tbuckley/cabot-search huggingface dataset:
SC-39026, a serine elastase inhibitor, prevents muscularization of peripheral arteries, suggesting a mechanism of monocrotaline-induced pulmonary hypertension in rats.
Authors: RIlkiw, LTodorovich-Hunter, KMaruyama, JShin, MRabinovitch
Journal: Circulation Research (1989)

In rats injected with the toxin monocrotaline, altered synthesis and distribution of pulmonary artery elastin suggest that increased elastase activity may be important in the development of vascular changes and progressive pulmonary hypertension. To test this hypothesis, male Sprague-Dawley rats (250-300 g) were given 40 mg/kg of the elastase inhibitor SC-39026 in a carboxymethylcellulose vehicle or vehicle only by gavage, 12 hours before and twice daily for 8 days after a single subcutaneous injection of either monocrotaline (60 mg/kg) or saline. Thirteen days after injection, indwelling cardiovascular catheters were inserted under pentobarbital anesthesia, and at 15 days after injection, pulmonary and systemic hemodynamic measurements were recorded with the animals awake. At post-mortem examination, the lungs were perfused and morphometric techniques applied for light and electron microscopic evaluation. Saline-injected rats given either SC-39026 or vehicle were similar in all features assessed. In cont...
Attenuation of the stress response to cardiopulmonary bypass by the addition of pulsatile flow.
Authors: D MPhilbin, F HLevine, KKono, C HCoggins, JMoss, E ESlater, M JBuckley
Journal: Circulation (1981)

The effect of pulsatile flow during cardiopulmonary bypass on the hormonal stress response was studied in 26 patients. Thirteen had routine and 13 had pulsatile bypass with an average pulse pressure of 30 mm Hg. Plasma vasopressin levels were significantly elevated during bypass in both groups, but were lower with pulsation (66 +/- 11 vs 36.3 pg/ml, p less than 0.05). Epinephrine levels increased in both groups during bypass, but were higher after bypass (1179 +/- 448 vs 713 +/- 140 pg/ml, p less than 0.05) and in the recovery room (1428 +/- 428 vs 699 +/- 155 pg/ml, p less than 0.05) in the nonpulsatile group. The same response was noted in the norepinephrine levels (924 +/- 225 vs 465 +/- 90 pg/ml, p less than 0.05; 1015 +/- 491 vs 717 +/- 112 pg/ml, p less than 0.05). There were no significant changes in renin activity in either group, but the increase after cardiopulmonary bypass was greater in the nonpulsatile group (2.0 +/- 0.7 vs 1.36 +/- 0.4 ng/ml/hr, NS). These data suggest that pulsatile flow si...
Pulmonary vascular impedance analysis of adaptation to chronically elevated blood flow in the awake dog.
Authors: R AHopkins, J WHammon, P AMcHale, P KSmith, R WAnderson
Journal: Circulation Research (1979)

Pulsatile pulmonary hemodynamics were analyzed in a chronic awake canine high flow model. Standard mean flow and pulsatile flow hemodynamics were measured and alterations in the proximal pulmonary vascular physical properties were quantified by the characteristic impedance (Zo). Pulmonary vascular resistance (PVR), which assesses arteriolar-capillary recruitment of perfusing radius and measures a more distal pulmonary vascular response to changing flows, also was calculated. Twelve control dogs were studied and had mean Qpa (pulmonary blood flow) = 2.02 +/- 0.15 liters/min, Zo = 193 +/- 20 dyne sec cm-5 and PVR = 416 +/- 32 dyne sec cm-5. Ten dogs were studied awake 20 weeks after creation of bilateral arteriovenous fistulae. Five of these shunted dogs, designated group A, developed Qpa = 3-4 liters/min (mean = 3.80 +/- 0.09, P less than 0.001 different from control group); the other five dogs (group B) developed Qpa = 4-8 liters/min (mean = 5.87 +/- 0.16, P less than 0.001). In group A, Zo = 143 +/- 8 (P...
Eliminating postnatal HIV transmission in high incidence areas: need for complementary biomedical interventions
Authors: Philippe Van de Perre, Ameena Goga, Nobubelo Ngandu, Nicolas Nagot, Dhayendre Moodley, Rachel King, Jean-Pierre Molès, Beatriz Mosqueira, Witness Chirinda, Gabriella Scarlatti, Thorkild Tylleskär, François Dabis, Glenda Gray
Journal: The Lancet (2021)
Engineering of an IL-2 immunocytokine with very low toxicity that retains potent anti-tumor activity in immune competent and immune deficient mouse tumor models
Authors: Stephen D. Gillies, Yan Lan, Scott Lauder, Beatrice Brunkhorst, Yaping Sun, Kin-Ming Lo
Journal: Cancer Research (2004)

