bluuebunny/crossref_metadata_2025_split huggingface dataset:
From ionic to cellular variability in human atrial myocytes: an integrative computational and experimental study
Authors: Muszkiewicz Anna , Liu Xing , Bueno-Orovio Alfonso , Lawson Brodie A. J. , Burrage Kevin , Casadei Barbara , Rodriguez Blanca 
Published: December 2017

Variability refers to differences in physiological function between individuals, which may translate into different disease susceptibility and treatment efficacy. Experiments in human cardiomyocytes face wide variability and restricted tissue access; under these conditions, computational models are a useful complementary tool. We conducted a computational and experimental investigation in cardiomyocytes isolated from samples of the right atrial appendage of patients undergoing cardiac surgery to evaluate the impact of variability in action potentials (APs) and subcellular ionic densities on Ca2+ transient dynamics. Results showed that 1) variability in APs and ionic densities is large, even within an apparently homogenous patient cohort, and translates into ±100% variation in ionic conductances; 2) experimentally calibrated populations of models with wide variations in ionic densities yield APs overlapping with those obtained experimentally, even if AP characteristics of the original generic model differed significantly from experimental APs; 3) model calibration with AP recordings restricts the variability in ionic densities affecting upstroke and resting potential, but redundancy in repolarization currents admits substantial variability in ionic densities; and 4) model populations constrained with experimental APs and ionic densities exhibit three Ca2+ transient phenotypes, differing in intracellular Ca2+ handling and Na+/Ca2+ membrane extrusion. These findings advance our understanding of the impact of variability in human atrial electrophysiology. NEW & NOTEWORTHY Variability in human atrial electrophysiology is investigated by integrating for the first time cellular-level and ion channel recordings in computational electrophysiological models. Ion channel calibration restricts current densities but not cellular phenotypic variability. Reduced Na+/Ca2+ exchanger is identified as a primary mechanism underlying diastolic Ca2+ fluctuations in human atrial myocytes.
Norepinephrine-induced β1-adrenergic peripheral vasodilation in conscious dogs
Authors: Vatner Stephen F. , Knight Delvin R. , Hintze Thomas H. 
Published: December 2017

Page H49: Stephen F. Vatner, Delvin R. Knight, and Thomas H. Hintze. “Norepinephrine-induced β1-adrenergic peripheral vasodilation in conscious dogs.” Figure 1 and Figure 4 were reversed. The figures and their correct legends should appear as follows. (See PDF)
THE FLOW OF LYMPH FROM THE LUNGS OF THE DOG
Authors: Warren Madeleine F. , Drinker Cecil K. 
Published: December 2017

Volume 136: No. 1, p. 207, 1941. M. F. Warren and C. K. Drinker, The Flow of Lymph from the Lungs of the Dog. P. 208, change (Drinker et al., 1941) to (Drinker et al., 1940). P. 213, change Maurer (1941) to Maurer (1940). P. 221, insert the following references in the bibliography: Drinker, C. K., M. F. Warren, F. W. Maurer and J. D. McCarrell. This Journal 130: 43, 1940. Maurer, F. W. This Journal 131: 331, 1940.
A 90-kDa surface antigen of immature smooth muscle cells is ICAM-1
Authors: Printseva O. Yu. , Peclo M. M. , Tjurmin A. V. , Gown A. M. 
Published: December 2017

A monoclonal antibody, designated 10F3, that reacts with an antigen of molecular mass 90,000 Da has been developed by immunization of BALB/c mice with smooth muscle cells in long-term culture. The cells were originally isolated from fetal human aorta. The 10F3 was identified as an antibody that reacts with the ICAM-1 molecule. ICAM-1 is a mesenchymal antigen that is lost during differentiation of cells other than endothelium but is reexpressed by the intimal cells of vessels involved in atherogenesis. atherosclerosis; monoclonal antibodies
Impact for molecular biology in cardiology
Authors: Roberts Robert 
Published: December 2017

