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Biomedical subjects

J L Samuel

Publications and source records attributed to J L Samuel.

At least 91 records · Page 5Linked to original sources
PubMed1989

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↗
PubMed1988

Storage of phosphorylated desmin in a familial myopathy.

The quantity and the electrophoretic characteristics of desmin were analyzed in a familial skeletal muscle disorder, characterized by the intra-sarcoplasmic accumulation of an electron-dense granulo-filamentous material facing the Z-lines and reacting strongly with polyclonal anti-desmin antibodies. The analysis was performed on biopsies from the deltoid muscles of 4 patients, members of 2 families. In the 4 biopsies, an increase in the relative amount of desmin compared to that of actin or insoluble proteins (3 fold) and in the number of isovariants (6 instead of 3) was observed. The isovariants of desmin were similar to those described in Purkinje fibres of the heart as a phosphorylated form of the protein [(1987) Eur. J. Cell Biol. 44, 68-78]. Therefore, post-translational events could affect both the polymerization and the amount of desmin filaments in this autosomal dominant familial myopathy.

Adult↗
PubMed1988

Serological response of chickens to oral vaccination with Newcastle disease virus.

Conventional Newcastle disease vaccines are not suitable for application to village chickens in tropical countries of Asia. Trials with food-based vaccines are being initiated and the following experiments were performed to evaluate oral vaccination with Newcastle disease virus. Experimental chickens were vaccinated orally with the avirulent V4 strain of Newcastle disease virus and haemagglutination-inhibition antibody responses were measured. V4 virus was introduced into the crop by tube and total faecal output was collected daily and assayed for Newcastle disease virus. Virus was recovered on Days 5 and 6 after vaccination from most chickens that had received 10(7.4) and 10(6.4) 50% egg-infectious doses (EID50) of virus. There was no recovery of virus from birds receiving a lower dose of vaccine. Groups of chickens kept in cages with wire floors were given various doses of vaccine into the crop. Higher antibody titres were achieved with higher doses of virus. This dose responsiveness was not observed when various doses of vaccine were presented on food pellets and the groups of chickens were kept on concrete floors. Similar antibody responses were then seen with nominal doses of 10(5.2) and 10(8.2) EID50 per bird, possibly as a result of excretion and re-ingestion of the vaccine virus. Spread of the vaccine virus was demonstrated when control chickens and chickens receiving 10(7.7) EID50 of V4 virus on food pellets were housed together on a concrete floor. Similar antibody titres were achieved in both vaccinated and in-contact chickens.

Administration, Oral↗
PubMed1988

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↗
PubMed1988

Synthesis of stress proteins in rat cardiac myocytes 2-4 days after imposition of hemodynamic overload.

Isolated adult myocytes incubated with [35S]methionine were used to study the expression of proteins in the rat heart during the first 2 wk after either pressure or volume overload. In both models an early (2-4 d) and transient expression of three major stress proteins (heat shock protein [HSP] HSP 70, HSP 68, and HSP 58) was observed together with an increased synthesis of putative ribosomal proteins. Only traces of 35S-labeled HSPs were detected in controls and sham-operated animals. The three stress proteins were identified by their migration in two-dimensional gels, by comigration with HSPs, which had been induced in myocytes by incubation at 41 degrees C and immunoblot analysis using antisera directed against the 70-kD protein. Immunohistochemical staining of HSP 70 in rod-shaped myocytes and detection by immunoblot showed that HSP 70 was equally present and distributed in both sham-operated and overloaded hearts, and provided no evidence for a subpopulation of myocytes acutely involved in the increased expression of HSP 70. It is suggested that the transient expression of HSPs that occurs during the early adaptation of the myocardial cells to overload could confer some degree of protection to the actively growing myocytes.

Animals↗
PubMed1988

Characterization of a cytosolic triiodothyronine binding protein in atrium and ventricle of rat heart with different sensitivity toward thyroid hormone levels.

