tbuckley/cabot-search huggingface dataset:
Letter: Breast cancer regression under oestrogen therapy.
Authors: M L'Hermite, C Robyn, J C Heuson, M Rozencweig
Journal: BMJ (1974)

diarrhoea that are often provoked and by increased elimination of potassium by the normal kidney," though of course if the kidney is diseased, dangerous hyperkalaemia may ensue.Though this child vomited and apparently had normal kidneys he evidently absorbed enough potassium to overwhelm the excretory mechanism.The final serum level was probably inflated by the effects of anoxia and acidosis.The electrocardiogram shows an advanced stage of hyperkalaemia5 where atrial activity has stopped and there is an irregular ventricular rhythm with grossly elongated complexes.Asystole or fibrillation is imminent.This sad case again illustrates how dangerous pills that look like sweets can be for children,67 and re-emphasizes that all medicaments, even those as apparently innocuous as Slow-K, should be kept securely out of reach.-Iam, etc.,
Is hypertension more benign when associated with obesity
Authors: EBarrett-Connor, K TKhaw
Journal: Circulation (1985)

To determine the effect of obesity on prognosis in hypertensive subjects, a population of 1727 men 50 to 79 years of age was dichotomized by baseline body mass index (less than 27 and greater than or equal to 27 kg/m2) and systolic blood pressure (less than 160 and greater than or equal to 160 mm Hg). After 9 years of follow-up, age-adjusted all-cause, cardiovascular, and ischemic heart disease mortality rates were highest in the nonobese hypertensive subjects. The relative risk for mortality associated with a systolic blood pressure of 160 mm Hg or higher was significantly increased only in the nonobese group, with the largest difference in relative risk between obese and nonobese for ischemic heart disease. Results were consistent after separately excluding those with a history of heart disease, diabetes, current use of antihypertensive medication, and cigarette smoking, and those who died within 2 years of the baseline examination. When the independent effect of risk factors, including age, plasma chol...
Functional expression of an inactivating potassium channel cloned from human heart.
Authors: SPo, D JSnyders, RBaker, M MTamkun, P BBennett
Journal: Circulation Research (1992)

Recently a putative K+ channel with homology to the Shaker family of potassium channels has been cloned from human ventricular myocardium. However, proof that the cDNA encodes a K+ channel requires appropriate translation and expression of a functional ion-selective channel. Therefore, expression of this putative human K+ channel DNA was attempted by cytoplasmic injections of in vitro transcribed cRNA into Xenopus laevis oocytes and screening by two-electrode voltage-clamp methods. This resulted in expression of voltage-gated channels that rapidly inactivated (time constant of inactivation, 47.6 +/- 3.6 msec; 0 mV; n = 10) and were at least 50 times more selective for K+ than Na+ (Na+/K+ permeability ratio of 0.02). The channels showed voltage-dependent activation (half-maximal voltage, -34 +/- 0.7 mV; n = 5), and 50% of the channels were inactivated within 2 seconds when the membrane potential was clamped near -60 mV (half-maximal voltage, -62 +/- 7 mV; n = 10). The expressed protein resulted in a K+ cur...
"VISUAL FACTORS IN EQUILIBRATION, ESPECIALLY AVIATION"
Authors: Eugene R. Lewis
Journal: JAMA (1918)

<h3>To the Editor:</h3> —In his article on "Visual Factors in Equilibration, Especially Aviation" (The Journal, April 6, 1918, p. 991), it is apparent that Dr. Fridenberg has been under a misapprehension as to the character and scope of the physical examination of applicants for flying service. Let me first recommend that he secure Blank 609, A. G. O., which is the physical examination blank for these applicants. He will at once be struck by the fact that of the thirty-two items of this examination, the first twelve are solely concerned with a complete examination of the eye. On the other hand, he will be equally struck with the fact that only one item (No. 20) deals in any way with the internal ear balance mechanism. This, I think, will give him a different attitude toward the ideas of those concerned in the examination of applicants for this service, and will
Distribution of conduction system fibers in the developing and adult rabbit heart revealed by an antineurofilament antibody.
Authors: LGorza, MVitadello
Journal: Circulation Research (1989)

