tbuckley/cabot-search huggingface dataset:
Monoclonal Anti-CD18 Antibody Prevents Transcellular Biosynthesis of Cysteinyl Leukotrienes In Vitro and In Vivo and Protects Against Leukotriene-Dependent Increase in Coronary Vascular Resistance and Myocardial Stiffness
Authors: Angelo Sala, Giuseppe Rossoni, Ferruccio Berti, Carola Buccellati, Albino Bonazzi, Jacques Maclouf, Giancarlo Folco
Journal: Circulation (2000)

Background —Cysteinyl leukotrienes (cys-LT) can constrict small and large vessels and increase vascular permeability. Formation of cys-LT arising from polymorphonuclear leukocytes (PMNL) and endothelial cell cooperation (transcellular synthesis) led to the hypothesis that PMNL–endothelial cell adhesion may represent a key step toward the formation of vasoactive cys-LT. Methods and Results —We studied the effect of pretreatment with a monoclonal antibody directed against the CD18 subunit of PMNL β 2 -integrin on the synthesis of cys-LT in a PMNL-perfused isolated rabbit heart in vitro and in a model of permanent ligature of the left descending coronary artery in the rabbit in vivo. Challenge of PMNL-perfused rabbit hearts with formyl-met-leu-phe (0.3 μmol/L) caused synthesis of cys-LT and increase in coronary perfusion pressure that were prevented by the anti-CD18 antibody. Similar results were obtained with the use of A-23187 (0.5 μmol/L) as a challenge. Persistence of PMNL-associated myeloperoxidase activity in the perfusion buffer was observed in the presence of the anti-CD18 antibody, indicating decreased PMNL infiltration. Coronary artery ligature in vivo increased urinary excretion of leukotriene E 4 , supporting the activation of the 5-lipoxygenase pathway during experimental acute myocardial infarction. Pretreatment with the anti-CD18 antibody (1 mg/kg) prevented the increase in leukotriene E 4 excretion. Conclusions —These data support the importance of adhesion in promoting cys-LT formation, originating from PMNL–endothelial cell cooperation, and contributing to myocardial stiffness and increased coronary resistance.
Electrophysiological actions of disopyramide phosphate on canine ventricular muscle and purkinje fibers.
Authors: T Kus, B I Sasyniuk
Journal: Circulation Research (1975)

Disopyramide phosphate is a new antiarrhythmic drug that has been shown to possess significant antiarrhythmic effects in animals and man. In the present investigation, the effects of 2, 5, and 10 mug/ml of disopyramide phosphate were studied on the electrophysiological properties of canine Purkinje fibers and ventricular muscle superfused in vitro. Transmembrane action potentials were recorded from Purkinje fibers in the region of maximum action potential duration (gate), from Purkinje fibers proximal and distal to the gate, and from ventricular muscle. Disopyramide phosphate produced a concentration-dependent decrease in the slope of phase 4 diastolic depolarization of spontaneously beating Purkinje fibers. In all electrically stimulated fibers, the drug decreased the amplitude and the maximum upstroke velocity of the action potential. This depression of phase 0 characteristics was accompanied by a decrease in conduction velocity. In Purkinje fibers located at the gate, a concentration-dependent parallel shift to the right and a depression of the maximum of the membrane responsiveness curve occurred. Effects on action potential duration were variable. Repolarization was altered so that action potentials with dissimilar durations recorded from sites proximal to, at, and distal to the gate became equal. The total action potential duration and the effective refractory period of gate Purkinje fibers were prolonged, but the change in action potential duration was always greater than the change in effective refractory period so that the ratio of the change in duration to the change in refractory period was always greater than one.
The role of mitochondrial function and cellular bioenergetics in ageing and disease
Authors: M.D. Brand, A.L. Orr, I.V. Perevoshchikova, C.L. Quinlan
Journal: British Journal of Dermatology (2013)

