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Comparison of physiologic ejection fraction responses to activities of daily living: implications for clinical testing.

The recent development of the VEST, an ambulatory radionuclide detector, to measure left ventricular ejection fraction may enhance the detection of ischemia during daily activities in patients with coronary artery disease. The normal range and determinants of ejection fraction responses to stimuli other than physical exercise, however, are not adequately characterized. Therefore, ejection fraction responses to various activities were measured in 18 normal subjects utilizing the VEST. Uniform increases (greater than 5%) in ejection fraction were seen during physical exercise, uniform decreases were seen during cold pressor testing and modest changes (including decreases greater than 5%) were seen in ejection fraction during mental stress, micturition and hyperventilation. Different forms of stress produced significantly different changes in ejection fraction, even when values were controlled for changes in heart rate. Ventricular loading conditions in the form of enhanced blood pressure responses during mental stress may have contributed to the relatively smaller changes in ejection fraction compared with those during exercise. Subjects demonstrating a decrease in ejection fraction during mental stress did not differ from other subjects in hemodynamic reactivity during mental testing but did have evidence of increased parasympathetic tone during cold pressor and bicycle exercise testing. The results reveal that normal ejection fraction response differs among varying physiologic stimuli. These changes are in part related to changes in heart rate and blood pressure; however, other factors, such as neurohumoral regulation, may also play a role. These findings indicate that the patient's activity and the setting in which it occurs must be considered when interpreting ambulatory ejection fraction responses.

Activities of Daily Living↗

Two-dimensional echocardiographic estimation of right ventricular ejection fraction in patients with coronary artery disease.

Two-dimensional echocardiographic determination of right ventricular ejection fraction was compared with right ventricular ejection fraction obtained by first pass radionuclide angiography in 39 patients with coronary artery disease. Apical four chamber and two chamber right ventricular views were obtained in 34 (87%) of the 39 patients, while a subcostal four chamber view was obtained in 31 patients (80%). Right ventricular ejection fraction by two-dimensional echocardiography was calculated by the biplane area-length and Simpson's rule methods using two paired orthogonal views and utilizing a computerized light-pen method for tracing the right ventricular endocardium. A good correlation (r = 0.74 to 0.78) was found between radionuclide angiographic and two-dimensional echocardiographic right ventricular ejection fraction for each method used. Patients with acute inferior myocardial infarction had the lowest right ventricular ejection fraction by radionuclide angiography and two-dimensional echocardiography (p less than 0.05 compared with patients with right coronary artery obstruction and no infarction). There were no differences in right ventricular ejection fraction between patients with acute and old inferior myocardial infarction by both techniques. No correlation was found between left and right ventricular ejection fraction by radionuclide angiography (r = 0.16). It is concluded that 1) right ventricular ejection fraction by two-dimensional echocardiography correlates well with radionuclide angiographic measurements and can reliably evaluate right ventricular function in coronary artery disease, 2) patients with inferior myocardial infarction have reduced right ventricular ejection fraction, and 3) changes in left ventricular ejection fraction do not directly influence right ventricular function.

Adult↗

Distribution of aged 14C-PCB and 14C-PAH residues in particle-size and humic fractions of an agricultural soil.

Organic matter is considered to be the single most importantfactor limiting availability and mobility of persistent organic pollutants (POPs) in soil. This study aimed to characterize the distribution of 14C-PCB (congeners 28 and 52) and 14C-PAH (fluoranthene and benzo[a]pyrene) residues in an Orthic Luvisol soil obtained from two lysimeter studies initiated in 1990 at the Agrosphere Institute (Forschungszentrum Jülich GmbH, Germany). The lysimeter soils contained a low-density OM fraction, isolated during soil washing, which contained a significant fraction (3-12%) of the total 14C-activity. Soils were also fractionated according to three particle sizes: >20, 20-2, and <2 microm. Relative affinity values of 14C-activity for the different particle sizes varied in the order 20-2 microm > (<2 microm) approximately (>20 microm) for the PCBs. Relative affinity values of 14C-activity for the different particle sizes varied in the order 20-2 microm > (<2 microm) > (>20 microm) for the PAHs. The distribution of 14C-PCB or 14C-PAH residues in the organic and inorganic matrixes of the particle-size fractions was determined using methyl isobutyl ketone (MIBK). 14C-PCB and 14C-PAH-associated activities were primarily located in the humin fraction of the 20-2 and <2 microm particle-size fractions of the soil. A small fraction was associated with the fulvic and humic acid fractions; these were quantitatively more important for the PAHs than the PCBs. There appeared to be a high degree of association of 14C-activity with the mineral fraction following MIBK separation of the humic fractions, ranging between 8 and 52% for 14C-PCBs and 57-80% for 14C-PAHs. The mineral (inorganic) component of the soils apparently played a significant (previously unreported) role in the sequestration of both PCBs 28 and 52 and the PAHs fluoranthene and benzo[a]pyrene.

