tbuckley/cabot-search huggingface dataset:
Tricarbocyclic core formation of tyrosine-decahydrofluorenes implies a three-enzyme cascade with XenF-mediated sigmatropic rearrangement as a prerequisite
Authors: Zhiguo Liu, Wei Li, Peng Zhang, Jie Fan, Fangbo Zhang, Caixia Wang, Shuming Li, Yi Sun, Shilin Chen, Wenbing Yin
Journal: Acta Pharmaceutica Sinica B (2021)

Tyrosine-decahydrofluorene derivatives feature a fused [6.5.6] tricarbocyclic core and a 13-membered para-cyclophane ether. Herein, we identified new xenoacremones A, B, and C (1-3) from the fungal strain Xenoacremonium sinensis ML-31 and elucidated their biosynthetic pathway using gene deletion in the native strain and heterologous expression in Aspergillus nidulans. The hybrid polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) XenE together with enoyl reductase XenG were confirmed to be responsible for the formation of the tyrosine-nonaketide skeleton. This skeleton was subsequently dehydrated by XenA to afford a pyrrolidinone moiety. XenF catalyzed a novel sigmatropic rearrangement to yield a key cyclohexane intermediate as a prerequisite for the formation of the multi-ring system. Subsequent oxidation catalyzed by XenD supplied the substrate for XenC to link the para-cyclophane ether, which underwent subsequent spontaneous Diels-Alder reaction to give the end products. Thus, the results indicated that three novel enzymes XenF, XenD, and XenC coordinate to assemble the [6.5.6] tricarbocyclic ring and para-cyclophane ether during biosynthesis of complex tyrosine-decahydrofluorene derivatives.
Dose-response effects of TPI ASM8 in asthmatics after allergen
Authors: Gauvreau, Pageau, Seguin, Carballo, Gauthier, D'Anjou, Campbell, Watson, Mistry, Parry-Billings, Killian, Renzi
Journal: Allergy (2011)

BACKGROUND: TPI ASM8 contains two modified antisense oligonucleotides (AON) targeting the beta subunit (beta(c) ) of the IL-3, IL-5, GM-CSF receptors and the chemokine receptor CCR3. A previous study suggested that TPI ASM8 had broader effects than just inhibition of eosinophils in asthmatics. OBJECTIVE: We assessed whether TPI ASM8 caused a dose-dependent attenuation in the inflammatory and physiological changes after inhaled allergen challenge (AIC). METHODS: This single-center, open-label, stepwise-ascending dose study was conducted in fourteen stable, mild allergic asthmatics. Following placebo AIC, subjects underwent AIC after 4 days treatment with 1, 2, and 4 mg BID and finally 8 mg once daily (OD) of TPI ASM8, inhaled via the I-Neb nebuliser. Treatments were separated by 2-3-week washout periods. RESULTS: TPI ASM8 was safe and well tolerated at all doses. TPI ASM8 8 mg OD reduced eosinophils in sputum after AIC (by 60.9% at 7 h and 68.4% at 24 h post-AIC, P=0.016 and P=0.007, respectively). Additionally, TPI ASM8 8 mg OD significantly attenuated the early and late airway responses as shown by the reduction in the area under the curve by 45% (P=0.016) and 59%, (P=0.0015), respectively, the increase in eosinophil cationic protein (ECP) by up to 57% (P=0.021), and airway responsiveness to methacholine by more than 1 doubling dose (P=0.012). A dose-response relationship was noted, and efficacy was maintained with once per day administration. CONCLUSIONS: TPI ASM8 attenuated a broad range of inflammatory and physiological changes after AIC, suggesting that CCR3, IL-3, and GM-CSF also are important targets for the management of asthma
THE ROENTGEN-RAY TREATMENT OF VERRUCA PLANTARIS
Journal: JAMA (1920)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
80P Prospective analysis of patients with non-small cell lung cancer (NSCLC) receiving neoadjuvant (chemo-) immunotherapy (C-IO) prior to resection or definitive radiochemotherapy (RCT) in routine clinical care (KOMPASS neo)
Authors: M. Faehling, A. Türk, R. Saetzler, S. Fallscheer, J. Sträter, S. Eschmann, F. Heinzelmann, H. Witte
Journal: Journal of Thoracic Oncology (2021)
Replacement of aortic valve combined with myocardial revascularization: determinants of early and late risk for 500 patients, 1967-1981.
Authors: B WLytle, D MCosgrove, F DLoop, P CTaylor, C CGill, L AGolding, MGoormastic, L KGroves
Journal: Circulation (1983)