The recent development and application of the techniques of recombinant DNA and molecular biology ignited an explosion in biomedical research, which has been embraced by medicine. However, cardiology as a subspecialty has been slower in adopting these techniques, in part because the heart is a nonproliferating organ and in part because it was not easily accessible until recently. The techniques of recombinant DNA were not possible until the 1970s. In that decade four major discoveries occurred that launched molecular biology into the 21st century. These seminal contributions were 1) the discovery and application of specific restriction endonucleases, 2) the discovery of reverse transcriptase, 3) the development of the cloning technique, and 4) the ability to rapidly sequence nucleic acids. The techniques of recombinant DNA offer several unique advantages over existing scientific disciplines, such as the abilities: 1) to perform in vivo structure-function analysis, 2) to genetically engineer drugs, 3) to perform diagnostic in situ hybridization, 4) to isolate genes responsible for hereditary disorders, and 5) to understand the genetic regulation of cardiac growth. These techniques are discussed in their application to cardiac disorders, including the development of new recombinant molecules for the treatment of coronary thrombosis and the potential to modulate the cardiac growth response to various forms of injury such as myocardial infarction and hypertension. cardiac growth; genetic engineering; molecular genetics; structure function analysis
Febrile nonresponsiveness of vagotomized animals: is it due to endotoxin translocation from the gut and tolerance?
Authors: Romanovsky Andrej A. 
Published: December 2017

The following is the abstract of the article discussed in the subsequent letter:Scammell, Thomas E., John D. Griffin, Joel K. Elmquist, and Clifford B. Saper. Microinjection of a cyclooxygenase inhibitor into the anteroventral preoptic region attenuates LPS fever. Am. J. Physiol.274 ( Regulatory Integrative Comp. Physiol. 43): R933–R935, 1998.—Considerable evidence supports the role of prostaglandins in fever production, but the neuroanatomic sites of prostaglandin synthesis that produce fever remain unknown. With the use of a novel microinjection technique, we injected the cyclooxygenase inhibitor ketorolac into the preoptic area (POA) to determine which preoptic regions produce the prostaglandins required for fever. Initial experiments demonstrated that intravenous ketorolac blocked the fever normally produced by lipopolysaccharide (LPS) 5 μg/kg iv. Microinjection of ketorolac into the POA had no effect on body temperature, and injection of artificial cerebrospinal fluid into the POA did not alter LPS fever. Injection of ketorolac into the anteroventral POA markedly decreased the fever produced by LPS, compared with injections into more rostral, caudal, or dorsal locations. These observations indicate that prostaglandin synthesis in the anteroventral preoptic region is necessary for the production of fever.
Glial angiotensinogen regulates brain angiotensin II receptors in transgenic rats TGR(ASrAOGEN)
Authors: Monti Jan , Schinke Martina , Böhm Manfred , Ganten Detlev , Bader Michael , Bricca Giampiero 
Published: December 2017

TGR(ASrAOGEN)680, a newly developed transgenic rat line with specific downregulation of astroglial synthesis of angiotensinogen, exhibits decreased brain angiotensinogen content associated with a mild diabetes insipidus and lower blood pressure. Autoradiographic experiments were performed on TGR(ASrAOGEN) (TG) and Sprague-Dawley (SD) control rats to quantify AT1 and AT2 receptor-binding sites in different brain nuclei and circumventricular organs. Dose-response curves for drinking response to intracerebroventricular injections of ANG II were compared between SD and TG rats. In most of the regions inside the blood-brain barrier [paraventricular nucleus (PVN), piriform cortex, lateral olfactory tract (LOT), and lateral preoptic area (LPO)], AT1 receptor binding (sensitive to CV-11974) was significantly higher in TG compared with SD. In contrast, in the circumventricular organs investigated [subfornical organ (SFO) and area postrema], AT1 receptor binding was significantly lower in TG. AT2 receptors (binding sensitive to PD-123319) were detected at similar levels in the inferior olive (IO) of both strains. Angiotensin-binding sites sensitive to both CV-11974 and PD-123319 were detected in the LPO of SD rats and specifically upregulated in LOT, IO, and most notably PVN and SFO of TG. The dose-response curve for water intake after intracerebroventricular injections showed a higher sensitivity to ANG II of TG (EC50 = 3.1 ng) compared with SD (EC50 = 11.2 ng), strongly suggesting that the upregulation of AT1 receptors inside the blood-brain barrier of TG rats is functional. Finally, we showed that downregulation of angiotensinogen synthesized by astroglial cells differentially regulates angiotensin receptor subtypes inside the brain and in circumventricular organs.
Purinergic contribution to circulatory, metabolic, and adrenergic responses to acute hypoxemia in fetal sheep
Authors: Giussani Dino A. , Gardner David S. , Cox David T. , Fletcher Andrew J. W. 
Published: December 2017

