tbuckley/cabot-search huggingface dataset:
The Role of Collagen Quaternary Structure in the Platelet:Collagen Interaction
Authors: Lawrence F. Brass, Howard B. Bensusan
Journal: Journal of Clinical Investigation (1974)

WE HAVE INVESTIGATED WHETHER COLLAGEN QUETERNARY STRUCTURE IS REQUIRED FOR THE PLATELET: collagen interaction. Quaternary structure refers to the assembly of collagen monomers (tropocollagen) into polymers (native-type fibrils). Purified monomeric collagen was prepared from acetic acid extracts of fetal calfskin. Polymeric collagen was prepared by dispersion of bovine Achilles tendon collagen and by incubation of monomeric collagen at 37 degrees C and pH 7.4. The state of polymerization was confirmed by electron microscopy. Release of platelet serotonin in the absence of platelet aggregation was used to determine the effectiveness of the platelet: collagen interaction. All forms of collagen produced serotonin release only after a lag period, but polymeric collagen gave a shorter lag period than did monomeric collagen. Monomeric collagen was also quanidinated selectively to convert collagen lysine groups to homoarginine, while leaving the arrangement of polar groups intact. Guanidination of monomeric collagen increased the rate of polymerization and reduced the lag time in serotonin release. Glucosamine (17 mM) retarded polymerization and inhibited the release of platelet serotonin by monomeric collagen but had little effect on release produced by thrombin or polymeric collagen. At the same concentration, glucosamine did not reduce the sensitivity of platelets to stimulation by collagen or block the platelet: collagen interaction. The only effect of glucosamine was on the collagen: collagen interaction. Galactosamine had a similar effect, but glucose, galactose, and N-acetylglycosamine had no effect. We conclude from this data that collagen monomers cannot effectively interact with platelets and that, therefore, collagen quaternary structure has a role in the recognition of collagen by platelets.
Ecogenomics of Respiratory Diseases of Public Health Significance
Authors: Stavros Garantziotis, David A. Schwartz
Journal: Annual Review of Public Health (2010)

Gene-environment interactions are the indisputable cause of most respiratory diseases. However, we still have very limited understanding of the mechanisms that guide these interactions. Although the conceptual approaches to environmental genomics were established several decades ago, the tools are only now available to better define the mechanisms that underlie the interactions among these important etiological features of lung disease. In this article, we summarize recent insights in the environmental genomics (ecogenomics) of common nonmalignant respiratory diseases (asthma, COPD, pulmonary fibrosis, and respiratory infections), describe the framework of gene-environment interactions that inform the pathogenesis of respiratory diseases, and propose future research directions that will help translate scientific advances into public health gains.
US campaigners challenge abortion law changes
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

Fiber tracts should use space and energy efficiently, because both resources constrain neural computation. We found for a myelinated tract (optic nerve) that astrocytes use nearly 30% of the space and &gt;70% of the mitochondria, establishing the significance of astrocytes for the brain9s space and energy budgets. Axons are mostly thin with a skewed distribution peaking at 0.7 μm, near the lower limit set by channel noise. This distribution is matched closely by the distribution of mean firing rates measured under naturalistic conditions, suggesting that firing rate increases proportionally with axon diameter. In axons thicker than 0.7 μm, mitochondria occupy a constant fraction of axonal volume—thus, mitochondrial volumes rise as the diameter squared. These results imply a law of diminishing returns: twice the information rate requires more than twice the space and energy capacity. We conclude that the optic nerve conserves space and energy by sending most information at low rates over fine axons with small terminal arbors and sending some information at higher rates over thicker axons with larger terminal arbors but only where more bits per second are needed for a specific purpose. Thicker axons seem to be needed, not for their greater conduction velocity (nor other intrinsic electrophysiological purpose), but instead to support larger terminal arbors and more active zones that transfer information synaptically at higher rates.
Identification of Natural RORγ Ligands that Regulate the Development of Lymphoid Cells
Authors: Fabio R. Santori, Pengxiang Huang, Serge A. van de Pavert, Eugene F. Douglass, David J. Leaver, Brad A. Haubrich, Rok Keber, Gregor Lorbek, Tanja Konijn, Brittany N. Rosales, Damjana Rozman, Simon Horvat, Alain Rahier, Reina E. Mebius, Fraydoon Rastinejad, W. David Nes, Dan R. Littman
Journal: Cell Metabolism (2015)
Nephrocystin Specifically Localizes to the Transition Zone of Renal and Respiratory Cilia and Photoreceptor Connecting Cilia
Authors: Manfred Fliegauf, Judit Horvath, Christian von Schnakenburg, Heike Olbrich, Dominik Müller, Julia Thumfart, Bernhard Schermer, Gregory J. Pazour, Hartmut P.H. Neumann, Hanswalter Zentgraf, Thomas Benzing, Heymut Omran
Journal: Journal of the American Society of Nephrology (2006)

