[Modifications of myocardial protein phenotype in cardiac hypertrophy and failure].
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Actinin↗
Biomedical subjects
K Schwartz
Publications and source records attributed to K Schwartz.
Characterization and expression of the rat heart sarcoplasmic reticulum Ca2+-ATPase mRNA.
Sarcoplasmic reticulum Ca2+-ATPase cDNA clones have been isolated from an adult rat heart cDNA library and the nucleotide sequence of the Ca2+-ATPase mRNA determined. The sequence has an open reading frame of 997 codons. It is identical to a cDNA isolated from a rat stomach cDNA library and 90% isologous to the rabbit and human slow/cardiac cDNAs. Nuclease S1 mapping analysis indicates that this sequence corresponds to the main Ca2+-ATPase mRNA present in heart and in slow skeletal muscle and that it is expressed in various proportions in smooth and non-muscle tissues, together with another isoform which differs from the cardiac form in the sequence of its 3'-end.
Amino Acid Sequence↗
Atrial natriuretic factor messenger ribonucleic acid and peptide in the human heart during ontogenic development.
We have investigated the level of expression of the atrial natriuretic factor (ANF) gene in the human heart during ontogenic development by determining the concentrations of ANF messenger ribonucleic acid (ANF mRNA), of immunoreactive ANF (IR ANF) and of receptor reactive ANF (RR ANF), in myocardial samples of the various heart chambers. We found the level was high and almost identical in the left and right ventricles in utero. It gradually decreased during ontogenic development to reach the low adult levels, with a more rapid decrease in the right than in the left ventricle after birth. In the atria, ANF gene expression was high as early as the 13th week of gestation, was higher in the right than in the left atrium, and appeared little affected by ontogenic development.
Aging↗
Comparison of Sinemet CR4 and standard Sinemet: double blind and long-term open trial in parkinsonian patients with fluctuations.
"Wearing-off" effect, the most common form of levodopa-induced fluctuations, seems to be related to the short plasma half-life of the drug. More sustained plasma levodopa levels may be achieved with a new controlled-release formulation of carbidopa/levodopa, Sinemet CR4. We studied 20 patients, 12 men and 8 women, with Parkinson's disease complicated by "wearing-off" phenomenon. Mean age was 61.1 +/- 8.1 years, duration of symptoms 8.3 +/- 2.4 years, and the Hoehn-Yahr stage 3.0 +/- 0.9. In a 12-week double-blind study, the average number of tablets administered per day decreased from 5.7 +/- 1.2 to 3.8 +/- 0.7 when Sinemet CR4 (50/200) was substituted for the standard Sinemet (25/100) (p less than 0.001). However, this was at the expense of reducing the "on" time (without dyskinesia) from 9.3 +/- 4.6 to 7.5 +/- 4.3 (p less than 0.05), although the total "on" time did not significantly change. In a long-term follow-up of 18 patients, the "on" time with dyskinesia and morning dystonia significantly increased (p less than 0.05). There was no significant change in the total daily dosage of levodopa, but the daily number of doses and tablets significantly decreased (p less than 0.001). Despite increased dyskinesia, most patients preferred taking fewer tablets and have elected to continue taking Sinemet CR4 instead of standard Sinemet. Sinemet CR4 seems to offer a new and effective strategy for the management of levodopa-related fluctuations.
Aged↗
Cardiac hypertrophy: from fetal to fatal?
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Adaptation, Physiological↗
Atrial natriuretic factor gene expression in rat ventricle during experimental hypertension.
Activation of atrial natriuretic factor (ANF) gene expression has been reported in the rat ventricle in several models of hemodynamic overload, including hypertension. However, nothing is known about the potential trigger(s) and the time course of this activation during the development of hypertension. We measured aortic blood pressure, left ventricular hypertrophy (LVH), and left ventricular ANF mRNA concentration (LV ANF mRNA) in a first group of rats (study A) killed at 5 and 18 h and 2, 4, 6, 9, 15, and 30 days after suprarenal coarctation of the abdominal aorta. Coarctation induced a progressive rise in aortic blood pressure and left ventricular mass. We observed a biphasic accumulation of ANF mRNA in the left ventricle with a peak at day 4 averaging 20 times the control value long before stable hypertension and hypertrophy were achieved, followed by a decrease until day 9. This decrease was followed by a new rise, which stabilized around 10 times the control value seen during stable hypertension and hypertrophy. In a second group of rats killed at days 4 and 30 (study B), we determined, in addition to the previous parameters, left ventricular end-diastolic pressure (LVEDP), plasma renin (PRC), and plasma ANF concentrations. LVEDP and PRC were markedly increased at day 4, but at day 30, during stable hypertension and hypertrophy, these parameters returned to control values, whereas plasma ANF was increased. Using immunocytochemistry, we looked in a third group of rats (study C) for the presence of the immunoreactive peptide at days 4 and 30.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Saccadic tracking of a periodic target motion in the cat.
