Shape coexistence and extreme deformations near A=80.
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Biomedical subjects
Publications and source records attributed to P Ring.
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The Na+/K+ ionophore monensin is known to arrest the intracellular transport of newly synthesized proteins in the Golgi complex. In the present investigation the effect of monensin on the secretion of 3H-galactose-labeled and 3H-sialic acid-labeled thyroglobulin was studied in open thyroid follicles isolated from porcine thyroid tissue. Follicles were incubated with 3H-galactose at 20 degrees C for 1 h; at this temperature the labeled thyroglobulin remains in the labeling compartment (Ring et al. 1987a). The follicles were then chased at 37 degrees C for 1 h in the absence or presence of 1 microM monensin. Without monensin substantial amounts of labeled thyroglobulin were secreted into the medium, whereas in the presence of the ionophore secretion was inhibited by 80%. Since we have previously shown (Ring et al. 1987b) that monensin does not inhibit secretion of thyroglobulin present on the distal side of the monensin block we conclude that galactose is incorporated into thyroglobulin on the proximal side of this block. Secretion was also measured in follicles continuously incubated with 3H-galactose for 1 h at 37 degrees C in the absence or presence of monensin. In these experiments secretion of labeled thyroglobulin was inhibited by about 85% in the presence of monensin. Identically designed experiments with 3H-N-acetylmannosamine, a precursor of sialic acid, gave similar results, i.e., almost complete inhibition of secretion of labeled thyroglobulin in the presence of monensin. The agreement between the results of the galactose and sialic acid experiments indicates that sialic acid, like galactose, is incorporated into thyroglobulin on the proximal side of the monensin block.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of cooling to 20 degrees C on the intracellular transport and secretion of thyroglobulin was studied by incubating open thyroid follicles isolated from porcine thyroid tissue. Follicles were labeled with 3H-leucine or 3H-galactose and the secretion of labeled thyroglobulin into the incubation medium was followed by chase incubations under various experimental conditions. The observations indicate that the transport of thyroglobulin is inhibited at three sites of the intracellular pathway by cooling to 20 degrees C, i.e., between the RER cisternae and the Golgi cisternae, between the latter and the exocytic vesicles, and between these vesicles and the extracellular space (corresponding to the follicle lumen). The secretion of 3H-leucine-labeled thyroglobulin decreased linearly between 37 degrees and 20 degrees C; within this temperature range the activation energy for secretion, calculated from Arrhenius plots, was found to be 37 kcal/mol. Below 20 degrees C the secretion was scarcely measurable. It is suggested that the three transport blocks at 20 degrees C result mainly from inhibition of membrane fission and fusion due to phase transition in membrane lipids.
To improve the understanding of diphosphonate affinity to metabolically active bone, the underlying diphosphonate kinetics have been evaluated and compared to Cr-EDTA kinetics. MDP binds to plasma proteins, varying from 25% initially to approximately 70% after 24 h. The renal clearance of diphosphonate is found to be equal to Cr-EDTA clearance. Using simultaneous bolus injection of 99Tc-MDP and 51Cr-EDTA, it has been possible to obtain a coarse estimate of bone uptake of MDP. This uptake is found to correlate well with s-alkaline phosphatase, but since MDP binding to bone is reversible, the plasma elimination curve is not monoexponential. Therefore it has not been possible to describe the uptake of MDP in bone mathematically.
To elaborate the understanding of diphosphonate kinetics, a non compartmental analysis is introduced. Using continuous infusion of 99mTc-methylene diphosphonate (Tc-MDP) and 51Cr-EDTA, as a cotracer, the diphosphonate clearance to bone (BDC) can be calculated. BDC is found to correlate well with the 24 h whole body retention of diphosphonate (WBR) (r = 0.89, P less than 0.01) when renal function is normal, but not in cases of reduced 51Cr-EDTA clearance. These findings indicate that BDC measurements are superior to the WBR technique in the estimation of bone turnover, especially when renal function is reduced. The BDC measurements may also constitute a useful tool for studies of diphosphonate uptake in bone, the foundation of bone scintigraphy.
