Search PubMed⌕ Search

Biomedical subjects

E Page

Publications and source records attributed to E Page.

At least 73 records · Page 4Linked to original sources
PubMed1985

Developmental changes in internal structure of chick heart plasma membrane.

Although changes in electrophysiologically measurable membrane properties of chick embryo cardiac plasma membrane have been repeatedly documented during embryonic development, ultrastructural techniques were heretofore too insensitive to detect developmental changes in internal structure of this membrane. We report here significant structural changes detected by applying the quantitative analysis of Kordylewski, Karrison, and Page (Amer. J. Physiol. 245, H992-H997, 1983 and 248, H297-H304, 1985) to stereo imaged electron microscopic negatives of glutaraldehyde-fixed chick embryo hearts, freeze fractured and photographed with a goniometer stage. Between Hamburger-Hamilton stages 12+ (about 48 hr incubation) and 24 (about 96 hr incubation), plasmalemmal P-face particle density of ventricular myocytes increased from 2228 +/- 139 to 3063 +/- 109 (P less than 0.01); thereafter, measurements at stages 30, 37, 40, and 45 (7, 11, 15, and 19 days incubation) showed a slower significant linear increase which gave a least-squares line with a slope of 41 +/- 13 particles/day (P less than 0.01). Just before hatching, (stage 45) the value of 3762 +/- 234 was similar to, though slightly smaller than, the values of 4122 +/- 153 (8 days after hatching) and 4281 +/- 218 (adult chicken). These results indicate striking stage-dependent changes in the population of integral membrane proteins (channels, carriers, receptors, etc.), especially marked during early embryogenesis.

Animals↗
PubMed1985

Measurements on the internal structure of freeze-fractured cardiac plasma membrane.

We describe a quantitative analysis of the internal structure of cardiac plasma membranes freeze fractured in situ, including the P-face particle density (lambda), the P-face particle diameter (d), the percent of fracture face area occupied by particles (Ap), and the spatial distribution of particles (random, clustered, or ordered). This analysis has been applied to seven sheep hearts to compare the plasmalemmal internal structures in ventricular and atrial myocytes and Purkinje strands of the same hearts and also to myocytes of frog, chicken, rabbit, and rat ventricles (to compare internal plasmalemmal structure of different vertebrate classes). Measurements were made on tissues conventionally prepared for freeze fracture by glutaraldehyde fixation and cryoprotection. We found that, in the same sheep hearts, lambda and Ap for ventricular plasmalemma significantly exceeded those for atrial plasmalemma and that the distribution of atrial P-face particles was more clustered than that for ventricle. d and Ap for frog ventricular plasmalemmal P-face significantly exceeded values for some of the other vertebrates.

Animals↗
PubMed1985

Cell biology and protein composition of cardiac gap junctions.

The gap junctions that electrically couple mammalian myocardial cells have high (12,000-17,000/micron2)surface densities of channel-containing elements (connexons), undulating surfaces, and approximately hexagonally arrayed connexons disposed in small domains rotated with respect to one another. Optical diffraction combined with image processing of negatively stained isolated rabbit heart gap junctions shows six protein subunits surrounding the cell-to-cell channel and suggestive (but not conclusive) evidence for protein connections between connexons. Biochemical studies indicate that the six identical relative molecular weight (Mr) 47,000 subunits of mammalian cardiac gap junctions differ from liver gap junctions in the presence of a covalently bound Mr 17,500 cytoplasmic surface component that can be visualized electron microscopically in thin-sectioned and freeze-etched hearts. The cytoplasmic surface component is susceptible to cleavage by an alkaline serine protease released from mast cell granules by high ionic strength solutions (0.6 M KI) used to extract myofibrils during gap junction purification. Interlocking of connexons from coupled cells in the gap involves hydrogen bonding between protein subunits of the connexons.

Animals↗
PubMed1985

Saxitoxin binding and "fast" sodium channel inhibition in sheep heart plasma membrane.