Cats were tested for their ability to follow a dot target which periodically jumps horizontally from side to side. They can learn to perform saccadic tracking of various stimulus frequencies, and often they produce saccades predicting the target displacements. The preferred stimulus frequency for response to synchronize was in the 0.5-Hz range. Cats tend to undershoot the target. They also tend to adopt a strategy of locking predominantly to one direction of displacement, but they can be trained to reverse this preferred side or to lock to both sides. Saccades to the preferred side are more accurate, and longer and slower in comparison to saccades to the other side, thus demonstrating a velocity-accuracy trade-off phenomenon in the cat responses. Saccadic characteristics as expressed by the main sequence are apparently a stable property independent of the stimulus frequency.
Acceleration↗
Nonsynchronous accumulation of alpha-skeletal actin and beta-myosin heavy chain mRNAs during early stages of pressure-overload--induced cardiac hypertrophy demonstrated by in situ hybridization.
The development of cardiac hypertrophy secondary to pressure overload is accompanied by isoformic changes of contractile proteins such as myosin and actin. 35S-Labeled complementary RNA (cRNA) probes and in situ hybridization procedures were used for analysis of the regional distribution of newly formed transcripts from alpha-skeletal actin (alpha-sk-actin) and beta-myosin heavy chain (beta-MHC) genes during the early stages of pressure overload. The study was performed in 25-day-old rats submitted to a thoracic aortic stenosis and killed after surgery at times ranging from 4 hours to 3 days. Neither alpha-sk-actin nor beta-MHC messenger RNA (mRNA) was detected in the hearts of normal and sham-operated animals. However, alpha-sk-actin mRNA accumulated throughout the entire left ventricle as early as 4 hours after aortic stenosis, and by 12 hours was also detected in the left atrium. In contrast, beta-MHC mRNA was hardly detectable before day 1, and by days 2-3 was mainly restricted to the inner part of the left ventricle and around the coronary arteries. The absence of spatial and temporal coordination in the accumulation of alpha-sk-actin and beta-MHC mRNAs indicates that different signals and/or regulatory mechanisms are implicated in the induction of the two genes in response to hemodynamic overload.
Actins↗
[Left ventricular accumulation of messenger ribonucleic acid coding for the natriuretic atrial factor in various experimental models of cardiac hypertrophy in rats].
Cardiac hypertrophy secondary to chronic hemodynamic overload is associated with an increase in the ventricular concentration of the messenger ribonucleic acid (mRNA) coding for the atrial natriuretic factor (ANF). We have compared, in male Wistar rats (10 week old, 200-220 g), using dot blot hybridization and a specific oligonucleotide probe, the left ventricular concentration of ANF mRNA (LV ANF mRNA) in 4 models of chronic hemodynamic overload inducing various patterns of left ventricular hypertrophy (LVH): a model of volume overload, the aortocaval fistula (ACF, n = 15); a model of pressure overload, coarctation of the abdominal aorta (CoA, n = 13) and 2 models of mixed overload, aortic regurgitation (AR, n = 7) and myocardial infarction (INF, n = 18). A month after surgery, LVH was 49 p. 100 for AR, 41 p. 100 for Co A and 21 p. 100 for ACF. Instead of a severe infarction, LVH was 6 p. 100 in INF demonstrating a marked hypertrophy of the non infarcted myocardium. For each model, LV ANF mRNA was compared to that in a corresponding group of sham-operated control rats and expressed as the percentage of ANF mRNA concentration in the pooled atria of the controls. In the 4 control groups LV ANF mRNA was 1 +/- 0.5 p. 100 that in the corresponding atria and the sham-operated animals were thus pooled in a single group (n = 19). In the 4 models of LVH, LV ANF mRNA markedly increased as compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Characterization of the atrial natriuretic peptide clearance receptor using a vaccinia virus expression vector.
