[A new adaptive mechanism in chronic mechanical overload: isozyme changes in myosin].
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Biomedical subjects
Publications and source records attributed to J L Samuel.
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Salmonella was sought in 100 normal, slaughtered cattle, most of which had been held for at least four days before slaughter. The organism was isolated from 76 cattle: from the rumen contents of 62, the ruminal lymph nodes of two and the mesenteric lymph nodes of 54. The mesenteric nodes of 35 of the cattle yielded salmonellae by direct plating; plate counts indicated that some nodes contained over 2500 organisms per gram. S typhimurium was the most prevalent serotype in the mesenteric nodes but not in the rumen; up to seven serotypes were isolated from one animal. In animals which have travelled or been held for several days before slaughter, the mesenteric lymph nodes may be a source of contamination for meat and edible offal in the abattoir.
Lymph nodes and other tissues from a number of sites in the viscera, carcase and head were collected from 28 cattle which had been held for at least four days before slaughter. Salmoinella was isolated from 21 of these cattle, but in al except three of them it was confined to the gastrointestinal tract and the mesenteric lymph nodes. There was no evidence, in any of the animals, of spread beyond these nodes via the circulatory system. The distribution of infection suggested that the ileum and perhaps the caecum were the primary sites for invasion of the animal. Individual mesenteric nodes were collected from a further 85 cattle, and the number of salmonellae present in each was estimated by direct plating. Salmonella was isolated from 61 of these animals, and in each of 29 animals at least one node contained more than 5000 organisms per g. The predominant serotype in the mesenteric lymph nodes was Salmonella typhimurium.
A retrospective study of adult congestive cardiomyopathy was carried out; the admission criteria being heart failure with cardiomegaly after the exclusion of known causes of heart failure. Coronary artery disease was excluded by forming two sub groups, one with proven normal coronary arteries at angiography or autopsy and the other with only assumedly normal coronary arteries. The results concern the study of the incidence of this disease which has been regularly seen over the last 10 years in departments with a large number of referrals of cardiomyopathy. --Professional factors are analysed to see if there is a higher incidence amongst the working classes. --Other factors are analysed by comparison with three control groups: normal, coronary and valvular disease, and diabetes which may be a predisposing factor, but not the serum cholesterol which is decreased in these patients. There is a significant association with smoking and alcoholism and the main biological sign of the latter condition, macrocytosis. This is also found in both coronary sub groups. The isolation of this alcohol factor in the genesis of congestive cardiomyopathy implies the possibility of reversing or stabilising the myocardial damage after its withdrawal, so changing the severe diagnosis associated with this disease.
Troponin inhibitory factor, TNI, was prepared by affinity chromatography from different mammalian hearts. (i) Structure. These different TNI have the same M.W. (28000), which is higher than that found in rabbit skeletal muscle (23000). Nevertheless they differ with respect of their charge as shown by alkaline urea polyacrylamide gel electrophoresis using cardiac TNI which has previously been bound to an excess of skeletal troponin Ca2+-binding factor. These changes do not correlate with the PO4 content of TNI. They are associated with structural differences demonstrated by peptide mapping of the unfolded molecule after papain treatment. The structure of cardiac TNI from rat and rabbit differs clearly from that of crow and pig. (ii) Biological activity. These different TNI have the same inhibitory effect on skeletal actomyosin. ATPase, the same content of PO4 and the same ability to be phosphorylated in-vitro by a bovine heart c-AMP-dependent protein kinase.
Very recent experimental data, obtained by using the permeabilized cell technique or tissue homogenates for investigation of the mechanisms of regulation of respiration in the cells in vivo, are shortly summarized. In these studies, surprisingly high values of apparent Km for ADP, exceeding that for isolated mitochondria in vitro by more than order of magnitude, were recorded for heart, slow twitch skeletal muscle, hepatocytes, brain tissue homogenates but not for fast twitch skeletal muscle. Mitochondrial swelling in the hypo-osmotic medium resulted in the sharp decrease of the value of Km for ADP in correlation with the degree of rupture of mitochondrial outer membrane, as determined by the cytochrome c test. Very similar effect was observed when trypsin was used for treatment of skinned fibers, permeabilized cells or homogenates. It is concluded that, in many but not all types of cells, the permeability of the mitochondria outer membrane for ADP is controlled by some cytoplasmic protein factor(s). Since colchicine and taxol were not found to change high values of the apparent Km for ADP, the participation of microtubular system seems to be excluded in this kind of control or respiration but studies of the roles of other cytoskeletal structures seem to be of high interest. In acute ischemia we observed rapid increase of the permeability of the mitochondrial outer membrane for ADP due to mitochondrial swelling and concomitant loss of creatine control of respiration as a result of dissociation of creatine kinase from the inner mitochondrial membrane. The extent of these damages was decreased by use of proper procedures of myocardial protection showing that outer mitochondrial membrane permeability and creatine control of respiration are valuable indices of myocardial preservation. In contrast to acute ischemia, chronic hypoxia seems to improve the cardiac cell energetics as seen from better postischemic recovery of phosphocreatine, and phosphocreatine overshoot after inotropic stimulation. In general, adaptational possibilities and pathophysiological changes in the mitochondrial outer membrane system point to the central role such a system may play in regulation of cellular energetics in vivo.
Histoenzymological techniques were used to examine ATPase activity in rat heart muscle fibres after experimental infarction. 25 hours after coronary ligation, ATPase activity in all ventricular section fibres was high, homogeneous at pH 9.4, sections. 48 hours after ligation, necrotic ventricular fibres appeared, leaving only a thin layer of fibres which had apparently preserved their myofibrillar ATPase. These results indicate that, unlike mitochondrial enzyme activity, myofibrillar ATPase activity is relatively resistant to ischaemia.
The characteristics of cultured myocardial cells isolated from small mammals are well documented, but there is a dearth of data on cultured human cardiocytes. The aim of this study was to determine the main features of myocytes isolated from human atria and maintained in culture in the presence of 10% fetal calf serum (FCS), according to the age of the donor. The following characteristics were analysed: (1) yield and viability; (2) adhesive properties; and (3) changes in cell morphology. Myocytes preferentially adhered to laminin-coated dishes and could be maintained in culture for at least 2 weeks, whatever the age of the donor (which was from 6 days to 85 yr). Maintenance in culture induced morphologic changes characterized by myocyte spreading and changes in myofibrillar organization. Interestingly, the time of onset of these changes depended on the age of the donor: they occurred earlier in young atrial myocytes (< 1 yr) than in older cells (> 13 yr).
Conduit arteries of hypertensive rats are thicker and stiffer than those of normotensive controls. The possible role played by collagen type I and II subtypes in the mechanism of arterial stiffness remains unknown. The carotid and aortic arterial wall of rats of Japanese (Wistar-Kyoto and spontaneously hypertensive rats) and Lyon (normotensive and hypertensive rats) origin were studied. The stiffness of the carotid wall material (ultrasound), the histomorphometry of the aortic wall with the content in collagen I and III subtypes and their corresponding mRNA were analyzed. Independently of hypertension, the Japanese group differed from the Lyon group by a stiffer carotid wall material at any given value of wall stress; a lesser degree of aortic hypertrophy with a higher percentage of elastin, and a higher density of collagen III but not of collagen I. All other hemodynamic and histomorphometric parameters were affected by both the origin of the rats (Japanese vs. Lyon) and the presence of hypertension. Large artery stiffness in genetically hypertensive rats was not only influenced by hypertension itself, but also by differences in the contents of collagen subtypes which are also found in their corresponding normotensive controls.
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