bluuebunny/crossref_metadata_2025 huggingface dataset:
Conduction Slowing and Sudden Arrhythmic Death in Mice With Cardiac-Restricted Inactivation of Connexin43
Authors: Gutstein David E. , Morley Gregory E. , Tamaddon Houman , Vaidya Dhananjay , Schneider Michael D. , Chen Ju , Chien Kenneth R. , Stuhlmann Heidi , Fishman Glenn I.
Published: June 2012

Abstract
—Cardiac arrhythmia is a common and often lethal manifestation of many forms of heart disease. Gap junction remodeling has been postulated to contribute to the increased propensity for arrhythmogenesis in diseased myocardium, although a causative role in vivo remains speculative. By generating mice with cardiac-restricted knockout of connexin43 (Cx43), we have circumvented the perinatal lethal developmental defect associated with germline inactivation of this gap junction channel gene and uncovered an essential role for Cx43 in the maintenance of electrical stability. Mice with cardiac-specific loss of Cx43 have normal heart structure and contractile function, and yet they uniformly (28 of 28 conditional Cx43 knockout mice observed) develop sudden cardiac death from spontaneous ventricular arrhythmias by 2 months of age. Optical mapping of the epicardial electrical activation pattern in Cx43 conditional knockout mice revealed that ventricular conduction velocity was significantly slowed by up to 55% in the transverse direction and 42% in the longitudinal direction, resulting in an increase in anisotropic ratio compared with control littermates (2.1±0.13 versus 1.66±0.06;
P
<0.01). This novel genetic murine model of primary sudden cardiac death defines gap junctional abnormalities as a key molecular feature of the arrhythmogenic substrate.
Absence of CD40 Signaling Is Associated With an Increase in Intimal Thickening After Arterial Injury
Authors: Remskar Mojca , Li Hongyan , Chyu Kuang-Yuh , Shah Prediman K. , Cercek Bojan
Published: June 2012

Abstract
—Immune-mediator CD40 ligand is expressed on a variety of cell types involved in the immune response and on the cells of the vascular system. Inhibition of CD40 signaling has been associated with reduction of experimental atherosclerosis and transplant-associated vasculopathy. Immune response also plays a cardinal role in intimal thickening after acute arterial-wall injury. After carotid artery injury in CD40 ligand knockout (CD40L
−/−
) mice, the intimal thickening was increased 3-fold compared with the thickening in background B6/129 mice. The extent of thickening was similar to the thickening in B6/129 mice depleted of T lymphocytes with anti-CD4 and anti-CD8 antibodies. Injection of splenocytes from B6/129 mice into the CD40L
−/−
mice reduced the intimal thickening to the level comparable to the thickening in background B6/129 mice. These data suggest that CD40 signaling plays a significant role in the inhibitory effect of T lymphocytes on intimal thickening after arterial injury.
Identification of the T-Type Calcium Channel (Ca
V
3.1d) in Developing Mouse Heart
Authors: Cribbs Leanne L. , Martin Beverly L. , Schroder Elizabeth A. , Keller Bradley B. , Delisle Brian P. , Satin Jonathan
Published: June 2012

Abstract
—During cardiac development, there is a reciprocal relationship between cardiac morphogenesis and force production (contractility). In the early embryonic myocardium, the sarcoplasmic reticulum is poorly developed, and plasma membrane calcium (Ca
2+
) channels are critical for maintaining both contractility and excitability. In the present study, we identified the Ca
V
3.1d mRNA expressed in embryonic day 14 (E14) mouse heart. Ca
V
3.1d is a splice variant of the α1G, T-type Ca
2+
channel. Immunohistochemical localization showed expression of α1G Ca
2+
channels in E14 myocardium, and staining of isolated ventricular myocytes revealed membrane localization of the α1G channels. Dihydropyridine-resistant inward Ba
2+
or Ca
2+
currents were present in all fetal ventricular myocytes tested. Regardless of charge carrier, inward current inactivated with sustained depolarization and mirrored steady-state inactivation voltage dependence of the α1G channel expressed in human embryonic kidney-293 cells. Ni
2+
blockade discriminates among T-type Ca
2+
channel isoforms and is a relatively selective blocker of T-type channels over other cardiac plasma membrane Ca
2+
handling proteins. We demonstrate that 100 μmol/L Ni
2+
partially blocked α1G currents under physiological external Ca
2+
. We conclude that α1G T-type Ca
2+
channels are functional in midgestational fetal myocardium.
Activation of Human Neutrophil by Cytokine-Activated Endothelial Cells
Authors: Takahashi Tatsuji , Hato Fumihiko , Yamane Takahisa , Fukumasu Hiroshi , Suzuki Kenichi , Ogita Sachio , Nishizawa Yoshiki , Kitagawa Seiichi
Published: June 2012

