tbuckley/cabot-search huggingface dataset:
Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid–inducible gene-I and melanoma differentiation–associated gene 5
Authors: Hiroki Kato, Osamu Takeuchi, Eriko Mikamo-Satoh, Reiko Hirai, Tomoji Kawai, Kazufumi Matsushita, Akane Hiiragi, Terence S. Dermody, Takashi Fujita, Shizuo Akira
Journal: The Journal of Experimental Medicine (2008)

The ribonucleic acid (RNA) helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation–associated gene 5 (MDA5) recognize distinct viral and synthetic RNAs, leading to the production of interferons. Although 5′-triphosphate single-stranded RNA is a RIG-I ligand, the role of RIG-I and MDA5 in double-stranded (ds) RNA recognition remains to be characterized. In this study, we show that the length of dsRNA is important for differential recognition by RIG-I and MDA5. The MDA5 ligand, polyinosinic-polycytidylic acid, was converted to a RIG-I ligand after shortening of the dsRNA length. In addition, viral dsRNAs differentially activated RIG-I and MDA5, depending on their length. Vesicular stomatitis virus infection generated dsRNA, which is responsible for RIG-I–mediated recognition. Collectively, RIG-I detects dsRNAs without a 5′-triphosphate end, and RIG-I and MDA5 selectively recognize short and long dsRNAs, respectively.
Regional myocardial blood flow and coronary vascular reserve in unanesthetized young calves exposed to a simulated altitude of 3500 m for 8--10 weeks.
Authors: M Manohar, C M Parks, M A Busch, W J Tranquilli, G E Bisgard, T A McPherron, M C Theodorakis
Journal: Circulation Research (1982)

We determined regional myocardial blood flow (15-micrometer tracer microspheres) and hemodynamics in nine normal calves, seven calves with right ventricular (RV) hypertrophy induced by pulmonary artery banding (PAB) at sea level, and five calves exposed to simulated high altitude (HA) of 3,500 m (PB = 500 mm Hg) for 8--10 weeks. Progression of RV hypertrophy was very rapid in HA calves. RV weight:body weight ratio of 2.74 +/- 0.20 g/kg at 8--10 weeks of sojourn at HA significantly exceeded that in PAB calves (1.98 +/- 0.11 g/kg) 20 weeks post-banding. All calves were studied unanesthetized at sea level before (control) and during maximal coronary vasodilation (iv adenosine; 4 microM/kg per min). Normal and HA calves were also studied during acute hypoxemia (PaO2: 42 +/- 1 mm Hg) induced by administration of 12--13% O2 + N2 in the inhaled gas. RV myocardial blood flow was significantly increased only in PAB calves, whereas in HA calves it was similar to that in normal calves. Left ventricular (LV) mass and blood flow were identical in three groups of calves. Polycythemia did not occur in HA calves. Minimal coronary vascular resistance per unit weight of the hypertrophied RV was identical to that in the normal RV myocardium. This suggested that, despite very fast progression of RV hypertrophy in HA calves, functional cross-sectional area of the RV coronary vascular bed kept pace with the increase in cardiac mass. Minimal coronary vascular resistance per unit weight of the left ventricular myocardium was also identical in three groups of calves. This suggested that chronic hypoxemia by itself did not cause an increase in the functional cross-sectional area of the LV coronary vascular bed. Acute hypoxemia resulted in a significant increase in myocardial blood flow in all calves, but in HA calves, RV endo:epi perfusion ratio decreased below 1.00. Transmural RV myocardial blood flow and RV systolic pressure in HA calves during acute hypoxemia significantly exceeded that in normal calves.
Angiotensin II Activates Phosphatidylinositol 3-Kinase in Vascular Smooth Muscle Cells
Authors: Laura Saward Peter Zahradka
Journal: Circulation Research (1997)