654  The use of IL-2 for cancer therapy has been limited by its side effect profile that primarily includes effects in the vascular compartment such as vascular leak syndrome and hypotension. Many theories have been proposed to explain the mechanism of IL-2 toxicity including direct binding to endothelial cells as well as over-stimulation of intermediate affinity IL-2 receptor (IL-2R) bearing cells (e.g. NK cells) in the bloodstream. In our studies of IL-2 toxicity we have identified a specific IL-2 mutant, D20T, which has little selectivity for high over intermediate affinity IL-2 receptors as a free IL-2 molecule but which has profound selectivity when it is fused to the carboxyl terminus of an antibody to form an immunocytokine. Measurements in vitro show it to have near normal biological activity using T cell lines expressing the high affinity IL-2R but little or no activity using lines expressing only the intermediate IL-2R. This mutation also removes a sequence motif proposed earlier to resemble a binding site for endothelial cells found in many bacterial exotoxins. Surprisingly, this mutation within IL-2 had a detrimental effect on the circulating half-life of the immunocytokine that could only be reversed by removing the N-linked glycosylation site within the IgG constant region (CH2 domain). The final molecule was engineered using the V regions from a human antibody, NHS76, with high affinity for the necrotic core of solid tumors, thus allowing for selective targeting of this modified IL-2 to virtually any tumor with necrosis. Our in vitro studies with this molecule show that the binding to necrotic tissue is mediated through its high affinity for single or double-stranded DNA, despite original reports that the NHS76 antibody recognized DNA-histone complexes. Studies in several mouse tumor models demonstrate that this immunocytokine, NHS-IL2(D20T), is extremely well tolerated in immune competent mice and retains most of its anti-tumor activity against established metastases. It also retains significant anti-tumor activity in immune deficient SCID mice lacking functional T cells, although somewhat higher doses are required to achieve equivalent effects. These results suggest additional effector cells expressing high-affinity IL-2R, besides T cells, are functioning in these tumor models. They also show that small metastatic tumors can be targeted using an immunocytokine with specificity for a necrotic marker such as DNA.
Effects of activation sequence and anisotropic cellular geometry on the repolarization phase of action potential of dog ventricular muscles.
Authors: TOsaka, IKodama, NTsuboi, JToyama, KYamada
Journal: Circulation (1987)

The influence of activation sequences on action potential configuration, especially in the repolarization phase, was examined in isolated canine ventricular muscles. Action potentials were recorded from the epicardial surface in the center of a preparation having nearly uniform fiber orientation (25 X 25 mm). Stimuli applied just adjacent to the recording site produced nearly centrifugal propagation. An activation sequence either parallel (longitudinal) or perpendicular (transverse) to the long axis of the muscle fibers was produced by peripheral stimulation. Action potential duration at -60 mV (APD-60 mV) during centrifugal propagation was significantly longer than that during longitudinal propagation. Further shortening of APD-60 mV was observed during transverse propagation. When a collision of longitudinal or transverse wavefronts (longitudinal or transverse collision) was produced at the action potential recording site, the shortest APD was recorded. During centrifugal propagation, action potential m...
Variable effect of nifedipine on myocardial blood flow at three grades of coronary occlusion in the dog.
Authors: W SWeintraub, SHattori, JAgarwal, M MBodenheimer, V SBanka, R HHelfant
Journal: Circulation Research (1981)

The effect of nifedipine on myocardial blood flow at various grades of coronary stenosis is unknown, Thus 22 open-chest dogs underwent carotid to left anterior descending perfusion with flow and perfusion pressure monitoring. Grades of coronary occlusion were defined by minimum diastolic perfusion pressure. six dogs (group 1) underwent moderate occlusion to 50 to 55 mm Hg diastolic perfusion pressure; (group 2), severe occlusion to 40 mm Hg perfusion pressure; and six (group 3), more severe occlusion at 25 mm Hg. Regional myocardial blood flow was measured with radioactive microspheres before and after the intracoronary injection of 10 microgram of nifedipine. In group 1, nifedipine induced epicardial hyperemia and little change in endocardial flow in the ischemic zone. In group 2, nifedipine induced epicardial hyperemia from 1.06 to 1.39 mg/g per min, but endocardial flow decreased from 0.70 to 0.60 ml/g per min. In group 3, there was no change in blood flow. Thus the effect of nifedipine on myocardial b...
Pulmonary vasoconstrictor response to soluble fibrin in isolated lungs: possible role of thromboxane generation.
Authors: WSeeger, HNeuhof, JHall, LRoka
Journal: Circulation Research (1988)

