bluuebunny/crossref_metadata_2025 huggingface dataset:
The Transient Receptor Potential Protein Homologue TRP6 Is the Essential Component of Vascular α
1
-Adrenoceptor–Activated Ca
2+
-Permeable Cation Channel
Authors: Inoue Ryuji , Okada Takaharu , Onoue Hitoshi , Hara Yuji , Shimizu Shunichi , Naitoh Shinji , Ito Yushi , Mori Yasuo
Published: June 2012

Abstract
—The
Drosophila
transient receptor potential protein (TRP) and its mammalian homologues are thought to be Ca
2+
-permeable cation channels activated by G protein (G
q/11
)–coupled receptors and are regarded as an interesting molecular model for the Ca
2+
entry mechanisms associated with stimulated phosphoinositide turnover and store depletion. However, there is little unequivocal evidence linking mammalian TRPs with particular native functions. In this study, we have found that heterologous expression of murine TRP6 in HEK293 cells reproduces almost exactly the essential biophysical and pharmacological properties of α
1
-adrenoceptor–activated nonselective cation channels (α
1
-AR–NSCC) previously identified in rabbit portal vein smooth muscle. Such properties include activation by diacylglycerol; S-shaped current-voltage relationship; high divalent cation permeability; unitary conductance of 25 to 30 pS and augmentation by flufenamate and Ca
2+
; and blockade by Cd
2+
, La
3+
, Gd
3+
, SK&F96365, and amiloride. Reverse transcriptase–polymerase chain reaction and confocal laser scanning microscopy using TRP6-specific primers and antisera revealed that the level of TRP6 mRNA expression was remarkably high in both murine and rabbit portal vein smooth muscles as compared with other TRP subtypes, and the immunoreactivity to TRP6 protein was localized near the sarcolemmal region of single rabbit portal vein myocytes. Furthermore, treatment of primary cultured portal vein myocytes with TRP6 antisense oligonucleotides resulted in marked inhibition of TRP6 protein immunoreactivity as well as selective suppression of α
1
-adrenoceptor–activated, store depletion–independent cation current and Ba
2+
influx. These results strongly indicate that TRP6 is the essential component of the α
1
-AR–NSCC, which may serve as a store depletion–independent Ca
2+
entry pathway during increased sympathetic activity.
Fast High-Resolution Magnetic Resonance Imaging Demonstrates Fractality of Myocardial Perfusion in Microscopic Dimensions
Authors: Bauer Wolfgang R. , Hiller Karl-Heinz , Galuppo Paolo , Neubauer Stefan , Köpke Julian , Haase Axel , Waller Christiane , Ertl Georg
Published: June 2012

Abstract
—The fractal nature of heterogeneity of myocardial blood flow and its implications for the healthy and diseased heart is not yet understood. The main hindrance for investigation of blood flow heterogeneity and its role in physiology and pathophysiology is that conventional methods for determination of myocardial perfusion have severe limitations concerning temporal and spatial resolution and invasiveness. In isolated rat hearts, we developed a nuclear magnetic resonance technique that does not depend on contrast agents and in which the apparent longitudinal relaxation time is made perfusion sensitive by selective preparation of the imaging slice. This perfusion-sensitive relaxation time is determined within 40 seconds as a map with a high spatial in-plane resolution of 140×140 μm
2
and a thickness of 1.5 mm. Perfusion imaging was validated with the established microsphere technique. Additionally, the congruence between perfusion-sensitive
T
1
maps and first-pass perfusion imaging was demonstrated. As an application of high-resolution perfusion imaging, fractal analysis of the spatial distribution of perfusion was performed. We were able to demonstrate that the fractality of this distribution exists even in microscopic dimensions. Vasodilation by nitroglycerin modulated the fractal pattern of perfusion, and the decrease of the fractal dimension indicated a shift toward homogeneity. This implies that parameters of the fractal distribution depend on the microvascular tone rather than on anatomic preformations; ie, fractality is a functional characteristic of perfusion.
Heterogeneity of Kv2.1 mRNA Expression and Delayed Rectifier Current in Single Isolated Myocytes From Rat Left Ventricle
Authors: Schultz Jobst-Hendrik , Volk Tilmann , Ehmke Heimo
Published: June 2012

Abstract
—Expression of the voltage-gated K
+
channel Kv2.1, a possible molecular correlate for the cardiac delayed rectifier current (
I
K
), has recently been shown to vary between individual ventricular myocytes. The functional consequences of this cell-to-cell heterogeneity in Kv2.1 expression are not known. Using multiplex single-cell reverse transcriptase–polymerase chain reaction (RT-PCR), we detected Kv2.1 mRNA in 47% of isolated midmyocardial myocytes from the rat left ventricular free wall that were positive for α-myosin heavy chain mRNA (n=74). Whole-cell patch-clamp recordings demonstrated marked differences in the magnitude of
I
K
(200 to 1450 pA at
V
Pip
=40 mV) between individual myocytes of the same origin. Furthermore, the tetraethylammonium (TEA)–sensitive outward current (
I
TEA
), known to be partly encoded by Kv2.1 in mice, revealed a wide range of current magnitudes between single cells (150 to 1130 pA at
V
Pip
=40 mV). Combined patch-clamp recordings and multiplex single-cell RT-PCR analysis of the same myocytes, however, showed no differences in
I
K
or
I
TEA
magnitude or inactivation kinetics between myocytes expressing Kv2.1 mRNA and those that did not express Kv2.1 mRNA. In contrast, in all midmyocardial myocytes expressing the transient outward potassium current (
I
to1
), Kv4 mRNA, which has been shown to underlie
I
to1
, was detected (n=10). These results indicate that
I
K
heterogeneity among individual left ventricular myocytes cannot be explained by the distribution pattern of Kv2.1 mRNA. Other mechanisms besides Kv2.1 mRNA expression appear to determine magnitude and kinetics of
I
K
in rat ventricular myocytes.
Gene Expression Patterns in the Lungs of Patients With Primary Pulmonary Hypertension
Authors: Geraci Mark W. , Moore Mark , Gesell Tracy , Yeager Michael E. , Alger Lori , Golpon Heiko , Gao Bifeng , Loyd James E. , Tuder Rubin M. , Voelkel Norbert F.
Published: June 2012