This study investigated the effects on femoral vascular resistance, blood glucose and lactate levels, and plasma catecholamine concentrations of fetal treatment with an adenosine receptor antagonist during acute hypoxemia in fetal sheep during late gestation. Under anesthesia, seven fetal sheep were instrumented between 117 and 118 days gestation (term is ∼145 days) with vascular and amniotic catheters and an ultrasonic probe around a femoral artery. Six days after surgery, all fetuses were randomly subjected to a 3-h experiment consisting of 1 h of normoxia, 1 h of hypoxemia, and 1 h of recovery. This was done during either intravenous infusion of vehicle or the adenosine receptor antagonist [8-( p-sulfophenyl)-theophylline; 8-SPT] dissolved in vehicle. During vehicle infusion, all fetuses responded to hypoxemia with bradycardia, an increase in arterial blood pressure, and femoral vasoconstriction. Increases in blood glucose and lactate concentrations and in plasma epinephrine and norepinephrine concentrations also occurred in all fetuses during hypoxemia. Fetal treatment with 8-SPT markedly attenuated the bradycardic, hypertensive, vasoconstrictor, glycemic, and adrenergic responses to hypoxemia, but it did not affect the increase in blood lactate concentrations during hypoxemia. These data show that adenosine is involved in the mechanisms mediating fetal cardiovascular, metabolic, and adrenergic responses to hypoxemia in fetal sheep. Fetal treatment with 8-SPT mimics the effects of carotid sinus nerve section on fetal cardiovascular function during hypoxemia, suggesting a role for adenosine in mediating fetal cardiovascular chemoreflexes.
Acupuncture effects on reflex responses to mental stress in humans
Authors: Middlekauff Holly R. , Yu Jun Liang , Hui Kakit 
Published: December 2017

In animal studies, acupuncture has been shown to be sympathoinhibitory, but it is unknown if acupuncture is sympathoinhibitory in humans. Nineteen healthy volunteers underwent mental stress testing pre- and postacupuncture. Muscle sympathetic nerve activity (MSNA), blood pressure, and heart rate during mental stress were compared pre- and postacupuncture. Control acupuncture consisted of acupuncture at nonacupoints and “no-needle” acupuncture. Acupuncture had no effect on resting MSNA, blood pressure, or heart rate. After real acupuncture, the increase in mean arterial pressure (pre- vs. postacupuncture 4.5 vs. 1.7 mmHg, P < 0.001), but not MSNA or heart rate, was blunted during mental stress. Similarly, following nonacupoint acupuncture, the increase in mean arterial pressure was blunted during mental stress (5.4 vs. 2.9 mmHg, P < 0.0003). No-needle acupuncture had no effect on these variables. In conclusion, acupuncture at traditional acupoints, nonacupoints, and no-needle acupuncture does not modulate baseline MSNA or MSNA responses to mental stress in normal humans. Acupuncture significantly attenuates the increase in blood pressure during mental stress. Needling nonacupoints, but not “no-needle” acupuncture, have a similar effect on blood pressure.
Postischemic thyroxin stimulates renal mitochondrial adenine nucleotide translocator activity
Authors: Boydstun Ivy , Najjar Samer , Kashgarian Michael , Carpenter Thomas , Siegel Norman 
Published: December 2017

Postischemic thyroxin (T4) enhances restitution of cellular ATP and accelerates recovery of renal function. This effect is not related to global improvement in cell integrity. To determine the mechanism by which recovery of cellular ATP is enhanced, the effect of T4 on mitochondrial ATP production was evaluated using specific inhibitor stop assays for mitochondrial phosphate transport and ADP translocator activity. Rats were subjected to 45-min renal ischemia and given normal saline (NS, 0.5 ml) or T4 (20 μg/kg) during the reflow period. By 30-min reflow, the values for apparent endpoint of phosphate transport (PiTm, nmol Pi/mg mitochondrial protein) had recovered to rates seen in nonischemic animals (10.3 ± 0.9) and remained stable at 120 min. T4 treatment did not affect PiTm. In contrast, the apparent endpoint of ADP transport (ADPTm, nmol ADP/mg mitochondrial protein) was dramatically decreased in NS rats at 30-min (6.7 ± 0.5) and 120-min (13.7 ± 1.0) reflow compared with nonischemic control rats (24.7 ± 2.4). T4 significantly improved ADPTm by 30 min (10.1 ± 0.6, P < 0.05). By 120 min T4 stimulated ADPTm (37.7 ± 5.2, P < 0.05) to exceed nonischemic control values. These data suggest the following: 1) postischemic mitochondrial PiTm recovers to control values by 30 min of reflow; 2) T4 does not augment PiTm; 3) renal ischemia causes a dramatic decrease in mitochondrial ADPTm; 4) postischemic T4 significantly enhances mitochondrial nucleotide transport at 30-min reflow; 5) by 120-min reflow, T4 rats have ADPTm which exceeds control values. These findings provide an understanding of at least one of the metabolic components that contribute to the enhanced recovery of cellular ATP resulting from postischemic T4 administration. acute renal failure; mitochondrial transport; cellular adenosine triphosphate recovery Submitted on January 24, 1994 Accepted on November 1, 1994
Ca-induced Ca release: lessons regarding cell models
Authors: Harder David R. 
Published: December 2017