Five hundred consecutive patients underwent aortic valve replacement and coronary revascularization in the years from 1967 to 1981, with 29 (5.9%) in-hospital deaths. Current operative mortality (1978-1981) is 3.4%. Univariate and multivariate analyses were used to identify determinants of early and late risk. Female sex, aortic insufficiency, and advanced age increased in-hospital mortality, whereas use of cardioplegia decreased it. At follow-up of 471 patients who survived hospitalization for 1 to 135 months (mean 41) after surgery, 96 late deaths were documented. Survival rates were 87%, 80%, and 55%, and event-free survival rates were 80%, 65%, and 39% at 2, 5, and 10 years after surgery, respectively. The late survival rate was unfavorably influenced by the presence of moderately or severely impaired left ventricular function and double-vessel coronary disease; the rate was enhanced for patients in age group from 50 to 59 years old and was not influenced by the method of myocardial protection. The ev...
Decreased basal cardiac interstitial norepinephrine release after neuronal uptake inhibition in dogs.
Authors: DCousineau, C AGoresky, C PRose
Journal: Circulation Research (1986)

The effect of neuronal uptake inhibition on basal interstitial release of norepinephrine in the canine heart was examined by use of the multiple tracer dilution-bulk balance technique. A kinetic model incorporating the effects of flow, capillary permeability-surface product for norepinephrine, the interstitial uptake rate constant for neurotransmitter, and plasma norepinephrine input and output values was used to estimate rates of uptake from and release of norepinephrine into the interstitial space. The intravenous injection of the neuronal uptake inhibitor desipramine in anesthetized dogs under basal conditions reduced interstitial uptake of tracer norepinephrine in the heart, without significant changes in plasma concentration of norepinephrine in aorta and coronary sinus. The lack of change in the arteriovenous balance for norepinephrine across the heart, in the face of the lowered uptake for this amine, suggested that the liberation of norepinephrine by cardiac sympathetic fibers was reduced. Analysi...
The role of canine superficial ventricular muscle fibers in endocardial impulse distribution.
Authors: R JMyerburg, HGelband, KNilsson, ACastellanos, A RMorales, A LBassett
Journal: Circulation Research (1978)

Thin sections of canine right and left ventricular endocardium and myocardium were studied in a tissue bath to compare conduction properties of intraventricular specialized conducting tissue [Purkinje fibers (PF)], the superficial layers of subendocardial ventricular muscle (SVM), and the deeper ventricular muscle (DVM) below this level. The study was carried out because of observations that some areas of the endocardium, which are devoid of either specialized conducting tissue or of PF-VM junctions between specialized conducting tissue and ventricular muscle, conduct relatively rapidly, favoring specific orientations of propagation. Preparations containing PF, SVM, and DVM were studied electrophysiologically and histologically. A technique of stripping limited areas of endocardium was used to expose DVM in order to determine its intrinsic calculated conduction velocity. In 12 preparations, the average calculated conduction velocity in PF was 1.62 m/sec, and the average in DVM was 0.26 m/sec. The SVM cond...
Covid-19: All Johnson and Johnson vaccine in use is safe, says US regulator
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

The acting head of the US Centers for Medicare and Medicaid Services gave reassurances on 5 April that the Johnson & Johnson vaccine was safe, after a mix-up at a production plant in Maryland ruined 15 million potential doses of the vaccine. 1 Andy Slavitt said at a press briefing, "All of the Johnson & Johnson vaccine that'
The Physical Properties of Skin in Cutis Laxa
Authors: Martin M. Black, Sam Shustbr
Journal: British Journal of Dermatology (1971)

Journal Article The Physical Properties of Skin in Cutis Laxa Get access Martin M. Black, Martin M. Black Institute of Dermatology, London W.C.2, University Department of Dermatology, Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar Sam Shustbr Sam Shustbr Institute of Dermatology, London W.C.2, University Department of Dermatology, Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 85, Issue 6, 1 December 1971, Pages 598–599, https://doi.org/10.1111/j.1365-2133.1971.tb14094.x Published: 01 December 1971
Prevalence of arrhythmias during 24-hour electrocardiographic monitoring and exercise testing in patients with obstructive and nonobstructive hypertrophic cardiomyopathy.
Authors: D DSavage, S FSeides, B JMaron, D JMyers, S EEpstein
Journal: Circulation (1979)