Abstract
— Primary pulmonary hypertension (PPH) is a disease of unknown etiology characterized by lumen-obliterating endothelial cell proliferation and vascular smooth muscle hypertrophy of the small precapillary pulmonary arteries. Because the vascular lesions are homogeneously distributed throughout the entire lung, we propose that a tissue fragment of the lung is representative of the whole lung. RNA extracted from the fragments is likely to provide meaningful information regarding the changes in gene expression pattern in PPH when compared with structurally normal lung tissue. We hypothesize that the lung tissue gene expression pattern of patients with PPH has a characteristic profile when compared with the gene expression pattern of structurally normal lungs and that this characteristic gene expression profile provides new insights into the pathobiology of PPH. Using oligonucleotide microarray technology, we characterized the expression pattern in the lung tissue obtained from 6 patients with primary pulmonary hypertension (PPH)—including 2 patients with the familial form of PPH (FPPH)—and from 6 patients with histologically normal lungs. For the data analysis, gene clusters were generated and the gene expression pattern differences between PPH and normal lung tissue and between PPH and FPPH lung tissue were compared. All PPH lung tissue samples showed a decreased expression of genes encoding several kinases and phosphatases, whereas several oncogenes and genes coding for ion channel proteins were upregulated in their expression. Importantly, we could distinguish by pattern comparison between sporadic PPH and FPPH, because alterations in the expression of transforming growth factor-β receptor III, bone morphogenic protein 2, mitogen-activated protein kinase kinase 5, RACK 1, apolipoprotein C-III, and the gene encoding the laminin receptor 1 were only found in the samples from patients with sporadic PPH, but not in FPPH samples. We conclude that the microarray gene expression technique is a new and useful molecular tool that provides novel information pertinent to a better characterization and understanding of the pathobiology of the distinct clinical phenotypes of pulmonary hypertension.
Dobutamine-Stress Magnetic Resonance Microimaging in Mice
Authors: Wiesmann Frank , Ruff Jan , Engelhardt Stefan , Hein Lutz , Dienesch Charlotte , Leupold Andrea , Illinger Ralf , Frydrychowicz Alex , Hiller Karl-Heinz , Rommel Eberhard , Haase Axel , Lohse Martin J. , Neubauer Stefan
Published: June 2012

Abstract
— The aim of this study was to assess the capability of MRI to characterize systolic and diastolic function in normal and chronically failing mouse hearts in vivo at rest and during inotropic stimulation. Applying an ECG-gated FLASH-cine sequence, MRI at 7 T was performed at rest and after administration of 1.5 μg/g IP dobutamine. There was a significant increase of heart rate, cardiac output, and ejection fraction and significant decrease of end-diastolic and end-systolic left ventricular (LV) volumes (
P
<0.01 each) in normal mice during inotropic stimulation. In mice with heart failure due to chronic myocardial infarction (MI), MRI at rest revealed gross LV dilatation. There was a significant decrease of LV ejection fraction in infarcted mice (29%) versus sham mice (58%). Mice with MI showed a significantly reduced maximum LV ejection rate (
P
<0.001) and LV filling rate (
P
<0.01) and no increase of LV dynamics during dobutamine action, indicating loss of contractile and relaxation reserve. In 4-month-old transgenic mice with cardiospecific overexpression of the β
1
-adrenergic receptor, which at this early stage do not show abnormalities of resting cardiac function, LV filling rate failed to increase after dobutamine stress (transgenic, 0.19±0.03 μL/ms; wild type, 0.36±0.01 μL/ms;
P
<0.01). Thus, MRI unmasked diastolic dysfunction during dobutamine stress. Dobutamine-stress MRI allows noninvasive assessment of systolic and diastolic components of heart failure. This study shows that MRI can demonstrate loss of inotropic and lusitropic response in mice with MI and can unmask diastolic dysfunction as an early sign of cardiac dysfunction in a transgenic mouse model of heart failure.
Cellular Pathology of Atherosclerosis
Authors: Rainger G. Ed , Nash Gerard B.
Published: June 2012