Mitochondria constitute an important topic of biomedical enquiry (one paper in every 154 indexed in PubMed since 1998 is retrieved by the keyword 'mitochondria') because of widespread recognition of their importance in cell physiology and pathology. Mitochondrial dysfunction is widely implicated in ageing and in the diseases of ageing, through dysfunction in adenosine triphosphate (ATP) synthesis, Ca2+ homeostasis, central metabolic pathways or radical production. Nonetheless, the mechanisms and regulation of superoxide and hydrogen peroxide formation by mitochondria remain poorly described. Measurement of the capacities of different sites of superoxide and hydrogen peroxide production in isolated skeletal muscle mitochondria show that the maximum capacities of sites in complexes I, II and III and in several associated redox enzymes greatly exceed the native rates observed in the absence of respiratory chain inhibitors. In vitro, the native rates and the relative importance of different sites both depend on the substrate being oxidized, with sites IQ, IIF, GPDH, IF and IIIQo each being important with particular substrates. The techniques involved in measuring rates from each site should become applicable to cell cultures and in vivo in the future.
Regulation of neutrophils by interferon-γ limits lung inflammation during tuberculosis infection
Authors: Bisweswar Nandi, Samuel M. Behar
Journal: The Journal of Experimental Medicine (2011)

Resistance to Mycobacterium tuberculosis requires the host to restrict bacterial replication while preventing an over-exuberant inflammatory response. Interferon (IFN) γ is crucial for activating macrophages and also regulates tissue inflammation. We dissociate these two functions and show that IFN-γ−/− memory CD4+ T cells retain their antimicrobial activity but are unable to suppress inflammation. IFN-γ inhibits CD4+ T cell production of IL-17, which regulates neutrophil recruitment. In addition, IFN-γ directly inhibits pathogenic neutrophil accumulation in the infected lung and impairs neutrophil survival. Regulation of neutrophils is important because their accumulation is detrimental to the host. We suggest that neutrophilia during tuberculosis indicates failed Th1 immunity or loss of IFN-γ responsiveness. These results establish an important antiinflammatory role for IFN-γ in host protection against tuberculosis.
A novel and cytogenetically cryptic t(7;21)(p22;q22) in acute myeloid leukemia results in fusion of RUNX1 with the ubiquitin-specific protease gene USP42
Authors: K Paulsson, A N Békássy, T Olofsson, F Mitelman, B Johansson, I Panagopoulos
Journal: Leukemia (2005)
Inspiratory flow rates at different levels of resistance in elderly COPD patients
Authors: W. Janssens, P. VandenBrande, E. Hardeman, E. De Langhe, T. Philps, T. Troosters, M. Decramer
Journal: European Respiratory Journal (2007)

Dry powder inhalers (DPIs) are increasingly replacing metered dose inhalers in elderly chronic obstructive pulmonary disease (COPD) patients. However, most DPIs are dependent on inspiratory flow, which is compromised by the ageing process itself. Using the in-check dial method, the present study compared peak inspiratory flow (PIF) rates in 26 elderly COPD patients and 14 matched control subjects, at a pre-set resistance level of the Aeroliser, Diskus and Turbuhaler inhalers. It was found that the PIF measured by the in-check method positively correlated with the PIF derived from spirometry, forced vital capacity and maximal inspiratory pressure, while a negative, but significant, correlation was observed with age. PIF derived from spirometry and age were independent variables which determined PIF across the device, whereas the presence or absence of COPD was not related. When comparing elderly COPD patients with matched elderly controls no difference could be found in PIF at the different resistances. However, an important number of patients did not reach the recommended flow rate, especially when using the Turbuhaler (30%). In conclusion, the present study demonstrates that, in elderly patients, the ability to generate sufficient inspiratory flow across a dry powder inhaler is compromised, irrespective of the presence of chronic obstructive pulmonary disease.
A disintegrin and metalloproteinases 10 and 17 modulate the immunogenicity of glioblastoma-initiating cells
Authors: Fabian Wolpert, Isabel Tritschler, Alexander Steinle, Michael Weller,, Günter Eisele
Journal: Neuro-Oncology (2013)