Nephronophthisis (NPHP) is a hereditary cystic kidney disorder that causes renal failure in children and young adults and can be associated with various extrarenal disorders, including retinitis pigmentosa. Six NPHP genes, whose functions are disrupted by autosomal recessive mutations in patients with NPHP, have been identified. The majority of patients with NPHP carry homozygous deletions of NPHP1 encoding nephrocystin. Previous data indicate that nephrocystin forms a complex at cell junctions and focal adhesions. Here, it is shown that nephrocystin specifically localizes at the ciliary base to the transition zone of renal and respiratory cilia and to photoreceptor connecting cilia. During in vitro ciliogenesis of primary human respiratory epithelial cells, nephrocystin can be detected first with a diffuse cytoplasmic localization as soon as cell polarization starts, and translocates to the transition zone when cilia are formed. In columnar respiratory cells, nephrocystin is attached tightly to the axonemal structure of the transition zone at a region that contains the calcium-sensitive cilia autotomy site. In patients with homozygous NPHP1 deletions, nephrocystin is absent from the entire respiratory cell, including the transition zone, which might be of interest for future diagnostic approaches. Cilia formation is not altered in primary nephrocystin-deficient respiratory cells, which is consistent with previous findings obtained for the Caenorhabditis elegans ortholog. In addition, it is shown that the localization pattern of intraflagellar transport proteins and nephrocystin differs, suggesting distinct functional roles. In conclusion, nephrocystin deficiency or dysfunction at the transition zone of renal monocilia and the photoreceptor connecting cilium might explain renal failure and retinal degeneration that are observed in patients with NPHP1.
A controlled trial of nandrolone decanoate in the treatment of rheumatoid arthritis in postmenopausal women.
Authors: H A Bird, L Burkinshaw, D Pearson, P J Atkinson, P A Leatham, J Hill, A Raven, V Wright
Journal: Annals of the Rheumatic Diseases (1987)

To determine whether an anabolic steroid had any benefit in the treatment of rheumatoid arthritis 47 patients entered a parallel group study. Twenty four received nandrolone decanoate 50 mg intramuscularly every third week for two years and 23 patients received no anabolic steroids. Other therapy was unaltered. Patients attended for clinical and biochemical assessments as well as the objective assessments of elementary body composition by in vivo neutron activation analysis and measurement of the mineral content of the distal femur by single photon absorptiometry on five occasions. A modest clinical deterioration (except for grip strength) was seen in both groups. No significant changes in calcium or alkaline phosphatase were seen. There was no significant change in total body calcium, total body phosphorus, body weight, or bone index/bone width measurements in either group. Significant increases occurred in total body nitrogen, total body potassium, haemoglobin, and packed cell volume (by six months) in the group treated with nandrolone decanoate. Comparison of 10 patients in the group treated with nandrolone decanoate also receiving oral steroid therapy with 14 patients in this group not receiving oral steroid therapy showed no significant differences. The main side effect of nandrolone decanoate was hoarseness. No radiological changes were seen. Nandrolone decanoate, in a dose that produces a significant anabolic effect, has no demonstrable action on bone metabolism in rheumatoid arthritis but may improve the chronic anaemia by six months.
NOXA and PUMA Expression Add to Clinical Markers in Predicting Biochemical Recurrence of Prostate Cancer Patients in a Survival Tree Model
Authors: Jean-Simon Diallo, Abdulhadi Aldejmah, Abdelali Filali Mouhim, Benjamin Péant, Mona Alam Fahmy, Ismaël Hervé Koumakpayi, Kanishka Sircar, Louis R. Bégin, Anne-Marie Mes-Masson, Fred Saad
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To assess the expression of proapoptotic NOXA and PUMA in prostate tissues and delineate their association with prostate cancer (PCa) recurrence. Experimental Design: Normal, prostatic intraepithelial neoplasia (PIN), hormone-sensitive (HS) PCa, and hormone-refractory (HR) PCa tissues were used to build tissue microarrays encompassing a total of 135 patients. Two observers assessed the intensity of NOXA and PUMA immunohistochemical staining using a composite color scale. One hundred and eighty recursive partitioning and regression tree (RPART) models were generated to predict biochemical recurrence (BCR) within HS cancer patients using NOXA, PUMA, and clinical parameters. Models were then ranked according to the integrated Brier score (IBS). Results: Increasing NOXA expression was associated with PCa progression, reaching the highest levels in HR PCa. Increased NOXA expression was observed in 68% of HS cancer patients and was predictive of BCR (LR = 8.64; P = 0.003). In contrast, PUMA expression was highest in HS cancer, and although 70% of HS cancer patients exhibited increased PUMA expression, PUMA alone could not predict the onset of BCR. Interestingly, the top-ranking RPART model generated [IBS = 0.107; 95% confidence interval (95% CI), 0.065-0.128] included surgical margin status and NOXA and PUMA expression, although recurrent prognostic classification schemes obtained in the top 10 models favored a survival tree model containing margin status, NOXA expression, and preoperative prostate-specific antigen (PSA) (IBS = 0.114; 95% CI, 0.069-0.142). Conclusion: We conclude that NOXA and PUMA expression may be linked to PCa progression and propose further validation of a survival tree model including surgical margin status, NOXA expression, and preoperative PSA for predicting BCR.
Hypertriglyceridaemia during treatment with adalimumab in psoriatic arthritis
Authors: G. Stinco, F. Piccirillo, P. Patrone
Journal: British Journal of Dermatology (2007)