Abstract—
During the development of an atherosclerotic plaque, mononuclear leukocytes infiltrate the artery wall through vascular endothelial cells (ECs). At the same time, arterial smooth muscle cells (SMCs) change from the physiological contractile phenotype to the secretory phenotype and migrate into the plaque. We investigated whether secretory SMCs released cytokines that stimulated ECs in a manner leading to increased leukocyte recruitment and thus might accelerate atheroma formation. SMCs and ECs were established in coculture on the opposite sides of a porous membrane, and the cocultured cells were incorporated into a flow-based assay for studying leukocyte adhesion. We found that coculture primed ECs so that their response to the inflammatory cytokine tumor necrosis factor-α was amplified. ECs cocultured with SMCs supported greatly increased adhesion of flowing leukocytes and were sensitized to respond to tumor necrosis factor-α at concentrations 10 000 times lower than ECs cultured alone. In addition, coculture altered the endothelial selectin adhesion molecules used for leukocyte capture. EC priming was attributable to the cytokine transforming growth factor-β
1
, which was proteolytically activated to a biologically active form by the serine protease plasmin. These results suggest a new role for secretory SMCs in the development of atheromatous plaque. We propose that paracrine interaction between ECs and SMCs has the potential to amplify leukocyte recruitment to sites of atheroma and exacerbate the inflammatory processes believed to be at the heart of disease progression.
Retinoids Inhibit the Actions of Angiotensin II on Vascular Smooth Muscle Cells
Authors: Haxsen Volker , Adam-Stitah Sylvie , Ritz Eberhard , Wagner Jürgen
Published: June 2012

Abstract
— Retinoids are derivatives of vitamin A and powerful inhibitors of cell proliferation and inflammation. Angiotensin II (Ang II) contributes to vascular lesions by promoting cell growth of vascular smooth muscle cells (VSMCs). Therefore, we examined whether retinoids interfere with the proproliferative actions of Ang II in VSMCs via AT
1
receptor–dependent or activator protein-1 (AP-1)–dependent mechanisms. VSMCs express retinoid receptor proteins, ie, retinoic acid receptor (RAR) α and retinoid X receptor (RXR) α. Long-term exposure to 1 μmol/L all-
trans
retinoic acid (RA) dose-dependently inhibited Ang II–induced cell proliferation (
P
<0.005) as well as DNA and protein synthesis (
P
<0.001). All-
trans
RA blocked Ang II stimulation of transforming growth factor-β
1
mRNA (
P
<0.005). All-
trans
RA inhibition of vascular VSMC growth was mediated both via RAR- and RXR-dependent pathways, as shown by receptor-specific synthetic retinoids. Transfection experiments revealed that inhibition of AP-1–dependent gene transcription is one mechanism by which all-
trans
RA inhibits Ang II action. RARα cotransfection enhanced the anti–AP-1 effects of all-
trans
RA dose-dependently. AP-1 activity was similarly inhibited by cotransfection with either RARα or RXRα. Ang II–induced gene expression of c-fos was abrogated by all-
trans
RA treatment (
P
<0.005). In VSMCs, all-
trans
RA downregulated AT
1
receptor mRNA (
P
<0.01) and reduced B
max
(
P
<0.001). All-
trans
RA repressed Ang II–stimulated AT
1
receptor promoter activity. The all-
trans
RA inhibitory effect was abolished when the AP-1 consensus site on the AT
1
receptor promoter was deleted. Our findings demonstrate that retinoids are potent inhibitors of the actions of Ang II on VSMCs. The findings support the notion that retinoids may interfere with proliferative vascular disease.
Instantaneous Dimensional Changes of the Left Ventricle in Dogs
Authors: HAWTHORNE EDWARD W.
Published: June 2012

The cardiac cycle in dogs starts with an isovolumic period in which there is shortening of the base-to-apex length with an increase in cross-sectional area. Total shortening is about one-fourth of that in open-chest dogs. Minimal changes in base-to-apex length occur during the ejection phase, and there is a typical pattern of decrease in cross-sectional area. During isovolumic relaxation, the left ventricular base-to-apex length increases. Rapid filling is characterized by a sudden increase in cross-sectional area and is followed by a diastasis of varying lengths. Atrial systole is associated with a sudden significant increase in cross-sectional area and a decrease in base-to-apex length. The magnitude of change in cross-sectional area about the left ventricle during ejection may be used as an index of stroke volume. Our studies suggest that the ventricle contracts in an "eccentric manner," and relaxes in a "concentric fashion." Simultaneous monitoring of the instantaneous changes in cross-sectional area and circumference about the middle of the left ventricle may be used as an index of its efficiency of contraction in awake, intact dogs.
Pulmonary Blood Volume in Experimental Unilateral Pulmonary-Artery Occlusion
Authors: ARAMENDÍA PEDRO , FERMOSO JOSÉ D. , TAQUINI ALBERTO C.
Published: June 2012

In a series of 11 dogs in which the left pulmonary artery was ligated, the blood from the occluded lung was absorbed by the remainder of the vascular bed and, consequently, there was no significant alteration in the pulmonary blood volume. This adaptation took place, apparently, with only slight modifications in the circulation time and the pressure of the system. Examination of the variables investigated suggests, to a certain extent, that the increased flow brings about the opening-up of new vascular channels.
Chronic Extrinsic Cardiac Denervation by Regional Neural Ablation
Authors: COOPER THEODORE , GILBERT JOSEPH W. , BLOODWELL ROBERT D. , CROUT J. RICHARD
Published: June 2012

A technique for complete extrinsic denervation of the heart by the ablation of neural structures in the mediastinum is described. The completeness of denervation was verified by direct electrical stimulation of the main vagal and sympathetic trunks. Total deple tion of myocardial catecholamines followed the procedure in chronic survivors. Animals prepared in this manner are useful in the study of the neurologically isolated heart and simulate this aspect of the problem of cardiac transplantation.
Autocorrelation of Ventricular Response in Atrial Fibrillation
Authors: BRAUNSTEIN JOHN R. , FRANKE ERNST K.
Published: June 2012

