tbuckley/cabot-search huggingface dataset:
Gene therapy reforms photoreceptor structure and restores vision in NPHP5-associated Leber congenital amaurosis
Authors: Gustavo D. Aguirre, Artur V. Cideciyan, Valérie L. Dufour, Ana Ripolles-García, Raghavi Sudharsan, Malgorzata Swider, Roman Nikonov, Simone Iwabe, Sanford L. Boye, William W. Hauswirth, Samuel G. Jacobson, William A. Beltran
Journal: Molecular Therapy (2021)

The inherited childhood blindness caused by mutations in NPHP5, a form of Leber congenital amaurosis, results in abnormal development, dysfunction, and degeneration of photoreceptors. A naturally occurring NPHP5 mutation in dogs leads to a phenotype that very nearly duplicates the human retinopathy in terms of the photoreceptors involved, spatial distribution of degeneration, and the natural history of vision loss. We show that adeno-associated virus (AAV)-mediated NPHP5 gene augmentation of mutant canine retinas at the time of active degeneration and peak cell death stably restores photoreceptor structure, function, and vision with either the canine or human NPHP5 transgenes. Mutant cone photoreceptors, which failed to form outer segments during development, reform this structure after treatment. Degenerating rod photoreceptor outer segments are stabilized and develop normal structure. This process begins within 8 weeks after treatment and remains stable throughout the 6-month posttreatment period. In both photoreceptor cell classes mislocalization of rod and cone opsins is minimized or reversed. Retinal function and functional vision are restored. Efficacy of gene therapy in this large animal ciliopathy model of Leber congenital amaurosis provides a path for translation to human treatment. The inherited childhood blindness caused by mutations in NPHP5, a form of Leber congenital amaurosis, results in abnormal development, dysfunction, and degeneration of photoreceptors. A naturally occurring NPHP5 mutation in dogs leads to a phenotype that very nearly duplicates the human retinopathy in terms of the photoreceptors involved, spatial distribution of degeneration, and the natural history of vision loss. We show that adeno-associated virus (AAV)-mediated NPHP5 gene augmentation of mutant canine retinas at the time of active degeneration and peak cell death stably restores photoreceptor structure, function, and vision with either the canine or human NPHP5 transgenes. Mutant cone photoreceptors, which failed to form outer segments during development, reform this structure after treatment. Degenerating rod photoreceptor outer segments are stabilized and develop normal structure. This process begins within 8 weeks after treatment and remains stable throughout the 6-month posttreatment period. In both photoreceptor cell classes mislocalization of rod and cone opsins is minimized or reversed. Retinal function and functional vision are restored. Efficacy of gene therapy in this large animal ciliopathy model of Leber congenital amaurosis provides a path for translation to human treatment.
The accuracy of Doppler ultrasound measurement of pressure gradients across irregular, dual, and tunnellike obstructions to blood flow.
Authors: P STeirstein, P GYock, R LPopp
Journal: Circulation (1985)

The accuracy of Doppler-estimated pressure gradients in the setting of irregular, multiple, and tunnellike stenoses was investigated. An in vitro model of the left ventricular outflow tract was designed to allow pulsatile flow of red cells in saline across valve orifices from 0.01 to 2.5 cm2. Simultaneous pressure gradients were estimated by both Doppler and direct-pressure manometer techniques. Gradients obtained by the two methods correlated well for valve areas in the range of clinical stenoses at pressure gradients of 10 to 150 mm Hg (r = .97 to .99). Model valves were constructed with a large orifice (0.75 to 1.25 cm2) placed beside a small orifice (0.02 to 0.25 cm2) in the same outflow tract. A distinct jet was recorded when the Doppler transducer was aligned with each orifice. Doppler-estimated gradients for each pair of large and small orifices were identical and correlated well with those measured by manometer (r = .97 to .99). Irregularly shaped orifices also provided good correlation between th...
Urinary Infection in Childhood
Authors: J. D. Davis
Journal: BMJ (1964)

Rule of Three" SIR,-Some official rebuke from the B.M.A. should surely be made to the Minister of Transport in his recommendation that three drinks should be taken before driving at Christmas.His "rule of three" must surely be the most imprudent advice given to motorists for many a decade.The rule of "none for the road" should always apply.-I am, etc., lo0n1(101 W.1. Guy
CD34+細胞の可動化を加速し,陳旧梗塞領域を減すことによって,梗塞後の心臓機能をシクロホスファミドは改善する
Authors: Misao Yu, Arai Masazumi, Ohno Takamasa, Ushikoshi Hiroaki, Takahashi Tomoyuki, Takemura Genzou, Minatoguchi Shinya, Fujiwara Takako, Fujiwara Hisayoshi
Journal: Circulation (2005)
Structural Requirements for Substrates and Inhibitors of Angiotensin I-Converting Enzyme In Vivo and In Vitro
Authors: SUZANNE OPARIL, TERRY KOERNER, J. KEVIN O'DONOGHUE
Journal: Circulation Research (1974)

