tbuckley/cabot-search huggingface dataset:
Dose-dependent effects of mandibular protrusion on genioglossus activity in sleep apnoea
Authors: F.R. Almeida, S. Tsuiki, Y. Hattori, Y. Takei, Y. Inoue, A.A. Lowe
Journal: European Respiratory Journal (2010)

To the Editors:

In individuals with a compromised upper airway, the activity of the genioglossus (GG) muscle is augmented to maintain upper airway patency during wakefulness 1. However, sleep greatly suppresses GG muscle activity, which may lead to partial or complete upper airway collapse in patients with obstructive sleep apnoea (OSA). Mandibular-advancing oral appliances are currently accepted as one promising approach to the treatment of mild-to-moderate OSA 2, 3. Although enlargement of the upper airway at multiple levels may be important for producing a clinical effect, the contributions of oral appliances to functional aspects, in terms of GG muscle activity, have hardly been documented.

If mandibular advancement increased the electromyographic activity of the GG muscle (GGEMG), this effect should help to maintain the patency of the airway, since the activation of GGEMG could stiffen the compliant airway wall 4. In contrast, if we consider that mandibular advancement increases the cross-sectional area and decreases the propensity for upper airway occlusion, it would be reasonable to hypothesise that a larger, less collapsible upper airway could improve airflow dynamics, which would require less GGEMG 5. Accordingly, we investigated the effects of mandibular advancement by an experimental oral appliance on GGEMG and the severity of OSA during sleep.

The study protocol was approved by the Clinical Research Ethics Board at the University of British Columbia (UBC), Vancouver, Canada. A 54-yr-old male patient with severe OSA (body mass index 31.2 kg·m−2 and apnoea/hypopnoea index (AHI) 30.3 events·hr−1) who showed a resolution of symptoms, including daytime sleepiness, snoring and/or apnoea, after complete titration of the oral appliance (Klearway™; Great Lakes Orthodontics, Tonawanda, NY, USA) was recruited into the study. The patient had used the oral appliance for a period of 4 months prior to the …
Asch and the balance of values
Authors: Bert H. Hodges
Journal: Behavioral and Brain Sciences (2004)

Values will be central to developing a more balanced social psychology. A nonconformist account of Asch's (1956) experiments is used to illustrate the role of multiple values and to support and extend Krueger &amp; Funder's (K&amp;F's) claims. A balance of values, one that goes beyond accuracy and truth, and that avoids absolutism and relativism, is needed.
A brain-targeted, modified neurosin (kallikrein-6) reduces α-synuclein accumulation in a mouse model of multiple system atrophy
Authors: Brian Spencer, Elvira Valera, Edward Rockenstein, Margarita Trejo-Morales, Anthony Adame, Eliezer Masliah
Journal: Molecular Neurodegeneration (2015)

Multiple system atrophy (MSA) is a progressive, neurodegenerative disease characterized by parkinsonism, resistance to dopamine therapy, ataxia, autonomic dysfunction, and pathological accumulation of α-synuclein (α-syn) in oligodendrocytes. Neurosin (kallikrein-6) is a serine protease capable of cleaving α-syn in the CNS, and we have previously shown that lentiviral (LV) vector delivery of neurosin into the brain of a mouse model of dementia with Lewy body/ Parkinson's disease reduces the accumulation of α-syn and improves neuronal synaptic integrity. In this study, we investigated the ability of a modified, systemically delivered neurosin to reduce the levels of α-syn in oligodendrocytes and reduce the cell-to-cell spread of α-syn to glial cells in a mouse model of MSA (MBP-α-syn). We engineered a viral vector that expresses a neurosin genetically modified for increased half-life (R80Q mutation) that also contains a brain-targeting sequence (apoB) for delivery into the CNS. Peripheral administration of the LV-neurosin-apoB to the MBP-α-syn tg model resulted in accumulation of neurosin-apoB in the CNS, reduced accumulation of α-syn in oligodendrocytes and astrocytes, improved myelin sheath formation in the corpus callosum and behavioral improvements. Thus, the modified, brain-targeted neurosin may warrant further investigation as potential therapy for MSA.
Lipotoxicity Causes Multisystem Organ Failure and Exacerbates Acute Pancreatitis in Obesity
Authors: Sarah Navina, Chathur Acharya, James P. DeLany, Lidiya S. Orlichenko, Catherine J. Baty, Sruti S. Shiva, Chandra Durgampudi, Jenny M. Karlsson, Kenneth Lee, Kyongtae T. Bae, Alessandro Furlan, Jaideep Behari, Shiguang Liu, Teresa McHale, Larry Nichols, Georgios Ioannis Papachristou, Dhiraj Yadav, Vijay P. Singh
Journal: Science Translational Medicine (2011)

Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid-mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis.
The role of H-2 linked genes in helper T-cell function. II. Isolation on antigen-pulsed macrophages of two separate populations of F1 helper T cells each specific for antigen and one set of parental H-2 products.
Authors: J E Swierkosz, K Rock, P Marrack, J W Kappler
Journal: The Journal of Experimental Medicine (1978)

A method was established for isolating antigen-specific murine helper T cells by selective binding to antigen-pulsed macrophage (Mphi) monolayers. Sheep erythrocyte (SRBC)-primed T cells, which remained strongly adherent to SRBC-pulsed syngeneic Mphi after 20 h in culture, were markedly enriched for helper activity when tested in the in vitro antitrinitrophenol (TNP) response to TNP-SRBC. Successful binding and enrichment occurred only if the Mphi were pulsed with the specific antigen to which the T-cell donors had been primed. The genetic control governing helper function in this system was then examined by using primed F1 T cells isolated on Mphi monolayers from congenic strains bearing parental H-2 haplotypes. SRBC-primed BDF1 (H-2b X H-2d) T cells, which bound to SRBC-pulsed H-2d Mphi, subsequently functioned as helper cells in cultures containing H-2d B cells and Mphi, but not in those containing H-2b B cells and Mphi. They remained unable to collaborate with B cells of the H-2B haplotype even in the presence of additional H-2d Mphi, indicating that H-2 restriction occurs at least at the level of the B cell. Similary, primed BDF1 T cells isolated on H-2b Mphi cooperated preferentially with H-2b B cells and Mphi. In both cases, the haplotype preference of the T cell was not due to alloreactive suppressor activity. These results suggest that primed F1 mice contain individual populations of helper T cells, each of which recognize antigen in association with a parental H-2 gene product(s) expressed during both Mphi-T cell and T cell-B cell interactions.
Hypoxia Promotes Danger-mediated Inflammation via Receptor for Advanced Glycation End Products in Cystic Fibrosis
Authors: Rossana G. Iannitti, Andrea Casagrande, Antonella De Luca, Cristina Cunha, Guglielmo Sorci, Francesca Riuzzi, Monica Borghi, Claudia Galosi, Cristina Massi-Benedetti, Tim D. Oury, Lisa Cariani, Maria Russo, Luigi Porcaro, Carla Colombo, Fabio Majo, Vincenzina Lucidi, Ersilia Fiscarelli, Gabriella Ricciotti, Cornelia Lass-Flörl, Luigi Ratclif, Antonella Esposito, Fernando Maria De Benedictis, Rosario Donato, Agostinho Carvalho, Luigina Romani
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Hypoxia regulates the inflammatory-antiinflammatory balance by the receptor for advanced glycation end products (RAGE), a versatile sensor of damage-associated molecular patterns. The multiligand nature of RAGE places this receptor in the midst of chronic inflammatory diseases.Objectives: To characterize the impact of the hypoxia-RAGE pathway on pathogenic airway inflammation preventing effective pathogen clearance in cystic fibrosis (CF) and elucidate the potential role of this danger signal in pathogenesis and therapy of lung inflammation.Methods: We used in vivo and in vitro models to study the impact of hypoxia on RAGE expression and activity in human and murine CF, the nature of the RAGE ligand, and the impact of RAGE on lung inflammation and antimicrobial resistance in fungal and bacterial pneumonia.Measurements and Main Results: Sustained expression of RAGE and its ligand S100B was observed in murine lung and human epithelial cells and exerted a proximal role in promoting inflammation in murine and human CF, as revealed by functional studies and analysis of the genetic variability of AGER in patients with CF. Both hypoxia and infections contributed to the sustained activation of the S100B-RAGE pathway, being RAGE up-regulated by hypoxia and S100B by infection by Toll-like receptors. Inhibiting the RAGE pathway in vivo with soluble (s) RAGE reduced pathogen load and inflammation in experimental CF, whereas sRAGE production was defective in patients with CF.Conclusions: A causal link between hyperactivation of RAGE and inflammation in CF has been observed, such that targeting pathogenic inflammation alleviated inflammation in CF and measurement of sRAGE levels could be a useful biomarker for RAGE-dependent inflammation in patients with CF.
Cloning and expression of cDNA and genomic clones encoding three delayed rectifier potassium channels in rat brain
Authors: Richard Swanson, John Marshall, Jeffrey S. Smith, Jacinta B. Williams, Mary B. Boyle, Kimberly Folander, Christopher J. Luneau, Joanne Antanavage, Carlos Oliva, Susan A. Buhrow, Carl Bennet, Robert B. Stein, Leonard K. Kaczmarek
Journal: Neuron (1990)
Apnoeic and obstructive nonapnoeic sleep respiratory events
Authors: J. F. Masa, J. Corral, J. Teran, M. J. Martin, C. Disdier, M. Rubio, M. Mota, J. Zamorano, J. M. Montserrat
Journal: European Respiratory Journal (2009)

