tbuckley/cabot-search huggingface dataset:
Monocyte Human Leukocyte Antigen–DR Transcriptional Downregulation by Cortisol during Septic Shock
Authors: Yves Le Tulzo, Celine Pangault, Laurence Amiot, Valérie Guilloux, Olivier Tribut, Cédric Arvieux, Christophe Camus, Renée Fauchet, Rémi Thomas, Bernard Drénou
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Monocyte deactivation has been identified as a major factor of immunosuppression in sepsis and is associated with a loss of surface human leukocyte antigen–DR (HLA-DR) expression on circulating monocytes. Using flow cytometry, quantitative reverse transcription-polymerase chain reaction, we investigated this phenomenon in septic patients. We confirmed the early loss of monocyte HLA-DR expression in all infected patients and demonstrated that this persistent lowered expression at Day 6 correlated with severity scores, secondary infection, and death. This phenomenon occurred at a transcriptional level via a decrease in the class II transactivator A (CIITA) transcription. Furthermore, these abnormalities correlated with the high cortisol levels observed in sepsis and not with those of other putative factors such as catecholamines or interleukin-10. Finally, in vitro studies evidenced that glucocorticoids decrease HLA-DR expression at a transcriptional level via a decrease in CIITA mRNA levels, mainly by down modulating its isoforms I and III. We conclude that in human sepsis, the loss of HLA-DR expression on circulating monocytes is associated with a poor outcome. We suggest that the high endogenous cortisol level observed in septic shock may be a possible new factor involved in the loss of HLA-DR expression on monocytes via its effect on HLA-DR and CIITA transcription.
Doctors and politicians clash over size of flu problem
Authors: R. Woodman
Journal: BMJ (2000)

Doctors and politicians clashed this week over whether influenza was being made the scapegoat for this year's winter problems in the NHS. The health secretary, Alan Milburn, warned that Britain could be heading for the worst flu epidemic in 10 years after a fourfold increase in reported cases since December.

But figures collected by the Royal College of General Practitioners show that GP …
Commentaries on the IK1 blockade controversy (March Issue) Reply from MJ Curtis
Authors: M. J Curtis
Journal: Cardiovascular Research (1994)

Commentaries on the IK1 blockade controversy (March Issue) Reply from MJ Curtis Get access Michael J Curtis Michael J Curtis Cardiovascular Research Laboratories Pharmacology Group, King's College, London SW3, United Kingdom Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 7, July 1994, Pages 1118–1119, https://doi.org/10.1093/cvr/28.7.1118b Published: 01 July 1994
Eosinophil adhesion under flow conditions activates mechanosensitive signaling pathways in human endothelial cells
Authors: Susan L. Cuvelier, Smitha Paul, Neda Shariat, Pina Colarusso, Kamala D. Patel
Journal: The Journal of Experimental Medicine (2005)

Leukocyte transmigration can be affected by shear stress; however, the mechanisms by which shear stress modulates transmigration are unknown. We found that adhesion of eosinophils or an eosinophilic cell line to intereukin 4–stimulated endothelial cells led to a shear-dependent increase in endothelial cell intracellular calcium and increased phosphorylation of extracellular signal-regulated kinase (ERK) 2, but not c-Jun NH2-terminal kinase or p38 mitogen-activated protein kinase. Latex beads coated with antibodies were used to characterize the role of specific endothelial cell surface molecules in initiating signaling under shear conditions. We found that ligation of either vascular cell adhesion molecule–1 or E-selectin, but not major histocompatibility complex class I, induced a shear-dependent increase in ERK2 phosphorylation in cytokine-stimulated endothelial cells. Disassembly of the actin cytoskeleton with latrunculin A prevented ERK2 phosphorylation after adhesion under flow conditions, supporting a role for the cytoskeleton in mechanosensing. Rapid phosphorylation of focal adhesion kinase and paxillin occurred under identical conditions, suggesting that focal adhesions were also involved in mechanotransduction. Finally, we found that Rho-associated protein kinase and calpain were both critical in the subsequent transendothelial migration of eosinophils under flow conditions. These data suggest that ligation of leukocyte adhesion molecules under flow conditions leads to mechanotransduction in endothelial cells, which can regulate subsequent leukocyte trafficking.
Visceromotor organization within descending spinal sympathetic pathways in the dog.
Authors: S M Barman, R D Wurster
Journal: Circulation Research (1975)