The mechanism of action of peptide inhibitors on angiotensin I-converting enzyme (Al-converting enzyme) was studied in relation to the substrate requirements of the enzyme in vivo in the dog lung and in vitro in plasma. 1- d -Asp-8-Ile-AI prepared by the solid-phase technique was compared with the known peptide inhibitors of Al-converting enzyme. BPP 5a (Pyr-Lys-Trp-Ala-Pro) and SQ 20881 (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) 125 I-1- d -Asp-8-Ile-AI was evaluated for susceptibility to cleavage by the Al-converting enzyme. In vitro and in vivo, 125 I-1- d -Asp-8-Ile-AI or BPP 5a in 50,000-fold molar excess produced only a slight delay in conversion of 125 1-AI to 125 I-angiotension II (AII); SQ 20881 blocked conversion completely. In vivo, l- d -Asp-8-Ile-AI or BPP 5a injected into the pulmonary circulation in 250-fold molar excess (250 nmole/kg) did not cause a diminution in the pressor response to AI administered 30 seconds later; SQ 20881 blocked the pressor response to Al for 60-90 minutes. 1- d -Asp-8-Ile-AI was a poor substrate for converting enzyme, since 125 I-1- d -Asp-8-Ile-AI was not converted to 125 I-1- d -Asp-8-Ile-AII, and unlabeled 1- d -Asp-8-Ile-AI did not block the pressor response to exogenous AII. 125 I-1- d -Asp-8-lle-AI was stable in plasma and in the pulmonary circulation The results suggest that since 1- d -Asp-8-Ile-AI is neither a substrate nor a blocker, substitution of the aliphatic residue Ile in the 8 position of AI may prevent binding to an active site in the AI-converting enzyme.
Exotic dried fruits caused Salmonella Agbeni outbreak with severe clinical presentation, Norway, December 2018 to March 2019
Authors: Tone Bjordal Johansen, Lin T Brandal, Emily MacDonald, Umaer Naseer, Pawel Stefanoff, Margrethe Hovda Røed, Turid M Berglund, Gro S Johannessen, Bjarne Bergsjø, Line Vold, Heidi Lange
Journal: Eurosurveillance (2021)

We describe an outbreak of Salmonella Agbeni sequence type (ST)2009 infections in Norway. Between 31 December 2018 and 16 March 2019, 56 cases (33 female and 23 male; median age: 50 years, range: 2–91) were reported, of which 21 were hospitalised. Cases were defined as people living in Norway, with laboratory-confirmed infection with S . Agbeni ST2009 and cluster type (CT)2489, reported between 31 December 2018 and 30 March 2019. We conducted a case–control study, with three controls per case (matched by age, sex and municipality), using the Norwegian National Registry. Cases were more likely to have consumed a commercial mix of dried exotic fruits than controls (cases = 8, controls = 31; odds ratio: 50; 95% confidence interval: 3–2,437). The outbreak strain was confirmed by whole genome sequencing (WGS) and was isolated from the fruit mix consumed by cases, resulting in withdrawal from the market on 6 March 2019.The fruit mix consisted of fruits from different countries and continents. It was packed in Italy and distributed to several European countries, including Norway. However, no other countries reported cases. This outbreak highlights that dried fruits could represent a risk in terms of food-borne infections, which is of particular concern in ready-to-eat products.
Granulocyte-macrophage colony-stimulating factor mRNA and Neuroprotective Immunity in Parkinson's disease
Authors: Katherine E. Olson, Krista L. Namminga, Yaman Lu, Mackenzie J. Thurston, Aaron D. Schwab, Seymour de Picciotto, Sze-Wah Tse, William Walker, Jared Iacovelli, Clayton Small, Brian T. Wipke, R. Lee Mosley, Eric Huang, Howard E. Gendelman
Journal: Biomaterials (2021)
Differentiation of neurogenic and myocardial angiotensin II receptors in isolated rabbit atria.
Authors: A LBlumberg, J AAckerly, M JPeach
Journal: Circulation Research (1975)