Obstructive nonapnoeic event (ONE) scoring is shrouded in confusion. This is important in patients with mild disease, in whom precision is crucial. The aims of the present study were: 1) to identify ONEs using oesophageal pressure (OP) (OP-ONEs) and a noninvasive (NI) method (NI-ONEs); 2) to compare both methods of scoring; and 3) to determine the contribution of ONE definitions to clinical findings. Patients with suspected sleep apnoeas (respiratory disturbance index ≤10) during a first polysomnography were subjected to a second with an OP measurement. OP-ONEs and NI-ONEs were defined as an increase in OP or discernible reduction in the amplitude of thoracoabdominal bands with both desaturation and/or arousal. Bland–Altman analysis established agreement. Comparisons were made between OP-ONEs, NI-ONEs and clinical findings. In our sample (n = 90), the addition of an arousal to the NI-ONEs or OP-ONEs with only desaturation increased the number of NI-ONEs by 329 and 362%, respectively. NI-ONEs with arousal and/or desaturation detected 91% of OP-ONEs. The association with sleepiness depended on the incorporation of arousal into the definition of ONEs. In patients with mild disease, the addition of an arousal to ONEs, with only desaturation, markedly increased respiratory disturbance index, with probable therapeutic implications. Scoring respiratory events as apnoea and ONEs is easier and sufficiently accurate.
Kinase Mutations and Imatinib Response in Patients With Metastatic Gastrointestinal Stromal Tumor
Authors: Michael C. Heinrich, Christopher L. Corless, George D. Demetri, Charles D. Blanke, Margaret von Mehren, Heikki Joensuu, Laura S. McGreevey, Chang-Jie Chen, Annick D. Van den Abbeele, Brian J. Druker, Beate Kiese, Burton Eisenberg, Peter J. Roberts, Samuel Singer, Christopher D.M. Fletcher, Sandra Silberman, Sasa Dimitrijevic, Jonathan A. Fletcher
Journal: Journal of Clinical Oncology (2003)