Abstract
—Cytokine activation of vascular endothelial cells renders the hyperadhesiveness for neutrophils. During the processes of inflammation and atherosclerosis, the production of reactive oxygen species by neutrophils contributes to endothelial cell (EC) damage and injury. However, the precise mechanisms for neutrophil activation by ECs remain unknown. Thus, we investigated what kinds of pathophysiological factors synthesized by inflammatory cytokine-activated ECs potentiated the activity of neutrophil functions. The magnitude of O
2
−
release from neutrophils, which is one of pivotal neutrophil functions, was measured as an indicator potentiated by activated ECs. Neutrophils release massive amounts of O
2
−
on coculture with activated ECs. Anti–granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody (Ab) or specific platelet-activating factor (PAF)-receptor antagonist suppressed the O
2
−
release from neutrophils on coculture with the activated ECs by 50% to 70%. The supernatants from activated ECs also induced O
2
−
release by neutrophils. This stimulatory effect of activated EC supernatants on O
2
−
release by neutrophils was abolished by anti–GM-CSF Ab or by PAF-receptor antagonist. As we previously reported, we demonstrated the expression of GM-CSF mRNA by Northern blotting and protein synthesis of GM-CSF by ELISA on tumor necrosis factor as well as interleukin-1–activated ECs. Although phosphorylation of mitogen-activated protein kinases was observed in ECs stimulated by tumor necrosis factor and interleukin-1, treatment of ECs with PD98059 (MEK1 inhibitor) and SB203580 (p38 mitogen–activated protein kinase inhibitor) in the presence of the cytokine failed to attenuate the stimulatory effect of activated ECs on neutrophil activation. We found that activated ECs regulated neutrophil function on coculture. We show here for the first time, to our knowledge, that the collaboration between GM-CSF and PAF synthesized by activated ECs markedly potentiated neutrophil activation.
Antigraft Antibody-Mediated Expression of Metalloproteinases on Endothelial Cells
Authors: Boulday Gwénola , Coupel Stéphanie , Coulon Flora , Soulillou Jean-Paul , Charreau Béatrice
Published: June 2012

Abstract
—Endothelial cell (EC) interaction with antigraft antibodies (Abs) mediates EC injury and activation involved in vascular graft rejection. The aim of this study was to identify EC genes regulated in response to antigraft Ab binding that contribute to the endothelium alterations implicated in graft rejection or survival. By means of RNA differential display, 13 cDNA fragments corresponding to genes differentially expressed in ECs incubated with antigraft Abs were identified. Among these cDNAs were found the tissue inhibitor of metalloproteinase-1 (TIMP-1) and a desintegrin and metalloproteinase (ADAM-10). We demonstrated that TIMP-1 and ADAM-10 mRNA and protein expression was rapidly upregulated in ECs in response to antigraft Ab binding. Our data showed that TIMP-1 was upregulated in response to human IgG but not IgM and anti-galactosyl (Gal) α1-3Gal human xenogeneic Abs. In contrast, upregulation of ADAM-10 in ECs was shown to be mostly mediated by anti–Galα1-3Gal IgM Abs. Specific effects of human IgG and IgM xenogeneic Abs on endothelial transcripts indicate that different isotypes and specificities of Abs may mediate different EC changes. Our results suggest that interaction of ECs with antigraft Abs, according to their specificity, selectively induces synthesis and release of metalloproteinases and inhibitors, controlling proteolytic processes and immunological events that respectively contribute to graft rejection or survival.
Independent Regulation of Cardiac Kv4.3 Potassium Channel Expression by Angiotensin II and Phenylephrine
Authors: Zhang Ting-Ting , Takimoto Koichi , Stewart Alexandre F. R. , Zhu Chongxue , Levitan Edwin S.
Published: June 2012

Abstract
—Hypertrophied cardiac myocytes exhibit prolonged action potentials and decreased transient outward potassium current (
I
to
). Because Kv4.3 is a major contributor to
I
to
, we studied regulation of its expression in neonatal rat cardiac myocytes in response to the known stimulators of cardiac myocyte hypertrophy, angiotensin II (Ang II) and phenylephrine (PE). RNase protection assays and immunoblots revealed that Ang II and PE each downregulate Kv4.3 mRNA and protein. However, although PE induces a faster and more extensive hypertrophic response than Ang II, the PE effect on Kv4.3 mRNA develops slowly and is sustained, whereas Ang II rapidly and transiently decreases Kv4.3 mRNA expression. Turnover measurements revealed that Kv4.3 mRNA is very stable, with a half-life >20 hours. This suggests that Ang II must destabilize the channel mRNA. In contrast, PE does not affect the rate of Kv4.3 mRNA degradation. To test for transcriptional regulation, the 5′ flanking region of the rat Kv4.3 gene was cloned, and Kv4.3 promoter-reporter constructs were expressed in cardiac myocytes. Whereas Ang II was found to have no effect on transcription, PE inhibits Kv4.3 promoter activity. Pharmacological experiments also indicate that PE and Ang II act independently to downregulate Kv4.3 gene expression. Thus, regulation of Kv4.3 gene expression is not a simple secondary response to hypertrophy. Rather, Ang II and PE use different mechanisms to decrease Kv4.3 channel expression in neonatal rat cardiac myocytes.
Lipopolysaccharide Internalization Activates Endotoxin-Dependent Signal Transduction in Cardiomyocytes
Authors: Cowan Douglas B. , Noria Sabrena , Stamm Christof , Garcia Lina M. , Poutias Dimitrios N. , del Nido Pedro J. , McGowan Francis X.
Published: June 2012