The effect of angiotensin on the action of tyramine was studied in isolated rabbit left atria paced by point and field stimulation to more clearly define the interaction of angiotensin with the sympathetic nervous system. Administration of angiotensin resulted in similar increases in contractility in both point- and field-stimulated atria. In point-stimulated preparations only the muscle is stimulated to contract, whereas in field-stimulated preparations both nerve and muscle are stimulated. 1-Sar-8-Ala-angiotensin II completely blocked the direct inotropic effect of angiotensin in a molar dose ratio of 3:1 in both point- and field-stimulated preparations. However, angiotensin (0.05-10 ng/ml) potentiated the inotropic effect of tyramine in field-stimulated atria only. This facilitatory effect was not inhibited by 1-Sar-8-Ala-angiotensin II at a molar dose ratio of 3:1; indeed, a ratio of 500:1 was necessary for complete blockade of this angiotensin-induced potentiation. This antagonist in odses of 0.1-100...
Comment on “CD4 <sup>+</sup> T Cell Autoimmunity to Hypocretin/Orexin and Cross-Reactivity to a 2009 H1N1 Influenza A Epitope in Narcolepsy”
Authors: Robbert van der Most, Martine Wettendorff, Bruce Innis, Emmanuel Hanon
Journal: Science Translational Medicine (2014)

Scientists from the maker of the Pandemrix vaccine for influenza present their views on results linking epitopes in influenza and narcolepsy.
Cardiovascular effects of neuropeptide Y in rat brainstem nuclei.
Authors: C JTseng, RMosqueda-Garcia, MAppalsamy, DRobertson
Journal: Circulation Research (1989)

Central catecholaminergic neurons are involved in cardiovascular regulation. Neuropeptide Y (NPY) coexists with adrenaline and noradrenaline in the rat brain, and interactions among these substances have been studied. The purpose of this study was to investigate the possible role of NPY in central cardiovascular control. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure was monitored intra-arterially. Intramedullary microinjection (60 nl) of NPY (0, 46.5 fmol, 465 fmol, 1.5 pmol, and 4.65 pmol) was made into the nucleus tractus solitarii (NTS), into the area postrema, and into the C1 area in the rostroventrolateral medulla. Injection site was identified by L-glutamate administration and confirmed histologically. Unilateral injection of NPY into the NTS produced a prominent dose-related decrease in heart rate and systolic and diastolic blood pressure (-106 +/- 8 beats/min, -56 +/- 2 mm Hg, and -33 +/- 2 mm Hg, respectively after 4.65 pmol NPY, n = 7, p less than 0.001). Maximal c...
Myocardial function and coronary blood flow response to acute ischemia in chronic canine diabetes.
Authors: BHaider, S SAhmed, C BMoschos, H AOldewurtel, T JRegan
Journal: Circulation Research (1977)

To examine the influence of preexistent diabetes mellitus on left ventricular performance and coronary blood flow responses to acute ischemia, mild normoglycemic diabetes was induced in nine mongrel dogs after three doses of alloxan, (20 mg/kg, iv), at monthly intervals. Hemodynamic measurements and coronary blood flow (85Kr clearance) were obtained before and after the onset of ischemia. This was produced by occlusion of the proximal left anterior descending coronary artery via a balloon-type catheter in nine intact anesthetized diabetic dogs and 10 nondiabetic dogs. During the 1st hour of ischemia in the diabetic group, the end-diastolic pressure rose from 7 +/- 1.1 (mean +/- SE) mm Hg to 23.8 +/- 2.3 without a significant increase of end-diastolic volume. In controls end-diastolic pressure rose from 8.6 +/- 1.1 mm Hg to 15.3 +/- 1.4, and end-diastolic volume was significantly increased, so that the ratio of end-diastolic pressure and volume was significantly higher in the diabetic group (P less than 0....
Prognostic implications and predictors of enhanced regional wall motion of the noninfarct zone after thrombolysis and angioplasty therapy of acute myocardial infarction. The TAMI Study Groups.
Authors: C LGrines, E JTopol, R MCaliff, R SStack, B SGeorge, DKereiakes, J MBoswick, EKline, W WO'Neill
Journal: Circulation (1989)

Although impairment of left ventricular function in acute myocardial infarction is closely related to extent of necrosis, function in the noninfarct zone also contributes to global performance and thus may be of prognostic importance. We evaluated left ventricular regional wall motion by the centerline chord method in 332 patients treated with intravenous tissue-type plasminogen activator (t-PA) in the multicenter Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) I trial. All patients had acute contrast ventriculograms of suitable quality for analysis, and 266 patients had paired acute and day 7 ventriculograms. Enhanced function of the noninfarct zone was present during acute catheterization (+0.3 SD/chord) and was associated with preservation of the acute ejection fraction (p = 0.0001). Multiple linear regression analysis revealed the most powerful clinical factor associated with enhanced function of the noninfarct zone was the absence of multivessel disease (p = 0.0001). Clinical factors tha...
Analysis of pulmonary vascular responses in cats to sympathetic nerve stimulation under elevated tone conditions. Evidence that neuronally released norepinephrine acts on alpha 1-, alpha 2-, and beta 2-adrenoceptors.
Authors: A LHyman, H LLippton, P JKadowitz
Journal: Circulation Research (1990)

