tbuckley/cabot-search huggingface dataset:
The effect of an acute increase in renal perfusion pressure on sodium transport in the rat kidney.
Authors: R TKunau, N HLameire
Journal: Circulation Research (1976)

We used micropuncture techniques to examine the intrarenal response to an acute elevation of the renal perfusion pressure. In one series of studies (epinephrine, group I) the renal perfusion pressure was acutely increased by intravenous epinephrine infusion; in another series, by bilateral carotid occlusion and vagotomy. A third series of studies (epinephrine, group II) was performed identically to the epinephrine, group I, studies except that the renal perfusion pressure was held constant during the epinephrine infusion by suprarenal aortic constriction. After epinephrine infusion (group I) and following bilateral carotid occlusion and vagotomy the renal perfusion pressure increased, from 119 +/- 1.0 (SEM) to 166 +/- 1.85 mm Hg and from 122 +/- 5.9 to 168 +/- 3.1 mm Hg, respectively. Fractional sodium excretion rose from 2.31 +/- 0.34% to 5.09 +/- 0.58% (P less than 0.001) after epinephrine and from 1.80 +/- 0.71 to 6.40 +/- 1.0% (P less than 0.01) following carotid occlusion and vagotomy. In neither stu...
Late survival and symptoms after repair of tetralogy of Fallot.
Authors: N MKatz, E HBlackstone, J WKirklin, A DPacifico, L MBargeron
Journal: Circulation (1982)

The long-term results of 414 patients who underwent repair of tetralogy of Fallot between 1967 and 1977 were studied and correlated with the results of others. There were nine late deaths (8-year actuarial survival 95.8%). Six of the deaths wee directly related to the malformation or its treatment. Eight patients (2.4%) required reoperation. Ten patients (4.8%) had arrhythmic symptoms. Eight (3.1%) had congestive heart failure that required treatment. The risk factors associated with late events of all types, including death, were: older age at repair, a high mean ratio of peak systolic right-to-left ventricular pressures (PLV/RV) immediately after repair, and the presence of a Potts anastomosis. Neither a transannular patch nor a previous Blalock-Taussig or Waterson anastomosis was an incremental risk factor. Bacterial endocarditis was not observed. Three hundred seven patients underwent repair primarily or after a single Blalock-Taussig or Waterston shunt and had a PRV/LV of 0.85 or less after repair. A...
Multiparametric flow cytometry highlights B7-H3 as a novel diagnostic/therapeutic target in GD2neg/low neuroblastoma variants
Authors: Alessandra Dondero, Martina Morini, Davide Cangelosi, Katia Mazzocco, Martina Serra, Grazia Maria Spaggiari, Gianluca Rotta, Annalisa Tondo, Franco Locatelli, Aurora Castellano, Francesca Scuderi, Angela Rita Sementa, Alessandra Eva, Massimo Conte, Alberto Garaventa, Cristina Bottino, Roberta Castriconi
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background High-risk neuroblastomas (HR-NBs) are rare, aggressive pediatric cancers characterized by resistance to therapy and relapse in more than 30% of cases, despite using an aggressive therapeutic protocol including targeting of GD2. The mechanisms responsible for therapy resistance are unclear and might include the presence of GD2neg/low NB variants and/or the expression of immune checkpoint ligands such as B7-H3. Method Here, we describe a multiparametric flow cytometry (MFC) combining the acquisition of 10 6 nucleated singlets, Syto16pos CD45neg CD56pos cells, and the analysis of GD2 and B7-H3 surface expression. 41 bone marrow (BM) aspirates from 25 patients with NB, at the onset or relapse, are analyzed, comparing results with cytomorphological analysis (CA) and/or immunohistochemistry (IHC). Spike in experiments assesses the sensitivity of MFC. Kaplan-Meier analysis on 498 primary NBs selects novel prognostic markers possibly integrating the MFC panel. Results No false positive are detected, and MFC shows high sensitivity (0.0005%). Optimized MFC identifies CD45negCD56pos NB cells in 11 out of 12 (91.6%) of BM indicated as infiltrated by CA, 7 of which coexpress high levels of GD2 and B7-H3. MFC detects CD45negCD56posGD2neg/low NB variants expressing high surface levels of B7-H3 in two patients with HR-NB (stage M) diagnosed at 53 and 139 months of age. One of them has a non-MYCN amplified tumor with unusual THpos PHOX2Bneg phenotype, which relapsed 141 months post-diagnosis with BM infiltration and a humerus lesion. All GD2neg/low NB variants are detected in patients at relapse. Kaplan-Meier analysis highlights an interesting dichotomous prognostic value of MML5, ULBPs, PVR, B7-H6, and CD47, ligands involved in NB recognition by the immune system. Conclusions Our study validates a sensitive MFC analysis providing information on GD2 and B7-H3 surface expression and allowing fast, specific and sensitive evaluation of BM tumor burden. With other routinely used diagnostic and prognostic tools, MFC can improve diagnosis, prognosis, orienting novel personalized treatments in patients with GD2low/neg NB, who might benefit from innovative therapies combining B7-H3 targeting.
Cystic medial necrosis in coarctation of the aorta: a potential factor contributing to adverse consequences observed after percutaneous balloon angioplasty of coarctation sites.
Authors: J MIsner, R FDonaldson, DFulton, IBhan, D DPayne, R JCleveland
Journal: Circulation (1987)