Journal Article Hypertriglyceridaemia during treatment with adalimumab in psoriatic arthritis Get access G. Stinco, G. Stinco Institute of Dermatology, Department of Clinical and Experimental Pathology and Medicine, University of Udine School of Medicine, Ospedale San Michele, Piazza Rodolone 1, 33013 Gemona del Friuli, Udine, Italy E‐mail: giuseppe.stinco@uniud.it Search for other works by this author on: Oxford Academic Google Scholar F. Piccirillo, F. Piccirillo Institute of Dermatology, Department of Clinical and Experimental Pathology and Medicine, University of Udine School of Medicine, Ospedale San Michele, Piazza Rodolone 1, 33013 Gemona del Friuli, Udine, Italy E‐mail: giuseppe.stinco@uniud.it Search for other works by this author on: Oxford Academic Google Scholar P. Patrone P. Patrone Institute of Dermatology, Department of Clinical and Experimental Pathology and Medicine, University of Udine School of Medicine, Ospedale San Michele, Piazza Rodolone 1, 33013 Gemona del Friuli, Udine, Italy E‐mail: giuseppe.stinco@uniud.it Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 157, Issue 6, 1 December 2007, Pages 1273–1274, https://doi.org/10.1111/j.1365-2133.2007.08188.x Published: 01 December 2007
Expression of Interneuron Markers in the Dorsolateral Prefrontal Cortex of the Developing Human and in Schizophrenia
Authors: Samantha J. Fung, Maree J. Webster, Sinthuja Sivagnanasundaram, Carlotta Duncan, Michael Elashoff, Cynthia Shannon Weickert
Journal: American Journal of Psychiatry (2010)

The onset of schizophrenia symptoms in late adolescence implies a neurodevelopmental trajectory for the disease. Indeed, the γ-aminobutyric acid (GABA) inhibitory system shows protracted development, and GABA-ergic deficits are widely replicated in postmortem schizophrenia studies. The authors examined expression of several interneuron markers across postnatal human development and in schizophrenia to assess whether protracted development of certain interneuron subpopulations may be associated with a particular vulnerability in schizophrenia.RNA was extracted postmortem from dorsolateral prefrontal cortex of individuals from age 6 weeks to 49 years (N=68) and from a cohort of normal comparison subjects and schizophrenia patients (N=74, 37 pairs). Expression levels of parvalbumin, cholecystokinin, somatostatin, neuropeptide Y, calretinin, calbindin, and vasoactive intestinal peptide were measured by quantitative reverse transcription-polymerase chain reaction. Changes in calretinin protein levels were examined by Western blot.Interneuron marker genes followed one of three general expression profiles: either increasing (parvalbumin, cholecystokinin) or decreasing (somatostatin, calretinin, neuropeptide Y) in expression over postnatal life, with the most dramatic changes seen in the first few years before reaching a plateau; or increasing to peak expression in the toddler years before decreasing (calbindin, vasoactive intestinal peptide). mRNA expression of all genes, with the exception of calbindin (which increased), showed a reduction (8%-31%) in schizophrenia. Somatostatin showed the most dramatic reduction (31%) in schizophrenia.It appears that a heterogeneous population of interneurons is implicated in schizophrenia. Further studies are needed to determine whether specific interneuron subpopulations are altered or whether common or distinct upstream pathways are responsible for interneuron deficits in schizophrenia.
Developmental Neuropathology of Environmental Agents
Authors: Lucio G. Costa, Michael Aschner, Annabella Vitalone, Tore Syversen, Offie Porat Soldin
Journal: The Annual Review of Pharmacology and Toxicology (2004)