The blood coagulation system is activated regularly in severe forms of shock, polytrauma, and sepsis. Arising thrombin cleaves the fibrinopeptides A and B from fibrinogen, and it generates monomers of fibrin, which are initially kept in solution by the remaining excess fibrinogen. The effects of soluble fibrin (fibrin monomer/oligomer-fibrinogen complexes) and fibrinopeptides A and B were investigated in blood-free perfused, isolated rabbit lungs. Urea Tris buffer-dissolved fibrin monomers were injected into the pulmonary artery in the presence of circulating excess fibrinogen. In doses above 5 mg, the monomers consistently provoked a sharp rise in pulmonary artery pressure, which was followed by an elevated pressure plateau. Changing to fresh perfusate devoid of soluble fibrin did not restore the pressure to baseline, and a second administration of the soluble fibrin caused a pressor response larger than the first. Only a modest increase in lung weight (less than 2 g) was observed, and lung inflation pre...
Enhanced revascularization of the ischemic limb by angiogenic therapy.
Authors: L QPu, A DSniderman, RBrassard, K JLachapelle, A MGraham, RLisbona, J FSymes
Journal: Circulation (1993)

BACKGROUNDThis study tests the efficacy of an angiogenic growth factor, endothelial cell growth factor, in a rabbit model of persistent hindlimb ischemia.METHODS AND RESULTSIschemia was induced in the left hindlimb of 22 New Zealand White rabbits by ligation of the distal external iliac artery and complete excision of the common and superficial femoral arteries. Two groups of animals were studied: Group 1 consisted of 11 animals who for 10 days received daily intramuscular injections of 4 mg of endothelial cell growth factor beginning on postoperative day 11, and group 2 consisted of 11 animals who underwent the same surgical ischemic procedure but received only injections of saline daily for the same postoperative period. Perfusion of the ischemic left limb was compared with the normal right limb in each animal on postoperative days 10, 20, 30, and 40 using the calf blood pressure ratio, 99mTc macroaggregate radioisotopic perfusion scans, and serial angiography. Neovascularization in the left thigh at da...
Early detection of myocardial reperfusion by assay of plasma MM-creatine kinase isoforms in dogs.
Authors: S RDevries, B ESobel, D RAbendschein
Journal: Circulation (1986)

To determine whether myocardial reperfusion can be detected promptly by changes in profiles of isoforms of MM-creatine kinase (CK) in plasma, coronary occlusion was induced in 30 conscious dogs and reperfusion was initiated after 1, 2, 3, or 4 hr in 21. The myocardial isoform of MM-CK, MMA, was quantified in serial plasma samples by chromatofocusing. Before coronary occlusion, MMA comprised 13 +/- 7% (SD) of the total CK activity in plasma. The percentage of MMA (MMA%) was elevated before reperfusion, but increased markedly and consistently to a peak of 52 +/- 13% (n = 21) between 30 min and 1 hr after the time of onset of reperfusion. The rate of increase in MMA% was significantly faster with reperfusion at 1 hr (1.44 +/- 0.42% min-1), 2 hr (1.28 +/- 0.45% min-1), or 3 hr (1.02 +/- 0.27% min-1) (p less than .001), but not with reperfusion at 4 hr (0.48 +/- 0.34% min-1) compared with the rate in nonreperfused control dogs (0.29 +/- 0.09% min-1). Furthermore, the rate of increase in MMA% was neither influe...
Dynamic interactions and mutual synchronization of sinoatrial node pacemaker cells. A mathematical model.
Authors: D CMichaels, E PMatyas, JJalife
Journal: Circulation Research (1986)

Dynamic interactions and mutual entrainment of coupled sinoatrial pacemaker cells with different intrinsic frequencies were investigated using a computerized mathematical model. Transmembrane potentials were simulated using equations of individual membrane currents based on voltage clamp data for the sinoatrial node. The intrinsic frequency of a given cell was altered by applying bias hyperpolarizing current, or by changing the amount of slow inward current. Cells were coupled through simple ohmic resistances to form linear arrays of two or more cells. Simulations closely reproduced previous experimental work showing that the mutual interactions between pacemakers are mediated electrotonically and show phase dependence. Results from the present simulations provide an explanation for the ionic basis of these phase-dependent interactions. In addition, it is demonstrated that the mutual entrainment of coupled pacemakers can lead to their coordinated behavior (synchronization). Two pacemaker cells can synchro...
Functional significance of hypertrophy of the noninfarcted myocardium after myocardial infarction in humans.
Authors: L EGinzton, RConant, D MRodrigues, M MLaks
Journal: Circulation (1989)