Percutaneous transluminal angioplasty has been shown to be both feasible and efficacious for the treatment of aortic coarctation. Recent reports, however, have indicated that the development of aortic aneurysms at or near the coarctation segment may complicate attempts to treat this lesion by catheter-based intervention. Accordingly, we examined the light microscopic features of coarctation segments excised at surgery (n = 31) or obtained at autopsy (n = 2) in 33 patients with coarctation of the aorta. Cystic medial necrosis, defined as depletion and disarray of elastic tissue, was observed in each of the 33 specimens. In the majority of coarctation specimens (22 of 33 or 67%) the extent of cystic medial necrosis, graded semiquantitatively on a scale of 0 (normal aorta) to 3+, was severe (3+). The finding that cystic medial necrosis represents a consistent histologic feature of coarctation of the aorta provides a pathologic basis for the formation of aneurysms observed after balloon angioplasty of coarcta...
Correction for preload in assessment of myocardial contractility in aortic and mitral valve disease. Application of the concept of systolic myocardial stiffness.
Authors: IMirsky, W JCorin, TMurakami, JGrimm, O MHess, H PKrayenbuehl
Journal: Circulation (1988)

With single-beat analysis, the new concept of systolic myocardial stiffness is applied to provide a new approach for the assessment of myocardial contractility in aortic and mitral valve disease. Seventy patients underwent diagnostic right and left heart catheterization. Twenty-six patients had aortic stenosis, 18 had aortic insufficiency, and 26 had mitral regurgitation. Patients with aortic stenosis were divided into two groups on the basis of left ventricular mass index less than 172 g/m2 (AS1) and mass index greater than or equal to 172 g/m2 (AS2). The mitral regurgitation patients were divided into those in normal sinus rhythm (MR1) and those in atrial fibrillation (MR2). Nine patients without significant coronary or cardiovascular disease served as controls. Thirteen patients with aortic stenosis and eight with aortic insufficiency were evaluated (average, approximately 18 months) after successful aortic valve replacement. With simultaneous left ventricular pressure and cineangiographic methods, myo...
Angiographic features in the infarct-related artery after intracoronary urokinase followed by prolonged anticoagulation. Role of ruptured atheromatous plaque and adherent thrombus in acute myocardial infarction in vivo.
Authors: SNakagawa, YHanada, YKoiwaya, KTanaka
Journal: Circulation (1988)

To unravel sequential morphological features in infarct-related coronary arteries (IRCA), we performed coronary angiography (CAG) before, during, and immediately after intracoronary urokinase infusion in 43 consecutive patients. After 1 month of rigorous anticoagulation by intravenous heparin and subsequent oral warfarin or after the same period of treatment by antiplatelet agents, we repeated CAG in all patients except for one, who died 6 days after thrombolytic therapy. Thirty-two IRCAs were totally occluded, and 11 were severely occluded at baseline. With recanalization and/or reduction in luminal narrowing at the site of the occlusion by progressive removal of the overlying thrombus and plaque content, we recognized the development of extraluminal contrast pooling in an ellipsoid shape (type A), single or paired linear radiolucency(ies) with or without outpouching (type B), and definite outpouching (type C). The development of type A, B, and C lesions occurred in 4, 6, and 0 IRCAs immediately after th...
Dual Peroxisome Proliferator-Activated Receptor alpha/delta Agonist GFT505 Improves Hepatic and Peripheral Insulin Sensitivity in Abdominally Obese Subjects.
Authors: Bertrand) Cariou, Hanf (Rémy), Lambert-Porcheron (Stéphanie), Zair (Yassine)
Journal: Diabetes Care (2013)
Notoginsenoside Ft1 acts as a TGR5 agonist but FXR antagonist to alleviate high fat diet-induced obesity and insulin resistance in mice
Authors: Lili Ding, Qiaoling Yang, Eryun Zhang, Yangmeng Wang, Siming Sun, Yingbo Yang, Tong Tian, Zhengcai Ju, Linshan Jiang, Xunjiang Wang, Zhengtao Wang, Wendong Huang, Li Yang
Journal: Acta Pharmaceutica Sinica B (2021)