The organization within the descending sympathetic pathways on the surface of the dorsolateral funiculus of the spinal cord was investigated in anesthetized dogs. Changes in heart rate and carotid, renal, and femoral resistances were calculated during electrical stimulation of the descending spinal sympathetic pathways; the location within the pathway of the maximum change in each of these parameters was then determined. Blood pressure increased at each stimulation point with the maximum increase at 3-3.5 mm ventrolateral to the dorsolateral sulcus (DLS). The maximum increases in carotid, renal, and femoral resistances occurred with stimulation at 0.5-1.5, 2, and 3 mm ventrolateral to the DLS, respectively. Maximum heart rate responses were elicited by stimulation 2 mm ventrolateral to the sulcus. These data demonstrate that the pathway is organized in a dorsal-to-ventral manner, with the most rostral parts of the body being represented most dorsally and the more caudal parts being represented more ventrally.
A quantitative approach to histopathological dissection of elastin-related disorders using multiphoton microscopy
Authors: P.L. Tong, J. Qin, C.L. Cooper, P.M. Lowe, D.F. Murrell, S. Kossard, L.G. Ng, B. Roediger, W. Weninger, N.K. Haass
Journal: British Journal of Dermatology (2013)

Background Multiphoton microscopy (MPM) is a novel imaging technology that has recently become applicable for diagnostic purposes. The use of (near) infrared light in MPM allows for deep tissue imaging. In addition, this modality exploits the autofluorescent nature of extracellular matrix fibres within the skin. Objectives To quantitate the structure and abundance of elastic fibres in human dermis in three dimensions utilizing autofluorescent signals generated by MPM for the objective examination of elastin-related skin disorders. Methods Cross-sections of skin samples from elastin-related disorders were analysed by MPM and correlated to histopathology. In situ visualization of elastic fibres by MPM was conducted by en face imaging of ex vivo skin samples through the intact epidermis. Image analysis software was used to quantify elastic fibres in three dimensions. Results Based on the MPM-detected elastin-specific autofluorescence, we developed the Dermal Elastin Morphology Index (DEMI), calculated as the ratio of elastic fibre surface area and volume. This enabled objective three-dimensional quantification of elastic fibres. Quantitative scoring of sun-damaged skin using DEMI correlated with qualitative histopathological grading of the severity of solar elastosis. Furthermore, this approach was applied to changes in elastic fibre architecture in other disorders, such as pseudoxanthoma elasticum (PXE), PXE-like syndrome, elastofibroma, focal dermal elastosis, anetoderma, mid-dermal elastolysis and striae distensae. We imaged elastic fibres in intact ex vivo skin imaged en face through the epidermis, indicating that this approach could be used in vivo. Conclusions MPM has the potential for noninvasive in vivo visualization of elastic fibres in the dermis with near histological resolution. DEMI allows objective assessment of elastic fibres to support diagnosis and monitoring of disease progress or therapy of elastin-related skin disorders.
DETECTION OF RUBELLA-SPECIFIC IgM IN SUBCLINICAL RUBELLA REINFECTION IN PREGNANCY
Authors: P Morgan-Capner, M.H Hambling, T.J Coleman, R.P Watkins, H Stern, J Hodgson, C Dulake, P.A Boswell, J Booth, J.M Best, J.E Banatvala
Journal: The Lancet (1985)
WPA guidance on how to combat stigmatization of psychiatry and psychiatrists
Authors: NORMAN SARTORIUS, WOLFGANG GAEBEL, HELEN-ROSE CLEVELAND, HEATHER STUART, TSUYOSHI AKIYAMA, JULIO ARBOLEDA-FLÓREZ, ANJA E. BAUMANN, OYE GUREJE, MIGUEL R. JORGE, MARIANNE KASTRUP, YURIKO SUZUKI, ALLAN TASMAN
Journal: World Psychiatry (2010)