The developing central nervous system (CNS) is more vulnerable to injury than the adult one. Although a great deal of research has been devoted to subtle effects of developmental exposure, such as neurobehavioral changes, this review instead focuses on a number of chemicals that have been shown, in several experimental models as well as humans, to cause morphological changes in the developing nervous system. Chemicals that are discussed include methylmercury (MeHg), lead (Pb), antiepileptic drugs, and ethanol. Additionally, the issue of silent neurotoxicity, i.e., persistent morphological and/or biochemical injury that remains clinically unapparent until later in life, is discussed.
Novel measurements of mammary stem cells in human umbilical cord blood as prospective predictors of breast cancer susceptibility in later life
Authors: L. Qiu, H.P. Low, C.-I. Chang, W.C. Strohsnitter, M. Anderson, K. Edmiston, H.-O. Adami, A. Ekbom, P. Hall, P. Lagiou, D. Trichopoulos, C.-C. Hsieh
Journal: Annals of Oncology (2011)
Severe liver fibrosis caused by Schistosoma mansoni: management and treatment with a transjugular intrahepatic portosystemic shunt
Authors: Joachim Richter, Johannes G Bode, Dirk Blondin, Gerald Kircheis, Ralf Kubitz, Martha C Holtfreter, Irmela Müller-Stöver, Matthias Breuer, Falk Hüttig, Gerald Antoch, Dieter Häussinger
Journal: The Lancet Infectious Diseases (2015)
Chemotherapy plus Involved-Field Radiation in Early-Stage Hodgkin's Disease
Authors: Christophe Fermé, Houchingue Eghbali, Jacobus H. Meerwaldt, Chantal Rieux, Jacques Bosq, Françoise Berger, Théodore Girinsky, Pauline Brice, Mars B. van't Veer, Jan A. Walewski, Pierre Lederlin, Umberto Tirelli, Patrice Carde, Eric Van Den Neste, Emmanuel Gyan, Mathieu Monconduit, Marine Diviné, John M.M. Raemaekers, Gilles Salles, Evert M. Noordijk, Geert-Jan Creemers, Jean Gabarre, Anton Hagenbeek, Oumédaly Reman, Michel Blanc, José Thomas, Brigitte Vié, Johanna C. Kluin-Nelemans, Fernando Viseu, Joke W. Baars, Philip Poortmans, Pieternella J. Lugtenburg, Christian Carrie, Jérôme Jaubert, Michel Henry-Amar
Journal: New England Journal of Medicine (2007)

Treatment of early-stage Hodgkin's disease is usually tailored in line with prognostic factors that allow for reductions in the amount of chemotherapy and extent of radiotherapy required for a possible cure.
Evaluation of oesophageal mucosa integrity by the intraluminal impedance technique
Authors: R. Farre, K. Blondeau, D. Clement, M. Vicario, L. Cardozo, M. Vieth, V. Mertens, A. Pauwels, J. Silny, M. Jimenez, J. Tack, D. Sifrim
Journal: Gut (2011)