Agriculture↗

Effects of dietary supplementation with Yucca schidigera Roezl ex Ortgies and its saponin and non-saponin fractions on rat metabolism.

Yucca schidigera Roezl ex Ortgies, family Lillaceae, was fractionated with butan-1-ol to yield a butanol extractable fraction (BE; saponin fraction) and a non-butanol fraction (NBE; non-saponin fraction). Four groups of eight male rats were allowed ad libitum access to diets supplemented with water (control) or 200 mg x kg(-1) total Y. schidigera (TOT) or 200 mg x kg(-1) of each of the fractions (NBE or BE). The effects of dietary supplementation with the fractions and their interactions in TOT were analyzed according to the factorial experimental design by two-way analysis of variance. All three supplementation groups displayed significantly reduced serum urea levels (P < 0.05). The TOT and NBE fractions were found to significantly increase serum insulin levels (P < 0.01) in the absence of any fluctuations in serum glucose levels. Urea cycle enzyme activities, namely, arginase (EC 3.5.3.1) and argininosuccinate lyase (EC 4.3.2.1), were significantly decreased (P < 0.05) in vivo, although no effect was observed in vitro. Both fractions displayed effects, indicating that the active constituents are present in both fractions.

Animal Feed↗

Analysis of carbon and nitrogen forms in soil fractions after the addition of 15N-compost by 13C and 15N nuclear magnetic resonance.

A quantitative laboratory assessment of the different C and N forms in soil humus fractions was carried out by incubation of a mineral substrate after the addition of (15)N-labeled compost. The experimental design included (i) preparation of the (15)N-labeled organic matter (city refuse compost, 640 g kg(-1) wheat straw and K(15)NO(3) composted for 80 days), (ii) a further 80 day incubation of a mixture of the labeled compost with a mineral soil (32 g kg(-1)), (iii) measurement of stable isotope ratios, and (iv) isolation and structural comparison by (13)C and (15)N cross-polarization, magic-angle spinning nuclear magnetic resonance (NMR) of different organic fractions, i.e., soluble, colloidal (humic and fulvic type), and particulate (free organic matter and humin), from both the compost and the compost-treated soil. The results showed that the amide forms dominated in all of the newly formed N compounds, but an increased amount of alkali insoluble organic fractions was observed after incubation of the soil. The analysis of the insoluble, particulate fractions shows that nonextractable amides constitute the major pool of newly formed N compounds. The particulate soil fraction isolated by flotation in CHBr(3)-MeOH contained 16.8% of the total soil N and 26% of the (15)N. The (13)C NMR spectra showed that the fulvic acid-like fraction (7.6% of the soil N, 8.8% of (15)N) consisted almost completely of a C=O-containing carbohydrate material, whereas the humic acid-like fraction (20.3% of the total soil N, 8.6% of (15)N) resembled an oxidized lignoproteic fraction containing the most significant aromatic domain. The water soluble fraction was, in both soil and compost, the one with the highest isotopic abundance of (15)N (96%), but the (15)N NMR spectrum revealed minor amounts of soluble mineral N in this fraction and the remainder consisting of amide compounds.

Carbon↗

Preparation and anti-HIV activities of aurintricarboxylic acid fractions and analogues: direct correlation of antiviral potency with molecular weight.