The influence of an increase in vascular tone on responses to sympathetic nerve stimulation and the receptors mediating these responses were investigated in the pulmonary vascular bed of the cat. Under conditions of controlled blood flow and constant left atrial pressure, stimulation of the sympathetic nerves to the lung elicited a biphasic response characterized by an initial increase in lobar arterial pressure followed closely by a decrease. The response to nerve stimulation was reproducible with respect to time and was not altered when a delay coil was added to the perfusion circuit, indicating that the response was directly mediated. The increase in pressure was reduced by prazosin and by yohimbine, whereas the decrease in pressure was blocked by propranolol or ICI 118551. These data suggest that the pressor component of the response is mediated by alpha 1- and postjunctional alpha 2-adrenoceptors, whereas the depressor response is mediated by beta 2-receptors. The pressor response was enhanced by pro...
Coronary angioplasty of multiple vessels: short-term outcome and long-term results.
Authors: M JCowley, G WVetrovec, GDiSciascio, S ALewis, P DHirsh, T CWolfgang
Journal: Circulation (1985)

Experience with percutaneous transluminal coronary angioplasty (PTCA) of multiple vessels was reviewed to assess short-term outcome and long-term results. PTCA of multiple vessels was performed in 100 of the initial 500 patients (20%) who underwent PTCA at the Medical College of Virginia between July 1979 and August 1984. Eighty-nine percent had class 3 or 4 angina, and 66% had unstable angina. Two-thirds had severe stenosis of two vessels or major branches and one-third had three-vessel disease. One or more significant lesions were dilated in two vessels in 84 patients, in three vessels in 14 patients, and in four vessels in two patients. PTCA of 273 lesions (2.7/patient) was attempted (range two to eight per patient) with angiographic success in 250 lesions (91.6%). Primary success (angiographic and clinical improvement) was achieved in 95 of 100 patients (95%); 84% had success in multiple vessels, and 79% had success in all attempted lesions. Complications occurred in 11 patients (11%); four patients (...
Diltiazem-induced blockade of sympathetically mediated constriction of normal and diseased coronary arteries: lack of epicardial coronary dilatory effect in humans.
Authors: K FHossack, B GBrown, D KStewart, H TDodge
Journal: Circulation (1984)

To determine mechanisms of benefit from diltiazem, 13 patients with coronary disease performed sustained isometric handgrip exercise and repeated the procedure during intravenous infusion of diltiazem (0.25 mg/kg bolus followed by 0.003 mg/kg/min). Cardiovascular responses to handgrip, diltiazem, their combination, and nitroglycerin were assessed by hemodynamic and electrocardiographic measurements and by computer-assisted measurements of normal and diseased segments of epicardial coronary arteries. Handgrip produced increases in heart rate (12%; p less than .001), pulmonary arterial pressure (19%; p less than .005), and pulmonary wedge pressure (33%; p less than .005). Diltiazem produced significant reductions in heart rate (7%; p less than .05) and aortic pressure (14%; p less than .001). Pulmonary arterial pressure and pulmonary wedge pressure were unchanged by diltiazem. Diltiazem did not prevent the increase in heart rate or in aortic or wedge pressure associated with handgrip. Diltiazem prolonged at...
Blood cyclosporin concentrations and renal allograft dysfunction.
Authors: D W Holt, J T Marsden, A Johnston, M Bewick, D H Taube
Journal: BMJ (1986)