﻿﻿Background. Little is known about the bacteriology of the pericolostomic skin region. Identifying these bacteria is important to reduce the morbidity resulting from this procedure both to control local infection and to reduce the risk of infection in other surgical sites.The scope of this study was to determine the prevalence and type of peristomal skin bacteria in colostomy patients.Thirty-four patients with a temporary colostomy were included in the study. Their mean age was 51.6 years. All patients had been colostomized for more than 7 weeks.Tissue samples were obtained from the peristomal skin and were cultured. Escherichia coli was present in the peristomal skin of 81.2% of patients with malignant colorectal disease and in all cases of benign colorectal disease. The proportion of patients with Bacteroides fragilis (P = 0.021) and Klebsiella spp (P = 0.003) was higher. The incidence of Peptococcus spp (P = 0.068) was lower in patients who had their colostomy for a longer period. The cultures in the 34 patients demonstrated that the most common bacteria present were: Escherichia coli (31/34), Bacteroides spp (13/34), Peptococcus spp (13/34), Klebsiella spp (11/34), and Enterobacter spp (06/34).The results of this study show that the dermal layer of the abdominal wall in the pericolostomic region is colonized by enteric bacteria.
Increased hydrogen peroxide and thiobarbituric acid-reactive products in expired breath condensate of asthmatic patients
Authors: A Antczak, D Nowak, B Shariati, M Krol, G Piasecka, Z Kurmanowska
Journal: European Respiratory Journal (1997)

Symptoms of bronchial asthma are a manifestation of airway inflammation. Circulatory leucocytes (predominantly eosinophils, mast cells and neutrophils), release inflammatory mediators, including reactive oxygen species, i.e. superoxide anion which is dismutated to hydrogen peroxide (H2O2). Neutrophils from asthmatics generate greater amounts of these species than those of healthy subjects. Some of the H2O2 and thiobarbituric acid-reactive products (TBARs) can evaporate from alveolar lining fluid, and could be expired from the airways of asthmatics. In this study, therefore, we determined whether asthmatic patients exhale more H2O2 and TBARs than healthy subjects. We examined 10 healthy subjects as a control group and 21 asthmatic subjects. In asthmatic subjects, forced expiratory volume in one second (FEV1), was 68+/-9% of predicted value, peak expiratory flow rate (PEFR) was 65+/-8% pred, and bronchial reversibility was 34+/-5% of prebronchodilated FEV1. The mean H2O2 level measured spectrofluorimetrically in the expired breath condensate of asthmatic subjects was 26 fold higher than that in healthy controls (0.26+/-0.29 vs 0.01+/-0.03 nM; p&lt;0.05). The concentration of TBARs in breath condensate was also higher in asthmatic patients compared with nonasthmatics (0.073+/-0.071 vs 0.004+/-0.009 nM; p&lt;0.05). There was a significant correlation between H2O2 level and concentration of TBARs in asthmatic patients (r=0.74; p&lt;0.01). There was also a strong inverse correlation between H2O2 content of all asthmatics and FEV1% pred (r=-0.63; p&lt;0.005) and PEFR% pred (r=-0.52; p&lt;0.05). We conclude that there are elevated levels of hydrogen peroxide and thiobarbituric acid-reactive products in expired breath condensate of asthmatic patients, and that measurement of these substances in the expired breath condensate could be a simple, noninvasive method that could be used as a biochemical marker of airway inflammation.
A Novel PTEN-Dependent Link to Ubiquitination Controls FLIPS Stability and TRAIL Sensitivity in Glioblastoma Multiforme
Authors: Amith Panner, Courtney A. Crane, Changjiang Weng, Alberto Feletti, Andrew T. Parsa, Russell O. Pieper
Journal: Cancer Research (2009)