Hypertrophy of the noninfarcted left ventricle as a chronic response to myocardial infarction has been demonstrated in animals and at autopsy in humans. However, the functional significance of postmyocardial infarction hypertrophy is a subject of dispute. The purpose of this study was to determine the time course of development of postmyocardial infarction hypertrophy of the noninfarcted myocardium in humans and to assess its functional significance. Subcostal view, two-dimensional echocardiograms were recorded at rest and during peak exercise, 6 and 40 weeks postmyocardial infarction in 45 patients (16 anterior, 20 inferior, nine non-Q wave infarcts), for measurement of left ventricular mass and ejection fraction. The left ventricular mass index increased from 94 +/- 30 to 118 +/- 27 g/m2 (p less than 0.01) during the time of the two studies. There was a significant correlation between the change in left ventricular mass index and improved resting ejection fraction (r = 0.48, p less than 0.001) and exerc...
Experimental sympathetic activation causes endothelial injury in the rabbit thoracic aorta via beta 1-adrenoceptor activation.
Authors: KPettersson, BBejne, HBjörk, W BStrawn, GBondjers
Journal: Circulation Research (1990)

Sympathetic activation appears to accelerate the development of atherosclerosis, an effect that may be inhibited by beta-receptor blockade. It is unclear, however, which mechanisms mediate this effect. In view of the significance attached to endothelial injury in the initial phases of atherogenesis, we decided to test whether sympathetic activation might lead to an increase in endothelial injury. Chloralose anesthesia was used to induce sympathetic activation and the presence of intracellular IgG as a criterion of endothelial cell injury. The beta 1-selective beta-blocker metoprolol was used to evaluate if the effect(s) of sympathetic activation might be mediated by beta 1-adrenoceptors. In normal rabbits, the frequency of injured endothelial cells in unbranched areas of the thoracic aorta was 0.23%, compared with 1.93% in circumostial areas. Chloralose anesthesia caused significant increases in blood pressure, heart rate, and plasma norepinephrine, that is, caused sympathetic activation, and led to an ap...
Measurement of lung microvascular pressure in the intact anesthetized rabbit by the micropuncture technique.
Authors: SBhattacharya, M RGlucksberg, JBhattacharya
Journal: Circulation Research (1989)

We have developed a micropuncture technique for the measurement of microvascular pressure in the intact lung of rabbit. We anesthetized 16 rabbits (halothane, 0.8%) and mechanically ventilated them through a tracheotomy. Then, we exposed the right lung by rib resection over the right anterior chest. We measured pulmonary artery, left atrial, and systemic pressures by direct catheterization and cardiac output by the thermodilution technique. For micropuncture, we stabilized the lung on a shelf and stopped ventilation for 3-4 minutes at an airway pressure of 7 cm H2O. We injected pancuronium intravenously to paralyze the diaphragm and intercostal muscles. Of the total pulmonary vascular pressure drop, 52% occurred in the microvascular segment between arterioles and venules of 20 micron diameter, 28% occurred in the arterial segment, and 20% occurred in the venous segment. We conclude that in the intact lung of rabbit, the major pressure drop occurs in the microvascular segment.
Polymyalgia Rheumatica and Giant-Cell Arteritis
Authors: Carlo Salvarani, Fabrizio Cantini, Luigi Boiardi, Gene G. Hunder
Journal: New England Journal of Medicine (2002)