Obesity and its associated complications are highly related to a current public health crisis around the world. A growing body of evidence has indicated that G-protein coupled bile acid (BA) receptor TGR5 (also known as Gpbar-1) is a potential drug target to treat obesity and associated metabolic disorders. We have identified notoginsenoside Ft1 (Ft1) from Panax notoginseng as an agonist of TGR5 in vitro. However, the pharmacological effects of Ft1 on diet-induced obese (DIO) mice and the underlying mechanisms are still elusive. Here we show that Ft1 (100 mg/100 diet) increased adipose lipolysis, promoted fat browning in inguinal adipose tissue and induced glucagon-like peptide-1 (GLP-1) secretion in the ileum of wild type but not Tgr5-/- obese mice. In addition, Ft1 elevated serum free and taurine-conjugated bile acids (BAs) by antagonizing Fxr transcriptional activities in the ileum to activate Tgr5 in the adipose tissues. The metabolic benefits of Ft1 were abolished in Cyp27a1-/- mice which have much lower BA levels. These results identify Ft1 as a single compound with opposite activities on two key BA receptors to alleviate high fat diet-induced obesity and insulin resistance in mice.
The interaction of sodium nitroprusside with human endothelial cells and platelets: nitroprusside and prostacyclin synergistically inhibit platelet function.
Authors: R ILevin, B BWeksler, E AJaffe
Journal: Circulation (1982)

Sodium nitroprusside (NP) is a potent vasodilator that also inhibits platelet aggregation. To test the hypothesis that NP causes both of these effects by altering the balance between prostacyclin (PGI2) produced by endothelial cells and thromboxane A2 (TXA2) produced by platelets, we incubated each of these cell types with NP for 5 minutes and assayed the PGI2 and TXA2 produced. NP at pharmacologically achieved doses (0.01--30 micrograms/ml) inhibited platelet aggregation and resultant TXA2 synthesis in a dose- and time-dependent manner (p less than 0.001). The inhibition was not dependent on cAMP production, external calcium concentration, or suppression of TXA2 synthesis. NP did not alter the production of PGI2 by cultured human endothelial cells as measured by radioimmunoassay for 6-Keto-PGF1 alpha, the stable hydrolysis product of PGI2. However, supernates of NP-treated endothelial cells containing low, noninhibitory concentrations of NP unexpectedly inhibited platelet aggregation. This inhibition of ...
Adherence to Recommendations of Anticoagulation Management Guidelines in Endoscopy Procedures at Tallaght University Hospital (TUH)
Authors: A Tawfik, R Ballester-Clau, F Lindsey, B Ryan
Journal: Endoscopy (2021)

Aims To assess the adherence of Warfarin (OAC) and Direct Oral Anticoagulants (DOAC) management to guidelines before endoscopy procedures at Tallaght University Hospital.
Quality of Life in Patients with β-Thalassemia: Transfusion Dependent Versus Non-Transfusion Dependent
Authors: Maria Domenica Cappellini, Antonis Kattamis, Vip Viprakasit, Pranee Sutcharitchan, Dalia Mahmoud, Joseph Pariseau, Abderrahmane Laadem, Anzalee Khan, X. Henry Hu, Ali Taher
Journal: Blood (2017)
Activity of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in the Blast Crisis of Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia with the Philadelphia Chromosome
Journal: New England Journal of Medicine (2001)

Correction from The New England Journal of Medicine — Activity of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in the Blast Crisis of Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia with the Philadelphia Chromosome
Systemic lupus erythematosus.
Authors: N. R. Rowell
Journal: BMJ (1969)