A recombinant vaccinia virus has been used to direct the expression of the atrial natriuretic peptide clearance receptor (ANP C-receptor) in mammalian cell lines normally deficient in this protein. The recombinant receptor binds 125I-ANP-(102-126) in a specific and saturable manner and carboxyl-terminal truncated and internal-deleted ANP analogs bind to this site with high affinity. Following the covalent attachment of 125I-ANP-(102-126) to the recombinant ANP C-receptor, the protein exhibits an electrophoretic mobility identical to that of the native ANP C-receptor of cultured vascular cells. Expression of the ANP C-receptor in heterologous cells does not affect ANP-stimulated cyclic GMP accumulation, confirming previous reports that this novel ANP receptor subpopulation is not coupled to cyclic GMP metabolism. Furthermore, specific antisera, generated by inoculating rabbits with living recombinant virus, block 125I-ANP binding to the ANP C-receptor but do not inhibit ANP stimulation of cyclic GMP, supporting the existence of two receptor subpopulations that are functionally and immunologically distinct.
Animals↗
D-amino acid-substituted atrial natriuretic peptide analogs reveal novel receptor recognition requirements.
The introduction of D-amino acid residues into peptide hormones has been traditionally utilized in structure-activity studies to probe the conformational requirements of ligand-receptor interactions. A study was undertaken to examine the effect of D-amino acid substitutions into the atrial natriuretic peptide molecule on interactions with distinct subpopulations of specific membrane-associated receptors of bovine aortic smooth muscle cells. Competitive binding analysis revealed that each of 15 synthetic D-amino acid-substituted analogs showed comparable affinities for C-ANP receptors, a class of specific receptors which have been proposed to mediate the sequestration and metabolic clearance of ANP. The relative affinities of all 15 analogs did not differ more than 10-fold. In contrast, the interaction of the ANP analogs with a second receptor pool (B-ANP receptors), which is coupled to the stimulation of particulate guanylate cyclase, varied over a 1000-fold range of potency consistent with expectations for a receptor that displays rigorous conformational specificity. The indiscriminant selectivity of C-ANP receptors for D-amino acid-substituted ANP analogs is unprecedented for hormone receptors involved in biological signal transduction. These results, when coupled with the inability to correlate any direct in vitro biological effect associated with C-ANP receptor occupancy supports the hypothesis that the C-ANP receptor protein is a novel transport protein involved in the metabolic clearance of ANP.
Affinity Labels↗
(Ca2+ + Mg2+)-dependent ATPase mRNA from smooth muscle sarcoplasmic reticulum differs from that in cardiac and fast skeletal muscles.
We have investigated some characteristics of the sarcoplasmic reticulum (Ca2+ + Mg2+)-dependent ATPase (Ca2+-ATPase) mRNA from smooth muscle using specific cDNA probes isolated from a rat heart cDNA library. RNA blot analysis has shown that the Ca2+-ATPase mRNA expressed in smooth muscle is identical in size to the cardiac mRNA but differs from that of fast skeletal muscle. S1 nuclease mapping has moreover shown that the cardiac and smooth muscle isoforms possess different 3'-end sequences. These results indicate that a distinct sarcoplasmic reticulum Ca2+-ATPase mRNA is present in smooth muscle.
Animals↗
Suicide attempts and resuscitation dilemmas.
The conventional psychiatric opinion that suicide is a manifestation of psychiatric illness may not apply to circumstances in which suicide or the refusal of life-sustaining medical treatment results from the rational decisions of autonomous individuals. As medical technology advances, questions about the prolongation of life and the discontinuation of medical treatment have become commonplace in the medical setting. In this context, contradictions may exist between the principle of patient autonomy and that of physician responsibility. Dilemmas about treatment decisions that emerge from these conflicting perspectives are highlighted in this article. We report two cases of attempted suicide in the context, respectively, of (1) terminal illness and (2) advanced age. Some of the complex psychiatric, ethical, and legal issues related to the case reports are addressed.
Acquired Immunodeficiency Syndrome↗
Effect of enprostil on plasma glucose, insulin and lipid metabolism in patients with non-insulin-dependent diabetes mellitus.