Abstract
—We tested the hypothesis that bacterial lipopolysaccharide (LPS) must be internalized to facilitate endotoxin-dependent signal activation in cardiac myocytes. Fluorescently labeled LPS was used to treat primary cardiomyocyte cultures, perfused heart preparations, and the RAW264.7 macrophage cell line. Using confocal microscopy and spectrofluorometry, we found that LPS was rapidly internalized in cardiomyocyte cultures and Langendorff-perfused hearts. Although LPS uptake was also observed in macrophages, only a fraction of these cells were found to internalize endotoxin to the extent seen in cardiomyocytes. Colocalization experiments with organelle or structure-specific fluorophores showed that LPS was concentrated in the Golgi apparatus, lysosomes, and sarcomeres. Similar intracellular localization was demonstrated in cardiomyocytes by transmission electron microscopy using gold-labeled LPS. The internalization of LPS was dependent on endosomal trafficking, because an inhibitor of microfilament reorganization prevented uptake in both cardiomyocytes and whole hearts. Inhibition of endocytosis specifically restricted early activation of extracellular signal–regulated kinase proteins and nuclear factor-κB as well as later tumor necrosis factor-α production and inducible nitric oxide synthase expression. In conclusion, we have demonstrated that bacterial endotoxin is internalized and transported to specific intracellular sites in heart cells and that these events are obligatory for activation of LPS-dependent signal transduction.
No-Flow Ischemia Inhibits Insulin Signaling in Heart by Decreasing Intracellular pH
Authors: Beauloye Christophe , Bertrand Luc , Krause Ulrike , Marsin Anne-Sophie , Dresselaers Tom , Vanstapel Florent , Vanoverschelde Jean-Louis , Hue Louis
Published: June 2012

Abstract
—Glucose-insulin-potassium solutions exert beneficial effects on the ischemic heart by reducing infarct size and mortality and improving postischemic left ventricular function. Insulin could be the critical protective component of this mixture, although the insulin response of the ischemic and postischemic myocardium has not been systematically investigated. The aim of this work was to study the insulin response during ischemia by analyzing insulin signaling. This was evaluated by measuring changes in activity and/or phosphorylation state of insulin signaling elements in isolated perfused rat hearts submitted to no-flow ischemia. Intracellular pH (pH
i
) was measured by NMR. No-flow ischemia antagonized insulin signaling including insulin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase, protein kinase B, p70 ribosomal S6 kinase, and glycogen synthase kinase-3. These changes were concomitant with intracellular acidosis. Perfusing hearts with ouabain and amiloride in normoxic conditions decreased pH
i
and insulin signaling, whereas perfusing at pH 8.2 counteracted the drop in pH
i
and the inhibition of insulin signaling by ischemia. Incubation of cardiomyocytes in normoxic conditions, but at pH values below 6.75, mimicked the effect of ischemia and also inhibited insulin-stimulated glucose uptake. Finally, the in vitro insulin receptor tyrosine kinase activity was progressively inhibited at pH values below physiological pH
i
, being abolished at pH 6.0. Therefore, ischemic acidosis decreases kinase activity and tyrosine phosphorylation of the insulin receptor thereby preventing activation of the downstream components of the signaling pathway. We conclude that severe ischemia inhibits insulin signaling by decreasing pH
i
.
Mitochondrial DNA Damage and Dysfunction Associated With Oxidative Stress in Failing Hearts After Myocardial Infarction
Authors: Ide Tomomi , Tsutsui Hiroyuki , Hayashidani Shunji , Kang Dongchon , Suematsu Nobuhiro , Nakamura Kei-ichiro , Utsumi Hideo , Hamasaki Naotaka , Takeshita Akira
Published: June 2012

Abstract
—Mitochondria are one of the enzymatic sources of reactive oxygen species (ROS) and could also be a major target for ROS-mediated damage. We hypothesized that ROS may induce mitochondrial DNA (mtDNA) damage, which leads to defects of mtDNA-encoded gene expression and respiratory chain complex enzymes and thus may contribute to the progression of left ventricular (LV) remodeling and failure after myocardial infarction (MI). In a murine model of MI and remodeling created by the left anterior descending coronary artery ligation for 4 weeks, the LV was dilated and contractility was diminished. Hydroxyl radicals, which originated from the superoxide anion, and lipid peroxide formation in the mitochondria were both increased in the noninfarcted LV from MI mice. The mtDNA copy number relative to the nuclear gene (18S rRNA) preferentially decreased by 44% in MI by a Southern blot analysis, associated with a parallel decrease (30% to 50% of sham) in the mtDNA-encoded gene transcripts, including the subunits of complex I (ND1, 2, 3, 4, 4L, and 5), complex III (cytochrome
b
), complex IV (cytochrome
c
oxidase), and rRNA (12S and 16S). Consistent with these molecular changes, the enzymatic activity of complexes I, III, and IV decreased in MI, whereas, in contrast, complex II and citrate synthase, encoded only by nuclear DNA, both remained at normal levels. An intimate link among ROS, mtDNA damage, and defects in the electron transport function, which may lead to an additional generation of ROS, might play an important role in the development and progression of LV remodeling and failure.
Inducible Gene Targeting in Postnatal Myocardium by Cardiac-Specific Expression of a Hormone-Activated Cre Fusion Protein
Authors: Minamino Tetsuo , Gaussin Vinciane , DeMayo Francesco J. , Schneider Michael D.
Published: June 2012

