprF) of P. aeruginosa is a promising vaccine candidate and our prior studies have shown that an adenovirus (Ad) vector expressing a secreted form of OprF (AdOprF), evokes protective immunity against P. aeruginosa. The present study is focused on development of a 2nd generation clinical vaccine candidate (AdOprF.RGD.Epi8) by two innovations to AdOprF to enhance the immunogenicity: (1) genetic modification of the Ad hexon to incorporate an epitope (Epi8) from OprF; and (2) genetic modification of the Ad fiber to incorporate an RGD sequence to enhance gene delivery to antigen presenting cells. We first evaluated the immunogenic properties of an Ad vector in which the Ad hexon protein was modified to include the 14-mer OprF epitope Epi8 in the hexon (AdZ.Epi8), with focus on the hypothesis that immune responses against epitopes that are part of the Ad capsid could be augmented with repeat administration. To evaluate the protective effect of immunization with AdZ.Epi8 against pulmonary infection with P. aeruginosa, C57Bl/6 mice, immunized with either AdZ.Epi8 or AdZ were challenged with a lethal dose of agar-encapsulated P. aeruginosa (laboratory strain PAO1 or two isolates of P. aeruginosa derived from patients with CF). Unimmunized mice or mice infected with AdZ died within the first 3 days. In contrast, more than 60% of the mice immunized with AdZ.Epi8 survived more than 2 wk (p 0.1, all comparisons). Similar results were observed in the CD4 Epi8-specific IL-4 as well as CD4 and CD8 Epi8-specific |[gamma]|-interferon cellular responses, suggesting that the addition of an OprF epitope to the Ad capsid enables boosting of the anti-OprF response. Finally, we evaluated the immunogenic properties of the combined AdOprF.RGD.Epi8 vector. Mice received AdOprF.RGD.Epi8, AdOprF, AdNull, (2|[times]|1011pu) or PBS and the anti-OprF antibody titers were determined at 2 and 4 wk. No anti-OprF antibodies were detected in the AdNull or PBS group. The mean titer for AdOprF was 5710 and 8602 at 2 and 4 wk, respectively, vs 11841 and 10632 for the AdOprFRGD.Epi8 injected mice, suggesting a faster and more robust induction of the anti-OprF humoral response with AdOprFRGD.Epi8. We conclude that the capsid modifications in AdOprF.RGD.Epi8 vector make it a more effective candidate vector for vaccination against P. aeruginosa.
Radiation pneumonitis complicating mediastinal radiotherapy postpneumonectomy
Authors: T Shulimzon, S Apter, R Weitzen, A Yellin, HJ Brenner, A Wollner
Journal: European Respiratory Journal (1996)

Radiation pneumonitis is a well-characterized clinicopathological syndrome. The severity of radiation-induced lung injury correlates, among other factors, with the extent of lung volume incorporated within the field of radiation. The present article describes the cases of two patients with radiation pneumonitis following pneumonectomy and mediastinal radiotherapy. Postpneumonectomy pulmonary-mediastinal shift of the remaining lung towards the operated side, with inclusion of lung parenchyma within the "mediastinal" radiation portals, resulted in a substantial (albeit clinically unsuspected) radiation pneumonitis. Chest computed tomography in the postpneumonectomy patient may be helpful to evaluate the degree of pulmonary-mediastinal shift and optimization of the radiotherapy field.
Idiotypy of clonal responses to influenza virus hemagglutinin.
Authors: Y N Liu, C A Bona, J L Schulman
Journal: The Journal of Experimental Medicine (1981)