Abstract Phosphatidylinositol 3-kinase (PI3K) is an important component of the signal transduction systems activated by tyrosine kinase receptors. It has not been established, however, whether PI3K is also an essential mediator for G protein–coupled receptors. The potential involvement of PI3K in G protein–linked angiotensin II (Ang II)–dependent signaling was assessed in a primary cell culture system of porcine coronary artery smooth muscle cells (SMCs). Treatment of quiescent SMCs with Ang II (10 −5 to 10 −8 mol/L) resulted in a dose-dependent activation of PI3K when assayed in vivo and in vitro. The Ang II receptor antagonists losartan and PD123319 were used to establish that Ang II stimulates PI3K through the Ang II type-1 (AT 1 ) receptor. Immunofluorescent microscopy revealed that Ang II (10 −6 mol/L) stimulated the translocation of p85, the regulatory subunit of PI3K, from the perinuclear region to distinct foci throughout the cell within 15 minutes. Western blot analysis of p85 subcellular distribution demonstrated that p85 concentrations were also increased within 15 minutes in the membrane fraction and concomitantly decreased in the cytoskeletal and nuclear fractions. These changes in PI3K location and activity were paralleled by increased tyrosine phosphorylation of p85. A potential correlation between angiotensin-mediated PI3K activation and SMC growth was found using LY294002, a specific inhibitor of PI3K, which blocked the increase in DNA and RNA synthesis as well as cellular hyperplasia generated by Ang II (10 −6 mol/L) stimulation of quiescent SMCs. These data indicate that PI3K may operate as a mediator of vascular SMC growth after stimulation with Ang II.
The shared circuits model (SCM): How control, mirroring, and simulation can enable imitation, deliberation, and mindreading
Authors: Susan Hurley
Journal: Behavioral and Brain Sciences (2008)

Imitation, deliberation, and mindreading are characteristically human sociocognitive skills. Research on imitation and its role in social cognition is flourishing across various disciplines. Imitation is surveyed in this target article under headings of behavior, subpersonal mechanisms, and functions of imitation. A model is then advanced within which many of the developments surveyed can be located and explained. The shared circuits model (SCM) explains how imitation, deliberation, and mindreading can be enabled by subpersonal mechanisms of control, mirroring, and simulation. It is cast at a middle, functional level of description, that is, between the level of neural implementation and the level of conscious perceptions and intentional actions. The SCM connects shared informational dynamics for perception and action with shared informational dynamics for self and other, while also showing how the action/perception, self/other, and actual/possible distinctions can be overlaid on these shared informational dynamics. It avoids the common conception of perception and action as separate and peripheral to central cognition. Rather, it contributes to the situated cognition movement by showing how mechanisms for perceiving action can be built on those for active perception.;>;>The SCM is developed heuristically, in five layers that can be combined in various ways to frame specific ontogenetic or phylogenetic hypotheses. The starting point is dynamic online motor control, whereby an organism is closely attuned to its embedding environment through sensorimotor feedback. Onto this are layered functions of prediction and simulation of feedback, mirroring, simulation of mirroring, monitored inhibition of motor output, and monitored simulation of input. Finally, monitored simulation of input specifying possible actions plus inhibited mirroring of such possible actions can generate information about the possible as opposed to actual instrumental actions of others, and the possible causes and effects of such possible actions, thereby enabling strategic social deliberation. Multiple instances of such shared circuits structures could be linked into a network permitting decomposition and recombination of elements, enabling flexible control, imitative learning, understanding of other agents, and instrumental and strategic deliberation. While more advanced forms of social cognition, which require tracking multiple others and their multiple possible actions, may depend on interpretative theorizing or language, the SCM shows how layered mechanisms of control, mirroring, and simulation can enable distinctively human cognitive capacities for imitation, deliberation, and mindreading.
Human inward rectifier potassium channels in chronic and postoperative atrial fibrillation
Authors: D Dobrev
Journal: Cardiovascular Research (2002)