Abstract Phosphatase and tensin homologue (PTEN) loss and activation of the Akt-mammalian target of rapamycin (mTOR) pathway increases mRNA translation, increases levels of the antiapoptotic protein FLIPS, and confers resistance to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–induced apoptosis in glioblastoma multiforme (GBM). In PTEN-deficient GBM cells, however, the FLIPS protein also exhibited a longer half-life than in PTEN mutant GBM cells, and this longer half-life correlated with decreased FLIPS polyubiquitination. FLIPS half-life in PTEN mutant GBM cells was reduced by exposure to an Akt inhibitor, but not to rapamycin, suggesting the existence of a previously undescribed, mTOR-independent linkage between PTEN and the ubiquitin-dependent control of protein stability. Total levels of the candidate FLIPS E3 ubiquitin ligase atrophin-interacting protein 4 (AIP4) were comparable in PTEN wild-type (WT) and PTEN mutant GBM cells, although in PTEN-deficient cells, AIP4 was maintained in a stable polyubiquitinated state that was less able to associate with FLIPS or with the FLIPS-containing death inducing signal complex. Small interfering RNA–mediated suppression of AIP4 levels in PTEN WT cells decreased FLIPS ubiquitination, prolonged FLIPS half-life, and increased TRAIL resistance. Similarly, the Akt activation that was previously shown to increase TRAIL resistance did not alter AIP4 levels, but increased AIP4 ubiquitination, increased FLIPS steady-state levels, and suppressed FLIPS ubiquitination. These results define the PTEN-Akt-AIP4 pathway as a key regulator of FLIPS ubiquitination, FLIPS stability, and TRAIL sensitivity and also define a novel link between PTEN and the ubiquitin-mediated control of protein stability. [Cancer Res 2009;69(20):7911–6]
Neointimal smooth muscle cell phenotype is important in its susceptibility to cytomegalovirus (CMV) infection: a study in rat
Authors: M Persoons
Journal: Cardiovascular Research (1997)

Objective: Recently, we have found that rat CMV (RCMV) infected smooth muscle cells (SMCs) in rat carotid arteries when administered 14 days after balloon injury. In the present study we investigated (1) the long term effects of CMV infection on neointimal cross-sectional area, and (2) whether the phenotype of the intimal SMCs influences their susceptibility to active CMV infection. Methods: In the first part of the study, rats received RCMV intravenously, two weeks after balloon catheterisation of the left carotid artery and were sacrificed twenty weeks after catheterisation. Continuous BrdU infusion was performed by subcutaneously implanted osmotic pumps during the last two weeks of life. In the second part RCMV was administered eight weeks after catheterisation and rats were sacrificed two weeks later. Immunohistochemistry was used to detect viral antigens, to determine BrdU incorporation as well as the contents of α-actin, desmin and vimentin in the carotid arteries. Intima and media cross-sectional areas were determined using computerized morphometry. Results and conclusions: RCMV infection did not induce any differences in intima or media cross-sectional areas of the injured carotid artery, nor in the extent of SMC proliferation as shown by BrdU incorporation, 20 weeks after balloon catheterisation. Eight weeks after balloon catheterisation, RCMV no longer infected neointimal SMCs. This non-responsiveness to RCMV was associated with 're-differentiation' of the eight weeks old neointima, compared with two weeks after catheterization, as shown by the contents of α-actin, desmin and vimentin. Our data suggest that intimal SMC phenotype determines its susceptibility to active RCMV infection in vivo. Since de-differentiation of neointimal SMCs is associated with enhanced proliferation of these cells it is stated that de-differentiation or proliferation is prerequisite for infection.
Functionally Inert HIV-Specific Cytotoxic T Lymphocytes Do Not Play a Major Role in Chronically Infected Adults and Children
Authors: Philip J.R. Goulder, Yanhua Tang, Christian Brander, Michael R. Betts, Marcus Altfeld, Ken Annamalai, Alicja Trocha, Suqin He, Eric S. Rosenberg, Graham Ogg, Christopher A. O'Callaghan, Spyros A. Kalams, Ross E. McKinney, Kenneth Mayer, Richard A. Koup, Stephen I. Pelton, Sandra K. Burchett, Kenneth McIntosh, Bruce D. Walker
Journal: The Journal of Experimental Medicine (2000)