We compared specific [3H]saxitoxin (STX) binding to isolated sheep ventricular sarcolemmal vesicles with inhibition of maximal action potential upstroke velocity (V max) by STX and tetrodotoxin (TTX) in sheep trabeculae carneae. In sarcolemmal vesicles purified 30 to 40 times over cardiac homogenate, STX binding at 0 degrees C in Na-free solution exhibited both high-affinity sites (KD = 0.22 +/- 0.05 nM, n = 85 +/- 13 fmol/mg protein) and low-affinity sites (KD = 11 +/- 4 nM, n = 360 +/- 42). The STX-inhibition constant for V max in Tyrode solution at 37 degrees C was 280 nM. TTX was approximately 10% as effective as STX in displacing bound [3H]STX and inhibiting V max. Allowing for different experimental conditions during [3H]STX binding and V max measurements, we suggest that the low-affinity sites are physiologically relevant "fast" Na+ channels of myocardial cells. Combining morphometric data for plasmalemmal area of mammalian cardiac myocytes with n for low-affinity sites, we estimate 3.6-7.6 fast Na+ channels/micron2 plasmalemma.

Action Potentials↗
PubMed1985

Differences between cytoplasmic surfaces of deep-etched heart and liver gap junctions.

We have compared the ultrastructures of the cytoplasmic surfaces (CS) of isolated, glutaraldehyde-fixed gap junctional pellets from rat ventricles and liver by rapid freezing on a liquid helium-cooled surface, freeze fracture, deep etching, and double-axis rotary replication (J. Microsc. Oxford 137: 121-123, 1984). Deep-etched unproteolyzed cardiac junctions [protein subunit relative molecular wt (Mr) 44,000-47,000], isolated with phenylmethylsulfonylfluoride (PMSF) [Am. J. Physiol. 246 (Heart Circ. Physiol. 15): H865-H875, 1984; C.K. Manjunath, G.E. Goings, and E. Page. Proteolysis of cardiac gap junctions during their isolation from rat hearts. J. Membr. Biol. In press.] had particulate CS, while proteolyzed cardiac junctions (subunit Mr 29,500) made without PMSF and liver junctions (Mr 28,000) made with or without PMSF had nonparticulate CS. Taken together with our previous findings that electron micrographs of thin-sectioned isolated unproteolyzed cardiac junctions have urea-resistant fuzzy CS coatings [Am. J. Physiol. 246 (Heart Circ. Physiol. 15): H865-H875, 1984], that proteolyzed cardiac junctions and isolated liver junctions lack this fuzzy layer, and that the CS of in situ cardiac junctions is fuzzy [J. Membr. Biol. 78: 147-155, 1984; Am. J. Physiol. 246 (Heart Circ. Physiol 15): H865-H875, 1984], and published data that in situ freeze-etched liver gap junctions are nonparticulate (Cell 30: 395-406, 1982), these new observations strongly indicate that CS components of heart and liver gap junction proteins are structurally different.

Animals↗
PubMed1985

[Prospective study of the value of echocardiography and myocardial scintigraphy with Tc 99m pyrophosphate during the acute stage of right ventricular infarction].

The aim of this study was to compare the clinical values of 99mTc pyrophosphate scintigraphy and M mode and 2D echography in the diagnosis of right ventricular infarction and in the predicting of some of its complications. Fifty-two patients were prospectively studied by echocardiography and scintigraphy at the acute stage of inferior wall infarction. Scintigraphy was performed in the antero-posterior and 45 degrees left anterior oblique incidences during the first 3 days of infarction. Right ventricular infarction was diagnosed if the right ventricular fixation was separated from the left ventricle by fixation at the base of the septum. Echocardiography was performed at an early stage by the usual 3 incidence. Dilatation of the right ventricle on the parasternal and submitral incidences; abnormal right ventricular contraction was searched for in all the incidences. The following results were obtained: scintigraphy showed a localised fixation allowing a topographic study in 40/52 patients (77%); satisfactory echocardiographic studies were obtained in 46/52 patients (88.5%). Signs of right ventricular infarction: scintigraphy showed signs of necrosis of the right ventricle in 12/40 patients (30%) who had a localised fixation; echocardiography showed dilatation (greater than 25 mm) of the superior part of the right ventricle with a right/left ventricle ratio greater than 0.5 in 16/46 patients (37%) with interpretable studies and obvious abnormalities of right ventricular wall motion in 7 patients (15.2%), less obvious in 10 other patients (22%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1984

Detergent sensitivity and splitting of isolated liver gap junctions.

