[Double chambered right ventricle associated with tricuspid regurgitation--a 54-year-old case].
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Biomedical subjects
Publications and source records attributed to T Asakura.
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The effects of the mutation of the alpha 1 beta 2 contact in Hb Malmö (alpha 2 beta 2 97(FG4)His----Gln) on oxygen-binding properties, ease of dissociation into dimeric hemoglobin and stability were studied. The P50 value of Hb Malmö in the absence of organic phosphates was 1.9 mmHg, in contrast to 8.8 mmHg of Hb A. The n-value of Hb Malmö was 1.6. The overall free energy of interaction of oxygen with Hb Malmö was about 25% that of Hb A. The Adair constant, K1, of Hb Malmö was about 10-times larger than that of Hb A, but the K4 of Hb Malmö was similar to that of Hb A. The liganded form of Hb Malmö was found to dissociate into dimers more readily than Hb A by gel filtration on Sephadex G-100. Dissociation into dimeric hemoglobin was enhanced in dilute solutions. Increased instability during mechanical agitation of diluted samples was greater for Hb Malmö than for Hb A. The denaturation rate constants of tetramers of the oxyform of Hb A and Hb Malmö were about 20-times greater than those of dimers of these hemoglobins. The instability of Hb Malmö depends on a greater alpha 1 beta 2 dissociation constant compared with that of Hb A. These findings allow an examination of the role of the intersubunit contact in determining the functional properties and the stability of the hemoglobin molecule.
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When synaptosomes were depolarized in the presence of Ca2+, or when Ca2+ was added to synaptosomes pretreated with Ca2+ ionophore (A23187), free arachidonic acid was clearly increased within synaptosomes, and at the same time an efflux of gamma-aminobutyric acid from synaptosomes was observed. Moreover, when synaptosomes labelled with [14C]arachidonic acid were depolarized in the presence of Ca2+, there was a significant decrease in the radioactivity of the fatty acid of phosphatidylinositol and phosphatidylcholine. Exogenously added arachidonic acid, but not other fatty acids, stimulated the efflux of gamma-aminobutyric acid in the absence of Ca2+. These observations suggest that the release of arachidonic acid from phospholipids is an intrinsic part of the biochemical mechanism that modulates the gamma-aminobutyric acid efflux.
Asymmetrically cross-linked AS hybrid hemoglobin (Hb AS-fumarate) was prepared by reacting a mixture of oxy-Hb A and oxy-Hb S with a cross-linking agent, bis(3,5-dibromosalicyl)fumarate. Kinetics of the polymerization of Hb AS-fumarate in 1.8 M phosphate buffer showed that Hb AS-fumarate polymerized similarly to Hb S-fumarate despite the presence of a beta A chain. The kinetics of the polymerization of a mixture of Hb AS-fumarate and Hb S-fumarate was similar to that of Hb S-fumarate or Hb AS-fumarate alone. However, when Hb AS-fumarate was mixed with Hb A, the delay time prior to polymerization of the mixture was markedly prolonged. Although the solubility of Hb AS-fumarate was similar to that of Hb S-fumarate, it nearly doubled upon the addition of Hb A. Analysis of Hb A in the polymer phase showed that a significant amount (35-40%) of Hb A copolymerized with Hb AS-fumarate. No such effect was observed when Hb A was mixed with Hb S-fumarate, where the delay time prior to polymerization and the solubility of the mixture were regulated by the concentration of Hb S-fumarate in the mixture. The strong inhibitory effect of Hb A on the polymerization of Hb AS hybrid hemoglobin may help explain the benign clinical course in sickle cell trait.
Malondialdehyde (MDA) was found to react with normal hemoglobin A (Hb A), forming a number of less cationic components which were detected by cellulose acetate electrophoresis and gel electrofocusing. All the modified components moved down the cation-exchange resin at a quicker rate than Hb A, and this chromatographic behavior of the modified components was similar to that of glycosylated Hb A. Some of these modified components were intermolecularly crosslinked, and showed fluorescence with an excitation maximum at 390 nm and an emission maximum at 460 nm. It is likely that MDA reacts nonspecifically with the epsilon-amino groups of lysine and N-terminal amino groups to produce aminoacrolein, crosslinks, and strongly fluorescent 1,4-dihydropyridine-3,5-dicarbaldehyde. Oxygen affinity of the modified hemoglobins was increased. The modified hemoglobins were more readily oxidized into met-form. Mechanical stability of Hb A was also decreased by the modification. These results suggest that a considerable conformational change in Hb A was induced by the treatment with MDA. Since MDA is generated in erythrocytes as a consequence of liquid peroxidation, MDA may react with intracellular Hb A and influence the function and the stability of hemoglobin.