The autocorrelation function of the ventricular electrocardiogram was calculated on an IBM-650 computer. The resulting function can lie fitted by an exponential-cosine function. This result is typical for a mixture of periodic and unperiodic events. For different patients, various degrees of periodicity were put in evidence by this method on a quantitative basis; the ventricular response was never completely irregular. In all cases investigated so far, the period that corresponds to the periodic component of the autocorrelation function was more rapid than the average rate of ventricular conduction.
Effects of Quantitatively Controlled Left Ventricular-Atrial Regurgitation on Indicator - Dilution Curves in the Dog
Authors: LUKAS DANIEL S. , ARDITI LUCIEN I. , WINSTON A. LEE , PEARCE CHARLES W.
Published: June 2012

Dye-dilution curves were recorded from the aortic arch of dogs with left ventricular-atrial regurgitation produced surgically by a shunt from the apex of the left ventricle to the left atrial appendage. Rate of regurgitation was monitored by an electroturbinometer and was varied from 0.9 to 3.3 liters per minute. In each dog, reciprocal of the downslope and variance of curves obtained after injection of dye into the left atrium varied directly with rate of backflow and inversely with net cardiac output. These effects of regurgitation were not due to change in transit volume. Estimates of regurgitation based on change in reciprocal of slope correlated closely with flowmeter values and were more accurate than estimates based on change in variance. Back flow was underestimated by curves recorded after injection of dye into the pulmonary artery.
Detection of Ferritin in the Plasma of Guinea Pigs in Experimental Shock
Authors: JANOFF AARON , ZWEIFACH BENJAMIN W. , NAGLER ARNOL L. , OVARY ZOLTAN
Published: June 2012

Guinea pigs were subjected to shock by hemorrhage or by infusion of either E.
coil
or
S. enteritidis
endotoxin, and changes in levels of plasma-bound iron and ferritin were assayed. Of 12 bled animals, all showed increases in plasma-bound iron and half gave a positive test for ferritin. Of 12 guinea pigs treated with LD
80
doses of
E. coli
endotoxin, only 4 showed an elevation in plasma-bound iron. Of these only one was positive for ferritin. Of 10 guinea pigs treated with LD
80
doses of
S. enteritdis
endotoxin, only five showed elevations in plasma-bound iron, and three of these also showed detectable increases in plasma ferritin. Immunologically detect able increases in plasma ferritin were not found in any of the endotoxin-infused animals showing decreases in plasma-bound iron.

It was concluded: (a) that, in the guinea pig (as in the rabbit), hyperferremia is more frequent after hemorrhage than after the in fusion of Gram-negative bacterial endotoxin (b) that significant increases in ferritin do not appear simultaneously with decreases in total plasma-hound iron in endotoxic guinea pigs; and (c) that hyperferremia and hyperferritinemia do not play a direct role in the lethal progression of endotoxic shock in the guinea pig.
Effect of Heart Rate on Aortic Insufficiency as Measured by a Dye-Dilution Technique
Authors: WARNER HOMER R. , TORONTO ALAN F.
Published: June 2012

Measurements of the distance a labeled particle of blood travels back up the descending aorta during a single diastole have been carried out at two different heart rates in each of three patients with aortic insufficiency. From these measurements, the ratios of back flow per unit time at the slow heart rate to backflow at the faster heart rate were found to be 1.61, 1.71, and 1.75. From an analysis of the hemodynamic factors involved, it seems likely that backflow is overestimated at the slow heart rates by this technique due to the development of laminar flow late in diastole.
Fibrinolytic Activity of Arterial Tissues
Authors: LIEBERMAN JACK , KELLOGG FREDERICK
Published: June 2012

Arterial tissues were studied for plasminogen activator to demonstrate the possible relationship of its deficiency within the arterial wall to atherosclerosis. Activator was found primarily within the adventitia. The enzyme seemed to appear in fetuses at about the 2,000-Gm. stage of development. Different arteries showed varying activity, with the basilar artery showing least activity; the coronary and renal arteries showing the greatest activity; and the aortic arch; abdominal aorta, and pulmonary arteries falling between. The coronary arteries of females and the aortie arches of females under 60 years of age showed greater activity than those of comparable males. The degree of atherosclerotic in volvement of the coronahes or aorta could not be correlated with the level of plasminogen activator.
Cardiac Actions of Methoxamine
Authors: IMAI SHOICHI , SHIGEI TATSURO , HASHIMOTO KOROKU
Published: June 2012

The cardiac action of large doses of methoxamine and its antagonistic action to epinephrine were studied, using a dog heart-lung preparation. In doses of 4 mg. and above, methoxamine showed a marked negative inotropic action, while it produced only a slight decrease in the heart rate. Pretreatment of animals with 0.1 mg./Kg. of reserpine did not modify the inotropic action, but the decrease in the heart rate disappeared. Simultaneous with these changes, a decrease in the coronary flow and a rise of the pulmonary arterial pressure were observed. Methoxamine in doses of 1 mg. and more abolished both the positive inotropic and the positive chronotropic actions of epinephrine. The negative inotropic action of methoxamine was ascribed to a nonspecific, as yet undetermined mechanism, and the antagonistic action was ascribed to the competitive antagonism at the receptor site (thus methoxamine may be looked upon as a blocking agent of adrenergic β receptor). The weak negative chronotropic action was taken to be an expression of the blockade of the humoral effects of the intrinsic sympathomimetic amines.
Measurement of Central Blood Volume by External Monitoring
Authors: EICH ROBERT H. , CHAFFEE WILLIAM R. , CHODOS ROBERT B.
Published: June 2012