There are emerging reports that the family of a disintegrin and metalloproteinases (ADAM) are involved in the maintenance of the malignant phenotype of glioblastomas. Notably, ADAM proteases 10 and 17 might impair the immune recognition of glioma cells via the activating immunoreceptor NKG2D by cleavage of its ligands from the cell surface. Glioblastoma-initiating cells (GIC) with stem cell properties have been identified as an attractive target for immunotherapy. However, GIC immunogenicity seems to be low. Here,we show that ADAM10 and ADAM17 are expressed on the cell surface of GIC and contribute to an immunosuppressive phenotype by cleavage of ULBP2. The cell surface expression of ULBP2 is enhanced upon blocking ADAM10 and ADAM17, and treatment with ADAM10 and ADAM17specific inhibitors leads to enhanced immunerecognition of GIC by natural killer cells. Therefore, ADAM10 and ADAM17 constitute suitable targets to boost an immune response against GIC.
Genetic locus for the biosynthesis of the variable portion of Neisseria gonorrhoeae lipooligosaccharide.
Authors: E C Gotschlich
Journal: The Journal of Experimental Medicine (1994)

A locus involved in the biosynthesis of gonococcal lipooligosaccharide (LOS) has been cloned from gonococcal strain F62. The locus contains five open reading frames. The first and second reading frames are homologous, but not identical, to the fourth and fifth reading frames, respectively. Interposed is an additional reading frame which has distant homology to the Escherichia coli rfaI and rfaI genes, both glucosyl transferases involved in lipopolysaccharide core biosynthesis. The second and fifth reading frames show strong homology to the lex-1 or lic2A gene of Haemophilus influenzae, but do not contain the CAAT repeats found in this gene. Deletions of each of these five genes, of combinations of genes, and of the entire locus were constructed and introduced into parental gonococcal strain F62 by transformation. The LOS phenotypes were then analyzed by SDS-PAGE and reactivity with monoclonal antibodies. Analysis of the gonococcal mutants indicates that four of these genes are the glycosyl transferases that add GalNAc beta 1--&amp;gt;3Gal beta 1--&amp;gt;4GlcNAc beta 1--&amp;gt;3 Gal beta 1--4 to the substrate Glc beta 1--&amp;gt;4Hep--R of the inner core region. The gene with homology to E. coli rfaI/rfaI is involved with the addition of the alpha-linked galactose residue in the biosynthesis of the alternative LOS structure Gal alpha 1--&amp;gt;4Gal beta 1--&amp;gt;4Glc beta 1--&amp;gt;4Hep--&amp;gt;R. Since these genes encode LOS glycosyl transferases they have been named lgtA, lgtB, lgtC, lgtD, and lgtE. The DNA sequence analysis revealed that lgtA, lgtC, and lgtD contained poly-G tracts, which, in strain F62 were, respectively, 17, 10, and 11 bp. Thus, three of the LOS biosynthetic enzymes are potentially susceptible to premature termination by reading frame changes. It is likely that these structural features are responsible for the high-frequency genetic variation of gonococcal LOS.
Effects of obesity on quadriceps dynamic strengthening and isometrics exercise for the treatment of knee osteoarthritis patients
Authors: Aparna Sarkar, Nitesh Bansal, Shweta Singh
Journal: British Journal of Sports Medicine (2010)