This essay looks at the historical significance of an APS classic paper that is freely available online: Fabiato A. Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol Cell Physiol 245: C1—C14, 1983 ( http://ajpcell.physiology.org/cgi/reprint/245/1/C1 ).
Critical size of newborn homeotherms
Authors: Balmer R. T. , Strobusch A. D. 
Published: December 2017

Page 571: R. T. Balmer and A. D. Strobusch. “Critical size of newborn homeotherms.” Page 574: Eq. 31 has the wrong final exponent. It should read (See PDF) This error results in Eqs. 37, 39, 40, 41, and 42 also being wrong. Equation 37 now has the form (See PDF) where (See PDF and (See PDF) Equations 39, 40, and 41 are the algebraic manipulations required in using the new Eq. 37 (given above) in Eq. 38 of the paper. Equation 42 is the final result, which in its correct form is now (See PDF) where, for T0 – T∞ = 5°C, rocc = 0.80 cm. Thus, even though the error in Eq. 31 was rather significant, it had remarkably little effect on the final result, Eq. 42. Page 577: the line labeled cylinder in Fig. 5 should be raised slightly (it should pass through the point critical radius = 0.8 cm, T0 – T∞ = 5°C) bringing it closer to the line labeled sphere. (See PDF)
Brain hypoxia and control of breathing: neuromechanical control
Authors: Chapman R. W. , Santiago T. V. , Edelman N. H. 
Published: December 2017

The effects of graded brain hypoxia on respiratory cycle timing, the lung inflation reflex, and respiratory compensation for an inspiratory flow-resistive load were studied in unanesthetized goats. Two models, inhalation and CO and acute reduction of brain blood flow (BBF) were used to produce comparable levels of brain hypoxia. The lung inflation reflex was assessed as the ratio of inspiratory time of an occluded breath to that of the preceding spontaneous breath (TIoccl/TIspont). Compensation for flow-resistive loading was assessed as the effect of the load upon the airway occlusion pressure response to rebreathing CO2 (delta P 0.1/delta PCO2). Major findings were 1) severe brain hypoxia (HbCO of 60% or BBF of 42%) caused tachypnea due to a 50% or more reduction of expiratory time but only a 20% or less reduction of inspiratory time; 2) moderate carboxyhemoglobinemia (HbCO of 25-30%) enhanced TIoccl/TIspont from 1.5 +/- 0.1 at control to 2.1 +/- 0.1, while severe brain hypoxia (HbCO of 60% and BBF of 42%) reduced the ratio to 1.0 +/- 0.2; and 3) compensation for a flow-resistive load, manifested by increases of delta P 0.1/delta PCO2 of 75-300% in the control state, was abolished at HbCO of 45-50% and BBF of 60%. The data suggest that in unanesthetized animals brain hypoxia elicits tachypnea largely by an effect on the expiratory phase of the bulbopontine timing mechanism. The observed enhancement of the lung inflation reflex and abolition of flow-resistive load compensation are best explained by hypoxic depression of higher than brain stem neural function.
Modeling three-dimensional velocity-to-position transformation in oculomotor control
Authors: Schnabolk C. , Raphan T. 
Published: December 2017

Pages 623–638: C. Schnabolk and T. Raphan, “Modeling three-dimensional velocity-to-position transformation in oculomotor control.” Page 629, matrix Gp of Equation 44 should read: See PDF for Equation
NT-3 Increases Amplitude of EPSPs Produced by Axotomized Group Ia Afferents
Authors: Munson John B. , Johnson Richard D. , Mendell Lorne M. 
Published: December 2017