Using an immunological approach, we demonstrated previously that a neurofilament-like protein is expressed in rabbit heart conduction tissue myocytes, and we proposed that these specialized cardiac muscle cells are of neuroectodermal origin. In the present study, we used the expression of the neurofilament-like protein as a marker for identifying conduction tissue cells and studying their distribution in the developing heart. In 11-day-old rabbit embryos, myocytes expressing the neurofilament-like protein were localized at the atrioventricular and the sinoatrial junctions and had a ring-like distribution. At embryonic day 12, reactive myocytes were found also in the subendocardial layer of the dorsal ventricular wall, in continuity with labeled myocytes at the atrioventricular junction. Examination of older embryos and of neonatal and adult hearts revealed that the expression of the neurofilament-like protein was not restricted to myocytes of conduction tissue regions, but it was also detectable in myocyt...
The combined effect of smoking and coffee drinking on LDL and HDL cholesterol.
Authors: SHeyden, GHeiss, CManegold, H ATyroler, C GHames, A GBartel, GCooper
Journal: Circulation (1979)

Conflicting reports on the effect of smoking and coffee drinking on lipoproteins prompted us to study the combined effect of these two associated, widely prevalent habits in 361 persons randomly sampled from the Evans County cohort. Low-density lipoprotein (LDL) cholesterol levels were significantly higher among persons who smoked cigarettes and consumed five or more cups of coffee per day than among nonsmokers who abstained from coffee. Conversely, high-density lipoprotein (HDL) cholesterol was higher in persons who did not smoke or drink coffee than in coffee-consuming smokers. However, this trend was not statistically significant. Triglycerides and very low-density lipoprotein (VLDL) cholesterol were highest among smokers who drank five or more cups of coffee per day, but these differences did not reach statistical significance. Lipoprotein cholesterol levels were adjusted for age, sex and body mass. Smoking and coffee drinking interact in affecting LDL and total cholesterol, but coffee drinking alone ...
Nonlinear relation between Vmax and INa in canine cardiac Purkinje cells.
Authors: M FSheets, D AHanck, H AFozzard
Journal: Circulation Research (1988)

We studied the relation of the maximal upstroke velocity (Vmax) of action potentials to the peak sodium current (INa) under voltage clamp in single, internally perfused, canine cardiac Purkinje cells under conditions that ensured membrane action potentials due only to INa. Three different methods of altering sodium channel availability were investigated: voltage-dependent inactivation, tetrodotoxin (TTX) block, and use-dependent block by quinidine. Under all three conditions, the relation of Vmax to INa was nonlinear, and no relation was found that would allow prediction of INa results from Vmax measurements. With voltage-dependent inactivation or TTX block, sodium channel availability measured by Vmax was reduced less than availability measured by peak INa, so that Vmax overestimated sodium channel availability. This overestimation of sodium channel availability by Vmax could be attributed to greater sodium channel mobilization during the slowed action potential upstrokes. The overestimation varied with ...
Lysophosphatidylcholine in oxidized low-density lipoprotein increases endothelial susceptibility to polymorphonuclear leukocyte-induced endothelial dysfunction in porcine coronary arteries. Role of protein kinase C.
Authors: SSugiyama, KKugiyama, MOhgushi, KFujimoto, HYasue
Journal: Circulation Research (1994)

We have shown that transferred lysophosphatidylcholine (lysoPC) from oxidized low-density lipoprotein (Ox-LDL) to endothelial surface membrane activates protein kinase C (PKC) in endothelial cells, suggesting that Ox-LDL could alter endothelial functions through PKC activation. The purposes of the present study were to examine whether the endothelial susceptibility to polymorphonuclear leukocytes (PMNs) may be altered in Ox-LDL-treated coronary arteries, which have properties closely resembling those observed in atherosclerotic arteries, and to determine the mechanism(s) by which Ox-LDL may affect the endothelial susceptibility to PMNs. Isolated porcine coronary arteries were cannulated and perfused with oxygenated culture medium with or without LDLs or lipids at a constant flow (37 degrees C, pH 7.4). The treatment of porcine coronary arteries with Ox-LDL increased endothelial adhesiveness to PMNs and augmented PMN-induced impairment of endothelium-dependent arterial relaxation (EDR). Furthermore, Ox-LDL...
Effects of reperfusion on the regional contraction of ischemic and nonischemic myocardium following partial coronary obstruction.
Authors: K BRamanathan, SRaina, V SBanka, M MBodenheimer, R HHelfant
Journal: Circulation (1978)