Cytosolic T3-binding protein (CTBP) has been identified in both the ventricle and atrium of adult rat hearts. Its biochemical characteristics and concentration have been determined in the two tissues as a function of thyroid hormone level. In both tissues association and dissociation constants were, respectively, k+1 = 1.3 x 10(8) M-1/min and k-1 = 0.025 min-1. Scatchard analysis of T3 equilibrium binding data revealed a single class of binding sites (Ka = 3.8 x 10(8) M-1). The maximal binding capacity (MBC) was 1400 fmol/mg protein in the ventricle and 730 fmol/mg protein in the atrium. The apparent mol wt of CTBP, determined by gel filtration, was 63.000. Among the thyroid hormone analogs tested in ventricular cytosol, D-T3 had the highest affinity, followed by L-T3, L-T4, 3,3',5-triiodothyroacetic acid, and rT3. These characteristics were very similar to those previously described for rat brain, and dog and rat liver and kidney CTBP. In hypothyroid rats MBC was only increased in the atrium (50-100%); after a single injection of T4 (2 micrograms/10 g BW 3 or 18 h before death) values returned to normal in the atrium and declined in the ventricle (-35%). During postnatal development, the highest MBC value (2000 fmol T3/mg protein) was observed in atria on day 10, i.e. when the serum T4 level was still low, and in the ventricle on day 30 (4000 fmol T3/mg protein) when the serum T4 level was at its highest. Binding affinities were similar in the two tissues at all ages studied. It was twice as high in both these tissues during the first week of development than in adulthood. These results favor a thyroid hormone down-regulation of the binding capacity of CTBP that would be more sensitive to the hormone in the atrium than in the ventricle.

Aging↗
PubMed1988

Periodontal disease in feral pigs (Sus scrofa) from Queensland, Australia.

Periodontal lesions were present in 26 of 107 feral pigs (Sus scrofa) that were shot in southern Queensland. The severity of the lesions varied from gingivitis to extensive destruction of the alveolus and its contents. Examination of slaughtered domestic pigs revealed a similar prevalence of lesions (12 of 52). Only cheek teeth were affected, and molars were affected more frequently than premolars. In both feral and domestic pigs, prevalence of periodontal disease affecting bone increased with age. Although periodontal disease is recognized as a common and often serious problem in many mammalian species, both domestic and wild, it has rarely been recorded in the pig. It is considered that the most severe lesions would have interfered with mastication but that the contribution of the disease to mortality of feral pigs in Australia is probably not great.

Animals↗
PubMed1987

Skin cancer and papillomaviruses in cattle.

We examined proliferative lesions on the sun-exposed, unpigmented skin of 13 cattle. Ages of animals at first examination ranged from 4 to 15 years, and 4 were observed for from one to 3 years, during which time progression to malignancy occurred in 2 of them. Early lesions consisted of keratin scales and horns; histology showed underlying acanthosis and hyperkeratosis. Advanced lesions were either squamous cell carcinomas or basaloid tumours with sebaceous and/or squamous differentiation; some were locally invasive but no metastases were found in the 6 animals that were available for necropsy. All 3 types of lesion could occur on the same animal. In early lesions from 11 of 12 animals, there was evidence for the presence of papillomavirus, either virions or viral DNA, the latter detected by gel electrophoresis and/or molecular hybridization. Viral DNA was also detected in 3 basaloid tumours and 2 squamous cell carcinomas from 4 animals. The DNA bound to a probe of bovine papillomavirus type 1 DNA under conditions of low stringency. We suggest that both infection with papillomavirus and exposure to sunlight, possibly in conjunction with other factors such as a period of photosensitization, are involved in the production of this spectrum of proliferative lesions, which bear some resemblance to human skin cancer.

Aging↗
PubMed1987

Microtubules and desmin filaments during onset of heart hypertrophy in rat: a double immunoelectron microscope study.