Anti-idiotype antisera were raised in syngeneic (BALB/c mice) and homologous (A/J mice) systems to study the cross-reactive idiotypes among monoclonal antibodies to PR8 and B/Lee virus HA and the expression of these idiotypes during primary and secondary antiviral responses of BALB/c mice. Extensive idiotypic cross-reactivity was demonstrated among monoclonal antibodies specific for distinct antigenic determinants on PR8 hemagglutinin (HA). The study of idiotypy of monoclonal antibodies against the same or overlapping antigenic determinants on B/Lee HA showed that these monoclonal antibodies may bear (a) a true individual idiotype not shared by other monoclonal antibodies, (b) idiotypes shared by few monoclonal antibodies, and (c) true cross-reactive idiotypes shared by all of these monoclonal antibodies. In contrast, no cross-reactive idiotypes were detectable among monoclonal antibodies to B/Lee HA and monoclonal antibodies to PR8 HA. Furthermore, we have shown that the anti-idiotype antibodies we used recognize determinants on monoclonal antibodies closely associated with antigenic binding sites. Finally, studies of the idiotypes expressed during primary and secondary antiviral HA responses of mice immunized with B/Lee virus revealed persistence of some idiotypes during both primary and secondary responses, whereas others were only expressed in the primary or secondary response.
Docosahexaenoic Acid Protects from Dendritic Pathology in an Alzheimer's Disease Mouse Model
Authors: Frédéric Calon, Giselle P. Lim, Fusheng Yang, Takashi Morihara, Bruce Teter, Oliver Ubeda, Phillippe Rostaing, Antoine Triller, Norman Salem, Karen H. Ashe, Sally A. Frautschy, Greg M. Cole
Journal: Neuron (2004)
Association of All-Cause Mortality With Overweight and Obesity Using Standard Body Mass Index Categories
Authors: Katherine M. Flegal, Brian K. Kit, Heather Orpana, Barry I. Graubard
Journal: JAMA (2013)

MORTALITYdifferences between weight categories has sometimes been described as controversial. 1 The appearance of controversy may arise in part because studies of body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and mortality have used a wide variety of BMI categories and varying reference categories, which can make findings appear more variable than when standard categories are used and also can make it difficult to compare and synthesize studies.A report 2 in 1997 from the World Health Organization Consultation on Obesity defined BMI-based categories of underweight, normal weight, preobesity, and obesity.The same cutoff BMI values were adopted by the National Heart, Lung, and Blood Institute in 1998. 3n this study, we used the National Heart, Lung, and Blood Institute's
In vitro formation of osteoclasts from long-term cultures of bone marrow mononuclear phagocytes.
Authors: E H Burger, J W Van der Meer, J S van de Gevel, J C Gribnau, G W Thesingh, R van Furth
Journal: The Journal of Experimental Medicine (1982)

The origin of osteoclasts was studied in an in vitro model using organ cultures of periosteum-free embryonic mouse long-bone primordia, which were co-cultured with various cell populations. The bone rudiments were freed of their periosteum-perichondrium by collagenase treatment in a stage before cartilage erosion and osteoclast formation, and co-cultured for 7 d with either embryonic liver or mononuclear phagocytes from various sources. Light and electron microscopic examination of the cultures showed that mineralized matrix-resorbing osteoclasts developed only in bones co-cultured with embryonic liver or with cultured bone marrow mononuclear phagocytes but not when co-cultured with blood monocytes or resident or exudate peritoneal macrophages. Osteoclasts developed from the weakly adherent, but not from the strongly adherent cells of bone marrow cultures, whereas 1,000 rad irradiation destroyed the capacity of such cultures to form osteoclasts. In bone cultures to which no other cells were added, osteoclasts were virtually absent. Bone-resorbing activity of in vitro formed osteoclasts was demonstrated by 45Ca release studies. These studies demonstrate that osteoclasts develop from cells present in cultures of proliferating mononuclear phagocytes and that, at least in our system, monocytes and macrophages are unable to form osteoclasts. The most likely candidates for osteoclast precursor cells seem to be monoblasts and promonocytes.
The things our patients do to avoid operations (do-it-yourself Mohs’ surgery)!
Authors: M.J. Sladden
Journal: British Journal of Dermatology (2008)

Conflicts of interest: none declared. Sir, I read with interest the recent case of do‐it‐yourself Mohs’ surgery.1 I currently have a patient who is a 60‐year‐old ‘actinopath’, inherited when I moved to Tasmania last year. Reg (pseudonym to protect real identity) is an outdoor man, both by occupation and by his bush hobbies, and has never seen a hat nor bottle of sunblock. His saving grace is that he wears a (short‐sleeved) shirt and long pants (trousers). By definition, ‘actinopaths’ have little normal skin. There is ‘complete sun damage’, with field cancerization, present on all exposed areas. If one could only patent sheep dips full of liquid nitrogen and Efudix! Nevertheless, Reg has used several tubes of Efudix® (Valeant, Aliso Viejo, CA, U.S.A.; 5‐fluorouracil) and has had about 200 solar keratoses treated with liquid nitrogen cryotherapy. I have excised about 20 squamous cell carcinomas and basal cell carcinomas from Reg’s face, balding pate, arms and hands. Often we allow these to heal by secondary intention because there is insufficient ‘normal’ skin to flap and Reg does not believe in grafts.