Isolated rat liver gap junctions were split by two methods. In the first method, isolated gap junctions were stabilized by cross-linking their cytoplasmic surfaces with glutaraldehyde under conditions that prevented the entry of glutaraldehyde into the "gap" region. The "stabilized" junctions were then split in the junctional gap with SDS. In the second procedure, unfixed gap junctions were split by incubation in urea-containing solutions. Junctional splitting was monitored by electron microscopy of thin sectioned and freeze fractured membrane pellets. Sidedness of the split junctional membranes was defined by labeling their cytoplasmic surfaces with glutaraldehyde-activated ferritin before splitting with urea. Gap junctional splitting did not result in any loss of protein components as determined by SDS-gel electrophoresis. The glutaraldehyde cross-linking procedure was also used to determine the effects of various detergents on the protein-protein interactions in the "gap" region. Of the detergents tested, only SDS caused junctional splitting.

Animals↗
PubMed1984

Cytoplasmic surface and intramembrane components of rat heart gap junctional proteins.

Gap junctions were purified from rat hearts in the presence of absence of proteolysis inhibitors and examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and electron microscopy of thin sections. In absence of proteolysis inhibitors or in presence of ethylenediaminetetraacetic acid or leupeptin, gap junctions contained a single major protein band at relative molecular weight (Mr) 29,500 and minor bands at Mr 44,000-47,000, 17,750, and 16,500 and showed smooth cytoplasmic surfaces in electron micrographs. SDS-PAGE of junctions prepared with phenylmethylsulfonylfluoride (PMSF) showed markedly decreased intensity of the Mr 29,500 band and increased intensity of bands at Mr 44,000, 45,500, and 47,000; electron microscopy of these gap junctions showed presence of a fuzzy layer on their cytoplasmic surfaces. Urea (8 M) could not remove this fuzzy layer. In electron micrographs of rat ventricular myocytes, cytoplasmic surfaces of gap junctions were fuzzy. We conclude that rat heart gap junction protein consists of an intramembrane component (Mr 29,500) that extends into the "gap" and a cytoplasmic surface component (Mr 14,500-17,500) that corresponds to the fuzzy layer and is hydrolyzable by a serine protease.

Animals↗
PubMed1984

[Bilateral coronaro-pulmonary fistula. Apropos of a new case with review of the literature].

Two coronary pulmonary fistulae were demonstrated between the right coronary and left anterior descending arteries and the main pulmonary artery at coronary angiography, in a 66 year old woman with a continuous murmur in the third left intercostal space. This double malformation, though uncommon is not rare (18 previously published cases). It is usually diagnosed late (17 to 76 years) and the presentation is limited in half the cases to a localised continuous murmur, the localisation of which may simulate a patent ductus arteriosus. The hypothesis of a supernumerary coronary artery arising from the main pulmonary artery is suggested by the constancy of the anatomical characteristics of the reported cases. Eight patients presented typical attacks of angina which were due to severe coronary atherosclerosis, affecting two or three main vessels except in one case. Therefore, it is unlikely that these fistulae cause coronary insufficiency by a coronary steal syndrome. However, this mechanism may aggravate symptoms in patients with coronary artery disease and necessitate surgical cure of the fistulae at the same time as coronary bypass surgery. On the other hand, surgery does not seem to be indicated in asymptomatic patients.

Aged↗
PubMed1984

[Role of left ventricle angioscintigraphy during exercise in the diagnosis of coronary disease. Comparison of static and dynamic exercise].