<h3>Background</h3> Oesophageal intraluminal impedance is currently used for assessment of reflux in gastro-oesophageal reflux disease (GORD). Oesophageal mucosa integrity may have a key role in heartburn perception in non-erosive reflux disease (NERD). Severe erosive oesophagitis is associated with low impedance baseline. We hypothesised that impedance baseline measurements could be used to evaluate changes in oesophageal mucosa integrity in man. <h3>Methods</h3> We measured oesophageal impedance baseline before, during and after acid perfusion in rabbits and healthy subjects. Transepithelial resistance (TER) was determined and dilated intercellular spaces (DIS) were assessed in isolated rabbit oesophageal mucosa. Impedance baseline was measured retrospectively at different levels of the oesophagus in impedance-pH recordings from asymptomatic volunteers and patients with GORD. <h3>Results</h3> In healthy subjects and rabbits, impedance baseline dropped dramatically during perfusion of control solution (pH 7.2) but after perfusion, impedance recovered. In rabbits, after perfusion with saline pH 1.5 and 1.0 impedance values remained a 39.1±7.0% and 63.9±6.5% (p&lt;0.05) lower respectively. There was a positive correlation between in vivo basal impedance and in vitro TER values (r=0.72, p=0.0021). Tissue showed no erosions but both acidic solutions induced DIS. In healthy subjects, after perfusion with saline pH 2.0 and 1.0 the impedance baseline remained lower a 21.9±6.5% and 52.7±5.0%, (p&lt;0.0001) respectively. Patients with GORD have a lower impedance baseline than healthy volunteers at the distal oesophagus. <h3>Conclusions</h3> Impedance baseline measurements might be used to evaluate the status of the oesophageal mucosa and to study the role of the impaired mucosal integrity in acid-induced heartburn in healthy volunteers and in patients with GORD.
N-3 fatty acids stimulate intracellular degradation of apoprotein B in rat hepatocytes.
Authors: H Wang, X Chen, E A Fisher
Journal: Journal of Clinical Investigation (1993)

When rat hepatocytes were incubated with albumin complexed to the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), rather than to oleic acid (OA), the secretion of newly synthesized apoprotein B100 (apoB100) or B48 (apoB48) was reduced, despite stimulation of cellular triglyceride synthesis by all three fatty acids. When pulse-chase studies of apoB synthesis and secretion were performed in the presence of OA, EPA, or DHA, there were no significant changes in the initial synthetic rates of either apoB species. However, during the chase period, the total recovery of labeled apoB100 and apoB48 from the cell and medium was less in the n-3 fatty acid groups, so that by 150 min, approximately half as much labeled apoB was recovered as in the OA group. Overall, the decreased accumulation in medium of labeled apoB in the presence of EPA and DHA could be quantitatively accounted for by increased degradation of intracellular apoB. Thus, in the primary hepatocyte, apoB degradation is not constitutive, but can be regulated by n-3 fatty acids.
MiR-20a regulates ASK1 expression and TLR4-dependent cytokine release in rheumatoid fibroblast-like synoviocytes
Authors: Lucas Philippe, Ghada Alsaleh, Angélique Pichot, Eleonore Ostermann, Guy Zuber, Benoit Frisch, Jean Sibilia, Sébastien Pfeffer, Seiamak Bahram, Dominique Wachsmann, Philippe Georgel
Journal: Annals of the Rheumatic Diseases (2012)

Objective To evaluate whether miR-20a belonging to the cluster miR-17–92 is a negative regulator of inflammation in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) by modulating expression of apoptosis signal-regulating kinase (ASK) 1, a key component of the toll-like receptors 4 pathway, upstream of p38 mitogen-activated protein kinase. Methods Evaluation of miR-20a and ASK1 mRNA was performed by RT-qPCR. ASK1 protein expression was assessed by western blotting. Overexpression of miR-20a was performed by transfection of RA FLS and THP-1 cells with miR-20a mimics. Interleukin (IL)-6, CXCL-10, IL-1β and TNF-α release were measured by ELISA. The role of miR-20a in vivo was assessed by IL-6 release from macrophages obtained from mice injected intraperitoneally with vectorised miR-20a mimics. Results We showed that stimulation of RA FLS with lipopolysacharide (LPS) and bacterial lipoproteins (BLP) induces a drop in expression of miR-20a and that this decrease is associated with an upregulation of ASK1 expression. Using transfection of Ask1 3′UTR reporters, we demonstrate that Ask1 is a direct target of miR-20a. Overexpression of miR-20a led to a global decrease in ASK1 protein in BLP- and LPS-activated cells indicating that miR-20a regulates the expression of ASK1 at the translational level. Transfection of miR-20a mimics decreases IL-6 and CXCL10 release by RA FLS and IL-1β and TNF-α by activated THP-1 cells but only in response to LPS. Last, injection of vectorised miR-20a mimics to mice led to a global decrease in ASK1 protein expression and IL-6 secretion in LPS-activated macrophages. Conclusions Our data point toward an important role for miR-20a in the regulation of pro-inflammatory cytokines release, by controlling ASK1 expression in RA FLS.