Many patients with hypertrophic cardiomyopathy die suddenly and unexpectedly, a significant number perhaps due to arrhythmia. Of 100 patients initially evaluated for signs or symptoms suggestive of heart disease or a family history of hypertrophic cardiomyopathy, 51 were selected solely because they met the echocardiographic criteria for the disease, and 49 patients were selected primarily because they had: 1) normal sinus rhythm despite left atrial enlargement, 2) a history of syncope, 3) a family history of premature death, or 4) a history of paroxysmal atrial fibrillation. All 100 patients were studied by 24-hour ambulatory electrocardiographic monitoring and 74 of them also underwent treadmill exercise testing. More than 50% of patients in repetitive ventricular premature depolarizations, including 19% who had ventricular tachycardia. Monitoring was superior to exercise testing for exposing these arrhythmias. Two patients experienced cardiac arrest within 2 months of monitoring; in each, monitoring ha...
Dudley trust faces criminal charges over deaths of two patients from sepsis
Authors: Clare Dyer
Journal: BMJ (2021)

The Care Quality Commission (CQC) is bringing a criminal prosecution against a hospital trust after two patients died following alleged exposure to “significant risk of avoidable harm.”

The Dudley Group NHS Foundation Trust faces charges over care given before the deaths of a mother of six, Natalie Billingham, 33, and 14 year-old Kaysie-Jane Robinson, who both died of sepsis. Lawyers for the trust appeared before Dudley magistrates on 7 April for a brief initial hearing. District Judge Graham Wilkinson said that the trust would be required to enter pleas to …
Temporal multiomic modeling reveals a B-cell receptor proliferative program in chronic lymphocytic leukemia
Authors: Cedric Schleiss, Raphael Carapito, Luc-Matthieu Fornecker, Leslie Muller, Nicodème Paul, Ouria Tahar, Angelique Pichot, Manuela Tavian, Alina Nicolae, Laurent Miguet, Laurent Mauvieux, Raoul Herbrecht, Sarah Cianferani, Jean-Noel Freund, Christine Carapito, Myriam Maumy-Bertrand, Seiamak Bahram, Frederic Bertrand, Laurent Vallat
Journal: Leukemia (2021)

B-cell receptor (BCR) signaling is crucial for the pathophysiology of most mature B-cell lymphomas/leukemias and has emerged as a therapeutic target whose effectiveness remains limited by the occurrence of mutations. Therefore, deciphering the cellular program activated downstream this pathway has become of paramount importance for the development of innovative therapies. Using an original ex vivo model of BCR-induced proliferation of chronic lymphocytic leukemia cells, we generated 108 temporal transcriptional and proteomic profiles from 1 h up to 4 days after BCR activation. This dataset revealed a structured temporal response composed of 13,065 transcripts and 4027 proteins, comprising a leukemic proliferative signature consisting of 430 genes and 374 proteins. Mathematical modeling of this complex cellular response further highlighted a transcriptional network driven by 14 early genes linked to proteins involved in cell proliferation. This group includes expected genes (EGR1/2, NF-kB) and genes involved in NF-kB signaling modulation (TANK, ROHF) and immune evasion (KMO, IL4I1) that have not yet been associated with leukemic cells proliferation. Our study unveils the BCR-activated proliferative genetic program in primary leukemic cells. This approach combining temporal measurements with modeling allows identifying new putative targets for innovative therapy of lymphoid malignancies and also cancers dependent on ligand-receptor interactions.
Reduction of CK and CK-MB indexes of infarct size by intravenous nitroglycerin.
Authors: W DBussmann, DPassek, WSeidel, MKaltenbach
Journal: Circulation (1981)

The effect of i.v. nitroglycerin administration on indexes of infarct size was examined in 31 patients with acute myocardial infarction. Serial creatine kinase (CK) and CK-MB isoenzyme determinations were used to calculate infarct size. Twenty-nine patients served as controls. Two subgroups of the study group were formed to evaluate differences between early and late intervention. In the first group (n = 22), continuous infusion of nitroglycerin over 48 hours was initiated within 8 hours (mean 4.5 hours) after the onset of symptoms. Peak CK activity for the nitroglycerin-treated patients (n = 9) in this subgroup was 544 U/1 vs 871 U/1 for the controls (n = 13) (p less than 0.05). The rate of CK release was reduced from 79 to 33 U/1.hr (58%), as was total CK and CK-MB release (p less than 0.02). Calculated infarct size was 69 gEq in the controls and 48 gEq in patients receiving nitroglycerin (CK-MB: 69 vs 43 gEq, p less than 0.05). In the late intervention subgroup, nitroglycerin therapy was begun more tha...
Demonstration of sustained sinus and atrial re-entry as a mechanism of paroxysmal supraventricular tachycardia.
Authors: DWu, FAmat-y-leon, PDenes, R CDhingra, R JPietras, K MRosen
Journal: Circulation (1975)