The aim of this study was to compare the diagnostic value of exercise stress testing, Thallium 201 myocardial scintigraphy or after administration of dipyridamole and left ventricular angioscintigraphy performed either during a static (handgrip) or dynamic exercise (bicycle ergometry) for the positive diagnosis of stenosing coronary artery disease. The exercise angioscintigraphy was performed at equilibrium with 99m Tc red blood cell labelling. The global ejection fraction and that of seven radial segments of the left ventricle were measured, the data being recorded within a period of 2 minutes. The handgrip consisted in compressing a dynamometric ball at 1/3 maximal force for 3 minutes, with both hands; the ergometric exercise was increased by 30 Watt 2 minute increments until a positive ECG or 85% of the theoretical maximal heart rate for age was obtained. Normal subjects (n = 29) increased their global (+ 8%) and regional ejection fractions in each of the seven segments (p less than 0.05) during ergometric exercise: there was no significant change of global (-3% NS) or segmental ejection fractions during the handgrip exercise. In the coronary group (at least one greater than 70% stenosis) (n = 61) the fall in global ejection fraction was the same (-14%) with both forms of exercise; a similar fall in the segmental ejection fraction in the territory distal to the stenosis was observed with the handgrip (-22%) and bicycle ergometry (-28% NS). Dynamic exercise testing seemed superior to handgrip exercise. Therefore, the finding of an abnormal global ejection fraction on exercise (i.e. either a global ejection fraction less than the lower limit of normal on exercise, or lower than the global ejection fraction at rest), or of an abnormal regional ejection fraction (i.e. either a regional ejection fraction less than the lower limit of normal over at least 3 segments, or a regional ejection fraction on exercise lower than the regional ejection fraction at rest over at least 3 segments) detected coronary artery disease with a sensitivity of 94% and a specificity of 72%. Dynamic exercise angiography seemed to be more sensitive than maximal ECG stress testing (94% compared to 64%) more rapidly positive (p less than 0.05), as sensitive (94% compared to 83% NS) than Thallium myocardial scintigraphy, but less specific (72% compared to 90%, p less than 0.05), and as unspecific as ECG stress testing.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

[Hyperaldosteronism in the acute phase of myocardial infarction. Effects of its treatment on the prevention of ventricular fibrillation].

Many metabolic and hormonal changes are observed during the acute phase of myocardial infarction (glucose metabolism, lipoproteins...). Mineralocorticoid function may also be disturbed but there have been few studies of this problem. The aim of this study was to confirm the elevation of serum aldosterone during the acute phase of myocardial infarction and to determine the effects of antialdosterone treatment in these patients. Hyperaldosteronism was confirmed in 74% of 72 consecutive patients admitted for acute myocardial infarction, in 85% if patients previously treated by an antialdosterone drug or admitted after the acute phase are excluded, and in 96% if patients with cardiac failure are included. One thousand consecutive patients admitted for myocardial infarction were given an antialdosterone agent systematically (intravenous potassium canrenoate , 600 mg daily for 5 days). The serum and red blood cell potassium concentrations rose, the number of ventricular extrasystoles and the administration of anti-arrhythmic drugs fell, and, above all, the prevalence of ventricular fibrillation decreased significantly: 0,8% (p less than 0,001), compared with comparable previously reported series.

Acute Disease↗
PubMed1984

[Treatment of cardiac failure with refractory edema using extracorporeal ultrafiltration].

Thirteen patients with chronic congestive cardiac failure and refractory oedema were treated by haemodialysis. All patients had severe cardiac failure (Class IV NYHA) due to primary myocardial disease (5 cases), ischaemic heart disease (4 cases) or valvular heart disease (4 cases). Haemodialysis was performed via a Shaldon Y-shaped catheter in the internal jugular vein, with input and output through the same catheter using an alternating clamp. Filtration was carried out through a highly permeable membrane by a simple hydrostatic pressure gradient without a dialysis bath. The sessions were monitored haemodynamically by measuring the pulmonary artery pressures. The mean weight loss was 4.9 +/- 0.4 kg obtained after 3 three hour dialysis sessions with 24 hour intervals between each session (mean filtration flow = 12 ml/min). Hypotension was observed in one patient with low initial pulmonary artery pressures; two patients with severe valvular stenosis (1 mitral stenosis; 1 aortic stenosis) failed to lose weight. In the 10 remaining cases, there was a clearcut symptomatic improvement (5 patients Class III; 5 patients Class II NYHA) with total regression of oedema. There was a significant fall in pulmonary artery (mean PAP 40.5 +/- 6.5 mmHg to 34.6 +/- 6.5 mmHg; p less than 0.001) and pulmonary capillary pressure (27.6 +/- 6.9 mmHg to 22.5 +/- 5.8 mmHg; p less than 0.05) in these 10 cases. Cardiac output did not change significantly (cardiac index 2.2 +/- 0.5 l/m2/min compared to 2.3 +/- 0.4 l/m2/min after dialysis).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1983

Freeze-fractured cardiac gap junctions: structural analysis by three methods.