Aurintricarboxylic acid (ATA) was fractionated by a combination of dialysis, ultrafiltration, and gel permeation chromatography. The number average and weight average molecular weights of the ATA fractions were determined by the universal calibration method. The sulfonic acid analogue of ATA was prepared and separated in high and low molecular weight fractions. The phosphonic acid analogue of ATA was also synthesized. All of the ATA fractions were tested for prevention of the cytopathic effect of HIV-1 and HIV-2 in MT-4 cell culture as well as against HIV-1 in CEM cell culture. The abilities of the fractions and analogues to inhibit syncytium formation between HIV-1- and HIV-2-infected HUT-78 cells and uninfected MOLT-4 cells were evaluated. In addition, the fractions and analogues were tested for cytotoxicity in mock-infected MT-4 cells, prevention of the binding of the OKT4A monoclonal antibody to the CD4 receptor, inhibition of the binding of anti-gp120 monoclonal antibody to gp120, inhibition of attachment of HIV-1 virions to MT-4 cells, and inhibition of HIV-1 reverse transcriptase. In all of these assays except cytotoxicity, there was a correlation of potency with molecular weight. The higher the molecular weight, the higher the activity. Several of the lower molecular weight fractions of ATA, which bound to gp120 but not to CD4, prevented HIV-1 and HIV-2 cytopathicity. A similar profile was observed for the phosphonic acid analogue of ATA and the lower molecular weight fraction of the sulfonic acid analogue. The results on the ATA fractions indicate that the binding of ATA to gp120 in the absence of CD4 binding is sufficient for anti-HIV activity. The active compounds bind more avidly to gp120 than to CD4. The anti-HIV activity of the ATA fractions is due to inhibition of virus binding due to an interference with the gp120-CD4 interaction.

Antiviral Agents↗

Different immunoaffinity fractionation strategies to characterize the human plasma proteome.

Plasma proteins may often serve as indicators of disease and are a rich source for biomarker discovery. However, the intrinsic large dynamic range of plasma proteins makes the analysis very challenging because a large number of low abundance proteins are often masked by a few high abundance proteins. The use of prefractionation methods, such as depletion of higher abundance proteins before protein profiling, can assist in the discovery and detection of less abundant proteins that may ultimately prove to be informative biomarkers. But there are few studies on comprehensive investigation of the proteins both in the fractions depleted and remainder. In the present study, two different immunoaffinity fractionation columns for the top-6 or the top-12 proteins in plasma were investigated and both the proteins in column-bound and flow-through fractions were subsequently analyzed. A two-dimensional peptide separation strategy, utilizing chromatographic separation techniques, combined with tandem mass spectrometry (MS/MS) was employed for proteomic analysis of the four fractions. Using the established HUPO PPP criteria, a total of 2401 unique plasma proteins were identified. The Multiple Affinity Removal System yielded 921 and 725 unique proteins from the flow-through and bound fractions, respectively, whereas the Seppro MIXED 12 column yielded identification of 897 and 730 unique proteins from the flow-through and bound fractions, respectively. When more stringent criteria, based on searching against the reversed database, were implemented, 529 unique proteins were identified from the four fractions with the confidence in peptide identification increased from 73.6% to 99%. To determine whether the presence of nontarget proteins in the immunoaffinity-bound fraction could be attributed to their interaction with high abundance proteins, co-immunoprecipitation analysis with an antibody to human plasma albumin was performed, which resulted in an identification of 40 unique proteins from the coimmunoprecipitate with the more stringent criteria. This study illustrated that combining the column-bound and flow-through fractions from immunoaffinity separation affords more extensive profiling of the protein content of human plasma. The presence of nontarget proteins in the column-bound fractions may be induced by their binding to the higher abundance proteins targeted by the immunoaffinity column.

Amino Acid Sequence↗

Interactions of F1 fractions from different strains of Paracoccidioides brasiliensis with human complement and with human neutrophils.

The aim of our study was to investigate differences that might exist in the activation of the human complement system by F1 fractions from four different isolates of P. brasiliensis. Isolates HC and 18 (virulent), 265 (low virulence), and 9 (intermediate virulence, attenuated) were used; before the experiments, the virulence of isolates HC and 18 was recovered by in vivo passage in guinea pigs. The four isolates of the fungus were processed for purification of F1 fractions and the activation of the human complement system was studied by a kinetic method of hemolytic activity measurement. The incubation of F1 fractions in normal human serum resulted in different degrees of inhibition of the classical and alternative pathways. The F1 fraction from the low virulence isolate was more efficient than the F1 fraction from the virulent isolates (HC and 18). Previous absorption of sera with F1 fractions completely abolished classical pathway activation. Using zymosan, instead of F1, in the absorption process caused the same phenomenon, suggesting that natural or nonspecific antibodies are responsible for the classical pathway activation. The alternative pathway activation did not depend on these antibodies, but was enhanced by their presence. On the other hand, F1 fractions from virulent isolates were more active in the stimulation of neutrophil chemiluminescence compared with the F1 fraction from the low virulence isolate. Whole P. brasiliensis yeast cells (WYC) from two distinct strains, 18 and 265, showed the same patterns of response of those observed with the F1 fractions in the functions tested. These differences in the behavior of the F1 fractions as well as WYC in relation to human complement activation and consequently to neutrophil stimulation may correlate with the virulence of individual isolates and may contribute to the understanding of the inflammatory response generation and maintenance processes in paracoccidioidomycosis.