The highly sensitive quantitation of virus-specific CD8(+) T cells using major histocompatibility complex-peptide tetramer assays has revealed higher levels of cytotoxic T lymphocytes (CTLs) in acute and chronic virus infections than were recognized previously. However, studies in lymphocytic choriomeningitis virus infection have shown that tetramer assays may include measurement of a substantial number of tetramer-binding cells that are functionally inert. Such phenotypically silent CTLs, which lack cytolytic function and do not produce interferon (IFN)-gamma, have been hypothesized to explain the persistence of virus in the face of a quantitatively large immune response, particularly when CD4 help is impaired. In this study, we examined the role of functionally inert CTLs in chronic HIV infection. Subjects studied included children and adults (n = 42) whose viral loads ranged from <50 to >100,000 RNA copies/ml plasma. Tetramer assays were compared with three functional assays: enzyme-linked immunospot (Elispot), intracellular cytokine staining, and precursor frequency (limiting dilution assay [LDA]) cytotoxicity assays. Strong positive associations were observed between cell numbers derived by the Elispot and the tetramer assay (r = 0.90). An even stronger association between tetramer-derived numbers and intracellular cytokine staining for IFN-gamma was present (r = 0.97). The majority (median 76%) of tetramer-binding cells were consistently detectable via intracellular IFN-gamma cytokine staining. Furthermore, modifications to the LDA, using a low input cell number into each well, enabled LDAs to reach equivalence with the other methods of CTL enumeration. These data together show that functionally inert CTLs do not play a significant role in chronic pediatric or adult HIV infection.
Synergistic effect of sustained delivery of basic fibroblast growth factor and bone marrow mononuclear cell transplantation on angiogenesis in mouse ischemic limbs
Authors: Oju Jeon, Sun-Woong Kang, Hee-Won Lim, Dongho Choi, Dong-Ik Kim, Sung Hee Lee, Ji Hyung Chung, Byung-Soo Kim
Journal: Biomaterials (2005)
IL-10–producing and naturally occurring CD4+ Tregs: limiting collateral damage
Authors: Anne O’Garra, Pedro L. Vieira, Paulo Vieira, Anne E. Goldfeld
Journal: Journal of Clinical Investigation (2004)

Effective immune responses against pathogens are sometimes accompanied by strong inflammatory reactions. To minimize damage to self, the activation of the immune system also triggers anti-inflammatory circuits. Both inflammatory and anti-inflammatory reactions are normal components of the same immune response, which coordinately fight infections while preventing immune pathology. IL-10 is an important suppressive cytokine, produced by a large number of immune cells in addition to the antigen-driven IL-10-producing regulatory and the naturally occurring suppressor CD4+ T cells, which is a key player in anti-inflammatory immune responses. However, additional mechanisms have evolved to ensure that pathogen eradication is achieved with minimum damage to the host. Here we discuss those mechanisms that operate to regulate effector immune responses.
MOLECULAR ANALYSIS OF THE MEMBRANE ATTACK MECHANISM OF COMPLEMENT
Authors: William P. Kolb, James A. Haxby, Carlos M. Arroyave, Hans J. Müller-Eberhard
Journal: The Journal of Experimental Medicine (1972)

The molecular arrangement of the membrane attack mechanism of complement was explored. The molar ratios of the components within the C5-9 assembly on the target cell surface were determined using human complement proteins in highly purified and radiolabeled form. With the aid of monospecific complement antisera it was possible to probe the spatial relationships between the components of the assembly. C5 and C6, in the presence of C7, were bound to EAC1-3 in equimolar quantities irrespective of the amounts and the relative proportions of C5, C6, and C7 offered. The amount of C8 bound to EAC1-7 increased with input and at saturation of all C8 binding sites the molar ratio of bound C8/bound C5 approached 1.0. Uptake of C9 by EAC1-8 increased with input and at saturation of all C9 binding sites the molar ratio of bound C9/bound C8 became 6.0. However, calculations suggest that the binding of three C9 molecules to one C8 molecule is sufficient to achieve a full hemolytic effect. Evidence was obtained indicating that binding and hemolytic function of C9 depends upon cooperative interaction of multiple C9 molecules. Binding of C8 to EAC1-7 and the generation of hemolytic C8 sites were inhibited by antibody to either C5, C6, or C7. Uptake of C9 by EAC1-8 and the generation of hemolytic C9 sites were strongly inhibited by anti-C8 and to a lesser degree by anti-C5. Binding of C9 (but not hemolysis) was also reduced by antibody to C6 or C7. The data are consistent with the concept that the fully assembled membrane attack mechanism of complement consists of a decamolecular complex: a trimolecular arrangement composed of C5, C6, and C7 forms the binding site for one C8 molecule which in turn furnishes binding sites for six C9 molecules, saturation of three sites apparently being sufficient for expression of full cytolytic activity of the complex. This work made it possible to design a simple molecular model.