Abstract
—Cardiac-restricted expression of Cre recombinase can provoke lineage-specific gene excision in the myocardium. However, confounding early lethality may still preclude using loss-of-function models to study the postnatal heart. Here, we have tested whether inducible, heart-specific recombination can be triggered after birth by transgenic expression of a Cre fusion protein that incorporates a mutated progesterone receptor ligand binding domain (PR1) that is activated by the synthetic antiprogestin, RU486, but not by endogenous steroid hormones. CrePR1 driven by the α-myosin heavy chain (αMHC) promoter was expressed specifically in heart. Translocation of CrePR1 from cytoplasm to nuclei in ventricular myocytes was induced by RU486. To establish whether this approach can mediate cardiac-specific, drug-dependent excision between loxP sites in vivo, we mated αMHC-CrePR1 mice with a ubiquitously expressed (ROSA26) Cre reporter line. Offspring harboring αMHC-CrePR1 and/or the floxed allele were injected with RU486 versus vehicle, and the prevalence of β-galactosidase (β-gal)–positive cells was determined, indicative of Cre-mediated excision. Little or no baseline recombination was seen 1 week after birth. Cardiac-restricted, RU486-inducible recombination was demonstrated in bigenic mice at age 3 and 6 weeks, using each of 3 independent CrePR1 lines. Recombination in the absence of ligand paralleled the levels of CrePR1 protein expression and was more evident at 6 weeks. Thus, conditional, posttranslational activation of a Cre fusion protein can bypass potential embryonic and perinatal effects on the heart and permits inducible recombination in cardiac muscle. High levels of the chimeric Cre protein, in particular, were associated with progressive recombination in the absence of drug.
Physiologic and Pathologic Influences on the Metabolism of Rat Aorta
Authors: WERTHEIMER H. ERNST , BEN-TOR VICTORIA
Published: June 2012

Oxygen uptake of aortas of young rats is higher than that of old rats in KRP solution. In serum of young rats, oxygen uptake and especially glucose uptake is higher than in serum of old rats in either young or old aortas. Anaerobic formation of lactic acid by the rat aorta is greater in serum of old rats than in serum of young rats. A fat-rich diet with 55 per cent butter fat, given for 6 weeks, significantly decreases oxygen and glucose uptake. This effect is not seen if soya oil is used instead of butter fat. A cholesterol-rich, atherosclerosis-producing diet decreases the glucose uptake. Norepinephrine, in vitro and in vivo, increases the oxygen and glucose uptake and the glycogen synthesis; epinephrine has no influence; acetylcholine decreases the oxygen and glucose uptake. The oxygen and glucose uptakes of aortic tissue from alloxandiabetic rats are lower than those from normal rats. Insulin in vitro increases oxygen and glucose uptake of the aorta in a Gey and Gey medium, this effect being greater in aorta of old rats.
Vasomotor Responses in the Human Arm During Leg Exercise
Authors: BLAIR DAVID A. , GLOVER WALTER E. , RODDIE JAN C.
Published: June 2012

Blood flow was measured in the hands and forearms of recumbent subjects by venous occlusion plethysmography during leg exer cise on a bicycle ergometer. In three highly practiced subjects, exercise resulted in a small fall in forearm flow and a moderate rise in arterial pressure. Resistance to blood flow was therefore considerably increased. Blocking the vasomotor fibers to forearm skin did not affect this, but blocking the deep nerves to the muscle vessels prevented the increase in vascular resistance during exer cise. Treating the forearm with bretyliurn tosylate had the same effect as deep nerve block. It was concluded that vasoconstrictor tone in muscle is increased during exercise.

Since treating the forearm with atropine did not affect the normal response, it was concluded that activation of vasodilator fibers to muscle is not an integral part of the gen eral vasomotor response to exercise. Evidence was also found that the vasodilator outflow to a specific muscle group is not specifically activated when the muscle group in question is exercised.

During fairly heavy exercise, vasodilatation occurred in both hand and forearm skin. In the hand this was preceded by vasoconstric tion. Evidence was found that the vasodila tation in the hand was due to release of vaso constrictor tone, whereas that in the forearm was mediated through vasodilator fibers. It is likely that the increase in heat production during exercise was responsible for the reflex vasodilatation in skin.
Study of Ventricular Response in Atrial Fibrillation
Authors: HORAN LEO G. , KISTLER JACK C.
Published: June 2012

A study was made of the variation in R-R interval in 47 long electrocardiographic recordings from 17 patients with atrial fibrillation. The distribution curve of ventricular intervals was found to vary in configuration according to the mean ventricular rate. A single high peak was seen at fast rates, two peaks at intermediate rates, and a single low peak flattening to a long low curve at slow rates.
Electrocardiogram of the Diving Seal
Authors: MURDAUGH HERSCHEL V. , SEABURY JAMES C. , MITCHELL WILLIAM L.
Published: June 2012

During the normal dive, the seal has a reflex bradycardia that is not accompanied by inversion of P waves or T waves or by atrial or ventricular arrhythmias, although the seal does have an occasional block of conduction across the A-V node during normal diving. The reflex bradycardia during the dive appears to be mediated through vagal stimulus.

The electrocardiograms of the seal during voluntary diving and during forced submersion with struggle are different.
Intimal Thickening After Ligature of Arteries An Electron-Microscopic Study
Authors: BUCK ROBERT C.
Published: June 2012

Concentric thickening of the tunica intima was observed in a short length of common carotid artery which had been tied off between two ligatures, and also in the pieces immediately proximal and distal to the doubly ligated part. The thickening was not due to hyperplasia of endothelial cells; in fact, the endothelium in the doubly ligated part was necrotic a short time after ligature. This piece then became lined with macrophage-like cells, thought to be derived from monocytes of the blood contained in the lumen. These cells retained quantities of colloidal thorium dioxide which had been given intravenously just be fore applying the ligatures. On the other hand, the thickening of the intima seen in the doubly ligated segment, as well as in the adjoining lengths of artery, was principally due to the growth of a cell derived from the smooth muscle of the tunica media, for which the term "myo-intimal" cell is suggested.
Relation Between Lung Volume and Pulmonary Vascular Resistance
Authors: SIMMONS DANIEL H. , LINDE LEONARD M. , MILLER JOSEPH H. , O'REILLY RONALD J.
Published: June 2012

Ten experiments were conducted on anesthetized dogs ventilated with a Starling pump and breathing oxygen. While tidal volume, respiratory rate, and arterial pH and pCO
2
were kept constant, lung volume was varied by using either a negative, zero, or positive end-expiratory pressure, leading to average changes in lung volume of -32, 0, and +75 per cent. Pulmonary vascular resistance (PVR) increased with either decreased or increased lung volume, indicating that the relationship between resistance and lung volume is a U-shaped curve. Since the transmural distending pressures of large pulmonary vessels either increased or remained unchanged during these procedures, changes in PVR cannot be ascribed to changes in systemic circulatory dynamics, such as cardiac output.

