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Biomedical subjects

F Sawano

Publications and source records attributed to F Sawano.

At least 19 recordsLinked to original sources

An organic thyristor.

Thyristors are a class of nonlinear electronic device that exhibit bistable resistance--that is, they can be switched between two different conductance states. Thyristors are widely used as inverters (direct to alternating current converters) and for the smooth control of power in a variety of applications such as motors and refrigerators. Materials and structures that exhibit nonlinear resistance of this sort are not only useful for practical applications: they also provide systems for exploring fundamental aspects of solid-state and statistical physics. Here we report the discovery of a giant nonlinear resistance effect in the conducting organic salt theta-(BEDT-TTF)2CsCo(SCN)4, the voltage-current characteristics of which are essentially the same as those of a conventional thyristor. This intrinsic organic thyristor works as an inverter, generating an alternating current when a static direct-current voltage is applied. Whereas conventional thyristors consist of a series of diodes (their nonlinearity comes from interface effects at the p-n junctions), the present salt exhibits giant nonlinear resistance as a bulk phenomenon. We attribute the origin of this effect to the current-induced melting of insulating charge-order domains, an intrinsically non-equilibrium phenomenon in the sense that ordered domains are melted by a steady flow.

Journal Article↗

Baroreflex attenuation after hypotension induced by vena caval occlusion in anesthetized dogs.

We determined effects of vena caval occlusion-induced systemic hypotension of 50 mmHg lasting 10 min (VCO) on efferent sympathetic nerve activity (SNA) and sympathetic baroreflex responsiveness. We recorded simultaneously SNA to the kidney (RNA), heart (CNA), spleen (SpNA), and liver (HNA) in anesthetized dogs. Baroreflex sensitivity was assessed using the ratio of a reflex SNA increase to a mean arterial pressure fall, which was also induced by caval occlusion. During VCO, SNA initially and equivocally increased, followed by recovery toward baseline. Cervical vagotomy attenuated the VCO-induced initial sympathoexcitation and subsequently maintained SNA at higher levels than those of intact animals, a finding basically similar to hemorrhagic hypotension [S. Koyama, F. Sawano, Y. Matsuda, Y. Saeki, T. Shibamoto, T. Hayashi, Jr., Y. Matsubayashi, and M. Kawamoto. Am. J. Physiol. 262 (Regulatory Integrative Comp. Physiol. 31): R579-R585, 1992]. At 5 min after releasing VCO, the baroreflex responsiveness was significantly attenuated: RNA, 79 +/- 11%; CNA, 78 +/- 8%; HNA, 60 +/- 16%; SpNA, 81 +/- 13% of the corresponding baseline. Fifteen minutes after VCO, this attenuation disappeared. Either vagotomy or pretreatment with intravenous vasopressin V1 receptor antagonist abolished this baroreflex attenuation. In conclusion, systemic hypotension to 50 mmHg for 10 min causes transient attenuation of sympathetic baroreflex sensitivity due to circulating vasopressin released by unloading of cardiopulmonary receptors during hypotension.

Animals↗

Role of sympathetic nervous system in hypotension induced by platelet-activating factor in anesthetized dogs.

This experiment was designed to investigate whether platelet-activating factor (PAF)-induced hypotension in anesthetized dogs produces changes in sympathetic activity in the heart, kidney, liver, and adrenal gland in intact animals (n = 5) and in animals with complete systemic baroreceptor denervation (n = 5). Following intravenous injection of PAF (10 micrograms/kg) in animals with intact baroreceptors, systemic blood pressure fell significantly. However, sympathetic nerve activity in the kidney, liver, and adrenal gland revealed a biphasic pattern: an initial increase (within 30 sec) followed by a progressive reduction below the preinjection level. In contrast to these nerve responses to PAF, only cardiac nerve activity showed an initial and significant increase, and it remained elevated above the preinjection level until the end of the experiment (10 min). In animals with complete systemic baroreceptor denervation, these sympathetic responses to PAF did not differ significantly from the responses in the intact animals. These results indicate that intravenous injection of PAF produces differential control of sympathetic nerve activity in different organs. The contribution of systemic baroreceptors to reflex compensations is minor in PAF-induced hypotension.

Adrenal Glands↗

Acute effect of hypobaria and hypoxia on renal nerve activity in anaesthetized rabbits.