Purpose: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. The relationship between mutations in these kinases and clinical response to imatinib was examined in a group of patients with advanced GIST. Patients and Methods: GISTs from 127 patients enrolled onto a phase II clinical study of imatinib were examined for mutations of KIT or PDGFRA. Mutation types were correlated with clinical outcome. Results: Activating mutations of KIT or PDGFRA were found in 112 (88.2%) and six (4.7%) GISTs, respectively. Most KIT mutations involved exon 9 (n = 23) or exon 11 (n = 85). All KIT mutant isoforms, but only a subset of PDGFRA mutant isoforms, were sensitive to imatinib, in vitro. In patients with GISTs harboring exon 11 KIT mutations, the partial response rate (PR) was 83.5%, whereas patients with tumors containing an exon 9 KIT mutation or no detectable mutation of KIT or PDGFRA had PR rates of 47.8% (P = .0006) and 0.0% (P &lt; .0001), respectively. Patients whose tumors contained exon 11 KIT mutations had a longer event-free and overall survival than those whose tumors expressed either exon 9 KIT mutations or had no detectable kinase mutation. Conclusion: Activating mutations of KIT or PDGFRA are found in the vast majority of GISTs, and the mutational status of these oncoproteins is predictive of clinical response to imatinib. PDGFRA mutations can explain response and sensitivity to imatinib in some GISTs lacking KIT mutations.
Multiallelic polymorphism of the cartilage collagen gene: no association with osteoarthrosis.
Authors: M Vikkula, M Nissila, E Hirvensalo, P Nuotio, A Palotie, K Aho, L Peltonen
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--To determine whether any of the type II collagen alleles are associated with generalised osteoarthrosis or osteoarthrosis of the finger joints in the genetically isolated Finnish population. METHODS--Two patient cohorts with evidence for only primary osteoarthrosis and a cohort of healthy control subjects were selected from the Helsinki University Central Hospital and the Rheumatism Foundation Hospital in Finland. Forty one patients with primary generalised osteoarthrosis, 49 patients with osteoarthrosis of the finger joints, and 48 control subjects were included. Two markers of the type II collagen gene, a PvuII polymorphism and a VNTR polymorphism, were analysed from each subject. RESULTS--Four different alleles of the VNTR marker were observed and the relative risks associated with the different VNTR alleles varied between 0.39 and 1.24 among the patients with generalised osteoarthrosis and between 0.67 and 2.33 among the patients with osteoarthrosis of the finger joints. The PvuII polymorphism detected two different alleles and the associated relative risks were 0.82 and 1.82 for the patients with generalised osteoarthrosis, and 1.04 and 0.96 for the patients with osteoarthrosis of the finger joints. CONCLUSIONS--A major predisposing allele of the type II collagen gene as the causative factor for osteoarthrosis could be excluded in this population. A spectrum of mutations associated with different alleles of this gene could not be excluded, however. Further, these two forms of cartilage disease can be caused by gene defects with reduced penetrance and the effect of such an allele is easily masked under the high frequency of normal alleles.
Behavioral Risk Factors in Coronary Artery Disease
Authors: C D Jenkins
Journal: Annual Review of Medicine (1978)

The belief that personality, emotions, and disturbing life experiences play a part in the development of c ardiovascular disease s is widely held, both by t he general public and by the medical practitioners who treat their illnesses. This possible association is treated with great skepticism, however, by many of those aca­ demic and research physicians and biologists who are more laboratory or statis­ tically oriented. Consensus between practitioners and researchers is slow in developing, not because the clinical observations lack merit, but because of the great difficulty of defining and measuring psychosocial and behavioral concepts. This, in turn, has delayed the rigorous research that is essential to distinguish fortuitous observations from genuine patterns in nature. Recently, more rig­ orous epidemiological study designs and more quantitative techniques for as­ sessing psychological and social factors have permitted substantial scientific progress. The role of psychosocial and behavioral factors in cardiovascular disease, particularly in coronary artery disease (CAD), has already become important to the teacher of medicine, and may soon take on sufficiently valid operational forms as to be of utility to the medical practitioner. This review focuses first on that segment of social-behavioral resear�h into the etiology of CAD that we believe to be currently the most advanced-that dealing with the coronary-prone behavior pattern (Type A). We then review additional psychosocial risk factors whose association with CAD has been shown repeatedly, and finally, close with discussion about implications for medical education and practice.
A2.7 Concomitant transverse myelitis and guillain-barre syndrome after adalimumab therapy in a case with ankylosing spondylitis
Authors: Serdal Ugurlu, Caner Saygin, Didem Uzunaslan, Koray Tascilar, Birsen Ince, Sabahattin Saip
Journal: Annals of the Rheumatic Diseases (2014)