Patients suffering from systemic lupus erythematosus are frequently demonstrated at meetings and attract great interest, consequently doctors may be led to believe that this is a relatively common disease.However, at the General Infirmary at Leeds, for every case of systemic lupus erythematosus there are six cases of pernicious anaemia and ten of leukaemia.Thus experience in managing and treating a large number of cases is not easily obtained.I have been fortunate in seeing about 80 cases in the last ten years and have been able to assess both the longand short-term prob- lems of management.It used to be considered that the diagnosis of this condition in a young patient implied a very poor prognosis, but since the description of the L.E. cell phenomenon by Hargreaves and coworkers in 1948 and the development of other serological techniques our knowledge of the commoner subacute and chronic varieties of the condi- tion has been extended, and many such patients have survived for 15 or more years in comparatively good health.Systemic lupus erythematosus is a systemic disease with pathological changes affecting the connective tissues and vas- cular system.Clinical features1 2 include fever, rashes, arthritis, involvement of the kidneys, lungs, heart, and other organs.The onset usually is in early adult life, the peak age of onset being about 30 in females and nearly 40 in males.Approximately eight women are affected for every man.This characteristic female sex predominance and age distribution of the disease suggests that only certain individuals are pre- disposed to the disorder, the genotype probably involving three dominant X-linked alleles and also autosomal factors.3The initiation of the disease may result from somatic mutation in stem cells of the lymphoid series which give rise to for- bidden clones of lymphocytes carrying cellular autoantibodies.An endogenous defence mechanism, which tends to inhibit the development of -these forbidden clones, may be interfered with by drugs, infections, and stress, thus precipitating clinical manifestations of the disorder.Drugs which have been implicated in precipitating or activating the disease include hydrallazine, sulphonamides, certain anticonvulsants such as diphenylhydantoin, methylthiouracil, and troxidone, procain- amide, penicillin, and tetracycline. Clinical FeaturesThe initial manifestations vary, but at some time fever occurs in 90% of patients, a rash in 80%, involvement of the kidneys in about 67%, lymphadenopathy in 50%, central nervous system manifestations in 25 %, pulmonary involve- ment in about 20%, and abdominal symptoms in 20%.In acute cases there is usually marked loss of weight, anorexia, malaise, fever, and joint pains.A variety of rashes may be
The effects of gonadectomy on left ventricular function and cardiac contractile proteins in male and female rats.
Authors: T FSchaible, AMalhotra, GCiambrone, JScheuer
Journal: Circulation Research (1984)

To examine the influence of the sex hormones on mechanical properties and biochemistry of the adult heart, we studied left ventricular function and cardiac contractile proteins in hearts from 20-week-old male and female rats that had been gonadectomized at 18 days of age, compared with hearts from sham-operated animals. Testosterone and estradiol were not detectable in serum from male and female gonadectomized rats, respectively. The male rats had lower body and heart weights than male sham operated rats, whereas these values were higher in female gonadectomized than in female sham-operated rats. Left ventricular function was studied in a working heart apparatus at similar heart rate and at controlled levels of aortic diastolic pressure and left atrial pressure. At moderate left atrial pressure, end-diastolic pressure and volume per gram dry left ventricle were the same in all groups, but at high left atrial pressure, end-diastolic pressure, and volume per gram dry left ventricle were lower in male and fe...
Acetylcholine release from rat atria can be regulated through an alpha 1-adrenergic receptor.
Authors: G TWetzel, DGoldstein, J HBrown
Journal: Circulation Research (1985)

Isolated superfused rat atria release [3H]acetylcholine when depolarized with 57 mM potassium. The depolarization-induced overflow of [3H]acetylcholine is markedly inhibited by micromolar concentrations of epinephrine and norepinephrine. The alpha 1-selective adrenergic agonist methoxamine also inhibits tritium overflow, but the alpha 2-selective adrenergic agonist clonidine and the beta-adrenergic agonist isoproterenol do not. Prazosin, an selective alpha 1-adrenergic antagonist, blocks adrenergic inhibition of [3H]acetylcholine overflow with a Ki of approximately 0.4 nM. Yohimbine has approximately one-hundredth the potency of prazosin for blocking adrenergic inhibition of [3H]acetylcholine overflow. [3H]Norepinephrine overflow from isolated rat atria is also inhibited by norepinephrine, but this effect is antagonized by yohimbine and not by prazosin. We suggest that the release of acetylcholine from cardiac parasympathetic neurons can be regulated through an alpha 1-adrenergic receptor, and that this m...
Determinants of sensitization of carotid baroreceptors by pulsatile pressure in dogs.
Authors: M WChapleau, F MAbboud
Journal: Circulation Research (1989)