To determine the acute effect of reduced barometric pressure and hypoxia on renal nerve activity, urethane-anaesthetized and mechanically ventilated rabbits were randomly exposed to the following four separate conditions in a decompression chamber: hypoxic hypobaria (n = 7), hypoxic normobaria (n = 5), normoxic hypobaria (n = 8) and slow normoxic hypobaria (n = 7). A combination of rapid decompression and simultaneous adjustment of inspired PO2 was used to simulate an altitude of 6600 m, and renal nerve activity and haemodynamics, such as systemic blood pressure and heart rate, were measured. During both hypoxic hypobaria and hypoxic normobaria, there were significant and similar increases in renal nerve activity at 6600 m (54 +/- 7% and 61 +/- 13% from each baseline, respectively). However, there were no changes in renal nerve activity during normoxic hypobaria or slow normoxic hypobaria with decompression rates of 1000 or 400 m min-1, respectively. From these results, we conclude that a reduction in barometric pressure without hypoxia does not affect renal nerve activity in anaesthetized rabbits.

Anesthesia↗

Spatial and temporal differing control of sympathetic activities during hemorrhage.

We performed simultaneous multifiber recordings of cardiac, renal (RNA), hepatic (HNA), adrenal, and splenic sympathetic nerve activities during 10 min of sustained hemorrhagic hypotension to a mean blood pressure of 50 mmHg. One minute after bleeding in dogs with intact baroreceptors, all measured nerve activities increased significantly, and a gradual decline toward prebleeding level followed. Only RNA showed a great inhibition below prebleeding level. In cervically vagotomized dogs, all nerve activities showed significantly higher levels than prebleeding control throughout the experiment. The initial increase in HNA observed at 1 min postbleeding in animals with intact baroreceptors was attenuated. HNA in the vagotomized group showed a gradual increase so that 5 min postbleeding, HNA reached a peak level that was maintained until the end of the experiment. Sympathoinhibition in RNA and decrease in heart rate during hemorrhagic hypotension were reversed to significant increases after vagotomy. In contrast, animals with denervation of the carotid sinus and aortic nerves showed initial increases in nerve activities followed by recovery to prebleeding control level within 2 min postbleeding. After complete denervation of systemic baroreceptors, rapid hemorrhage did not cause any significant change in sympathetic nerve activity in any nerve. These results indicate that early reflex response to hemorrhage in regional sympathetic nerves is unidirectional sympathoexcitation mediated by summative unloading of both arterial baroreceptors and cardiopulmonary receptors. When greater than 1 min passed after bleeding and sustained hypotension of 50 mmHg was established, a reflex mechanism through the vagal afferents participated to inhibit the unidirectional sympathoexcitation mediated by unloading of arterial baroreceptors, with different magnitude in different innervated organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Pulmonary vascular response to anaphylaxis in isolated canine lungs.

We determined changes in vascular resistance and microvascular permeability during anaphylactic reaction in isolated canine lungs perfused at constant pressure with autologous blood. In lungs with anaphylaxis induced by an intra-arterial injection of Ascaris suum antigen (10 mg), pulmonary vascular resistance and capillary pressure assessed as double occlusion pressure increased transiently by 10 times and 6.3 mmHg, respectively. Pre- to postcapillary vascular resistance ratio decreased from 0.89 +/- 0.05 to 0.21 +/- 0.06, suggesting predominant pulmonary venoconstriction. In lungs perfused in the antidromic direction from the pulmonary vein to the artery, anaphylaxis caused marked precapillary vasoconstriction, consistent with pulmonary venoconstriction. Vascular permeability assessed using the capillary filtration coefficient and isogravimetric capillary pressure did not change significantly for 3 h in either group. No changes were found in any variables in the saline-injected control lungs. The final weight of the anaphylactic lungs was significantly greater than that of the control lungs. Thus we conclude that anaphylaxis in isolated canine lung produces an increase in capillary pressure due to pulmonary venoconstriction without significant changes in vascular permeability. Pulmonary edema accompanied by anaphylactic hypotension may result from an increase in pulmonary hydrostatic intravascular pressure but not an increase in pulmonary vascular permeability.

Anaphylaxis↗

Effect of hypertonic saline infusion on renal vascular resistance in anesthetized dogs.

Changes in renal vascular resistance (RVR) and their mechanisms were investigated following infusion of 7.5% hypertonic saline (4 ml/kg) in anesthetized dogs. In all animals the left kidney was perfused at a constant perfusion flow (59 +/- 6 ml/min) with heparinized blood using a pulsatile roller pump. Renal perfusion pressure (RPP), systemic blood pressure (SBP), central venous pressure (CVP), and heart rate (HR) were measured simultaneously. Electrical stimulation of renal sympathetic nerves was also performed to evaluate the neurally mediated change in renal vasculature before and after infusion of hypertonic saline. In animals with intact vagi, intravenous administration of hypertonic saline resulted in significant increases in both mean blood pressure (MBP) and CVP, and caused significant decreases in HR and RVR. These effects were not affected by bilateral cervical vagotomy. In both intact and vagotomized animals, changes in RVR in response to renal nerve stimulation were attenuated after infusion of hypertonic saline. These results suggest that reduction in RVR after intravenous infusion of hypertonic saline is not a reflex effect mediated by vagal afferents. Instead, vascular response of the renal artery to hypertonic saline may result from a suppression of neurotransmission from renal sympathetic nerve endings to renal vascular smooth muscle.