<b>Objective:</b> To evaluate the expression of human glucocorticoid receptors (hGRs), such as hGR (4H2), hGR-α, and hGR-β, in non-neoplastic lymphoid follicles and B cell type malignant lymphomas. <b>Methods:</b> The expression of hGRs in non-neoplastic lymphoid follicles and malignant lymphomas, including diffuse large cell lymphoma, mantle cell lymphoma, and follicular lymphoma, was examined immunohistochemically. HGR (4H2) expression was confirmed by double immunostaining of tissues and in isolated cells from tonsillar germinal centres, and by immunoelectronmicroscopy. <b>Results:</b> In secondary lymphoid follicles of any non-neoplastic diseases—such as chronic tonsillitis, reactive lymphadenitis, and Kimura's disease—the germinal centre cells often expressed hGR (4H2) and hGR-α. Double immunocytochemical staining of isolated germinal centre cells showed that the majority of hGR (4H2) positive cells were CD20 positive B cells, and that follicular dendritic cells also expressed hGR. Immunoelectronmicroscopy revealed the presence of nuclear hGR (4H2) in the binucleated follicular dendritic cells and germinal centre cells. The frequency of hGR (4H2) expression in diffuse large B cell lymphoma was higher, that in mantle cell lymphoma was lower, and that in follicular lymphoma was intermediate among the types of malignant lymphoma. The hGR (4H2) expression was less frequent in cases of grade I follicular lymphoma. <b>Conclusions:</b> There are differences in hGR expression between the germinal centre and the mantle zone in non-neoplastic lymphoid follicles, and differences of hGR (4H2) expression among the types of malignant lymphoma and grades of follicular lymphoma, which probably contribute to the different steroid sensitivities.
Functional Recovery of Damaged Skeletal Muscle Through Synchronized Vasculogenesis, Myogenesis, and Neurogenesis by Muscle-Derived Stem Cells
Authors: Tetsuro Tamaki, Yoshiyasu Uchiyama, Yoshinori Okada, Tetsuya Ishikawa, Masahiro Sato, Akira Akatsuka, Takayuki Asahara
Journal: Circulation (2005)

Recent studies have shown that skeletal muscle-derived stem cells (MDSCs) can give rise to several cell lineages after transplantation. However, the potential therapeutic uses of MDSCs, the functional significance of the transplanted tissue, and vasculogenesis, myogenesis, and reconstitution of other tissues have yet to be investigated in detail. In addition, the relationship between MDSCs and mesenchymal bone marrow cells is of interest.We developed a severe-damage model of mouse tibialis anterior muscle with a large deficit of nerve fibers, muscle fibers, and blood vessels. We investigated the potential therapeutic use of freshly isolated CD34+/45- (Sk-34) cells. Results showed that, after transplantation, implanted cells give rise to myogenic, vascular (pericytes, vascular smooth muscle cells, and endothelial cells), and neural (Schwann) cells, as well as contributing to the synchronized reconstitution of blood vessels, muscle fibers, and peripheral nerves, with significant recovery of both mass and contractile function after transplantation. Investigation of Sk-34 cell transplantation to the renal capsule (nonmuscle tissue) and fluorescence in situ hybridization analysis for the transplanted muscle detecting the Y chromosome revealed the intrinsic plasticity of the Sk-34 cell population. In addition, there were no donor-derived Sk-34 cells in the muscle of lethally irradiated bone marrow-transplanted animals, indicating that the Sk-34 cells were not derived from bone marrow.These findings indicate that freshly isolated skeletal muscle-derived Sk-34 cells are potentially useful for reconstitution therapy of the vascular, muscular, and peripheral nervous systems. These results provide new insights into somatic stem and/or progenitor cells with regard to vasculogenesis, myogenesis, and neurogenesis.
Cerebrospinal Fever. Analysis of 124 Cases
Authors: R. W. Cushing
Journal: BMJ (1940)

The cases herein analysed were admitted to the Military Isolation Hospital, Aldershot, during the winter of 1939 to the end of May, 1940.The type of case seen in this period appeared to show some clinical deviations from the normal as exhibited in the war of 1914-18 and it was thought worth while to analyse the cases and report on the -treatment with 'soluseptasine by the intra- venous route., Onset and IncidenceThe onset of the 'fever was very sudden.Many went to bed feeling quite well and awoke in the morning with intense headache, frequently accompanied with vomit- ing.The actual incubation periodcannot be definitely stated, but it appears to be of very short duration, mostly from twenty-four to forty-eight hours.Some cases, how- ever, had various symptoms, especially sore throat, last- ing from one to seven days before the appearance of the headache.Others complained of a feeling of general malaise for a similar period of time.The fulminatino septicaemic type is even more sudden than this.A man may be stricken to the ground in a fit simulating petit mal, others' suddenly become unconscious and fall into various stages of coma.The following tables show the incidence according to age, length of service, and date of occur- rence.