It was noted that cardiac output increased with negative end-expiratory pressure (effectively, negative-pressure breathing) and decreased with positive end-expiratory pressures (effective, positive-pressure breathing), as previously reported. A hypothesis is presented for explaining the U-shaped curve relating resistance and lung volume.
Studies of the Cerebral Circulation with Labeled Erythrocytes in Healthy Man
Authors: NYLIN GUSTAV , HEDLUNG SVEN , REGNSTRÖM OLOF
Published: June 2012

A thorough investigation of 10 healthy males, 26 to 46 years old, has been performed. One and a half ml. of their own erythrocytes, labeled with P
32
, was injected intravenously and dilution curves obtained simultaneously from one carotid artery and the two jugular bulbs. Thereafter, the same amount of labeled blood was injected into both carotid arteries, following one another, and dilution curves from the two jugular bulbs were simultaneously obtained. A total of seven dilution curves was collected in each case. The percutaneous punctures of the carotids were high enough in the neck so that it is highly probable that the injections were made into the internal carotid arteries. Calculations of the cerebral blood flow and the cerebral blood volume in absolute values were performed. The mean value of the cerebral blood flow amounted to 876 ml/min., i.e., 11.4 per cent of the cardiac output. The pool of the brain was calculated to about 100 ml. When a carotid artery was injected, the appearance and peak concentration times estimated from the dilution curves obtained from the ipsilateral bulbs were the same whether the injection was performed in the right or left side. The corresponding times for the dilution curves obtained from the contralateral bulb agreed, whichever the side on which the injection was performned. They were, however, one second longer than the ipsilateral ones. The determination of circulation time is of diagnostic value, according to an earlier publication. A simplified bloodless method has also been tried.
Studies on the Metabolism of Catecholamines
Authors: AXELROD JULIUS , WHITBY I. GORDON , HERTTING GEORG , KOPIN IRWIN L.
Published: June 2012

Administered H
3
-epinephrine and H
3
-nor-epinephrine are rapidly and selectively taken up by heart muscle and retained for many hours. The uptake and retention of circulating H
3
-norepinephrine by the heart is greater than that of H
3
-epinephrine. Two minutes after the administration of H
3
-catecholamines large amounts of metanephrine and normetanephrine are found in the heart indicating rapid O-methylation of these hormones during the period of their inactivation. H
3
-epinephrine is more readily O-methylated than H
3
-norepinephrine.

Enzyme inhibition studies indicate that catechol-O-methyl transferase is the enzyme mainly concerned with the metabolism of catecholamines in the heart.

Reserpine, cholorpromazine, imipramine, amphetamine, cocaine, and phenoxybenzamine markedly inhibit the uptake of circulating H
3
-norepinephrine by the heart.
Effect of Coronary Blood Flow on Radioisotope Dilution Curves Measured by Precordial Scintillation Detection
Authors: MENA ISMAEL , KATTUS ALBERT A. , GREENFIELD MOSES A. , BENNETT LESLIE R.
Published: June 2012

Two series of animal experiments are reported. In the first of these, the disappearance rates of intravenously injected radioactive boluses were monitored over the heart and from a peripheral artery. The disappearance rate over the heart was shown to be slower than in the artery. In a second series of experiments in which injection was made into the left ventricle or into a coronary artery while sampling from the right side of the heart, it was shown that the coronary transit time was several times longer than the left ventricular transit time. The prolonged presence of the radioactivity in the coronary vascular bed accounts for the difference in the heart and arterial disappearance slopes. A ratio of these two slopes may provide an index of coronary blood flow.
Linear System for Quantitating Hydrogen at a Platinum Electrode
Authors: HYMAN EDWARD S.
Published: June 2012

With a low impedance, transistor measuring circuit, the response of a platinum-platinum black electrode to hydrogen in solution is found to be linear with concentration. Hydrogen in solution can he qnantitated by this circuit. This offers the possibility of quanti tation of hydrogen by an intravascular plati num electrode. It may now be possible to quantitate, as well as detect, intracardiac shunts and repeat the observation without the withdrawal of blood.
Automatic Recognition of Electrocardiographic Waves by Digital Computer
Authors: STALLMANN FRIEDEMANN W. , PIPBERGER HUBERT V.
Published: June 2012