Measurements of various aspects of glucose, insulin and lipid metabolism were made before and after the administration of enprostil (a synthetic dehydroprostaglandin E2) for one week to ten patients with non-insulin-dependent diabetes mellitus (NIDDM). Both fasting (P less than 0.01) and postprandial (P less than 0.001) plasma glucose concentrations were significantly lower after one week of enprostil, and 24 hour urinary glucose excretion was reduced from (mean +/- SEM) 47 +/- 14 to 25 +/- 9 g/day. There was no change in either fasting or postprandial insulin concentration, but the postprandial GIP response was also significantly reduced (P less than 0.001). In addition, there were significant reductions in postprandial plasma free fatty acid (P less than 0.05) and triglyceride (P less than 0.001) concentrations, associated with a modest fall in fasting plasma triglyceride (P less than 0.05) and cholesterol (P less than 0.07) concentrations when measured after one week of treatment with enprostil. These results raise the possibility that enprostil may be of some benefit in the treatment of patients with non-insulin-dependent diabetes.
Aged↗
Striated muscle overload.
In response to increasing demand, cardiac muscle develops several adaptational mechanisms. Gene expression is modified: the heart hypertrophies and its structure changes in order to improve the efficiency of the contraction. The sarcomere modifications are both species and tissue specific. An isoenzymic shift of myosin from the high ATPase activity form V1 to the slow activity form V3 occurs in all conditions where V1 is initially predominant, i.e. rat (and also rabbit) ventricles and the atria of other species, including humans. The isoenzymic shift was not observed in conditions where V3 is predominant, as in human (and also cat and pig) ventricles. Similar changes are observed in skeletal muscle suggesting that the primary determinant of these modifications is not dependent on the innervation but only on the mechanical activity.
Adult↗
[Phenotype changes in myocardial proteins in hemodynamic overloads].
The phenotype of myocardial proteins is not set once and for all: it changes during ontogenesis, haemodynamic overload and in many other circumstances (e.g. dysthyroidism, diabetes). These changes are attributed either to the differential expression of multigenic protein families, or to modulation of single gene expression. In haemodynamic overload, this versatility of the myocardium enables it, usually by re-expression of its foetal phenotype, to find in itself the capacity for getting adjusted to new functioning conditions. The mechanisms that link the heart work overload to these phenotypic transitions, as well as their possible physiopathology, remain to be determined.
Cardiomegaly↗
Effect of latissimus dorsi dynamic cardiomyoplasty on ventricular function.
In our approach to dynamic cardiomyoplasty, which consists of wrapping a skeletal muscle around the heart and stimulating the former in synchrony with heart contractions to augment ventricular contractility, we have transferred a latissimus dorsi muscle flap to the heart by way of a partial resection of the second rib and subsequently suturing the muscle flap around the ventricles. The muscle flap is stimulated by a Cardio-Myostimulator burst-pulse generator (Medtronic SP 1005) connected to intramuscular electrodes. In preclinical animal research, the latissimus dorsi muscle flap was shown to maintain adequate contractile force and to increase its fatigue resistance by gradual conversion of glycolytic-fatigue-sensitive-to-oxidative-fatigue-resistant muscular fibers (100%). Histochemical and biochemical studies of chronically stimulated muscles showed a total transformation of muscle fast myosin to slow myosin with characteristics similar to those of myocardium. Electron microscopy showed preserved myofibrillar cytoarchitecture and increased mitochondrial density in the cell. At 9 months, cardiac output and ultrasonic Doppler studies showed a significant increase in ventricular function (cardiac output, +21%; peak blood velocity, +40% -80%; and stroke volume, +98% -102%) during muscle stimulation. In the clinical situation, long-term (range of follow-up interval, 4-42 months) beneficial cardiac effects of cardiomyoplasty have been documented in eight patients with various pathologies (ventricular tumor, left ventricular aneurysm, ischemic disease, and dilated cardiomyopathy). Our current understanding of this process is that dynamic cardiomyoplasty acts in two ways: 1) it promotes more vigorous systolic contraction, and 2) it appears to limit heart dilatation.
Animals↗
Effect of amiodarone on myosin isoenzymic distribution in rat ventricular myocardium.
Rats were given amiodarone (50 mg X kg-1 X day-1, orally) for 4 weeks and the distribution of ventricular isomyosins, a sensitive index of the effects of thyroid hormones on cardiac tissue, was analyzed. Amiodarone treatment induced a marked increase in both T4 and rT3 and tended to decrease T3 serum levels. At the pharmacologically active dosage we used, the drug induced a moderate redistribution of ventricular isomyosins in favour of V, at the expense of V1. Our results do not support the hypothesis that the major mechanism of action of amiodarone is mediated through hypothyroid-like effects.
Aging↗