Objective: We showed recently that the 825T allele of the G-protein β3-subunit C825T polymorphism is associated with large inward rectifier K+ currents IK1 but low acetylcholine-activated K+ current IK,ACh amplitudes. During chronic atrial fibrillation (AF), IK1 and IK,ACh current densities were increased when compared to sinus rhythm (SR). It is unknown whether chronic AF and Gβ3 gene status are independent contributors to atrial K+ current activity. We measured IK1 and IK,ACh in tissue from AF patients with different Gβ3 genotypes and assessed the relation between the IK1 and IK,ACh amplitudes and the incidence of postoperative AF. Methods: We measured the amplitudes of IK1 and IK,ACh in atrial myocytes from 26 patients with sinus rhythm (SR) and from 16 patients with chronic AF (<6 months). The K+ currents were measured with standard patch-clamp techniques. The Gβ3 gene status of the patients was determined by PCR and restriction analysis. Results: At −100 mV, the amplitude of IK1 was larger in AF (10.9±1.0 pA/pF, n=49/16, cells/patients) than in SR (6.3±0.6 pA/pF, n=68/26, P<0.05), whereas the amplitude of IK,ACh was smaller in chronic AF (2.9±0.7 pA/pF, n=49/16) than in SR (6.3±0.7 pA/pF, n=68/26, P<0.05). These changes were independent of the patient Gβ3 gene status. Eight patients out of 26 in the SR group (31%) developed postoperative AF. When analysed based on incidence of postoperative AF, current amplitudes did not differ significantly. Conclusion: We provide evidence for up-regulation of IK1 but down-regulation of IK,ACh in chronic AF which are independent of Gβ3 gene status. Atrial myocytes from patients who are in SR but later develop postoperative AF have no manifestation of altered IK1 and IK,ACh at the time of cardiac surgery. Our results suggest that the AF-related changes of IK1 and IK,ACh may be a consequence of or a contributory factor to chronic AF.
Long-Term Neurologic and Neurosensory Sequelae in Adult Survivors of a Childhood Brain Tumor: Childhood Cancer Survivor Study
Authors: Roger J. Packer, James G. Gurney, Judy A. Punyko, Sarah S. Donaldson, Peter D. Inskip, Marilyn Stovall, Yutaka Yasui, Ann C. Mertens, Charles A. Sklar, H. Stacy Nicholson, Lonnie K. Zeltzer, Joseph P. Neglia, Leslie L. Robison
Journal: Journal of Clinical Oncology (2003)

To describe the neurologic and neurosensory deficits in children with brain tumors (BTs), compare incidence of these deficits with that of a sibling control group, and evaluate the factors associated with the development of these deficits.Detailed questionnaires were completed on 1,607 patients diagnosed between 1970 and 1986 with a primary CNS tumor. Neurosensory and neurologic dysfunctions were assessed and results compared with those of a sibling control group. Medical records on all patients were abstracted, including radiotherapy dose and volume.Seventeen percent of patients developed neurosensory impairment. Relative to the sibling comparison group, patients surviving BTs were at elevated risk for hearing impairments (relative risk [RR], 17.3; P = <.0001), legal blindness in one or both eyes (RR, 14.8; P = <.0001), cataracts (RR, 11.9; P = <.0001), and double vision (RR, 8.8; P = <.0001). Radiation exposure greater than 50 Gy to the posterior fossa was associated with a higher likelihood of developing any hearing impairment. Coordination and motor control problems were reported in 49% and 26%, respectively, of survivors. Children receiving at least 50 Gy to the frontal brain regions had a moderately elevated risk for motor problems (RR, 2.0; P <.05). Seizure disorders were reported in 25% of patients, including 6.5% who had a late first occurrence. Radiation dose of 30 Gy or more to any cortical segment of the brain was associated with a two-fold elevated risk for a late seizure disorder.Children surviving BTs are at significant risk for both early and late neurologic or neurosensory sequelae. These sequelae need to be prospectively monitored.
miR-141 Regulates colonic leukocytic trafficking by targeting CXCL12β during murine colitis and human Crohn's disease
Authors: Zhen Huang, Tongguo Shi, Qian Zhou, Song Shi, Ran Zhao, Hao Shi, Lei Dong, Chenyu Zhang, Ke Zeng, Jiangning Chen, Junfeng Zhang
Journal: Gut (2013)

<h3>Abstract</h3> Symptom screening is a widely deployed strategy to mitigate the COVID-19 pandemic and many public health authorities are mandating its use by employers for all employees in the workplace. While symptom screening has the benefit of reducing the number of infected individuals in the workplace, it raises some inherently difficult privacy issues as a traditional approach requires the employer to collect symptom data from each employee which is essentially medical information. In this paper, we describe a system to implement Cryptographic Anonymous Symptom Screening (CASS) which allows for individuals to perform COVID symptom screening anonymously while avoiding the privacy issues of traditional approaches. In the system, individuals report their symptoms without any identifying information and are issued a completion certificate. This certificate contains a cryptographic code which certifies that the certificate was obtained from the screener after reporting no symptoms. The codes can be verified using a cryptographic algorithm which is publicly available. A standard cryptography approach to implement such a system would be to use digital signatures. Unfortunately, standard digital signatures have some limitations for this application in that the signatures are often hundreds of characters long and if the signature contains the name of the individual, then there is also a risk of compromising privacy. In our approach, we develop and utilize a relaxed digital signature scheme to provide 16 character long codes and handle names using equivalence classes which helps preserve privacy. Both of these extensions technically compromise the security but in a way that is negligible for this application. Our system can either serve the function of standard symptom screening system approaches for employees, but can also extend symptom screening to non-employees such as visitors or customers. In this case, the system can be utilized in retail, restaurants and schools to ensure that everyone in the physical space, including employees, customers, visitors and students have performed symptom screening.
The efficacy of canakinumab in the treatment of a patient with familial Mediterranean fever and longstanding destructive arthritis
Authors: I. Mitroulis, P. Skendros, A. Oikonomou, A. G. Tzioufas, K. Ritis
Journal: Annals of the Rheumatic Diseases (2011)