Knee osteoarthritis (KOA) is a major cause of pain and functional impairment among elders. Currently, there are neither feasible preventive intervention strategies nor effective medical remedies for the management of KOA. Of course, KOA is only one of many adverse consequences of obesity. Physical rehabilitation usually quadriceps exercises for the maintenance of joint range of motion and muscle strength is effective for the treatment of KOA. The aim of the study was to find out whether obesity has an adverse effect on the treatment of knee osteoarthritic patients when quadriceps dynamic strengthening and isometrics exercise were implemented. Sixty osteoarthritic knee patients with 30 patients each in two groups were randomly selected from Kailash Hospital and Obesity Clinics in Delhi. Patients were randomly divided into two groups (A and B) according to their BMI. In group A, non-obese KOA patients were assigned, and in group B, obese KOA patients were included. The quadriceps dynamic strengthening and isometrics exercise treatment protocol were introduced in both the groups and were given for 15 days. Pre- and post-treatment knee pain, range of motion of knee joint and quadriceps muscle strength were measured. Student t test was applied to find out the statistical level of significance. Pain was decreased with the intervention exercise, which was highly significant (p &lt; 0.05) in both the groups. The ranges of motion for knee joint were increased, which was found highly significant in both the cases of flexion and extension (p&lt; 0.001, &lt; 0.05, respectively) in group A but in group B, it was found significant for flexion (p&lt;0.001) but in case of extension ROM, it was insignificant (p&gt;0.05). The mean difference of pre-test and post-test muscle strength for flexor and extensors was significant (p&lt;0.01, &lt;0.001) in group A but in group B, for flexors, it was insignificant, and for the extensor group, it was significant (p&lt;0.01). It was found that the exercises given to group A (non-obese) were more effective than those given to group B (obese). Pain, ROM and MMT were improved significantly in group A but in group B, pain had reduced but MMT and ROM had no significant improvements. We concluded that because of more BMI in group B (obese group), effects of exercise for treatment of OA knee was not as significant as in case of group A subjects (non-obese group).
Pulmonary features of autosomal dominant hyper-IgE syndrome [AD HIES]
Authors: Hanna Dmenska, Edyta Heropolitanska, Barbara Pietrucha, Ewa Bernatowska
Journal: European Respiratory Journal (2011)

AD HIES is characterized by recurrent severe pulmonary infections, pneumatoceles, eczema, staphylococcal abscesses, mucocutaneous candidiasis, abnormalities of bone and connective tissue and elevated serum IgE. Mutations in signal transducer and activator of transcription 3 (STAT3) have recently been found to account for most cases.   Aim:  The aim of the study is to present clinical phenotype of AD HIES.   Materials and methods:  A group of 22 HIES pts were genetically analyzed. The mutations in STAT3 were confirmed in 7 AD HIES pts, presented here. Recurrent and severe pulmonary infections were found in all pts except one (pt 7) at various frequency. The typical complications of pneumonias were the formation of pulmonary cyst and abscesses. Long term complications included pneumatocele and bronchopleural fistulae. In several cases lobectomy was performed. The structural abnormalities were then sites of fungal and Gram (-) infection.   Results:    Conclusions:  1. Early recognition of the HIES enables to introduce the right kind of therapy. 2. Pneumonias should be treated aggressively to try to prevent parenchymal damage. 3. If pneumatocele and bronchiectasis are present, antimicrobial prophylaxis covering Gram (-) bacteria and fungi is needed.
Morphometric study of the esophageal mucosa in cirrhotic patients with variceal bleeding
Authors: Julio Ponce, Agustin Froufe, Eduardo de la Morena, José Mir, Miguel Rayón, Ramón Pina, Joaquin Berenguer
Journal: Hepatology (1981)

A morphometric study of the distal esophageal mucosa (within 5 cm above the gastroesophageal junction) has been carried out in a group of 11 cirrhotic patients undergoing esophageal transection with SPTU gun for variceal bleeding. The relative thickness of the papillae (62.2 +/- 3.9%) and basal zone (11.8 +/- 1.9%) were within normal limits. Polymorphonuclear infiltrates were not found either in the lamina propria or in the epithelium. The absence of histopathologic changes in the esophageal mucosa from patients with liver cirrhosis and bleeding esophageal varices confirms the hypothesis that gastroesophageal reflux does not play a pathogenic role in the development of variceal bleeding.
Sunitinib-induced reduction in skin microvascular density is a reversible phenomenon
Authors: M.P. de Boer, A.A.M. van der Veldt, N.A. Lankheet, N.J. Wijnstok, A.J.M. van den Eertwegh, E. Boven, E.H. Serné
Journal: Annals of Oncology (2010)
Noninvasive ventilation: a decade of progress
Authors: M. Elliott, N. Ambrosino
Journal: European Respiratory Journal (2002)