Central blood volume was measured in 39 normal subjects, using external monitoring and interrupted arterial samples. The volume obtained by external counting was 15 per cent of the total blood volume, compared with 42 per cent obtained with the arterial curve. The importance of collimation and counter position was evaluated, and only with a dualcounter setup could a mean circulation time (MCT) for each ventricle be obtained. An MCT was necessary for satisfactory reproducibility of externally measured central blood volume. While the method has limitations, it does appear to offer a technique for measuring just the amount of blood in the heart and lungs with a satisfactory reproducibility, and would appear to be worth further application in problems involving measurement of central blood volume.
Relationships Between Alterations in Amine Metabolism and Blood Pressure
Authors: SJOERDSMA ALBERT
Published: June 2012

The principal processes of synthesis and metabolism for aromatic amines have been discussed in terms of their status in essential hypertension and in relation to alterations induced by enzyme inhibitors with hypotensive properties. From a practical standpoint, the clinical use of monoamine oxidase inhibitors and a decarboxylase inhibitor (α-methyldopa) approach the achievement of medical sympathectomy without prohibitive side effects. From a basic standpoint, use of these inhibitors as biochemical tools affords a new perspective into connections between aromatic amine metabolism and blood-pressure regulation. A combined pharmacological-biochemical approach in man will be an important phase of future investigations.
Diagnosis of Pheochromocytoma by Assay of Catecholamine Metabolites
Authors: GITLOW STANLEY E. , MENDLOWITZ MILTON , KRUK ELIZABETH , KHASSIS SARAH
Published: June 2012

Methods for the determination of urinary vanillylmandelic acid (VMA) have been reviewed and variations in VMA excretion in different disease states summarized. The determination of VMA excretion is believed to represent a reliable method for the detection of a pheochromocytoma. Colorimetric screening tests for the detection of elevated VMA excretion have been reviewed and evaluated as laboratory aids in the diagnosis of pheochromocytoma.
Effect of Atrial and Ventricular Fibrillation and Ventricular Tachycardia on Carbohydrate Metabolism of the Heart
Authors: KLARWEIN MICHAEL , KAKO KYOHEI , CHRYSOHOU ATHANASIOS , BING RICHARD J.
Published: June 2012

Changes in the ratio phosphorylase a/total phosphorylase in heart muscle, as well as the myocardial concentrations of glycogen, glucose-6-phosphate (G-6-P), lactate, pyruvate, fructose-l,6-diphosphate (FDP), dihydroxyacetone phosphate (DHAP), were followed during artificially induced ventricular tachycardia, and ventricular fibrillation, and atrial fibrillation.These experiments were carried out with and without support of the coronary circulation. When coronary circulation was not maintained, active phosphorylase increased, then diminished in heart muscle during ventricular and atrial fibrillation and during ventricular tachycardia. The myocardial concentration of lactate and glucose-6-phosphate rose, while that of glycogen dim inished. No appreciable changes occurred in the concentration of fructose-1,6-diphosphate, dihydroxyacetone phosphate, and pyruvate. These changes were similar to those reported on skeletal muscle. When coronary circulation was maintained, no changes in carbohydrate intermediates or in phosphorylase a activity were recorded. These results demonstrate that the metabolic changes encountered in heart muscle during these arrhythrnias are the result of anoxia.
Response of Granular Juxtaglomerular Cells and Tissue Mast Cells in Various Experimental States
Authors: DEMOPOULOS HARRY , KALEY GABOR , ZWEIFACH BENJAMIK W.
Published: June 2012

Mast cells, granular juxtaglomerular (j.g.) cells, and renal renin levels were studied in five different experimental conditions involving renal hypertension, DOCA hypertension, prolonged administration of NaCl in the drinking water, and treatment with compound 48/80, and dextran. The j.g. cells and mast cells behaved differently in each of these cir cumstances. A correlation between refill con tent and j.g. cells was observed. Metachro inasia could not be detected in j.g. cells and their location appeared to he unique.
Mechanisms in the Return of Vascular Tone Following Sympathectomy in Man
Authors: Parks Veronica J. , Skinner Sandford L. , Whelan Robert F.
Published: June 2012

The response of the hand blood vessels has been determined to the intra-arterial administration of ephedrine and reserpine and to the intravenous administration of norepinephrine before and at intervals after sympatheetomy. The constrictor response to ephedrine slowly disappeared over a period of six weeks, during which time the vessels became increasingly sensitive to norepinephrine. The dilator effect of reserpine was abolished early after sympatheetomy but became slowly re-established over the subsequent three months. The findings suggest that residual vasoconstrictor fibers cannot account for the return of tone following sympatheetomy but that changes in the catecholamine content of the tissue and increasing sensitivity to both these and circulating amines may be closely related to this phenomenon.
Renin and Angiotensin Tachyphylaxis
Authors: BOCK K. D. , GROSS F.
Published: June 2012