Animals↗

Inhaled nitric oxide fraction is influenced by both the site and the mode of administration.

OBJECTIVE: Inhaled nitric oxide (NO) can be delivered continuously or sequentially (= during inspiration) at different locations of the ventilation circuit. We have tested the influence of locations, modes of NO administration and the ratio of the inspiratory time over the respiratory cycle time (I/I + E ratio) on the accuracy of NO fractions, delivered by 2 devices: Opti-NO and Flowmeter. METHODS: We used a simplified lung model consisting of a ventilation circuit with a Y piece, a tracheal tube, a 150 ml dead-space volume and a 5 liter balloon. Three fractions (3, 6, 9 ppm) were administered continuously or sequentially, in controlled volume, in 4 different sites on the inspiratory branch above the Y piece: i) just after the water trap, ii) just before the Y piece; below the Y piece: iii) just after the Y piece, iv) into the endotracheal tube. In addition, different I/I + E ratios (25, 33, 50, 80%) were studied. The delivered NO fractions were measured in the balloon by chemiluminescence (CLD 700, Ecophysics). A linear regression analysis was used to test the relationship between administered and measured NO fractions for the 3 fractions (3, 6 and 9 ppm) in sequential and continuous modes. Intercept values were compared to zero and slopes to the identity line. RESULTS: When NO was administered in the continuous mode upstream the Y piece, NO fractions measured in the balloon corresponded to the administered fractions. In contrast, below the Y piece, the measured NO fractions were significantly lower than the administered NO fractions. In the sequential mode, above and below the Y piece, the delivered NO fractions were within the manufacturer's range. CONCLUSIONS: For the continuous NO delivery, locations above the Y piece are mandatory. However, locations below the Y piece imposes a sequential system, which can also be used for the sites located above the Y piece.

Administration, Inhalation↗

Risk stratification for sudden death: do we need anything more than ejection fraction?

Recent studies have emphasized the prognostic significance of left ventricular ejection fraction in patients with coronary and other types of heart disease. Ejection fraction relates as a continuous variable to mortality risk. In patients with a variety of underlying heart diseases, the lower the ejection fraction, the higher observed mortality. However, while ejection fraction is statistically associated with mortality, it is only one of multiple factors that impact on mortality. In order to assess the clinical utility of ejection fraction, it is necessary to assess the sensitivity as well as the specificity of commonly used cut points in identification of patients at mortality risk. In this manuscript, it is shown that ejection fraction lacks sensitivity, and its specificity is suspect in patients with chronic coronary artery disease. The dangers of focusing on ejection fraction are that many patients whose ejection fractions exceed commonly used cut offs experience sudden death. Finally, because ejection fraction is not specific in predicting mode of death, utilization of expensive technology such as the implantable defibrillator based solely on ejection fraction will not be very cost-effective.

Death, Sudden, Cardiac↗

Squamous lesions in lungs of rats exposed to tobacco-smoke-condensate fractions by repeated intratracheal instillation.

Twice-weekly intratracheal instillations in rats of up to 24 mg of Fraction (R + P)G suspended in either infusine (I) or buffered saline/gelatine (BS/G) gave rise to foci of squamous metaplasia of alveolar epithelium (SqM) and squamous neoplasms (SqN). Fraction (R + P)G, which is a fraction of cigarette-smoke condensate almost as tumorigenic for mouse skin as the nearly 30 × larger mass of condensate from which it is derived, could be given in this way for up to 40 weeks without excessive mortality or any marked effect on the rate of body-weight gain. By contrast, similar treatment with Fraction N(QG), a fraction having very low tumorigenic activity for mouse skin, induced no SqN and barely any excess of SqM over that induced by either vehicle alone.The effects of Fraction (R + P)G on the incidence of SqM and SqN were both time and dose related, the effect on SqM incidence being already evident after 10 weeks of treatment. No SqN seen were unequivocally malignant, though, due to the design of the experiment, only 5 rats exposed to Fraction (R + P)G were observed more than 60 weeks after the start of the experiment.Other changes in the lung, including aggregates of alveolar macrophages laden with golden-brown pigment (GBM) and foci of cuboidal/columnar metaplasia of alveolar epithelium (CCM), were frequently seen in response to both fractions. Fraction (R + P)G administered in I was more effective in causing SqM and SqN than the same fraction administered in BS/G. The implications of the findings are discussed, particularly the possibility that the intratracheal/instillation technique might be useful as a rapid bioassay for comparing the tumorigenicity of different cigarette-smoke condensates.