The effect of monensin on the secretion of thyroglobulin was studied in open follicles isolated from pig thyroid tissue; in this system, thyroglobulin is secreted into the incubation medium. When monensin was present during a 4-h chase incubation after pulse-labelling with 3H-leucine, the secretion of labelled thyroglobulin was reduced by about 85%; in electron-microscopic autoradiographs of rat thyroid lobes labelled and chase-incubated under similar conditions the relative number of grains over follicle lumina was strongly reduced when monensin was present during the chase. These observations are in agreement with the consensus that monensin arrests transport of secretory proteins in the Golgi complex. In other experiments, pulse-labelled follicles were chase-incubated for 1.5 h whereby labelled thyroglobulin was transported from the RER to exocytic vesicles. Monensin present during a subsequent chase of 0.5 h caused only a moderate decrease of labelled thyroglobulin secretion. TSH present during the second chase-stimulated secretion in both control and monensin-exposed follicles. TSH also caused a drastic reduction of exocytic vesicles in rat thyroid lobes, and the number of vesicles remaining in the cells was the same in controls and lobes exposed to the ionophore. The observations are interpreted to show that monensin does not inhibit the basal or TSH-stimulated transport of thyroglobulin from the site of monensin-induced arrest in the Golgi complex to the apical cell surface or the exocytosis of thyroglobulin.
In order to evaluate a computerized modified acetylene rebreathing method for the determination of cardiac output, 15 healthy subjects were studied at different levels of their maximal oxygen uptake (VO2max). Submaximal exercise was performed on a cycle ergometer and maximal exercise on a treadmill. Oxygen uptake, heart rate, and cardiac output (acetylene method) were determined in all test situations. In seven subjects simultaneous determinations of cardiac output were made by a modified acetylene rebreathing method (QA) and a dye dilution method (QD). Furthermore, a new resting rebreathing technique was used. The methodological error for QA (means of double samples) was 0.37 litre min-1 (2.8%) in the same individual at 150 W. The corresponding values between individuals were 0.71 (rest), 0.41 (50 W), 0.69 (150 W), and 0.40 litre min-1 (VO2max). Thus the methodological error of the modified acetylene method was very low. There was a significant difference (P less than 0.01), however, between the acetylene method and the dye dilution method, which showed a lower value for QA at all levels. This was probably due to the long response time of the mass spectrometer combined with anatomical and physiological arteriovenous shunt effects in the lungs during exercise. When these factors were considered the correcting formula was: QAc = QA + 0.005 X Q2A. There was no significant difference between the corrected cardiac output values (QAc), and the corresponding QD values. In conclusion, this modified acetylene rebreathing method is a very useful non-invasive method for measuring cardiac output at rest as well as during heavy exercise.
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A new method of quantifying the heterogeneity of transit times through vascular beds, free from corrections for effects of recirculation, is applied to data of splanchnic transit times in eight normal subjects and three patients with cirrhosis and end-to-side portocaval shunts, as obtained by Bradley's method. There is proportionality between the heterogeneity, expressed as standard deviation and the mean transit time in the eight normal subjects. The heterogeneity of plasma transit times is not appreciably larger than that of red blood cells, despite the larger volume of distribution of plasma. This may suggest that the large vessels contribute substantially to the dispersions of vascular transits in the entire splanchnic system. Pearson Type III distribution is proposed for the frequency function of the splanchnic transit times, and the power of the pre-exponential factor is deduced for plasma and for red blood cells. It is found that the initial splanchnic transits are dominated by plasma, this may be due to sequestration of red cells in the spleen. The heterogeneity of transit times in normals is not appreciably different from that in patients with cirrhosis and portocaval shunt, which suggests that the extra heterogeneity of the cirrhotic liver is of the same order as the heterogeneity of the normal extrahepatic splanchnic organs. The method may be a useful tool to describe heterogeneity of vascular transits in other organs.
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The vascularization of 110 Human sternoclavicular articulations is studied after injection of China ink with gelosa. The arteries of the sternoclavicular articulation arise from the internal mammary arteria and form a periarticular arch from which start the peripheric, sub-synovial and central networks. These networks, whose architectony is in relation with the functional structure of sternoclavicular articulation, drains in peripheric venous arches which join anterior jugular and mediastinal veins.
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In vivo estimation of relaxation processes in the liver by magnetic resonance imaging (MRI) may be helpful for characterization of various pathological conditions in the liver. However, such measurements may be significantly hampered by movement of the liver with the respiration. The effect of synchronization of data acquisition to the respiratory cycle on measured T1- and T2-relaxation curves was studied in normal subjects, patients with diffuse liver disease, and patients with focal liver pathology. Multi spin echo sequences with five different repetition times were used. The measurements were carried out with and without respiratory gating/triggering. In the healthy subjects as well as in the patients with diffuse liver diseases respiratory synchronization did not alter the obtained relaxation curves. However, in the patients with focal pathology the relaxation curves were significantly different, when respiratory synchronization was employed. The results indicate that respiratory synchronization is only necessary for estimation of relaxation processes in the liver with focal pathology.