Tn the conscious dog, synthetic angioteiisin and crude hog renin produce dose-response curves which run strictly parallel if the max imum blood pressure attained is taken as the parameter. Repeated injections of small or medium closes of angioteitsiri or of small doses of renin do not l)roduce tachyphylaxis. In contrast, high closes of renin, as well as of angiotensin, diminish or abolish the pressor response to subsequent injections of the same substances. Furthermore, cros.s tachyphylaxis between renin and arigiotensin can be demon strated. infusions of renin and angiotensin in various dosages elicit characteristic blood pressure changes, which are very similar for both substances and also display tachyphy laxis at sufficiently high doses. It is concluded that so-called renin tachyphylaxis is, in fact, due to a diminished response to angiotensin. This might be takeii as an indirect proof that renin liberates aiigiotensiri not only iii vitro hut. also in the organism.
Localization of Renin in Juxtaglomerular Cells of Rabbit and Dog Through the Use of the Fluorescent-Antibody Technique
Authors: EDELMAN ROBERT , HARTROFT PHYLLIS M.
Published: June 2012

Canine antisera to rabbit and hog renin were coupled to several fluorescein dyes. The antiserum was immunologically adsorbed once each with rabbit-liver and with bone-marrow powder, thereby removing excess dye and eliminating nonspecific staining. Mounted frozen-dried sections of kidneys from sodium- deficient rabbits (in which hyperplasia and hypergranulation of juxtaglomerular [JG] cells were present), from control rabbits, from a sodium-deficient dog, and from sodium-deficient rats were treated with the adsorbed labeled antiserum. Ultraviolet microscopy (direct technique) revealed an intense yel low-green fluorescence sharply limited to the granules of the juxtagloinerular cells in all sections studied from kidneys of rabbit and dog. JG granules in rats did not fluoresce, an observation in accord with the species spe cificity of renin.

The indirect ("sandwich") method was also employed (with adsorbed, labeled, rabbit antiserum to canine globulin), and although slight staining of gloinerular epithelium resulted, that in the JG granules was far more intense. In our hands, the faint glornerular staining was not blocked by prior treatment with unlabeled renin. Staining of JG granules in any kidney paralleled the intensity of JG granulation by light microscopy and the amount of extractable renin in the same kidney. JG-granule staining (direct and indirect techniques) was blocked by neutralization of the antirenin with renin. Heterogenous anti sera (to insulin; to human gamma globulin) failed to stain. Other rabbit tissues (heart, lung, liver) similarly treated with labeled antirenin never stained.

If this work can be repeated with immunologically pure renin, the evidence presented here, together with previously published studies from this and other laboratories, will establish beyond any reasonable doubt that the source of renin in the kidney is the juxtaglomerular cell, as postulated first by Goormagh tigh nearly a quarter of a century ago.
Use of Krypton
85
for the Measurement of Cardiac Output by the Single-Injection Indicator-Dilution Technique
Authors: CORNELL WILLIAM P. , BRAUNWALD EUGENE , BROCKENBROUGH EDWIN C.
Published: June 2012

When krypton
85
in saline solution is injected into the left side of the heart and sampled from a systemic artery, or is injected into a peripheral vein and sampled from the pulmonary artery, only the primary time-concentration curve is obtained. Recirculation is eliminated by the diffusion of this indicator into the extravascular space and its loss from the pulmonary capillary bed. Determination of the radioactivity in a single blood sample, withdrawn at a constant rate throughout the period during which the Kr
85
passes across. the sampling site, permits calculation of the average concentration of Kr
85
during the inscription of the primary curve. The validity of this technique was tested in a circulatory model against actual flow determined by timed collection. One standard deviation of the differences in 27 trials equaled 5.1 per cent. In 26 comparisons of cardiac output determined simultaneously in dogs by a rotameter and the Kr
85
technique, one standard deviation of the differences equaled 8.4 per cent. In 19 comparisons of cardiac output in patients, determined by dye-dilution and Kr
85
techniques, one standard deviation of the differences equaled 11 per cent. The Kr
85
technique is simpler technically and requires less blood, instrumentation, and calculation than the standard dye techniques.
Influence of Induced Hypothermia on Digitalis Toxicity
Authors: ANGELAKOS E. T. , HURWITZ H. I.
Published: June 2012

Toxic doses of ouabain were injected in animals which were subsequently cooled. The mortality- in this group was compared to that of similarly treated controls. Lowering of body- temperature by 8 to 12 C. reduced the arrhythmias produced by the toxic doses of ouabain but did not alter the overall incidence of mortality from ventricular fibrillation when compared to the controls. However, cooled animals survived for considerably longer periods of time than the normothermic controls. It is concluded that subsequently induced hypothermia does not afford an effective protection from digitalis toxicity, even though arrhythmias are reduced and survival is prolonged. These results support the hypothesis that partial protection from ventricular arrhythmias is not necessarily associated with, protection from lethal ventricular fibrillation.
Cardiovascular-Respiratory Actions of Mephentermine in Mitral Stenosis and Its Effects on Pulmonary Function in Chronic Pulmonary Emphysema
Authors: BARRERA FRANK , REGALADO GABRIEL G. , CHANGSUT ROSA L. , DOMINGUEZ JOSÉ C.
Published: June 2012