Polymyalgia rheumatica is an inflammatory disorder manifested principally by stiffness of the neck, shoulder girdle, and pelvic girdle; giant-cell (or temporal) arteritis affects the cranial branches of arteries arising from the aortic arch. The two conditions are believed to be linked and may occur together. Giant-cell arteritis is a serious disorder that can cause blindness as a result of ischemia of the optic nerve or retina. Both disorders respond to corticosteroid therapy. This comprehensive article reviews the clinical manifestations, pathophysiology, and treatment of these disorders.
TB in migrant farmworkers
Authors: J. R. Richard
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The Office of Migrant Health, Department of Health and Human Services, estimates there to be more than 4 million migrant and seasonal farmworkers in the United States. Among other health problems, these workers suffer a significantly higher rate of tuberculosis (TB) infection compared with the general population. This also includes a high rate of asymptomatic TB, found to be 33% in Hispanic migrant workers in one typical study.<sup>1</sup>With a lifetime risk of 10% for developing active TB, it is understandable that this high-risk population constitutes one of the top priorities of the Advisory Council for Elimination of Tuberculosis, Department of Health and Human Services. In attempting to comply with Centers for Disease Control and Prevention recommendations for TB screening,<sup>2</sup>our mobile migrant worker clinic in north central Ohio offered Mantoux tuberculin skin testing to farmworkers and their families from June through September 1993. Approximately
Alterations in sarcoplasmic reticulum gene expression in human heart failure. A possible mechanism for alterations in systolic and diastolic properties of the failing myocardium.
Authors: MArai, N RAlpert, D HMacLennan, PBarton, MPeriasamy
Journal: Circulation Research (1993)

Recent studies have shown that intracellular Ca2+ handling is abnormal in the myocardium of patients with end-stage heart failure. Muscles from the failing hearts showed a prolonged Ca2+ transient and a diminished capacity to restore a low resting Ca2+ level during diastole. Accordingly, we examined whether this defect in Ca2+ transport function is due to alterations in sarcoplasmic reticulum gene expression. We determined the messenger RNA (mRNA) levels of sarcoplasmic reticulum Ca2+ transport proteins in failing human hearts from 17 cardiac transplant recipients with a diagnosis of dilated cardiomyopathy, primary pulmonary hypertension, or ischemic heart disease. The expression levels of each mRNA were compared with each other and then correlated with that of atrial natriuretic factor (ANF) mRNA in the failing ventricle. The mRNA levels for the calcium release channel (ryanodine receptor, RYR2), Ca2+ uptake pump (Ca(2+)-ATPase, SERCA2 isoform), and phospholamban differed significantly between heart samp...
Aortic valve replacement without myocardial revascularization in patients with combined aortic valvular and coronary artery disease.
Authors: R OBonow, K MKent, D RRosing, L CLipson, J SBorer, C LMcIntosh, A GMorrow, S EEpstein
Journal: Circulation (1981)

To test the hypothesis that coronary artery bypass grafting (CABG) is not routinely required in patients undergoing aortic valve replacement (AVR) who have coexistent coronary artery disease (CAD), we compared the results of operation in 55 consecutive symptomatic patients who had CAD and underwent AVR without CABG with results in another 142 patients without CAD who underwent AVR during the same period, and with published results from other centers in which CABG was used in patients with CAD who underwent AVR. Operative mortality was 4% in patients with CAD and 5% in patients without CAD. Late survival was not significantly different between the two groups when analyzed for the entire population (80% survival at 3 years in CAD patients, 82% for non-CAD patients), or for the subgroup of patients with aortic stenosis, aortic regurgitation or aortic stenosis plus regurgitation. Eight patients with CAD (15%) developed recurrent angina after AVR (mean follow-up 43 months); only three patients (6%) required CA...
Post-ERCP pancreatitis: still a major issue despite all efforts
Authors: Jacques Devière
Journal: Endoscopy (2021)

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most frequent complication associated with a technique that has otherwise dramatically improved the outcomes of patients with biliopancreatic diseases. Many factors have been associated with PEP, including those related to patients (young age, female sex, obesity), indications (sphincter of Oddi dysfunction, history of PEP), technique (precut sphincterotomy, pancreatic sphincterotomy, papillectomy, difficulty of cannulation, repeated pancreatic duct injections), and experience of the operator [1–3].
Clinical and immunological findings in 55 patients with anti‐laminin 332‐type mucous membrane pemphigoid
Authors: X. Li, H. Qian, Y. Natsuaki, H. Koga, T. Kawakami, C. Tateishi, D. Tsuruta, N. Ishii, T. Hashimoto
Journal: British Journal of Dermatology (2021)
Treatment of Cholera
Authors: J. Gardner
Journal: BMJ (1865)

my remarks on the subject of the pathology and treatment of cholera, inserted in the JOURNAL of September 16th, my principal object was to elicit from those in the profession who had previously had some experience of the disease such practical information as would serve as a guide, and assist us in deciding how to act, should the disease come upon us.Since that time, two more cases have occurred in my own practice, both more severe in their character than the former cases.Both occurred in the latter part of