The distribution of tubulin and desmin, the constituent proteins of microtubules and intermediate filaments, respectively, were studied in normal and hypertrophied rat myocardium by high-resolution immunofluorescence and immunoelectron microscopy. Cardiac hypertrophy was induced in 25-day-old rats by aortic stenosis. In the normal heart, double immunolabelling of ultrathin frozen sections of papillary muscle using gold-labelled probes for tubulin and desmin showed that microtubules ran primarily in a longitudinal direction through the intermyofibrillar spaces, perpendicularly to the desmin filaments. Microtubules were present near nuclei, mitochondria, and plasma membranes, while desmin filaments formed transverse connections between adjacent Z disks. No tubulin was observed near the intercalated disks, which were rich in desmin filaments. In hypertrophied hearts, myocytes exhibited the typical morphological features of developing hypertrophy. While there was little difference in the distribution of the microtubules around mitochondria and at the plasma membrane, considerable increases were seen near the nuclei and along the myofibrils. Desmin labelling was distributed transversely as in the controls; however, sometimes it was longitudinally oriented either in the intermyofibrillar space linking 2 Z disks out of register or along digitations of the intercalated disks connecting neighboring desmosomes. The unique rearrangement of desmin and tubulin filaments in hypertrophied cardiac myocytes emphasizes their distinct role in myocyte organization. We suggest that, during the development of cardiac hypertrophy, desmin filaments are mainly involved in maintaining the myofibrils in register, whereas the degree of assembly of microtubules is correlated with the rate of protein synthesis and with myofibrillogenesis.

Animals↗
PubMed1987

Adaptational changes of sarcomere and sarcolemma during chronic cardiac overloading in rats and in humans.

In response to increasing demand, the cardiac muscle has developed several adaptational mechanisms. Gene expression is modified in a quantitative and a qualitative way since the heart hypertrophies and since its structure changes to improve the efficiency of the contraction. The sarcomere modifications are both species- and tissue-specific. An isoenzymic shift of myosin from high adenosine triphosphatase (ATPase) activity form V-1 to low activity form V-3 occurs in all conditions in which V-1 is initially predominant, i.e., in rat (and also rabbit) ventricles and the atria of other species, including humans. It was not observed in conditions in which V-3 was predominant, as in human ventricles (and also in those of cats and pigs). Another shift from creatine kinase (CK) monomer M to CK B, the form that predominates in the fetal heart, is also observed. The sarcolemma is also modified, at least in rats. The digitalis receptor was characterized by studying the inotropic effect of the drug on an isolated heart preparation and on a purified preparation of sarcolemma with a high Na+,K(+)-ATPase activity by binding [3H]ouabain and ouabain-induced inhibition of the enzymatic activity. In hypertrophied heart, both the recovery of normal contractility after ouabain infusion and the release of previously bound ouabain infusion and the release of previously bound ouabain were slowed, as for fetal hearts. Changes in other inotropic receptors have also been reported. From a practical point of view, this means that screening of new inotropic agents has to be done on hypertrophied hearts and not, as usual, on normal tissue.

Adult↗
PubMed1986

Calcium antagonists stimulate prostaglandin synthesis by cultured rat cardiac myocytes and prevent the effects of hypoxia.

The effect of three calcium antagonists on the synthesis of prostacyclin (PGI2, assayed as 6-Keto-PGF1 alpha) and PGE2 by cultured rat cardiac myocytes and fibroblasts was investigated. In myocytes only, bepridil, diltiazem and verapamil (10(-9) to 10(-7) M) stimulated PGs synthesis by two- to three-fold, dose-dependently. At a concentration of 10(-6) or 10(-5) M the intensity of the stimulation of PGI2 and PGE2 decreased. Cobalt chloride (2 X 10(-3) M) did not change PGs synthesis (pg/mg of protein/30 min; means +/- SE, N = 10; PGE2: 365 +/- 59 and 463 +/- 89 treated vs controls; PGI2: 824 +/- 214 and 799 +/- 143 treated vs controls). After 30 min exposure of myocytes to hypoxic conditions (glucose-free medium and low PO2), the glycogen content was half that of the controls (P less than 0.001), ATP content did not change and PGI2 and PGE2 synthesis increased (X1.5, P less than 0.05). When applied to myocytes 30 min before inducing hypoxia, the three calcium antagonists stimulated PGs synthesis by three- to seven-fold at maximal effect, and bepridil (10(-8) M) or diltiazem (10(-7) M) prevented the hypoxia-induced decrease in glycogen content. With 10(-5) M drug concentration, the effect on PGs was not significant, except for the effect of bepridil on PGI2 (P less than 0.05). It is concluded that therapeutic concentrations of calcium antagonists simultaneously prevent the decrease in myocyte glycogen induced by hypoxia and stimulate PGs synthesis by myocytes.

Animals↗
PubMed1986

Isolation and localization of filamin in heart muscle.