Forty nine renal allograft recipients taking oral cyclosporin suffered 76 episodes of renal dysfunction within six months of transplantation. These episodes were diagnosed as graft rejection or cyclosporin induced nephrotoxicity on the basis of histological findings in allograft biopsy specimens and the response to treatment. Mean predose blood cyclosporin concentrations measured by radioimmunoassay during the week before the onset of renal dysfunction were significantly higher when the cause was cyclosporin toxicity rather than graft rejection (392 v 741 nmol/l (471 v 891 ng/ml). During this period there was a significant association between both the frequency of measurements above 666 nmol/l (800 ng/ml) and the diagnosis of toxicity and the frequency of measurements below 333 nmol/l (400 ng/ml) and the diagnosis of allograft rejection. Cyclosporin measurements made at the time of biopsy and reference to the highest or lowest concentrations measured during the week preceding biopsy were of less value in distinguishing between the two groups. Despite lacking specificity for the parent compound, the radioimmunoassay used produced results which were of clinical value in optimising cyclosporin treatment.
167P Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small cell lung cancer (aNSCLC): A pooled analysis of 6 randomized trials
Authors: P. Gargiulo, R. Di Liello, L. Arenare, C. Gridelli, A. Morabito, F. Ciardiello, V. Gebbia, P. Maione, A. Spagnuolo, G. Palumbo, G. Esposito, C.M. Della Corte, F. Morgillo, G. Mancuso, A. Gravina, C. Schettino, M. Di Maio, C. Gallo, F. Perrone, M.C. Piccirillo
Journal: Journal of Thoracic Oncology (2021)
Abstract 11796: Time of Exposure to Shunt, Surgical Timing and Prematurity Are Risk Factors for Pulmonary Vein Stenosis in Trisomy 21 Patients With Atrioventricular Canal or Septal Defects
Authors: Connie Choi, Abbas Zaidi, Kimberlee Gauvreau, Kathy J Jenkins, Ming Hui Chen
Journal: Circulation (2019)

Background: Pulmonary vein stenosis (PVS) is a rare, life-threatening condition affecting pediatric patients. Intraluminal obstruction is due to proliferation of myofibroblast-like cells, but the u...
The effect of digitalis on refractoriness of the intact canine His-Purkinje system.
Authors: J AGomes, A NDamato, G ABobb, S HLau
Journal: Circulation (1978)

The effect of therapeutic doses of digitalis on functional (F), relative (R) and effective (E) refractory periods (RP) of the His-Purkinje system (HPS) was studied in 12 open-chested, innervated adult mongrel dogs (10-20 kg) during control and 15, 30 and 45-60 min after 0.016 mg/kg of intravenous ouabain. To determine the stability of the preparation and to assess time-dependent changes in His-Purkinje refractoriness, another six dogs (Group II) had similar studies, but without drug administration. In all dogs, the His bundle was paced by using the plunge wire technique at a predetermined cycle length (CL) and a premature stimulus (S2) to the His bundle was introduced at decreasing S1 S2 intervals. Following ouabain, in Group I dogs, at the longest Cls tested (458 +/- 125 msec; +/- SD) there was significant increase in the FRP (+4.34%; P less than 0.05), RRP (S2 V2 (+6.57%, P less than 0.05), RRP (Ab) (+6%, P less than 0.05) and ERP (52%, P less than 0.05) of the HPS. These significant changes were genera...
Effect of capacitor size and pathway resistance on defibrillation threshold for implantable defibrillators.
Authors: C DSwerdlow, R MKass, P SChen, CHwang, SRaissi
Journal: Circulation (1994)

BACKGROUNDThe time constant of truncated exponential pulses used with implantable defibrillators is determined by the output capacitor size and defibrillation pathway resistance. The optimal capacitor size is unknown.METHODS AND RESULTSThis study compared defibrillation threshold (DFT) for standard 120-microF capacitors (DFT120) and smaller 60-microF capacitors (DFT60) at implantation of cardioverter-defibrillators in 67 patients using epicardial electrodes (15 patients) or one of four transvenous electrode configurations (52 patients). Paired comparisons of DFT60 and DFT120 were made for 44 defibrillation pathways using monophasic pulses and for 53 pathways using biphasic pulses. Truncated exponential pulses with 65% tilt were used. Pooled data from all electrode configurations showed a significant inverse correlation between pathway resistance and the ratio of stored energy DFT60 to DFT120 (monophasic pulses: r = .75, P = .0001; biphasic pulses: r = .68, P = .0001). Data from all electrode configuration...
Simultaneous or Rapid Sequence Initiation of Quadruple Medical Therapy for Heart Failure—Optimizing Therapy With the Need for Speed
Authors: Stephen J. Greene, Javed Butler, Gregg C. Fonarow
Journal: JAMA Cardiology (2021)

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Reply to: Cisplatin-induced primordial follicle oocyte killing and loss of fertility are not prevented by imatinib
Authors: Emiliano Maiani, Claudia Di Bartolomeo, Francesca G Klinger, Stefano M Cannata, Sergio Bernardini, Sebastien Chateauvieux, Fabienne Mack, Maurizio Mattei, Massimo De Felici, Marc Diederich, Gianni Cesareni, Stefania Gonfloni
Journal: Nature Medicine (2012)