During the 1990s, noninvasive ventilation moved from being almost unknown outside a few specialist centres to becoming a cornerstone in the management of patients with respiratory failure. As with many advances in medicine, the basic idea is not new. Indeed, the technique is almost as old as mankind itself. In Genesis, Chapter 2, verse 7 it is stated that “the Lord God formed the man from the dust of the ground and breathed into his nostrils the breath of life”. Sustained artificial ventilation of humans was first explored in the mid‐1700s using bellows and a tracheal tube in an attempt to resuscitate those who had drowned. However, following a dramatic series of experiments, which demonstrated fatal pneumothorax in animals subjected to ventilation with pressures greatly in excess of those likely in clinical practice, the technique was quickly condemned and banned from clinical practice in its infancy. Negative pressure devices were developed as an alternative, but only found widespread clinical use when the Drinker-Shaw iron lung was developed in 1928 1. For many years, external negative pressure was used for the treatment of respiratory paralysis, secondary to poliomyelitis. Positive pressure ventilation was only used in clinical practice during anaesthesia in the operating room. However, during the Copenhagen polio epidemic in the 1950s there were insufficient negative pressure ventilators available, so patients were intubated and hand ventilated by teams of technicians and students working round the clock in shifts. Survival rates using positive pressure ventilation were much better than those observed during use of negative pressure ventilation during the early stages of the …
Strategies for the Care of Adults Hospitalized for Active Ulcerative Colitis
Authors: Suresh Pola, Derek Patel, Sonia Ramamoorthy, Elisabeth McLemore, Marianne Fahmy, Jesus Rivera–Nieves, John T. Chang, Elisabeth Evans, Michael Docherty, Mark Talamini, William J. Sandborn
Journal: Clinical Gastroenterology and Hepatology (2012)
A phase Ib dose-escalation study of erlotinib, capecitabine and oxaliplatin in metastatic colorectal cancer patients
Authors: E. Van Cutsem, C. Verslype, P. Beale, S. Clarke, R. Bugat, A. Rakhit, S.H. Fettner, U. Brennscheidt, A. Feyereislova, J.-P Delord
Journal: Annals of Oncology (2007)
A cordial affair — erythropoietin and cardioprotection
Authors: J FANDREY
Journal: Cardiovascular Research (2006)

See article by Burger et al.  [8]  (pages 51–59) in this issue. 

Hypoxia and erythropoietin (EPO) were a couple from the very beginning. Hypoxia induces the production of EPO, which became the paradigm for oxygen-regulated gene expression [1]. Dissecting EPO gene regulation has lead to the discovery of the transcription factor complex hypoxia inducible factor-1 (HIF-1), the widespread “master regulator of O2 homeostasis” in the tissue, and the identification of cellular oxygen sensors in control of HIF-1 (reviewed by [2]). EPO as a erythropoietic hormone is mainly synthesized by the kidneys in the adult, and in the liver before birth [1]. However, EPO is also expressed in the brain, in the gonads and female reproductive tract, in the bone marrow, and in tumor cells [1] due to tissue specific transcription factors, e.g. WT1 [3], which are most likely integrated into oxygen-dependent regulation.

It is now well recognized that EPO has a much broader range of action than its well-known role as an erythropoiesis-stimulating hormone [4]. EPO inhibits apoptosis in neurons, endothelial smooth muscle cells, and cardiomyocytes, and EPO … 

*Tel./fax: +49 201 723 4600/4648. Email address: joachim.fandrey{at}uni-due.de
Remembering Ralph Steinman
Authors: Jacques Banchereau, Fern Cohn, Kayo Inaba, Bill Muller, Ira Mellman, Carl Nathan, Michel Nussenzweig, Anne O’Garra, Bob Seder, Gerold Schuler, Alan Sher
Journal: The Journal of Experimental Medicine (2011)

As detailed in the Appreciation piece written by Carol Moberg, Ralph’s discovery and investigation of DCs constituted an enormous contribution to immunology. However, Ralph’s influence extended far beyond the strictly scientific. Below, some of Ralph’s closest colleagues and friends reflect on the long-lasting effects of his unwavering mentorship, enthusiasm, generosity, and friendship. Also in this issue is a Perspective, originally commissioned by Ralph and written by Robin Weiss and Peter Vogt. Ralph passed away before he could read this engaging piece, which celebrates the centennial of the publication in the JEM of the Nobel Prize-winning work of Peyton Rous. In addition to their Nobel Prizes, Ralph and Peyton Rous shared the distinctions of being long-time leaders of Rockefeller laboratories and editors of this journal.