Mephentermine increased maximum breathing capacity in emphysema patients due to partial relief of existing bronehospasm. Small variations occurred in tidal volume, arterial-blood saturation, O
2
uptake and CO
2
removal per liter ventilation, and in respiratory quotient. There was an increase in expiratory minute volume, alveolar ventilation, frequency of respiration, O
2
consumption, CO
2
elimination, and arterial-blood pH; a decrease occurred in physiological dead space, physiological dead space/tidal volume ratio, and CO
2
content and tension in arterial blood. These changes were marked in normal individuals and in mitral stenosis patients, in contrast to the minimal effects obtained in emphysema cases. Bronehodilatation in emphysema, reduction of the physiological dead space and physiological dead space/tidal volume ratio, and changes in both direction in arterial-blood saturation as well as circulatory effects suggest that mephentermine affects the ventilation-perfusion relationships throughout the lung. The disproportionate increase in expiratory minute volume and frequency of respiration, while arterial-blood findings showed a significant decrease in CO
2
tension and a significant increase in pH, suggests an important central effect. In normal and in mitral stenosis patients, mephentermine produced an increase in heart rate, a decrease in mean right-atrial pressure, and an increase in cardiac output as a result of myocardial stimulation. Changes in pulmonary-artery pressure were variable. Pulmonary arteriolar resistance decreased in all three normal controls and in the majority of mitral stenosis cases, while wedge pressure changed very slightly. These changes are interpreted as pulmonary vaso-dilatation. Systemic pressure increased, while total systemic resistance decreased or remained essentially unchanged. Arteriovenous O
2
difference decreased in most eases with increased cardiac output, and vice versa. Increased cardiac output, associated with unchanged or falling systemic resistances and decreased arteriovenous O
2
difference, suggests vasodilatation with, increased peripheral blood flow. The fact that systemic resistance increases slightly in some cases must mean that vasocon-striction with decreased peripheral blood flow occurred in other vascular areas as a probable compensatory reaction. These effects led to an increase in arteriovenous O
2
difference and a reduction in cardiac output.
Distribution and Fate of I
131
-Labeled Components of the Fibrinolysin System
Authors: BACK NATHAN , AMBRUS JULIAN L. , MINK IRVING B.
Published: June 2012

The distribution, metabolism, and excretion of intravenously administered I131-labeled components of the fibrinolysin system were studied in dogs. lodination of plasmin tended to decrease slightly its in vitro fibrinolytie activity. Inaetivation appeared to depend on degree of iodination. Todination of strepto-kinase or urokinase did not decrease their plasminogen activator potential. All plasmins and plasminogen, regardless of the position of the iodine tag, adsorbed to preformed clots in the dog. Spontaneously activated human and chloroform-activated bovine plasmin adsorbed to a lesser extent than streptokinase-or urokinase-activated human plasmin. Clots removed from piasmin-treated dogs lysed in vitro within 24 hours. However, streptokinase or urokinase alone, on the basis of radioactivity measurements, did not exhibit any affinity for clots, nor did they cause any clot lysis. Plasma clearance curves revealed the presence of at least two processes in all preparations: a fast one (average half-life four minutes) responsible for the removal of over 60 per cent of the injected radioactivity and a slower process with a biological half-life greater than four hours. Pour hours after the injection of labeled compounds, the thyroid and stomach were the only organs which contained significant percentages of the injected radioactivity. Major excretory routes for the radioactivity were the urinary and biliary systems. Persistence of circulating radioactivity at a time when no free fibrinolytie activity could be determined in the blood was interpreted as complex formation between plasmin and antiplasmin.
Observations on the Heart-Lung Preparation in the Rat
Authors: LEDINGHAM J. M. , Burns B. F.
Published: June 2012

A technique for producing and studying a heart-lung preparation in the rat is described. The relationship between filling pressure and cardiac output was found to remain constant for 60 to 90 minutes after the start of the extracorporeal circulation. The influence on this relationship of alterations in pulmonary ventilation, arterial pulse pressure, and heart rate has not been found to be critical. The mechanisms underlying deterioration of the preparation have been investigated, but no firm conclusions have been reached. Deterioration was not prevented by the introduction of fresh blood into the circulation. During prolonged experiments, the extracellular-fluid content of the heart was found to increase, the intracellular potassium was unaltered, and the intracellular sodium was reduced. Acute elevation of the sodium concentration in the circulating blood lowered, whereas potassium raised, the cardiac output for a given filling pressure. These opposing actions were found to summate. Slowing of the heart brought about by high concentrations of potassium was antagonized by sodium.
Effect of Vagal Stimulation and Acetylcholine on the Ventricle
Authors: KLIP WILLEM
Published: June 2012

It is shown that in the presence of a marginal zone, which is free of corpuscles and which has a width independent of the tube radius, the existence in the central zone of unsheared laminae of finite thickness, which also is independent of the tube radius, tends to increase rather than decrease the apparent viscosity when the radius of the tube becomes smaller.
‘Giving a voice to the unheard’? Is female youth (15–24 years) suicide linked to restricted access to family planning? Comparing two Catholic continents
Authors: Pritchard Colin , Roberts Sion , Pritchard Claire E.
Published: June 2012

Suicide is a neglected area of social work research and suicides are often influenced by cultural factors. WHO data on female youth (15–24 years) suicide, and Undetermined Deaths (UnD), the most likely source of under-reported suicides, are analysed from two continents sharing religio-cultural views on suicide and family planning, that is, Western European Catholic countries (WECC) and Latin American countries (LatAC). It was found that LatAC female youth suicides and UnD were significantly higher than WECC, and correlated with higher birth rates and poverty. This may indicate that restricted access to family planning contributes to more births, poverty, unwanted pregnancies and suicides.
Complex Relationships Between Multicultural Education and Special Education
Authors: Irvine Jacqueline Jordan
Published: June 2012