To study the mode of interaction between hemoglobin (Hb) S and carbamylated Hb S, the kinetics of polymerization of various mixtures of deoxy-Hb S and NH2 termini carbamylated Hb S in concentrated phosphate buffer was determined. These mixtures were found to polymerize with a clear demonstration of a delay time as does each hemoglobin in its pure form. Both the delay and the polymerization times were prolonged as the fraction of carbamylated Hb S was increased. Electrophoretic analysis of the polymer fraction showed that the amount of carbamylated Hb S increased linearly in the polymer phase with increases in the fraction of carbamylated Hb S in the starting mixture. The ratio of Hb S to carbamylated Hb S in the polymer phase was slightly higher than that in the initial solution mixture, suggesting that Hb S polymerizes more easily than carbamylated Hb S. To examine the role of hybrid hemoglobin in the binary mixtures of carbamylated Hb S and Hb S, we compared the rate of polymerization under which hybrid formation may be prevented or allowed to take place. It was found that the rate of polymerization for the mixtures of carbamylated Hb S and Hb S mixed in the oxy state did not differ from that mixed in the deoxy state. In addition, polymerization occurred even when the critical concentration of each component in the mixture was lower than that of either pure Hb S or pure carbamylated Hb S. These results suggest that all hemoglobin species can participate in the nucleation and polymerization steps of mixtures of carbamylated Hb S and Hb S.
Asymmetrical hybrid hemoglobins formed from mixtures of two structurally different hemoglobins were found to be readily separated by cation-exchange high-performance liquid chromatography under anaerobic conditions. When oxyhemoglobins A and S were mixed and deoxygenated, the resulting HPLC chromatogram showed three peaks. The distribution of the three components follow the binomial expansion a2 + 2 ab + b2 = 1, where a and b are the initial fractions of parent hemoglobins. The middle peak was collected in a test tube saturated with CO gas and reanalyzed under the same experimental conditions. This middle component gave two peaks of equal areas with retention times identical to those of the CO-form of the parent hemoglobins without the appearance of the hybrid hemoglobin band. No intermediate peak was observed in solutions of mixtures of liganded hemoglobins under aerobic conditions. Hybrid hemoglobins AC and SC were also formed when oxyhemoglobins A and C,S and C were mixed, respectively. The separation and the identification of hemoglobins and hybrid hemoglobin employing cation-exchange HPLC can be achieved within 30 min by gradient elution. In addition, the ability to isolate hybrid hemoglobins may be a valuable tool for the study of physical and chemical properties of hybrid hemoglobins.
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The molecular stability and function of hemoglobin (Hb) Hasharon (alpha 2 H beta 2) and Hb Hasharon2 (alpha 2 H delta 2) were studied and compared to Hbs A, A2 and S. Hb Hasharon and Hb Hasharon2 had slightly lower P50 values than Hb A and Hb A2 but had normal responses to organic phosphates. The molecular stability of Hb Hasharon and Hb Hasharon2 (as measured by mechanical shaking and heat denaturation at 60 degrees C) were less than Hb A and Hb A2 but greater than Hb S in the oxy- and carbonmonoxy-forms. In the met-form, however, Hb Hasharon and Hb Hasharon2 were less stable than hemoglobins S, A and A2. The oxy-form of Hb Hasharon forms methemoglobin at a faster rate than Hb A and Hb S. The mechanical and heat stabilities and the rate of methemoglobin formation of oxy-Hb Hasharon were studied in the presence of sulfisoxazole. This drug increased the rate of methemoglobin formation, thus causing a further decrease in the stability of Hb Hasharon. The relationship between these laboratory findings and previously observed clinical findings associated with Hb Hasharon are discussed.