Animals↗

Potassium depletion and hypertonic medium reduce "non-coated" and clathrin-coated pit formation, as well as endocytosis through these two gates.

Intracellular potassium depletion inhibits receptor-mediated endocytotic processes occurring through clathrin-coated pits. Besides the clathrin-coated pit route, flask-shaped invaginations that do not bear a typical clathrin coat have been recently implicated in receptor-mediated endocytosis of cholera toxin. These invaginations are called "non-coated" to distinguish them from the typical clathrin-coated pits. In the present study, we have investigated whether "non-coated" invaginations are sensitive, as are clathrin-coated pits, to potassium depletion and whether hypertonic medium, which inhibits receptor-mediated endocytosis, also affects "non-coated" invaginations. We found that 1) both potassium depletion and hypertonic medium reduce "non-coated" invaginations on the cell surface; 2) similar to potassium depletion, hypertonic medium markedly decreases the number of clathrin-coated pits; 3) these changes are accompanied by an inhibition of the internalization (measured morphologically) of cholera toxin-gold through "non-coated" invaginations, as well as of alpha 2-macroglobulin-gold taken up by clathrin-coated pits; and 4) in addition, both the hypertonic medium and potassium depletion inhibit the uptake of horseradish peroxidase, a marker of fluid-phase endocytosis.

Animals↗

Ligands internalized through coated or noncoated invaginations follow a common intracellular pathway.

Cholera toxin (CT) represents a class of ligands that binds preferentially to noncoated pits on the cell surface. In the present study, we have investigated the mechanism of endocytosis of this class of ligand and compared it to the classic coated pit mechanism. When either CT coupled to colloidal gold particles (CT-gold) or 125I-labeled CT were incubated with 3T3 L1 fibroblasts at 4 degrees C, both ligands bound in a preferential fashion to small noncoated pits on the cell surface. CT-gold surface-labeled cells were then incubated at 22 degrees C. The labeled ligand progressively moved into noncoated vesicles and a tubulovesicular compartment composed of a network of tubules and vesicles closely associated with multivesicular bodies but distinct from the Golgi complexes. The ligand next passed into multivesicular bodies. By contrast, alpha 2-macroglobulin (alpha 2m)-gold initially localized preferentially to coated pits and subsequently to coated vesicles and tubulovesicular structures before associating with multivesicular bodies. To directly compare the intracellular pathway followed by CT-gold to that followed by alpha 2m-gold, CT-gold (7 nm) was coincubated with alpha 2m-gold (15 nm). By 10 min of incubation at 22 degrees C, up to 66% of tubulovesicular units contained both ligands when analyzed in serial sections. Subsequently, both ligands were colocalized in multivesicular bodies. We conclude that CT-gold endocytosed via noncoated vesicles and alpha 2m-gold endocytosed through coated vesicles subsequently associate with the same tubulovesicular units, multivesicular bodies, and lysosomes.

Animals↗

Internalization of 3H-glibenclamide in pancreatic islet cells.

As judged by autoradiographic criteria at the optical level, rat islet cells progressively accumulate 3H-glibenclamide over 1 to 30 min incubation at 24 degrees C. The labeled material associates with all endocrine cells, but is preferentially seen within B cells. The total uptake of 3H-glibenclamide (1.0 mumol/l) is little affected by the presence of unlabeled glibenclamide (0.2 mmol/l), but is significantly decreased at 4 degrees C (p less than 0.05). At the electron microscopic level, less than 15% of the autoradiographic grains are located at the B cell plasma membrane and 72-79% of the grains found over the cytoplasm are associated with insulin secretory granules. Such a pattern is observed both after short (1 min) or prolonged (30 min) incubation, and at 4 or 24 degrees C. It is proposed that the insulinotropic action of glibenclamide is not necessarily attributable to primary events located solely at the cell surface.

Animals↗

Horseradish peroxidase uptake and crinophagy in insulin-secreting cells.