In 14 dogs the effects on regional tension (Walton-Brodie gauges) and length (mercury-in-silastic) following 50% reduction (52.9 +/- 2.1) in coronary flow for two hours and reperfusion afterwards for one hour were addressed. Within five minutes of partial coronary occlusion, ejection tension in the ischemic zone decreased to 36.3 +/- 7.2% (P less than 0.001) and total tension to 64.4 +/- 5.7% of control (P less than 0.001) while phasic segment length increased to 165.2 +/- 16.3% control. No further significant changes in regional tension or length were observed throughout the two hour period of partial occlusion. Ejection tension remained positive and segment length maintained systolic shortening during the ejection phase throughout the period of occlusion. Following reperfusion, ejection tension in the ischemic zone increased from 35.1 +/- 5.9 to 87.0 +/- 22.0% (P less than 0.05) and total tension increased from 56.6 +/- 5.4 to 70.2 +/- 7.2% (P less than 0.02) while segment length decreased from 149.3 +/...
The role of mitochondria and sarcoplasmic reticulum calcium handling upon reoxygenation of hypoxic myocardium.
Authors: J APesaturo, J KGwathmey
Journal: Circulation Research (1990)

The mechanism of twitch prolongation of hypoxic myocardium after reoxygenation was studied before and after interventions that affect cellular cyclic nucleotide levels, subcellular calcium handling, or oxygen-derived free radical production/survival. Right ventricular ferret papillary muscles were subjected to two 20-minute periods of hypoxia, each followed by 1 hour of reoxygenation. The first sequence of hypoxia/reoxygenation was done without intervention. Before the second sequence, the pharmacological agent under study was added to the superfusate or the superfusate calcium concentration was increased from 2.5 to 8 mM. Time from peak to 80% decline in twitch tension was measured in the presence and absence of each intervention immediately before each period of hypoxia and after reoxygenation at maximal twitch prolongation. Interventions that affect Ca2+ flux across the sarcolemma (verapamil and 8 mM [Ca2+]o) or agents that affect oxygen free radical production/survival (dimethyl sulfoxide and allopuri...
Nitric oxide synthase in cardiac nerve fibers and neurons of rat and guinea pig heart.
Authors: LKlimaschewski, WKummer, BMayer, J YCouraud, UPreissler, BPhilippin, CHeym
Journal: Circulation Research (1992)

Participation of nitric oxide (NO) in the autonomic innervation of rat and guinea pig hearts was investigated by applying the NADPH diaphorase technique and immunohistochemistry with NO synthase antiserum. We present evidence that NO synthase is localized in cardiac ganglion cells and nerve fibers innervating the sinuatrial and atrioventricular nodes, the myocardium, local neurons, coronary arteries, and pulmonary vessels, suggesting an involvement of NO in neurogenic heart rate regulation, myocardial cell function, neuronal transmission in cardiac ganglia, and coronary as well as pulmonary vasodilation.
Cardiac Late Sodium Channel Current Is a Molecular Target for the Sodium/Glucose Cotransporter 2 Inhibitor Empagliflozin
Authors: Koenraad Philippaert, Subha Kalyaanamoorthy, Mohammad Fatehi, Wentong Long, Shubham Soni, Nikole J. Byrne, Amy Barr, Jyoti Singh, Jordan Wong, Taylor Palechuk, Chloe Schneider, Ahmed M. Darwesh, Zaid H. Maayah, John M. Seubert, Khaled Barakat, Jason R.B. Dyck, Peter E. Light
Journal: Circulation (2021)

SGLT2 (sodium/glucose cotransporter 2) inhibitors exert robust cardioprotective effects against heart failure in patients with diabetes, and there is intense interest to identify the underlying molecular mechanisms that afford this protection. Because the induction of the late component of the cardiac sodium channel current (late-
Drug and alcohol services for young people cut by £26m in six years
Authors: Zosia Kmietowicz
Journal: BMJ (2021)

Thousands of young people with drug and alcohol problems are missing out on specialist help because of £26m (€30m; $36m) (37%) worth of cuts to youth addiction services in England in real terms between 2013-14 and 2019-20, psychiatrists have warned.

An analysis by the Royal College of Psychiatrists found that eight of the nine regions in England made real terms cuts, with services in the north west (£9.3m), the west Midlands (£7.6m), and London (£4.6m) hit hardest.