A digital computer program for automatic recognition of electrocardiographic waves has been described. First, a filtering procedure was applied in order to eliminate extraneous noise. Consequently, the spatial velocity derived from three orthogonal electrocardio-graphic leads was determined for an entire cardiac cycle. It was found that a critical value of 3 µV per msec, was never exceeded during T-P intervals, P-R segments, and S-T segments. This limit for the spatial velocity could be used to indicate the beginning and end of electrocardiographic waves. The method was tested in a series of 395 records. The computer failed in 1.3 per cent of all expected measurements. "With one exception, failures were encountered only in eases with cardiac arrhythmias but not with regular sinus rhythm. Comparison between computed and visual time measurements showed close agreement, especially when limits of visual accuracy and beat-to-beat variations in wave duration were taken into account. The described procedure can serve as the basis for a complete electrocardiographic analysis by digital computer.
Experimental Myocardial Infarction
Authors: Salazah Andres E.
Published: June 2012

Coronary thrombosis can be consistently induced in the intact closed-chest dog by the passage of a low-grade direct electrical current through a circuit that includes a positive intraluminal electrode in a major coronary branch and a negative external electrode on the chest wall.
Chronic Matrix Metalloproteinase Inhibition Retards Age-Associated Arterial Proinflammation and Increase in Blood Pressure
Authors: Wang Mingyi , Zhang Jing , Telljohann Richard , Jiang Liqun , Wu James , Monticone Robert E. , Kapoor Kapil , Talan Mark , Lakatta Edward G.
Published: June 2012

Age-associated arterial remodeling involves arterial wall collagen deposition and elastin fragmentation, as well as an increase in arterial pressure. This arterial remodeling is linked to proinflammatory signaling, including transforming growth factor-β1, monocyte chemoattractant protein 1, and proendothelin 1, activated by extracellular matrix metalloproteinases (MMPs) and orchestrated, in part, by the transcriptional factor ets-1. We tested the hypothesis that inhibition of MMP activation can decelerate the age-associated arterial proinflammation and its attendant increase in arterial pressure. Indeed, chronic administration of a broad-spectrum MMP inhibitor, PD166739, via a daily gavage, to 16-month–old rats for 8 months markedly blunted the expected age-associated increases in arterial pressure. This was accompanied by the following: (1) inhibition of the age-associated increases in aortic gelatinase and interstitial collagenase activity in situ; (2) preservation of the elastic fiber network integrity; (3) a reduction of collagen deposition; (4) a reduction of monocyte chemoattractant protein 1 and transforming growth factor-β1 activation; (5) a diminution in the activity of the profibrogenic signaling molecule SMAD-2/3 phosphorylation; (6) inhibition of proendothelin 1 activation; and (7) downregulation of expression of ets-1. Acute exposure of cultured vascular smooth muscle cells in vitro to proendothelin 1 increased both the transcription and translation of ets-1, and these effects were markedly reduced by MMP inhibition. Furthermore, infection of vascular smooth muscle cells with an adenovirus harboring a full-length ets-1 cDNA increased activities of both transforming growth factor-β1 and monocyte chemoattractant protein 1. Collectively, our results indicate that MMP inhibition retards age-associated arterial proinflammatory signaling, and this is accompanied by preservation of intact elastin fibers, a reduction in collagen, and blunting of an age-associated increase in blood pressure.
Endothelin 1–Dependent Neurovascular Dysfunction in Chronic Intermittent Hypoxia
Authors: Capone Carmen , Faraco Giuseppe , Coleman Christal , Young Colin N. , Pickel Virginia M. , Anrather Josef , Davisson Robin L. , Iadecola Costantino
Published: June 2012

Obstructive sleep apnea, a condition resulting in chronic intermittent hypoxia (CIH), is an independent risk factor for stroke and dementia, but the mechanisms of the effect are unknown. We tested the hypothesis that CIH increases cerebrovascular risk by altering critical mechanisms regulating cerebral blood flow thereby lowering cerebrovascular reserves. Male C57Bl6/J mice were subjected to CIH (10% O
2
for 90 seconds/room air for 90 seconds; during sleep hours) or sham treatment for 35 days. Somatosensory cortex blood flow was assessed by laser Doppler flowmetry in anesthetized mice equipped with a cranial window. CIH increased mean arterial pressure (from 74±2 to 83±3 mm Hg;
P
<0.05) and attenuated the blood flow increase produced by neural activity (whisker stimulation; −39±2%;
P
<0.05) or neocortical application of endothelium-dependent vasodilators (acetylcholine response: −41±3%;
P
<0.05). The cerebrovascular dysfunction was associated with oxidative stress in cerebral resistance arterioles and was abrogated by free radical scavenging or NADPH oxidase inhibition. Furthermore, cerebrovascular dysfunction and free radical increase were not observed in mice lacking the NOX2 subunit of NADPH oxidase. CIH markedly increased endothelin 1 in cerebral blood vessels, whereas cerebrovascular dysfunction and oxidative stress were abrogated by neocortical application of the endothelin type A receptor antagonist BQ123. These data demonstrate for the first time that CIH alters key regulatory mechanisms of the cerebral circulation through endothelin 1 and NADPH oxidase–derived radicals. The ensuing cerebrovascular dysfunction may increase stroke risk in patients with sleep apnea by reducing cerebrovascular reserves and increasing the brain's susceptibility to cerebral ischemia.
Wind-Driven Variability of the Subtropical North Pacific Ocean
Authors: Giglio Donata , Roemmich Dean , Gille Sarah T.
Published: June 2012

The Argo array provides a unique dataset to explore variability of the subsurface ocean interior. This study considers the subtropical North Pacific Ocean during the period from 2004 to 2011, when Argo coverage has been relatively complete in time and space. Two distinct patterns of Argo dynamic height transport function () are observed: in 2004/05, the gyre is stronger, and in 2008/09 it is weaker. The orientation of the subtropical gyre also shifts over time: the predominantly zonal major axis shifts to a more northwest–southeast orientation in 2004/05 and to a more southwest–northeast orientation in 2008/09.