The threshold pressure of single baroreceptor units is decreased after compared with before exposure to pulsatile pressure according to previous studies in our laboratory. The purpose of the present study is to characterize the determinants of sensitization of arterial baroreceptors by pulsatile pressure. Carotid sinus nerve activity was recorded in dogs anesthetized with chloralose. Two indexes of baroreceptor sensitivity were obtained by comparing nerve activity before and immediately after exposure of the isolated carotid sinus to pulsatile pressure for periods up to 10 minutes. Sensitization occurred 1) when the threshold pressure of single baroreceptor units determined with a slow nonpulsatile ramp decreased after as compared with before pulsing and 2) when multiple unit activity increased after as compared with before pulsing at various mean levels of static pressure. Sensitization was evident after pulsing at mean pressure of 50 and 100 mm Hg, but not at 150 and 200 mm Hg, and was caused by the p...
DNA Breaks-Mediated Fitness Cost Reveals RNase HI as a New Target for Selectively Eliminating Antibiotic-Resistant Bacteria
Authors: Roberto Balbontín, Nelson Frazão, Isabel Gordo
Journal: Molecular Biology and Evolution (2021)

Antibiotic resistance often generates defects in bacterial growth called fitness cost. Understanding the causes of this cost is of paramount importance, as it is one of the main determinants of the prevalence of resistances upon reducing antibiotics use. Here we show that the fitness costs of antibiotic resistance mutations that affect transcription and translation in Escherichia coli strongly correlate with DNA breaks, which are generated via transcription-translation uncoupling, increased formation of RNA-DNA hybrids (R-loops), and elevated replication-transcription conflicts. We also demonstrated that the mechanisms generating DNA breaks are repeatedly targeted by compensatory evolution, and that DNA breaks and the cost of resistance can be increased by targeting the RNase HI, which specifically degrades R-loops. We further show that the DNA damage and thus the fitness cost caused by lack of RNase HI function drive resistant clones to extinction in populations with high initial frequency of resistance, both in laboratory conditions and in a mouse model of gut colonization. Thus, RNase HI provides a target specific against resistant bacteria, which we validate using a repurposed drug. In summary, we revealed key mechanisms underlying the fitness cost of antibiotic resistance mutations that can be exploited to specifically eliminate resistant bacteria.
Baroreflex control of muscle sympathetic nerve activity in borderline hypertension.
Authors: R FRea, MHamdan
Journal: Circulation (1990)

Patients with borderline hypertension have exaggerated vascular responses to orthostatic stress produced by tilt or lower body negative pressure (LBNP). It has been suggested that 1) in the supine position, these patients have augmented activity of cardiopulmonary baroreceptors that exerts an increased restraint on sympathetic vasoconstrictor tone; 2) withdrawal of this augmented inhibitory baroreceptor activity during orthostatic stress elicits augmented reflex sympathetic vasoconstrictor outflow; and 3) augmented cardiopulmonary baroreceptor activity may be secondary to impaired arterial baroreflex mechanisms. To test these hypotheses, we recorded muscle sympathetic nerve activity from the peroneal nerve in seven borderline hypertensive subjects and seven age-, sex-, and weight-matched normotensive subjects during three levels of nonhypotensive LBNP and infusions of phenylephrine and nitroprusside. During LBNP, reductions of central venous pressure were similar in borderline hypertensive and normotensiv...
Correlation of angiographic estimates of myocardial infarct size and accumulated release of creatine kinase MB isoenzyme in man.
Authors: W JRogers, H GMcDaniel, L RSmith, J AMantle, R ORussel, C ERackley
Journal: Circulation (1977)

Accumulated creatine kinase MB isoenzyme release (sigma CK-MB) during acute myocardial infarction was correlated with biplane left ventricular (LV) angiographic estimates of percent abnormally contracting segment (%ACS) and ejection fraction (EF) in 35 patients who underwent diagnostic angiography at a mean of 33 +/- 4 days post myocardial infarction (MI). Of the 35 patients, 18 had no evidence of prior MI and their sigma CK-MB showed good correlation with %ACS (r = 0.84) and with EF (r = - 0.78). An additional two patients with first (inferior) infarct secondary to stenosis of the right coronary artery proximal to the origin of the right ventricular arterial blood supply had disproportionately large sigma CK-MB, suggesting a combination of LV and RV necrosis. In the 15 patients with prior infarct, there was no significant correlation between sigma CK-MB and %ACS or EF. However, in the subgroup of patients with anterior MI, %ACS correlated with sigma CK-MB, both in patients with no prior MI (r = 0.88, N =...