Animals↗

The biosynthesis of cytochrome c. Sequence of incorporation in vivo of [14C]lysine into cytochrome c and total proteins of rat-liver subcellular fractions.

1. In order to determine the initial intracellular site of synthesis of cytochrome c in the liver cell, groups of rats were injected with [(14)C]lysine and killed 7.5, 15, 30 and 60min. later. The livers were homogenized in 0.3m-sucrose and subcellular fractions obtained. The mitochondrial fraction was further subfractionated. Pure cytochrome c was isolated from extracts of each fraction, obtained first with water at pH4.0 and then with 0.15m-sodium chloride. 2. A comparison of the kinetics of incorporation of [(14)C]lysine into total protein for each particulate fraction showed the usual two different kinds of kinetics. Incorporation into all the mitochondrial subfractions and the nuclear fraction rose gradually to a plateau value at about 20min., in contrast with that into the two microsomal fractions which rose rapidly to a peak value about seven times that for the mitochondrial fractions. The kinetics for the incorporation into mitochondrial cytochrome c showed a plateau value at 30min. about three times that for the total mitochondrial protein. There was no difference in the specific radioactivity of the mitochondrial cytochrome c extracted with water or 0.15m-sodium chloride or between the different mitochondrial subfractions. In contrast, the cytochrome c isolated from water extracts of the microsomal fractions had a lower specific radioactivity than that obtained from the 0.15m-sodium chloride extract. The specific radioactivity of the latter showed a rapid rise to a peak value about four times that for the mitochondrial cytochrome c, and the shape of the curve was similar to that for the total protein of the microsomal fraction. The results suggest that cytochrome c is synthesized in toto by the morphological components of the microsomal fraction. It seems first to be bound tightly to a microsomal particle, passing then to a looser microsomal binding and being finally transferred to the mitochondria. The newly synthesized cytochrome c in the mitochondrion could not be differentiated from the old by its degree of extractability at pH 4.0.

Animals↗

Rat small-intestinal beta-galactosidases. Kinetic studies with three separated fractions.

1. Three fractions of beta-galactosidase activity from the rat small-intestinal mucosa were separated chromatographically. Two of these fractions had an acid pH optimum at 3-4, and the third one had a more neutral pH optimum at 5.7. 2. The two ;acid' beta-galactosidase fractions had considerably lower K(m) values for hetero beta-galactosides than for lactose. The V(max.) values were similar for all the substrates used (lactose, phenyl beta-galactoside, o-nitrophenyl beta-galactoside, p-nitrophenyl beta-galactoside and 6-bromo-2-naphthyl beta-galactoside). No difference could be detected between the two ;acid' fractions with respect to their enzymic properties (pH optimum, K(m) for the different substrates, K(i) for lactose as an inhibitor of the hydrolysis of hetero beta-galactosides, K(i) for phenyl beta-galactoside as an inhibitor of the hydrolysis of lactose, and relative V(max.) for the hydrolysis of different substrates). These two fractions probably represent different forms of the same enzyme. 3. The ;neutral' fraction had similar K(m) values for all the substrates hydrolysed, but with lactose as substrate the V(max.) was much higher than with the hetero beta-galactosides. This fraction did not split phenyl beta-galactoside or 6-bromo-2-naphthyl beta-galactoside at a measurable rate. 4. Lactose was a competitive inhibitor of the hetero beta-galactosidase activities of all the three fractions, and K(i) for lactose as an inhibitor in each case was the same as K(m) for the lactase activity. Phenyl beta-galactoside was a competitive inhibitor of the lactase activity of all the three fractions. These facts strongly indicate that in all the three fractions lactose is hydrolysed by the same active sites as the hetero beta-galactosides. 5. Human serum albumin stabilized the separated enzymes against inactivation by freezing and thawing.