Self-limited, non-destructive arthritis is a common clinical presentation of familial Mediterranean fever (FMF), while protracted, refractory to standard treatment arthritis is a rare manifestation of the disease, potentially resulting in severe damage and disability.1,–,3

We report on a 25-year-old woman with FMF, homozygous for the MEFV gene M694V mutation, and with longstanding articular involvement affecting her hips and her left knee, effectively treated with canakinumab. She had been under treatment with colchicine since the age of 5. In 2005, she experienced long-lasting arthritis of her right hip and treatment with anakinra (100 mg/day) was added. Anakinra was discontinued shortly afterwards due to severe injection site reactions, precluding the evaluation of its efficacy. She was switched to treatment with etanercept (25 mg twice weekly) and low dose prednisone (5–7.5 mg/day). In 2008, she developed destructive arthritis of the right hip, which lead to total hip replacement, and chronic arthritis of her left knee. Methotrexate (10 mg/week) was added to the existent treatment. Long-term remission was not achieved, as indicated by the clinical findings and the elevated inflammatory …
A Diagnostic Strategy Involving a Quantitative Latex <scp>d</scp>-Dimer Assay Reliably Excludes Deep Venous Thrombosis
Authors: Shannon M. Bates, Clive Kearon, Mark Crowther, Lori Linkins, Martin O'Donnell, Jim Douketis, Agnes Y.Y. Lee, Jeffrey I. Weitz, Marilyn Johnston, Jeffrey S. Ginsberg
Journal: Annals of Internal Medicine (2003)

Background: Because clinical diagnosis is inaccurate, objective testing is usually considered necessary when patients present with suspected deep venous thrombosis (DVT). Objective: To determine whether a negative result on a quantitative latex d-dimer assay eliminates the need for further investigation in patients with a low or moderate pretest probability of DVT. Design: Prospective cohort study. Setting: Three tertiary care hospitals in Canada. Patients: 556 consecutive outpatients with suspected first DVT. Intervention: Patients were categorized as having a low, moderate, or high pretest probability of DVT and then underwent d-dimer testing. Patients with low or moderate pretest probability and a negative d-dimer result had no further diagnostic testing and received no anticoagulant therapy. Serial compression ultrasonography was performed in all other patients. Patients who did not receive a diagnosis of DVT were followed for symptomatic venous thromboembolism. Measurements: Objectively confirmed symptomatic venous thromboembolic events during 3 months of follow-up. Results: 283 patients (51%) had low or moderate pretest probability and a negative d-dimer result. One of these patients had DVT during follow-up (negative likelihood ratio, 0.05 [CI, 0.01 to 0.23]). The negative likelihood ratio of the d-dimer test in all patients was 0.03 (CI, 0.01 to 0.16). Conclusion: A negative result on a quantitative latex d-dimer assay safely eliminates the need for further testing in patients with low or moderate pretest probability of DVT.
I. CHOLESTEROL AND CHOLESTEROL ESTERS IN DOG BILE
Authors: Angus Wright
Journal: The Journal of Experimental Medicine (1934)

The colorimetric method for the determination of total cholesterol in dog bile is consistently accurate as checked by the oxidative digitonin method. This method has the further advantages of being simple, rapid and economical. A method for the determination of esterified cholesterol in bile is described and it is shown that there are no esters of cholesterol in normal dog bile.
Reactive Oxygen Species (ROS), Troublemakers between Nuclear Factor-κB (NF-κB) and c-Jun NH2-terminal Kinase (JNK)
Authors: Yadong Zhang, Fei Chen
Journal: Cancer Research (2004)