Electrophysiological studies in five patients with documented (4) or suspected (1) paroxysmal supraventricular tachycardia (PSVT), suggested sinus or atrial reentrance (SR or AR). Two of the patients had preexcitation, three had evidence of atrial enlargement, and all had organic heart disease. The following observations supported a diagnosis of SR and AR; 1) induction of sustained PSVT with atrial extrastimulus technique allowing definition of an echo zone; 2) induction of sustained PSVT during constant rapid atrial pacing at a rate less than that producing A-V nodal Wenckebach periods, or producing normalization of QRS complex in patients with pre-excitation: 3) P waves preceding each QRS during PSVT with an A-H interval appropriate for the rate of the PSVT; 4) antegrade P wave morphology during PSVT, a normal high to low sequence of right atrial activation (SR), or P wave morphology and atrial activation sequence different from sinus (AR); 5) lack of correlation of PSVT induction with critical A-H inte...
Noninvasive evaluation of pulmonary hypertension by a pulsed Doppler technique.
Authors: AKitabatake, MInoue, MAsao, TMasuyama, JTanouchi, TMorita, MMishima, MUematsu, TShimazu, MHori
Journal: Circulation (1983)

We used a pulsed Doppler technique to examine the flow velocity pattern in the right ventricular outflow tract in 33 adults. In the patients with normal pulmonary artery pressure (mean pressure less than 20 mm Hg, 16 patients), ejection flow reached a peak level at midsystole (137 +/- 24 msec, mean +/- SD), producing a domelike contour of the flow velocity pattern during systole. In contrast, the flow velocity pattern in patients with pulmonary hypertension (mean pressure greater than or equal to 20 mm Hg, 17 patients) was demonstrated to accelerate rapidly and to reach a peak level sooner (97 +/- 20 msec, p less than .01); in 10 of the pulmonary hypertensive patients a secondary slower rise in flow velocity was observed during a deceleration, resulting in the midsystolic notching. The time to peak flow (acceleration time, AcT) and right ventricular ejection time (RVET) were measured from the flow velocity pattern. Either AcT or AcT/RVET decreased with increase in mean pulmonary artery pressure, and a ver...
Nifedipine therapy for Prinzmetal's angina.
Authors: J EMuller, S JGunther
Journal: Circulation (1978)

A case is described in which nifedipine, a new coronary vasodilator, was effective in relieving attacks of Prinzmetal's angina unresponsive to conventional therapy. The extreme frequency of the anginal attacks provided evidence that lower doses of nifedipine lost their effectiveness approximately 4 hours after administration. A month after initiation of nifedipine, nitrates were withdrawn since they had been ineffective in controlling the attacks. A myocardial infarction occurred immediately, presumably due to coronary spasm.
Prostaglandins contribute to activation of baroreceptors in rabbits. Possible paracrine influence of endothelium.
Authors: H IChen, M WChapleau, T SMcDowell, F MAbboud
Journal: Circulation Research (1990)

The purpose of this study was to test the hypothesis that prostaglandins released from vascular endothelial cells contribute to activation of baroreceptors during increases in arterial pressure. Baroreceptor activity was recorded from the vascularly isolated carotid sinus in rabbits anesthetized with chloralose. Baroreceptor activity was measured during ramp or step increases in nonpulsatile carotid sinus pressure over a range of 0-175 mm Hg. Exposure of the isolated carotid sinus to inhibitors of prostaglandin formation (indomethacin [n = 10] or aspirin [n = 6]) decreased baroreceptor activity significantly (p less than 0.05). The slope of the pressure-activity relation averaged 0.80 +/- 0.07 %/mm Hg (mean +/- SEM) during control measurements and 0.72 +/- 0.06 and 0.63 +/- 0.05 %/mm Hg during exposure to 10 and 20 microM indomethacin, respectively. Exposure of the carotid sinus to exogenous prostacyclin (PGI2 [n = 11]) increased baroreceptor activity significantly. The slope of the pressure-activity rela...
Germline gain-of-function mutations in RAF1 cause Noonan syndrome
Authors: M Abdur Razzaque, Tsutomu Nishizawa, Yuta Komoike, Hisato Yagi, Michiko Furutani, Ryunosuke Amo, Mitsuhiro Kamisago, Kazuo Momma, Hiroshi Katayama, Masao Nakagawa, Yuko Fujiwara, Masaki Matsushima, Katsumi Mizuno, Mika Tokuyama, Hamao Hirota, Jun Muneuchi, Toru Higashinakagawa, Rumiko Matsuoka
Journal: Nature Genetics (2007)
Porcine coronary arteries with regenerated endothelium have a reduced endothelium-dependent responsiveness to aggregating platelets and serotonin.
Authors: HShimokawa, L LAarhus, P MVanhoutte
Journal: Circulation Research (1987)