Upon exposure of pancreatic B cells to exogenous horseradish peroxidase (HRP), a population of secretory granules becomes HRP-labelled. In isolated islets of Langerhans, we studied the fate of HRP-labelled secretory granules during a pulse-chase experiment with HRP in order to assess their relationship with lysosomes containing secretory granule cores. These structures (crinophagic or multigranular bodies) were previously shown to be a site of insulin degradation (Orci et al., J cell biol 98 (1984) 222) [4]. After a 15-min pulse of peroxidase, the number and volume density of HRP-labelled secretory granules decreased over an 85-min chase period, during which the number and volume density of multigranular bodies labelled with HRP was significantly increased. At both time points, the surface density of HRP-labelled Golgi elements was very small compared with that of unlabelled ones. By autoradiography after a 5-min pulse of [3H]leucine and a 55-min chase, followed by a 15-min pulse of HRP and a 85-min chase, we could show that the majority of HRP-containing secretory granules were not radioactively labelled granules. These results suggest that: The low degree of HRP labelling of the Golgi makes it unlikely that secretory granules derive their HRP by budding from HRP-labelled cisternae. HRP-labelled SGs are preferentially transferred to MGBs (which become HRP-labelled) for prospective degradation. HRP labelling does not involve newly-formed mature secretory granules.

Animals↗

Some findings on the cytochemistry of the thyroid follicle epithelial cell in rats and mice.

The fine structural localization of endogenous peroxidase was studied in follicle epithelial cells of the rat thyroid. The localization of thiamine pyrophosphatase (TPPase) and acid phosphatase (AcPase) as well as the result of long time osmium impregnation in thyroid follicle epithelial cells were examined in the mouse. All the subapical secretory granules are principally peroxidase-positive, while the reabsorbed colloid droplets are almost peroxidase-negative. In addition, the cisternae of the rough endoplasmic reticulum, the nuclear envelope, 1-3 lamellae on the trans-side of the Golgi apparatus, rigid lamellae, and small vesicles on the trans-side of the Golgi apparatus, and the peripheral part of the follicle lumen are usually positive for endogenous peroxidase activity. The Golgi lamellae of the cis-side are very weakly positive. The TPPase activity is localized in 1-3 lamellae and vesicles on the trans-side of the Golgi apparatus and sometimes in rigid lamellae, while the AcPase activity is in 1-3 lamellae and smooth or coated vesicles on the trans-side of the Golgi apparatus, rigid lamellae, lysosomes and some colloid droplets. The areas positive for both enzyme activities are fairly well overlapped. Functional heterogeneity in the Golgi lamellae is suggested by the fact that TPPase, AcPase and endogenous peroxidase activities are limited on the trans-side of the Golgi apparatus, while osmium tetroxide stains only the cisternae of 1-2 lamellae on the cis-side of the Golgi apparatus. From these findings, GERL can be considered a part of the Golgi apparatus and not independent from this organelle in the thyroid follicle epithelial cell.

Acid Phosphatase↗

Characteristic reaction of the mouse adrenal cortical cell to osmium impregnation.

The fine structural localization of osmium impregnation in the mouse adrenal cortical cell was studied using the electron microscope. After osmication for 40--48 hrs all kinds of adrenal cortical cells of the mouse exhibited a selective localization of osmium impregnation in almost all the cisternae of the smooth endoplasmic reticulum in addition to 1--2 or 3 stacks and vesicles of cis-side of the Golgi apparatus. This fact might be implicated with the steroid hormones which may be localized in the cisternae of smooth endoplasmic reticulum. Moreover, the cisternae of the nuclear envelope, and of the characteristic lamellar body closely related to the smooth endoplasmic reticulum, were also stained with OsO4.

Adrenal Cortex↗

Fine structural localization of endogeneous peroxidase in the endostyle of ascidians, Ciona intestinalis. A part of phylogenetic studies of the thyroid gland.

The fine structural localization of peroxidase activity in the endostyle of Ciona intestinalis was studied by cytochemistry at electron microscopic level. Only zone 7 cells in this organ are positive for this enzyme activity. The reaction product is recognized in the external surface of the apical plasma membrane, and in the cisternae of the rough endoplasmic reticulum, of the nuclear envelope, and of the Golgi lamellae, and small vesicles of the Golgi region and of the apical cytoplasm. By electron microscopic autoradiography of 125I, the main site of iodination of thyroglobulin-like protein is considered to be the apical plasma membrane region of the zone 7 cells. The possibility of iodination of protein taking place within the endostylar lumen near the zone 7 cell cannot be ruled out. The relationship between the fine-structural localization of peroxidase activity and the site of iodination of protein is discussed.

Animals↗