Animals↗

Comparison of left ventricular ejection fraction and volumes in heart failure by echocardiography, radionuclide ventriculography and cardiovascular magnetic resonance; are they interchangeable?

AIMS: To prospectively compare the agreement of left ventricular volumes and ejection fraction by M-mode echocardiography (echo), 2D echo, radionuclide ventriculography and cardiovascular magnetic resonance performed in patients with chronic stable heart failure. It is important to know whether the results of each technique are interchangable, and thereby how the results of large studies in heart failure utilizing one technique can be applied using another. Some studies have compared cardiovascular magnetic resonance with echo or radionuclude ventriculography but few contain patients with heart failure and none have compared these techniques with the current fast breath-hold acquisition cardiovascular magnetic resonance. METHODS AND RESULTS: Fifty two patients with chronic stable heart failure taking part in the CHRISTMAS Study, underwent M-mode echo, 2D echo, radionuclude ventriculography and cardiovascular magnetic resonance within 4 weeks. The scans were analysed independently in blinded fashion by a single investigator at three core laboratories. Of the echocardiograms, 86% had sufficient image quality to obtain left ventricular ejection fraction by M-mode method, but only 69% by 2D Simpson's biplane analysis. All 52 patients tolerated the radionuclude ventriculography and cardiovascular magnetic resonance, and all these scans were analysable. The mean left ventricular ejection fraction by M-mode cube method was 39+/-16% and 29+/-15% by Teichholz M-mode method. The mean left ventricular ejection fraction by 2D echo Simpson's biplane was 31+/-10%, by radionuclude ventriculography was 24+/-9% and by cardiovascular magnetic resonance was 30+/-11. All the mean left ventricular ejection fractions by each technique were significantly different from all other techniques (P<0.001), except for cardiovascular magnetic resonance ejection fraction and 2D echo ejection fraction by Simpson's rule (P=0.23). The Bland-Altman limits of agreement encompassing four standard deviations was widest for both cardiovascular magnetic resonance vs cube M-mode echo and cardiovascular magnetic resonance vs Teichholz M-mode echo at 66% each, and was 58% for radionuclude ventriculography vs cube M-mode echo, 44% for cardiovascular magnetic resonance vs Simpson's 2D echo, 39% for radionuclide ventriculography vs Simpson's 2D echo, and smallest at 31% for cardiovascular magnetic resonance-radionuclide ventriculography. Similarly, the end-diastolic volume and end-systolic volume by 2D echo and cardiovascular magnetic resonance revealed wide limits of agreement (52 ml to 216 ml and 11 ml to 188 ml, respectively). CONCLUSION: These results suggest that ejection fraction measurements by various techniques are not interchangeable. The conclusions and recommendations of research studies in heart failure should therefore be interpreted in the context of locally available techniques. In addition, there are very wide variances in volumes and ejection fraction between techniques, which are most marked in comparisons using echocardiography. This suggests that cardiovascular magnetic resonance is the preferred technique for volume and ejection fraction estimation in heart failure patients, because of its 3D approach for non-symmetric ventricles and superior image quality.

Echocardiography↗

Fractional statistical mechanics.

The Liouville and first Bogoliubov hierarchy equations with derivatives of noninteger order are derived. The fractional Liouville equation is obtained from the conservation of probability to find a system in a fractional volume element. This equation is used to obtain Bogoliubov hierarchy and fractional kinetic equations with fractional derivatives. Statistical mechanics of fractional generalization of the Hamiltonian systems is discussed. Liouville and Bogoliubov equations with fractional coordinate and momenta derivatives are considered as a basis to derive fractional kinetic equations. The Fokker-Planck-Zaslavsky equation that has fractional phase-space derivatives is obtained from the fractional Bogoliubov equation. The linear fractional kinetic equation for distribution of the charged particles is considered.

Algorithms↗

Reduced right ventricular ejection fraction as a marker for idiopathic dilated cardiomyopathy compared with ischemic left ventricular dysfunction.