To test the ability of regenerated endothelium to evoke endothelium-dependent relaxations, male Yorkshire pigs underwent balloon endothelial denudation of the proximal left anterior descending coronary artery. Endothelium-dependent responses were examined in vitro, in rings of coronary segments taken from the denuded area or from the proximal left circumflex coronary artery. The experiments were performed 8 days or 4 weeks after the denudation. Endothelial regrowth was confirmed by histologic examination 8 days after the denudation and by demonstrating the presence of endothelium-dependent relaxations to bradykinin; at that time aggregating platelets evoked normal endothelium-dependent responses. However, 4 weeks after the denudation, the relaxations to aggregating platelets were markedly depressed although continuous endothelial lining was present, and the endothelium-dependent responses to bradykinin, adenosine diphosphate, the Ca2+-ionophore A23187, platelet activating factor, and thrombin were unalter...
Flow through collapsible tubes at low Reynolds numbers. Applicability of the waterfall model.
Authors: C KLyon, J BScott, C YWang
Journal: Circulation Research (1980)

The applicability of the waterfall model was tested using the Starling resistor and different viscosities of fluids to vary the Reynolds number. The waterfall model proved adequate to describe flow in the Starling resistor model only at very low Reynolds numbers (Reynolds number less than 1). Blood flow characterized by such low Reynolds numbers occurs only in the microvasculature. Thus, it is inappropriate to apply the waterfall model indiscriminately to flow through large collapsible veins.
Rabbit heart fatty acid-binding protein. Isolation, characterization, and application of a monoclonal antibody.
Authors: A AKnowlton, R EBurrier, PBrecher
Journal: Circulation Research (1989)

A fatty acid-binding protein (FABP) was purified from rabbit heart and characterized with respect to size, isoelectric point, and tissue distribution. This protein was found in red muscle, diaphragm, and aorta, as well as in the heart. Amino acid composition of rabbit heart FABP differed only slightly from the human and rat proteins. Rabbit heart FABP was shown to bind two molecules of fatty acid. A monoclonal antibody was developed and used to demonstrate the feasibility of a one-step purification with affinity chromatography. Cross-reactivity was found between the human protein and the rabbit antibody, and an immunoassay was developed to human heart FABP. Levels of human heart FABP in the plasma of patients with acute myocardial infarction were significantly elevated (83 +/- 9 micrograms/ml) compared with patients with pulmonary edema (52 +/- 7 micrograms/ml) and normal volunteers (28 +/- 5 micrograms/ml; p less than 0.05, mean +/- SEM).
Protein C activation following coronary artery occlusion in the in situ porcine heart.
Authors: T RSnow, M TDeal, D TDickey, C TEsmon
Journal: Circulation (1991)

BACKGROUNDActivated protein C, the body's natural anticoagulant, may play a role in protecting the heart during and following an occlusion of the left anterior descending coronary artery (LAD) in the porcine heart.METHODS AND RESULTSInfusion of 1 unit thrombin over 30 seconds into the LAD of juvenile pigs produced a prolongation of the Xa clotting time (153 +/- 14%) in blood drawn from the anterior interventricular vein (AIV). The action of the anticoagulant was blocked by a polyclonal immunoglobulin G antibody directed against porcine activated protein C. A brief (30 seconds) occlusion of the LAD induced a similar prolongation of the Xa clotting time (138 +/- 11%), which was also blocked by the polyclonal antibody. To determine whether activated protein C helps sustain the heart during and following a 2-minute occlusion, three groups of pigs were studied: 11 controls, six receiving activated porcine protein C, and nine receiving a monoclonal antibody (HPC4) that blocks protein C activation. Relative to t...