Multicultural education and special education share historical roots, philosophies, theories, and pedagogies that provide unique opportunities to address the many challenges of underserved K-12 students. Without a more refined and critical analysis, however, the shared similarities could possibly mask the tensions and the complexities inherent in a relationship that directly confronts thorny and nuanced intersections of race, social class, gender, disability, and culture. This article focuses on the complexity of the relationship between multicultural education and special education from an African American perspective by exploring areas of divergence and conflict between special and multicultural education, specifically issues of disproportionate representation, cultural misunderstandings, tensions between home and school, and competition for limited resources. Finally, recommendations are offered that can more effectively prepare K-12 special education teachers who serve students who are culturally diverse and disabled.
Granulomatous Typhlocolitis, Lymphangitis, and Lymphadenitis in a Horse Infected With Listeria monocytogenes, Salmonella Typhimurium, and Cyathostomes
Authors: Nemeth N. M. , Blas-Machado U. , Hopkins B. A. , Phillips A. , Butler A. M. , Sánchez S.
Published: June 2012

A 15-year-old American Quarter horse mare was euthanized because of poor response to therapy for severe diarrhea. Significant gross findings were limited to the large intestines. The walls of the cecum and colon were thickened with widely scattered nodules in the mucosa and submucosa that extended into the enlarged colic lymph nodes. Microscopically, there was severe granulomatous typhlocolitis, lymphangitis, and lymphadenitis, with many intralesional Gram-positive, non-acid-fast coccobacilli and few cyathostomes. Intralesional bacteria were immunohistochemically and polymerase chain reaction (PCR) assay positive for Listeria monocytogenes. Concurrent infection with Salmonella enterica serovar Typhimurium was detected by PCR and culture. Infection with L. monocytogenes in horses is rare, and coinfection with Salmonella and small strongyles probably contributed to the development of granulomatous typhlocolitis.
Bilateral Buphthalmia in a 4-Month-Old Texas Longhorn Steer
Authors: Jones M. L. , Beck A. P. , Dubielzig R. R.
Published: June 2012

Congenital ocular disease occurs uncommonly in cattle, with multiple abnormalities reported only sporadically in the literature. This report describes a case of anterior segment dysgenesis resulting in glaucoma in a 4-month-old Texas Longhorn steer. On clinical exam, bilateral buphthalmia was present and intraocular pressures exceeded 47 mm Hg in both eyes. On histopathologic examination, the iridocorneal angle and filtration apparatus were distorted due to collapse of the ciliary cleft and anterior displacement of the anterior portion of the ciliary body. No evidence of inflammation or other causes of glaucoma were recognized.
Musical “Tune-Ups” for Couples
Authors: Duba Jill D. , Roseman Christopher
Published: June 2012

Some couples seek counseling to address warning signs. They may not be facing a relationship crisis but may be more concerned about where they are headed. Hence, a marriage makeover may not necessarily be needed, but instead couples in counseling may benefit from something rejuvenating. In such cases, brief interventions or techniques may be helpful. This article addresses how musical interventions can be used in couples counseling. A case example is introduced.
A preliminary evaluation of internalized stigma and stigma resistance in inflammatory bowel disease
Authors: Taft Tiffany H , Ballou Sarah , Keefer Laurie
Published: June 2012

Illness stigmatization among inflammatory bowel diseases (IBDs) is poorly understood. We aim to characterize internalized stigma and stigma resistance in IBD patients, and evaluate their relationships to outcomes. A total of 191 IBD patients reported internalized stigma, resistance, demographic and clinical information, and several outcomes: health-related quality of life (HRQOL), psychological distress, self-esteem, and self-efficacy. Overall 36% experienced internalized stigma and 88% moderate to high stigma resistance behaviors. Internalized stigma strongly related to poorer outcomes while resistance demonstrated a weaker, opposite effect. Internalized stigma and stigma resistance are important considerations for IBD outcomes. Interventions to reduce internalized stigma and leverage resistance are warranted.
Strategies to deliver dementia training and education in the acute hospital setting
Authors: Chater Kathryn , Hughes Nic
Published: June 2012

Aims and objectives:

This UK study aimed to generate new ideas about training strategies for healthcare staff caring for people with dementia in the acute hospital setting.

Background:

A review of related literature exposed topical debate regarding current educational deficits, yet revealed few examples of the implementation of training initiatives for practising healthcare professionals.

Design:

A descriptive qualitative approach was used.

Methods:

Data were generated using two focus groups comprised of Staff Nurses (four) and Healthcare Assistants (three) working in a mixed gender acute elderly care unit in the North of England. Dialogues explored individuals’ experiences of delivering care to people with dementia hospitalised with physical illnesses and, usefully, their thoughts about learning in the workplace.

Results:

Four broad categories emerged from transcript-based analysis: learning about dementia; learning about the person; learning from each other; learning from specialists. Specific recommendations included the improvement of staff preparedness through fundamental training, improved flow of information about individuals, dementia-specialist input for situation-based advice, and structured opportunities to reflect on practice.

Conclusion:

The National Dementia Strategy for England emphasises the pressing need to improve care for people with dementia when they are admitted to hospital with physical illness, and highlights the importance of staff education in contributing to improved care. This study provides an insider view from a potential target population of such healthcare providers regarding their perceived educational needs.

Relevance to clinical practice:

The results of this study point the way forward to practical and achievable ways of increasing and improving knowledge about dementia, and enhancing skills in caring for people who are cognitively impaired, among general hospital staff.