BACKGROUND: Evidence for the role of right ventricular (RV) function is emerging in patients with heart failure of different etiologies. Studies conducted in dilated cardiomyopathy (IDC) showed a high prevalence of RV dysfunction unrelated to the severity of pulmonary hypertension. The aim of the study was to investigate the role of RV dysfunction in ischemic versus nonischemic patients. METHODS: A series of 153 patients with left ventricular (LV) dysfunction (defined as a LV ejection fraction <45%) of either ischemic (n = 61, coronary artery disease [CAD] group) or nonischemic (n = 92, IDC group) origin were studied invasively. Besides routine catheterization data, RV volumes and ejection fractions were obtained angiographically. Reference data were collected in a control group of healthy subjects. RV dysfunction was defined as a RV ejection fraction <35% and ventricular concordance as a <10% difference between RV and LV ejection fraction. The LV/RV end-diastolic volume ratio was calculated to assess the relative dilatation of the ventricular chambers. Hemodynamic and angiographic data were compared in the 2 groups by univariate and multivariate logistic regression analysis. RESULTS: Patients with IDC and CAD had comparable LV ejection fractions (29% +/- 3% vs 31% +/- 8%, P not significant) and mean pulmonary pressures (27 +/- 12 mm Hg vs 26 +/- 11 mm Hg, P not significant); the LV/RV end-diastolic volume ratio was identical in the 2 groups (1.26 +/- 0.4 vs 1.24 +/- 0.4, P not significant). RV ejection fraction was significantly lower in IDC compared with CAD (33% +/- 10 % vs 46% +/- 11%, P <.0001), with a prevalence of RV dysfunction in the IDC group of 65% compared with 16% in the CAD group (P <.0001); similarly, the prevalence of ejection fraction concordance was 74% versus 33%, respectively (P <.0001). At multivariate analysis, a low RV ejection fraction was a powerful independent predictor of IDC compared with CAD (odds ratio 0.91, 95% confidence interval 0.87-0.94, P <.0001). RV dysfunction had a positive predictive value of 75% and a negative predictive value of 78% for the diagnosis of IDC; for ventricular concordance, these values were 81% and 69%, respectively. The correlation between mean pulmonary artery pressure and RV ejection fraction was weaker in the IDC group compared with the CAD group (R(2) = 0.032, P =.047 and R(2) = 0.172,P <.0001, respectively). CONCLUSION: In the presence of LV dysfunction, a reduced RV ejection fraction is a powerful marker for IDC compared with CAD, independent of age, pulmonary hypertension, LV function, and ventricular dimensions. These findings support the concept that IDC is frequently characterized by a biventricular involvement and that the presence of RV dysfunction represents a distinguishing feature of this disease.

Adult↗

Chemical and physical properties of fractionated chromatin.

Sonicated chicken reticulocyte chromatin was fractionated into transcriptionally active and transcriptionally repressed components. The active fraction is 8% of the whole chromatin but contains 70% of the newly synthesized chromosomal RNA. This RNA has five times as many hemoglobin RNA sequences as does the RNA in the repressed fraction. The amount of the active fraction in the chromatins of several tissues correlates with their synthetic activity. The molecular weight of the DNA of the repressed fraction is approximately twice that of the active fraction. Moreover, the configuration of repressed chromatin is much more compact, consistent with a much larger sedimentation constant. The transcriptionally active fraction displays a 6 degrees lower melting profile and is highly susceptible to DNase I relative to the repressed fraction. The active fraction contains twice as much non-histone protein and 15% less histone than the repressed fraction and is lacking the lysine-rich and much of the arginine-rich histones.

Animals↗

Isolation and characterization of three endosomal fractions from the liver of estradiol-treated rats.

Three distinct endosomal fractions were isolated in high purity from livers of estradiol-treated rats. Each fraction had characteristic physical and ultrastructural properties, but the lipid composition and major proteins of their membranes were similar and differed from those derived from the Golgi apparatus. Injected radioiodinated low density lipoproteins accumulated first in the fraction of intermediate density and later in the low density fraction. The latter was composed almost exclusively of lipoprotein-filled multivesicular bodies, most of which had a single membranous appendage. The fraction of intermediate density was composed of lipoprotein-filled vesicles that were smaller than multivesicular bodies and also had membranous appendages. The high density fraction was composed of membranes resembling the appendages of the two vesicular fractions. All three fractions were enriched in receptors for low density lipoproteins and asialoglycoproteins, but receptor concentrations were considerably reduced in multivesicular bodies. The fraction of intermediate density may represent the compartment of uncoupling of receptor and ligand (CURL) described by Geuze et al. [Geuze, H. J., Slot, J. W., Strous, G. J. A. M., Lodish, H. F. & Schwartz, A. L. (1983) Cell 32, 277-287]. CURL vesicles may lose some of their appendage as multivesicular bodies are formed. The high density fraction then may represent a receptor-recycling compartment.

Animals↗