Abstract Nuclear factor-κB (NF-κB) and c-Jun NH2-terminal kinase (JNK) are activated simultaneously under a variety of stress conditions. They also share several common signaling pathways for their activation in response to cytokines or growth factors. Recent studies, however, demonstrated a new form of interplay between these two allies. Inhibition of NF-κB by ikkβ or rela gene deficiency sensitizes stress responses through enhanced or prolonged activation of JNK. Conversely, sustained activation of NF-κB inhibits cytokine-induced JNK activation. The mechanisms of how NF-κB and JNK become rivals for each other are under extensive debate.
Long-term infliximab for severe hidradenitis suppurativa
Authors: A.-M. Thielen, C. Barde, J.-H. Saurat
Journal: British Journal of Dermatology (2006)

Journal Article Long‐term infliximab for severe hidradenitis suppurativa Get access A.‐M. Thielen, A.‐M. Thielen Department of Dermatology and Venereology, University Hospital of Geneva, 24 rue Micheli‐du‐Crest, 1211 Geneva 14, Switzerland E‐mail: anne‐marie@thielen.net Search for other works by this author on: Oxford Academic Google Scholar C. Barde, C. Barde Department of Dermatology and Venereology, University Hospital of Geneva, 24 rue Micheli‐du‐Crest, 1211 Geneva 14, Switzerland E‐mail: anne‐marie@thielen.net Search for other works by this author on: Oxford Academic Google Scholar J.‐H. Saurat J.‐H. Saurat Department of Dermatology and Venereology, University Hospital of Geneva, 24 rue Micheli‐du‐Crest, 1211 Geneva 14, Switzerland E‐mail: anne‐marie@thielen.net Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 155, Issue 5, 1 November 2006, Pages 1105–1107, https://doi.org/10.1111/j.1365-2133.2006.07528.x Published: 01 November 2006
The sports concussion picture: fewer ‘pixels’, more HD
Authors: Jon S Patricios, Michael Makdissi
Journal: British Journal of Sports Medicine (2013)

"The only ones who see the whole picture, are the ones who step out of the frame" Salman Rushdie, The Ground Beneath Her Feet In contrast to the 'whole picture' described by Salman Rushdie, the media attention that concussion is currently receiving resembles a series of 'pixels'. Not only journalists but coaches, athletes, parents and even medical colleagues often appear to focus on only one facet of the intricate picture that makes up the composite concussion portrait. Examples of 'pixels' include computerised cognitive tests, Rugby's pitch side suspected concussion assessment (PSCA) and chronic traumatic encephalopathy (CTE). Each of these topics is often scrutinised outside of the context of many other significant aspects of the concussion picture. CTE is one of the SEM's 'hot topics' and the concussion strategies incorporated in collision sport are under increased scrutiny; in this edition of BJSM we provide updates on both. Few other areas of clinical sports medicine have received as much systematic attention as concussion has in the last 12 years. Independent experts have summarised the published evidence following a review of the literature and critical discussion held in Zurich in November 2012. The medical community has embraced concussion understanding and the protocols defined by the 2013 Concussion in Sport Consensus Statement.1 The Concussion in Sport Consensus Statement is a document of significant gravitas because it captures the systematic NIH consensus format, which is inclusive of scientists and clinicians constituting more than just expert opinion. The protocol consists of
THE RENAL HANDLING OF HEMOGLOBIN
Authors: H. Franklin Bunn, William T. Esham, Robert W. Bull
Journal: The Journal of Experimental Medicine (1969)

The glomerular filtration of hemoglobin (alpha(2)beta(2)) was studied under conditions in which its dissociation into alphabeta dimers was experimentally altered. Rats receiving hemoglobin treated with the sulfhydryl reagent bis(N-maleimidomethyl) ether (BME) showed a much lower renal excretion and prolonged plasma survival as compared with animals injected with untreated hemoglobin. Plasma disappearance was also prolonged in dogs receiving BME hemoglobin. Gel filtration data indicated that under physiological conditions, BME hemoglobin had impaired subunit dissociation. In addition, BME hemoglobin showed a very high oxygen affinity and a decreased rate of auto-oxidation. Glomerular filtration was enhanced under conditions which favor the dissociation of hemoglobin into dimers. Cat hemoglobin, which forms subunits much more extensively than canine hemoglobin, was excreted more readily by the rat kidney. The renal uptake of (59)Fe hemoglobin injected intra-arterially into rabbits varied inversely with the concentration of the injected dose.