The limited temporal range of the Argo observations does not allow analysis of the correlation of ocean transport and wind forcing in the basin for the multiyear time scale (6–8-yr period) typical of the dominant gyre patterns. The meridional geostrophic transport anomaly between 180° and 150°E is computed both from Argo data (0–2000 db) and from the Sverdrup relation (using reanalysis winds): similarities are observed in a latitude–time plane, consistent with local forcing playing an important role. A forcing contribution from the eastern subtropics will also reach the region of interest, but on a longer time scale, and it is not analyzed in this study.

Compared with the 8-yr Argo record, the longer 19-yr time series of satellite altimetry shows a similar but somewhat modified pattern of variability. A longer Argo record will be needed to observe the decadal-scale fluctuations, to separate interannual and decadal signals, and to ensure statistical confidence in relating the wind forcing and the oceanic response.
Middle School Black and White Student Assignment to Disciplinary Consequences
Authors: Hilberth Michele , Slate John R.
Published: June 2012

Disciplinary consequences assigned to all Texas middle school Black and White students ( n = 172,551 Grade 6 students; 173,671 Grade 7 students; 175,730 Grade 8 students) for the 2008-2009 school year were analyzed to determine the extent to which statistically significant differences were present between the proportion of Black students and the proportion of White students assigned discipline consequences. Black students received in-school suspension at more than twice the percentage of their representation in the overall student sample population. Similar results were present for out-of-school suspension, with proportionately more Black students being assigned to out-of-school suspension than White students. Although the number of students assigned to disciplinary alternative education program placement was small, Black students were still assigned to this disciplinary consequence at a much higher percentage than were White students. A lack of equity was clearly demonstrated in the overrepresentation of Black middle school students assigned to disciplinary consequences.
Process Into Products
Authors: Abel Yolanda
Published: June 2012

This article addresses the need for novice teachers to receive exposure and experiences related to family engagement as part of their academic preparation to better facilitate their actual parent involvement practices. In a graduate-level parent involvement in education course, early childhood educators had an opportunity to engage in a variety of family engagement practices and reflect on the effectiveness and outcomes for the students and their families.
Acts of the Apostles and Ethics
Authors: Tannehill Robert C.
Published: June 2012

Acts provides ethical guidance through narrating the actions of persons who are models of good (or bad) behavior. Four topics are discussed from this perspective: ethics of witness, ethics of leadership, the mission and governing authorities, and ethics of possessions.
The Effects of a Family Math Night on Preservice Teachers’ Perceptions of Parental Involvement
Authors: Jacobbe Tim , Ross Dorene D. , Hensberry Karina K. R.
Published: June 2012

This study examined the impact of a Family Math Night on preservice teachers’ perceptions of low-income parents and their engagement in their children’s education. Participants were enrolled in an elementary mathematics methods course; one section served as the treatment group. Participants were required to aid in the planning and implementation of a Family Math Night held at a school serving a predominantly African American, high-poverty community. Results of a pre- and post-survey analysis indicate that the treatment group had more positive perceptions of parental involvement overall. These results were not sustained 1 year later, suggesting important implications for mathematics teacher educators.
‘Girl still burning inside my head’: Reflections on suicide in Sri Lanka
Authors: de Alwis Malathi
Published: June 2012

This chapter reflects on why suicide has become such a pervasive phenomenon in Sri Lankan society by engaging with the extensive scholarly literature that exists on this subject. Rather than trying to provide some overarching, mono-causal explanation, it seeks to illuminate the complexity of the issue and the varied and nuanced ways in which we might try to apprehend it, be it in conjunction with homicide or political conflict, social change or sexual anomie, restraint or collectivism. While problematising our re-course to the ‘work of culture’ and reading statistics against the grain, this chapter also highlights gendered dimensions and broader conceptual strands where we may not have thought to seek them.
‘I drank it to put an end to me’: Narrating girls’ suicide and self-harm in Sri Lanka
Authors: Marecek Jeanne , Senadheera Chandanie
Published: June 2012

Sri Lanka experienced a spiral of suicides in the 1980s and 1990s, with deaths rising to nearly 48 per 100,000 in 1995. Although reported rates of suicide have declined since then, the incidence of suicide and deliberate self-harm remains high, especially among young people. Data on hospital admissions showed that the number of adolescent girls admitted for deliberate self-harm more than doubled between 2001 and 2007. We conducted in-depth interviews with girls in the south of Sri Lanka who were hospitalised for deliberate self-harm. The interviews revealed several common themes in the girls’ accounts of the circumstances that prompted self-harm episodes, their motives and emotions, and others’ responses. Most episodes involved accusations and disputes regarding the girls’ sexual comportment and heterosexual relations. They often involved harsh scolding and beatings by parents. Themes in the girls’ accounts included anger, disappointment, shame, and acute distress; descriptions of their self-harm as an expressive act directed toward others; and disavowal of responsibility for their actions. We suggest that the rise in girls’ self-harm results from the clash between emergent expectations that young women hold regarding advanced education, heterosexual relations, and out-of-home employment and traditional ideals of appropriate feminine comportment and sexual respectability held by their parents.
The suicide niche: Accounting for self-harm in a South Indian leprosy colony
Authors: Staples James
Published: June 2012