We thank K. Foli for technical support and Regeneron Pharmaceuticals for providing NT-3. This research was supported by National Institute of Neurological Disorders and Stroke Grants NS-15913 (Javits Neuroscience Award) to J. B. Munson and NS-16996 (Javits Neuroscience Award) to L. M. Mendell. Additional support was furnished by NS-14899 and NS-32264 to L. M. Mendall. Present addresses: R. D. Johnson, Dept. of Physiological Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL 32610; L. M. Mendell, Dept. of Neurobiology and Behaviour, SUNY at Stony Brook, Stony Brook, NY 11794.
Functional Development of Intrinsic Properties in Ganglion Cells of the Mammalian Retina
Authors: Wang Guo-Yong , Ratto G.-M. , Bisti Silvia , Chalupa Leo M. 
Published: December 2017

Wang, Guo-Yong, G.-M. Ratto, Silvia Bisti, and Leo M. Chalupa. Functional development of intrinsic properties in ganglion cells of the mammalian retina. J. Neurophysiol. 78: 2895–2903, 1997. Sensory neurons manifest pronounced changes in excitability during maturation, but the factors contributing to this ubiquitous developmental phenomenon are not well understood. To assess the contribution of intrinsic membrane properties to such changes in excitability, in the present study whole cell patch-clamp recordings were made from developing ganglion cells in the intact retina of postnatal rats. During a relatively brief developmental period (postnatal days P7-P27) ganglion cells exhibited pronounced changes in the discharge patterns generated by depolarizing current injections. The youngest cells (P7-P17) typically responded to maintained depolarizations with only a single spike or a rapidly adapting discharge pattern. In contrast, the predominant response mode of more mature cells (P21-P27) was a series of repetitive discharges that lasted for the duration of the depolarization period, and by P25 all cells responded in this manner. These functional changes characterized all three morphologically defined cell classes identified by intracellular labeling with Lucifer yellow. To determine if expression of the potassium current ( I a) and the kinetics of the Na-channel related to the increased excitability of developing ganglion cells described above, current- and voltage-clamp recordings were made from individual neurons. The different firing patterns manifested by developing retinal ganglion cells did not reflect the presence or absence of the I a conductance, although cells expressing I a tended to generate spikes of shorter duration. With maturation the speed of recovery from inactivation of the Na current increased markedly and this related to the increased excitability of developing ganglion cells. Neurons yielding only a single spike to maintained depolarization were characterized by the slowest speed of recovery; cells with rapidly adapting discharges showed a faster recovery and those capable of repetitive firing recovered fastest from Na-channel inactivation. It is suggested that these changes in intrinsic membrane properties may relate to the different functional roles subserved by ganglion cells during development.
Drug and alcohol problems among Norwegian inmates
Authors: Ødegård E. 
Published: December 2017

Aim & Data Drug and alcohol problems among Norwegian inmates were explored in this study. Estimates of the portion of drug users among inmates were assessed on the most solid basis to date. The analysis was based on a survey of all Norwegian prisons. During the same week in December 2002 all Norwegian inmates received a questionnaire to survey demographic features, use of alcohol and illicit drugs. Results The findings suggest that nearly half of the prison population has regularly used hard drugs before the imprisonment, and a fourth were regular intravenous drug users. Polydrug use is highly prevalent. Almost one-third of the inmates used illicit drugs during the present stay in prison. The proportion of highly frequent drinkers appears to be three to four times that found in the general population.
Artikel
Authors: Pape Hilde 
Published: December 2017

H. Pape: School-based interventions that seem to work: Useful research on substance use prevention or suspicious stories of success? School-based prevention programmes targeted at adolescent substance use rarely seem to have the desired effects on behaviour. It is true that some outcome studies do conclude that such programmes have been successful, but they are relatively few and far between. Even so, one may ask whether the body of published research in this field may originate from unrealistic optimism due to publication bias and underreporting of no or counterproductive effects. Thus, anecdotal evidence suggests that the literature is biased in favour of studies with positive findings. Moreover, nearly all these studies have been carried out by programme developers, and it is well known that researchers with vested interests are more likely to bring “good news” than independent researchers. Indeed, rather than approaching the field with critical refelction, some evaluators have intended to prove that school-based prevention works and have conducted their research accordingly. Examples of questionable analytical approaches and selective reporting of positive findings are consequently not hard to find. The external validity of evaluation studies with favourable outcomes is also often questionable because they almost exclusively have assessed the effects of programmes delivered under optimal rather than real-life conditions. In conclusion, the empirical “evidence” in favour of school-based substance use prevention programmes is generally weak and does not allow recommendation of widespread dissemination of any specific programme.