The number of young people accessing treatment in England has …
Prediction of late survival in patients with mitral valve disease from clinical, hemodynamic, and quantitative angiographic variables.
Authors: K EHammermeister, LFisher, WKennedy, SSamuels, H TDodge
Journal: Circulation (1978)

Late follow-up (average = 7.2 years) has been obtained in 249 patients with mitral valve disease who had quantitative angiographic assessment of left ventricular function at thetime of initial catheterization in the 1960s. Surgically treated patients with mitral valve disease had significantly improved survival as compared to medically treated patients with mitral disease. The subgroup with mixed mitral stenosis and regurgitation and the subgroup with moderate impairment of ejection fraction account for this improved survival in surgically treated patients, which occurred despite greater functional and hemodynamic impairment in the surgical cohorts. Using univariate life table survival analysis, ten variables were found to be predictive of survival in the medical cohort, and three in the surgical cohort. With multivariate Cox's regression analysis, end-diastolic volume and arteriovenous oxygen difference were significantly predictive of survival in the medical cohort; age was predictive of survival in the...
Relaxation of rabbit ventricular muscle by Na-Ca exchange and sarcoplasmic reticulum calcium pump. Ryanodine and voltage sensitivity.
Authors: D MBers, J HBridge
Journal: Circulation Research (1989)

We studied relaxation during rapid rewarming of rabbit ventricular muscles that had been activated by rapid cooling. Rewarming from 1 degree to 30 degrees C (in less than 0.5 second) activates mechanisms that contribute to the reduction of intracellular calcium concentration and thus relaxation (e.g., sarcoplasmic reticulum [SR] calcium pump and sarcolemmal Na-Ca exchange and calcium pump). Rapid rewarming in normal Tyrode's solution induces relaxation with a half-time (t1/2) of 217 +/- 14 msec (mean +/- SEM). During cold exposure, changing the superfusate to a sodium-free, calcium-free medium with 2 mM CoCl2 (to eliminate Na-Ca exchange) slightly slows relaxation upon rewarming in the same medium (t1/2 = 279 +/- 44 msec). Addition of 10 mM caffeine (which prevents SR calcium sequestration) to normal Tyrode's solution during cold superfusion slows relaxation somewhat more (t1/2 = 376 +/- 31 msec) than sodium-free, calcium-free solution. However, if both interventions are combined (sodium-free + caffeine) ...
Reentry within the His-Purkinje system. Elucidation of reentrant circuit using right bundle branch and His bundle recordings.
Authors: MAkhtar, CGilbert, F GWolf, D HSchmidt
Journal: Circulation (1978)

Routes of impulse propagation during reentry in the His-Purkinje system (Re-HPS) in 13 patients were studied using the right ventricular extra stimulus (V2) method and right bundle branch (RBB) recordings in addition to the conventional His (H) bundle recordings. The H-V and RB-V intervals during sinus rhythm averaged 44.2 and 27.6 msec respectively, with the average antegrade H-RB interval 16.6 msec. All 13 patients demonstrated Re-HPS in the form of V3 showing a left bundle branch block (LBBB) pattern, and two of the 13 patients also manifested V3 with a right bundle branch block (RBBB) pattern. During Re-HPS showing a LBBB pattern, the retrograde activation of the His bundle (H2) in response to V2 occurred via the left bundle branch (LBB), as indicated by inscription of retrograde H2 prior to RB2 in nine of 13 cases (average H2-RB2 = 9.4 msec), and simultaneous incription of retrograde H2 and RB2 in the remaining four. When V3 showed a RBBB pattern the retrograde RB2 preceded H2, suggesting H2 activati...
Thrombolysis for Acute Stroke
Authors: Alfonso Ciccone
Journal: JAMA (1996)

To the Editor.  —We were interested in the results of the ECASS on rt-PA in acute stroke,1but we would like to express concern with particular regard to the conclusion. In the summary the authors state that intravenous thrombolysis in acute ischemic stroke is effective in improving some functional measures and neurologic outcome in a defined subgroup of stroke patients, implying that rt-PA could be recommended in selected populations of acute ischemic stroke patients. The selection to which the authors refer depends on recognition of early major computed tomographic (CT) signs of extensive infarction. However, the CT selection criteria failed to be applied by the same study researchers, although all centers received a booklet with detailed description and examples of CT-scan inclusion and exclusion criteria, so that 66 patients (11%) had to be excluded based on the CT-Scan Reading Panel review after randomization and treatment. Therefore, the proposed exclusion
Mutation of N-myristoylation site converts endothelial cell nitric oxide synthase from a membrane to a cytosolic protein.
Authors: W CSessa, C MBarber, K RLynch
Journal: Circulation Research (1993)