This article analyses the circumstances under which attempted suicide became an increasingly common possibility of thought and action among the young, healthy generation of people who had grown up in the South Indian leprosy community where I conducted long-term fieldwork, despite suicide remaining relatively uncommon amongst their leprosy-affected, and often physically disabled, parents and grandparents. Alert to the pitfalls of analytical approaches that either privilege over-arching structural explanations—like those favoured by Durkheim—or, conversely, give too much credence to individual agency and psychology, my analysis here attempts to chart a course through these polarities. It does so by drawing both on Ian Hacking’s ‘ecological niche’ metaphor—to explore how particular configurations of events and circumstances, at different times, might render suicide related behaviour more or less likely among different groups; and on Pierre Bourdieu’s notion of the ‘habitus’—to consider how particular sets of bodily dispositions might generate certain styles of attempted suicide and self-harm.
Social Functioning, Victimization, and Mental Health among Female Offenders
Authors: Anumba Natalie , Dematteo David , Heilbrun Kirk
Published: June 2012

Females who have experienced victimization or abuse during childhood tend to have poorer outcomes in adulthood with regard to criminal behavior, mental health, and social relationships. Although scholars have hypothesized that female offenders may benefit from programming that emphasizes empowerment and healthy relationships, empirical examination of this idea remains limited. Using a sample of 300 female offenders, this study empirically explored whether a history of victimization is a risk factor for future mental health problems and criminal behavior, and whether positive social functioning serves as a protective factor for females with histories of victimization. The results indicated that victimization history in this sample may not be associated with recidivism risk but with vulnerability to stress and mental health problems. In addition, the presence of social resources such as education and noncriminal friends appeared to act as a buffer against stress experienced as a result of life events.
Neither “Scientific” nor “Colonialist”
Authors: Giraudo Laura
Published: June 2012

Efforts to develop a shared, Pan-American indigenista plan, beginning with the creation of the Inter-American Indian Institute (Instituto Indigenista Interamericano—III) in 1940, had to overcome a series of problems, especially financial and political ones. Obtaining support from the Mexican government and, above all, from the United States allowed the III to launch some important projects, but it greatly limited the extent to which it could promote a truly Pan-American program. The historical record suggests that, in the end, the radical and ambitious indigenista plan was hard to realize. Moreover, this history was much more uncertain, mixed, and ambivalent than had been expected and challenged long-held assumptions about indigenismo and its role.

Con la creación del Instituto Indigenista Interamericano (III), en 1940, se pretendía elaborar un programa indigenista panamericano, pero había que superar una serie de problemas, sobre todo financieros y políticos. Gracias al apoyo inicial del gobierno mexicano y de los Estados Unidos, el III puso en marcha algunos proyectos importantes, pero ese mismo apoyo limitó, en buena medida, la posibilidad de promover un programa indigenista que fuera realmente panamericano. La evidencia histórica sugiere, de hecho, que este programa indigenista, ambicioso y radical, era de difícil realización. Además, su historia se revela mucho más incierta, incoherente y ambivalente de lo esperado, desafiando muchas de las ideas consolidadas sobre el indigenismo y su papel.
From ‘the best kept company secret’ to a more proficient structure of employee representation: The role of EWC delegates with a managerial background
Authors: Snook Jeremé Charles , Whittall Michael
Published: June 2012

This article is a longitudinal case study that demonstrates how company middle managers acting as European works council (EWC) delegates are well placed to represent the interests of the wider workforce. Contrary to widely held assumptions about the role of management on EWCs, namely that such delegates represent nothing more than the ‘managerial capture’ of this European institution, the article exemplifies such delegates as possessing skills sets which incorporate communication, organization, strategy, assertiveness, tact and diplomacy that can benefit the EWC. The delegates in this study developed both solidarity and a shared sense of identity among employees that spanned national borders; delegates also influenced both company policy and strategy. Ultimately these delegates operating in a strictly non-unionized IT company helped transform the company EWC from its initial description as ‘the best kept company secret’ into a more purposeful structure of employee representation.
Improving the Detection of Fungi in Eosinophilic Mucin
Authors: Guo Canting , Ghadersohi Saied , Kephart Gail M. , Laine Roger A. , Sherris David A. , Kita Hirohita , Ponikau Jens U.
Published: June 2012

Objective

To investigate the improvement in histologic detection of fungi with Gomori methenamine silver (GMS) stain by trypsin predigestion in the mucus of patients with chronic rhinosinusitis (CRS).

Study Design

Prospective, single group, descriptive analysis.

Setting

Multi‐institutional.

Subjects and Methods

Thirty‐four sinus specimens from 12 surgical patients with CRS were stained with hematoxylin and eosin, GMS stain, GMS with trypsin digestion, immunofluorescence stains for chitinase, and anti‐Alternaria. All patients received skin testing, total IgE serology, and radioallergosorbent tests (RAST) for 23 fungal‐specific IgE antibodies.

Results

The conventional GMS stain detected fungi in only 9 of 34 (27%) specimens. Predigesting the specimen with trypsin dramatically improved the visualization of fungi (31/34, 91%). The chitinase immunofluorescence visualized fungi in 32 of 34 (94%), and anti‐Alternaria visualized 33 of 34 specimens (97%). Only 8 of 12 (75%) patients had detectable allergies.

Conclusions

This report describes a simple modification of the conventional GMS stain that can significantly improve the visualization of fungi on histology and explains the lack of detection in previous studies. These novel, more sensitive histologic methods reveal the presence of fungi within the eosinophilic mucin in allergic and also nonallergic CRS patients, further questioning a crucial role of an IgE‐mediated pathophysiology.