In isolated rat left ventricles perfused at 37 degrees C with control, Ca2+-loading, and Ca2+-depleting solutions (pH 7.3-7.4), we have investigated freeze-fractured gap junctional membrane by three quantitative techniques designed to correlate changes in junctional permeability with changes in membrane ultrastructure, i.e., 1) optical diffraction, 2) direct measurement of center-to-center spacings and particle diameters, and 3) statistical analysis of the spatial distribution of P-face particles based on analysis of nearest neighbor center-to-center distances. Junctions fixed either with glutaraldehyde or by quick freezing were compact, with closely packed rather than dispersed membrane particles even in the permeable state. Analysis of variance for all three methods indicated that replication was a major variability source limiting structural discrimination. Discrimination between random, regular, and clustered distributions depended critically on particle diameter and particle density. The results differ from published data of others on mammalian ventricular gap junctions and from measurements by our laboratory on sheep cardiac Purkinje fibers (J. Ultrastruct. Res. 75: 195-204, 1981).

Animals↗
PubMed1983

P-face particle density of freeze-fractured vertebrate cardiac plasma membrane.

P-face particle density of freeze-fractured cardiac plasmalemma provides an estimate of the total population of membrane channels, carriers, and receptors that insert into or traverse unit area of lipid bilayer. We have determined the size of this population of integral membrane protein assemblies by counting the number of P-face particles per square micron of plasmalemma in freeze-fractured hearts, using stereoimaged replicas tilted with a goniometer stage in the electron microscope. Particle numbers per square micron were 4,525 +/- 231, 4,799 +/- 235, 4,122 +/- 153, 4,281 +/- 218, and 5,848 +/- 300 for ventricular myocyte plasmalemmas of rat, rabbit, 8-day chick, adult chicken, and frog, respectively. These values are at least two times greater than published values, in which stereo imaging was not used. Published ligand-binding studies indicate that only the surface density of the Na+-K+ pump sites can account for a significant fraction of P-face particles; the rest so far lack functional correlates. Particle density of frog heart plasmalemma significantly exceeded particle densities of chicken and mammalian plasma membranes.

Aging↗
PubMed1983

[Aortic and tricuspid valve involvement caused by myxoid degeneration associated with a severe mitral prolapse. Apropos of 2 patients undergoing a double valve replacement].

Idiopathic mitral valve prolapse due to severe myxoid degeneration may be associated with aortic and/or tricuspid valve disease of the same aetiology. These localisations, which usually give rise few symptoms, can be detected by echocardiography. Sometimes, however, they may give rise to serious valvular regurgitation requiring surgical correction at each diseased valve. The authors report two cases of "floppy" mitral valve prolapse, the first requiring mitral and tricuspid, and the second, mitral and aortic, valve replacement. These cases underline the value of especially by echocardiography, in view of their serious complications.

Adult↗
PubMed1982

Isolation and protein composition of gap junctions from rabbit hearts.

We have modified a method for isolating gap-junctional membrane from mouse hearts [Kensler & Goodenough (1980) J. Cell Biol. 86, 755-764] to isolate gap junctions of comparable purity from rabbit hearts more rapidly, with better yield, and without resort to non-ionic detergents. Purification was monitored by electron microscopy of thin-sectioned membrane pellets and by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Gap junctions were obtained as vesicles whose mean surface area approximated that of junctions in intact myocardial cells. About 10-20% of the vesicles were ferritin-impermeable. Approx. 125 micrograms of membrane protein was obtained per 8 g of rabbit heart. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of purified gap junctions showed five major protein bands of mol.wts. 46 000, 44 000, 33 000, 30 000 and 28 500 that co-purified with the junctions. This protein composition was nearly identical with that published for gap junctions of mouse hearts, and differed markedly from the protein composition of gap junctions from non-excitable cells (lens and liver). The constancy of junctional protein composition between hearts of two different species and its non-identity with that from liver and lens suggest that, although gap-junctional structure in mammalian tissues seems to be remarkably similar by electron-microscopic techniques, junctional-channel protein composition actually varies from tissue to tissue and may be adapted to the permeability requirements of the tissue.

Animals↗