Endothelial cell nitric oxide synthase (ECNOS) is a membrane-associated enzyme that generates endothelium-derived relaxing factor/nitric oxide (EDRF/NO) from L-arginine. We have suggested, from the cloning of the bovine ECNOS cDNA, that the presence of an N-myristoylation consensus sequence may impart its membrane localization since cytosolic forms of NOS do not contain such domains. To test the hypothesis that N-myristoylation is necessary for particulate ECNOS, we performed site-directed mutagenesis of the myristic acid acceptor site, Gly-2, and changed the glycine codon to alanine by a single nucleotide substitution. Expression of wild-type ECNOS in COS cells resulted in greater than 95% of the enzymatic activity in crude membrane fractions (as measured by the conversion of [3H]L-arginine to [3H]L-citrulline). In contrast, expression of the Gly-2 to Ala-2 mutant (G2A) demonstrated 8% ECNOS activity in membranes and 92% in the cytosol. The back mutation (from Ala-2 to Gly-2, A2G) restored ECNOS activity...
HYD-PEP06 suppresses hepatocellular carcinoma metastasis, epithelial–mesenchymal transition and cancer stem cell-like properties by inhibiting PI3K/AKT and WNT/β-catenin signaling activation
Authors: Wei Tian, Jiatong Li, Zhuo Wang, Tong Zhang, Ying Han, Yanyan Liu, Wenfeng Chu, Yu Liu, Baofeng Yang
Journal: Acta Pharmaceutica Sinica B (2021)

HYD-PEP06, an endostatin-modified polypeptide, has been shown to produce effective anti-colorectal carcinoma effects through inhibiting epithelial–mesenchymal transition (EMT). However, whether HYD-PEP06 has similar suppressive effect on hepatocellular carcinoma (HCC) remained unknown. In this study, HYD-PEP06 inhibited metastasis and EMT but not proliferation in vitro. Cignal finder pathway reporter array and Western blot analysis revealed that HYD-PEP06 suppressed HCCLM3 cell metastasis and EMT by inhibiting the PI3K/AKT pathway. Moreover, HYD-PEP06 exerted anti-metastasis effects in HepG2 cancer stem-like cells (CSCs) via suppressing the WNT/β-catenin signaling pathway. Finally, in HCCLM3 tumor-bearing BALB/c nu/nu nude mice, HYD-PEP06 substantially suppressed tumor growth, lung metastasis and HCC progress. Our results suggest that HYD-PEP06 inhibits the metastasis and EMT of HCC and CSCs as well, and thus has the potential as an agent for HCC treatment.
Hemodynamic effects of the beta 1-adrenoceptor partial agonist xamoterol in relation to plasma norepinephrine levels during exercise in patients with left ventricular dysfunction.
Authors: HSato, MInoue, TMatsuyama, HOzaki, TShimazu, HTakeda, YIshida, TKamada
Journal: Circulation (1987)

A new cardioselective beta 1-adrenoceptor partial agonist, xamoterol, has been developed for the treatment of heart failure, especially that associated with ischemic heart disease. To investigate the hemodynamic effect of xamoterol in relation to sympathetic nervous activity, hemodynamic variables and plasma norepinephrine (NE) levels were measured at rest and during three graded bicycle exercise tests before and after a single intravenous dose of 0.15 mg/kg xamoterol in 10 patients with mild-to-moderate left ventricular dysfunction. Plasma NE increased with increasing grade of exercise and a linear correlation between plasma NE and heart rate was observed at four time points (at rest and three exercise levels) before and after xamoterol. After administration of xamoterol, the slope of the regression line of plasma NE-heart rate relation was significantly less steep than that before drug. Predose and postdose regression lines crossed at 440 pg/ml of plasma NE. Similar effects were observed on the plasma N...
The role of sulfinpyrazone in the prevention of arterio-venous shunt thrombosis.
Authors: AKaegi, G FPineo, AShimizu, HTrivedi, JHirsh, MGent
Journal: Circulation (1975)

The effect of sulfinpyrazone on the incidence of thrombosis of arterio-venous shunts was investigated in a double-blind crossover study in 45 patients on chronic hemodialysis over a period of 12 months. The incidence of thrombosis was reduced from 0.64 thrombi per patient month when on placebo to 0.21 thrombi per patient month when on sulfinpryazone (P less than 0.001). The therapeutic effect was more striking in men than in women and became evident within a week of starting the drug. The side effects were minimal, requiring withdrawal from the study of only one patient. This crossover study strengthens the findings in the previous report that sulfinpyrazone is of value in the prevention of thrombosis.
Addition of Plerixafor Overcomes Poor Mobilization in Autologous and Allogeneic Stem Cell Grafts and Leads to Efficient and Sustained Engraftment
Authors: Sebastian Haen, Irmtraud Schober-Melms, Michael Schumm, Joerg Henes, Robert Möhle, Wolfgang Bethge, Lothar Kanz, Wichard Vogel
Journal: Blood (2017)