A velocimeter for measurements of blood flow velocity in microvessels was constructed with a microscope, a grating, a photomultiplier and a wave-period measuring circuit. A differential detection system seemed to be useful when the probing area was extremely small. A pulsating flow velocity contour and the velocity reduction caused by an application of noradrenaline were on-line recorded in an arteriole of foot web of frogs.
Venous blood samples were obtained from 18 marathon runners before and after the 27 km uphill portion of a 46 km transmountain race at altitudes of 1,950-3,400 m. There was an inverse correlation between blood lactate levels and running time (r = -0.83), with the runners with higher lactate levels completing the race in less time. The faster half of the group had higher blood levels of glucose and lactate and lower free fatty acid levels at 26 km distance and 3,400 m elevation. The elevated lactate concentrations in the blood of the faster runners suggest that anaerobic metabolism can contribute significantly to total energy production during prolonged exercise at high altitude.
The relationship between the morphologic characteristics of sickle erythrocytes and the method of deoxygenation was studied using rectangular glass capillary tubes (0.05 X 0.5 X 50 mm). Deoxygenated blood samples were anaerobically collected into the tubes and directly observed under a microscope. A high yield (90%) of sickled red blood cells was observed if the sample was deoxygenated slowly with nitrogen gas. However, rapid deoxygenation by sodium dithionite resulted in low percentages of sickling and high percentages of irregularly shaped cells (mosaic cells). Mosaic cells were also formed upon rapid deoxygenation with nitrogen gas and thus appear to result from the precipitation of intracellular deoxygenated hemoglobin S. Only 20% of the mosaic cells converted to sickle cells with prolonged incubation at 37 degrees C. However, if the mosaic cells were cooled, desickled, and deoxygenated again slowly by nitrogen gas, most could be converted to typical sickle-shaped cells. Further studies on the comparison of sodium dithionite and sodium metabisulfite as reducing agents showed that sodium dithionite reduced intracellular hemoglobin rapidly, and sodium metabisulfite reduced it slowly. This difference explains the high yield of sickling with sodium metabisulfite compared with sodium dithionite.
We, neurosurgeons have sometimes confronted with the case of posttraumatic cerebrovascular narrowing or spasm. However, there have been few reports on the pathophysiology of the posttraumatic narrowing or spasm in comparison with those the spasm following the subarachnoid hemorrhage caused by the rupture of the aneurysm. The authors report here a case of temporal lobe contusion who demonstrated cerebrovascular narrowing angiographically at the 21st days after head injury. This 53-years-old male was examined again by angiography one week after the above-described angiography and the narrowing disappeared. The authors reviewed the literature on the posttraumatic cerebrovascular narrowing or spasm. Thirty seven cases have been reported in detail. Under the conditions of these 38 cases including the present case, the pathophysiology of the posttraumatic cerebrovascular narrowing or spasm was discussed. Two theories had been suggested for a long time: one was vasospasm caused by the traumatic subarachnoid hemorrhage and the other by direct mechanical irritation of cerebral artery. Recently, neurogenic factor is thought to take a part of this to a great extent such as hypothalamic dysfunction or dysfunctioning fragile autoregulation mechanism. It is seemed to be that such spasm caused by these mechanism will exist sure. However, in the posttraumatic cerebrovascular vasospasm, there are other accompanying intracranial lesions such as cerebral swelling, cerebral contusion, fracture of the base of the skull and so on. It is not assumed to be so simple environment as the spasm following the rupture of the aneurysm, and also the mechanism of genesis of the posttraumatic cerebrovascular spasm is not to be so simple. Several factors and their duplication will play a role in the mechanism. Further investigation is necessary for the clearness of the problem.
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Potassium tellurite (K2TeO3) was found to be a potent antisickling agent that inhibited red cell sickling at concentrations less than 10 mumol/L. The inhibitory effect depended on the incubation time, with the effect increasing with longer incubation periods. Because tellurite causes swelling of red cells, and because the antisickling effect of tellurite correlated with the degree of red cell swelling, the antisickling effect of tellurite is assumed to be due to the decreased mean cell hemoglobin concentration. Swelling of red cells by tellurite was accelerated by the addition of reduced glutathione. Tellurite appears to be a new type of antisickling agent that interacts with the red cell membrane.