High-molecular-mass protein was isolated from chicken heart muscle. The apparent molecular mass of a single polypeptide chain is similar to that of chicken gizzard filamin: 250-270 kDa. The protein interacts with antibodies against chicken gizzard filamin and induces F-actin gelation in a concentration-dependent manner. Immunofluorescent staining of cardiomyocytes and chicken heart sections with antifilamin antibody demonstrates two types of filamin localization: filamin was located on the sarcomere border in the periphery of the Z-disk; filamin was found in intercalated disks between cardiomyocytes.

Animals↗
PubMed1986

Differential effect of thyroxine on atrial and ventricular isomyosins in rats.

Two myosin heavy chains (MHCs), alpha and beta, which exhibit different levels of ATPase activity related to the different velocities of muscle shortening, are differentially expressed in rat cardiac ventricles, depending on the developmental stage and the thyroid status of the animals. In contrast, no changes have been reported concerning the expression of atrial MHCs in the same physiological and pathological conditions. We have now performed studies with sensitive techniques to test the hypothesis that the expression of alpha- and beta-MHCs can also be modulated in the rat atria, although at a low level. Atrial and ventricular isomyosin patterns of various groups of rats were examined by two-dimensional peptide mapping, immunofluorescence with specific anti-alpha- and anti-beta-MHC immunoglobulins, and electrophoresis under nondenaturing conditions. Normal ontogenic development of the atria is characterized by the disappearance of a small amount of beta-MHC, present at 19 days in utero. At 3 wk of age, atria and ventricles both contain only alpha-MHC. Severe hypothyroidism, produced either by methylthiouracil (MTU) treatment of pregnant females and of their litters or by hypophysectomy of adult animals, did not significantly deinduce atrial alpha-MHC but was characterized by a significant although slight accumulation of beta-MHC (less than 5% of total myosin). This latter effect was abolished by L-thyroxine restoration. It is concluded that alpha- and beta-MHC are developmentally and hormonally regulated both in atria and ventricles, although the extent of regulation is very different for the two tissues.

Animals↗
PubMed1986

Microtubule reorganization is related to rate of heart myocyte hypertrophy in rat.

Since stimulation of heart hypertrophy by pressure overload was previously shown to be accompanied by a densification of microtubule network in rat heart myocytes, we verified that similar process occurred during postnatal growth in euthyroid rats and in hypothyroid rats whose growth was stimulated by 4 micrograms/day L-thyroxine (T4). For this purpose, tubulin, the constituent protein of microtubules, was immunolabeled in myocytes isolated at various times after birth. Myocyte hypertrophy was evaluated by myocyte size, the number of nuclei per cell and isomyosin expression. In hypothyroid rats, the microtubule network, which was underdeveloped, was most dense around the nucleus. During the phase of fast myocyte hypertrophy observed in euthyroid rats during late postnatal development and in hypothyroid rats after T4 administration, transient microtubule densification occurred in a myocyte subpopulation in which size was mainly determined by the rate of myocyte hypertrophy. The densification process and its kinetics resembled those observed when heart hypertrophy was induced by pressure overload. It is concluded that in rat heart myocytes undergoing hypertrophy, microtubule densification might be related to fast sarcomerogenesis, whether the stimulus is mechanical (e.g., pressure overload) or hormonal (e.g., T4).

Aging↗
PubMed1986

Physiological adaptation of the heart to pathological overloading.

Chronic overloading of the rat heart induces a cascade of adaptational events that compensate for the increase in work. At the myocardial level there are two types of adaptational mechanisms: qualitative, represented by the isomyosin changes leading to an improved efficiency; and quantitative, the hypertrophy. We present new approaches exploring possible adaptational changes at other levels within the myocardial cell. Studies of heart overload were performed either in young rats with experimental aortic stenosis or in humans with chronic compensatory hypertrophy. By means of double immunofluorescence labeling of isolated myocytes with anti-V1 and anti-V3 myosin immunoglobulins, we showed that the shift from high- to low-ATPase isomyosins occurs rapidly after aortic stenosis (2-3 days). Cardiac myocytes were shown to be poor in tubulin but a microtubule pattern was clearly visualized by an immunofluorescence approach. Their role in the onset of adaptational processes after aortic stenosis in not yet clear. On the other hand, we showed that in humans, contrary to small rodents, the adaptational process at the isomyosin level is very small or nonexistent.

Animals↗