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Biomedical subjects

Y Sawa

Publications and source records attributed to Y Sawa.

At least 217 records · Page 12Linked to original sources
PubMed1993

Defenestration of the sinusoidal endothelial cell in a rat model of cirrhosis.

We characterized the structural and immunohistological changes of sinusoidal endothelial cells that occur during cirrhosis in rats made cirrhotic with thioacetamide. Thioacetamide (200 mg/kg body wt) was injected intraperitoneally three times a week into male Wistar rats. Two, 4, 6 and 12 wk later, rat livers were observed under transmission and scanning electron microscopy and regular microscopy and immunostained with laminin and von Willebrand factor (factor VIII-related antigen) antibodies. The diameters and numbers of sinusoidal endothelial fenestrations did not change significantly after 2 wk in the thioacetamide-treated rats; however, they decreased within 4 wk after thioacetamide treatment. A basement membranelike structure in Disse's space was noted 6 wk after thioacetamide treatment. Laminin was detected in Disse's space after 4 wk. In vitro, in cultured sinusoidal endothelial cells, the diameter of sinusoidal endothelial fenestrations was significantly lower at 6 wk in thioacetamide-treated rats. von Willebrand factor was detected in the cytoplasm as granular fluorescence after 6 wk of thioacetamide treatment. These results suggest that as fibrosis develops in cirrhosis, the structural and immunohistochemical characteristics of sinusoidal endothelial cells change.

Animals↗
PubMed1992

Evidence that mutations in a loop region of the alpha-subunit inhibit the transition from an open to a closed conformation in the tryptophan synthase bienzyme complex.

Rapid-scanning stopped-flow (RSSF) UV-visible spectroscopy has been used to investigate the effects of single amino acid mutations in the alpha-subunit of the Salmonella typhimurium tryptophan synthase bienzyme complex on the reactivity at the beta-subunit active site located 25 to 30 A distant. The pyridoxal 5'-phosphate (PLP) cofactor provides a convenient spectroscopic probe to directly monitor catalytic events at the beta-active site. Single substitutions of Phe for Glu at position 49, Leu for Gly at position 51, or Tyr for Asp at position 60 in the alpha-subunit strongly alter the observed steady state and pre-steady state inhibitory effects of the alpha-subunit-specific ligand alpha-glycerophosphate (GP) on the PLP-dependent beta-reaction. However, similar GP-induced allosteric effects on the distribution of covalent intermediates bound at the beta-site that are observed with the wild-type enzyme (Houben, K.F., and Dunn, M.F. (1990) Biochemistry 29, 2421-2429) also are observed for each of the mutant bienzyme complexes. These results support the hypothesis that the preferred pathway of indole from solution into the beta-site is via the alpha-site and the interconnecting tunnel (Dunn, M.F., Aguilar, V., Brzović, P., Drewe, W.F., Houben, K.F., Leja, C.A., and Roy, M. (1990) Biochemistry 29, 8598-8607). Residues alpha E49, alpha G51, and alpha D60 are part of a highly conserved inserted sequence in the alpha/beta-barrel topology of the alpha-subunit. We propose that the GP-induced inhibition of the beta-reaction results, in part, from a ligand-dependent conformational change from an "open" to a "closed" structure of the alpha-subunit which involves this region of the alpha-subunit and serves to obstruct the direct access of indole into the tunnel. Our findings suggest that the altered kinetic behavior observed for the alpha-mutants in the presence of GP reflects an impaired ability of the modified bienzyme complex to undergo the conformational transition from the open to the closed form.

Allosteric Regulation↗
PubMed1992

Human fetal heart development after mid-term: morphometry and ultrastructural study.

A total of 44 normally developed human fetal hearts aged from 17 to 40 weeks gestation were provided for routine ultrastructural and morphometric studies. For morphometric analysis, the maximal thicknesses of the anterior, lateral and posterior wall of both ventricles and that of interventricular septum were measured and the left-to-right thickness ratios calculated. The cross-sectional areas of both ventricles in the plane of the greatest heart diameter were measured with computerized image analysis system. Data were analyzed using linear regression and one-way analysis of variance. Myofibril formation occurred by attachment of thin filaments into amorphous Z materials which were presented in sarcolemmal plaques, sarcoplasmic condensations, desmosomes and in Z lines. From these Z centers, myofibrils radiated many directions and branched and anastomosed with further development. This pattern of myofibrillar development continued throughout the whole fetal period. A transverse tubule system was clearly evident in later fetal development. It occurred by invagination of sarcolemma into myocardial cells and formation of subsarcolemmal caveolae. Mitochondria, well-developed Golgi complexes, glycogen granules and well-developed microvessels were found throughout the whole fetal period. Binucleated myocytes appeared by 32 weeks gestation and this suggests that myocyte hyperplasia may cease before birth in humans. The growth of both ventricular walls, the interventricular septum and that of both ventricular cross-sectional areas showed linear regression, and the left-to-right wall thickness ratios were nearly constant. Also, there were no differences in morphometric data between the left and right ventricles. In conclusion, development of the myocyte is an ongoing process which may be continued in the post-natal period in humans, and our statistical results do not support the theory of the right ventricular dominance during the fetal period.

Cell Differentiation↗
PubMed1992

Alterations in the beta-adrenergic receptor system after hypothermic ischemia in hearts with preischemic beta-receptor desensitization.

Although hypothermic cardioplegic arrest is a basic method of myocardial protection in cardiac surgery, the beta-adrenergic receptor (BAR) system has been little investigated in the heart subjected to hypothermic ischemia. Additionally, although the hypothermic arrest is often induced in hearts with preischemic desensitization of the BAR system by preceding congestive heart failure, the functional state of the BAR system after ischemia has not been studied in these hearts. We investigated alterations in the BAR system after hypothermic ischemia in normal rat hearts and in those with preischemic desensitization of the BAR system produced with isoproterenol (ISP: 400 micrograms/kg/hr for 24 hr). Both normal and BAR-desensitized hearts were isolated and subjected either to 40 min of hypothermic (10 degrees C) global ischemia followed by 40 min of reperfusion or subjected to time-matched aerobic perfusion with modified Krebs-Henseleit solution. At the end of perfusion (1) BAR binding properties with [3H]CGP-12177 and adenylate cyclase activity were measured in crude membrane fraction and (2) the inotropic response to ISP (delta LV + dP/dtmax) was evaluated in an isovolumetric contracting heart preparation. Following reperfusion, normal hearts without desensitized BAR showed a higher Bmax value than those of nonischemic time-matched hearts (41.8 +/- 3.1 vs 35.4 +/- 2.4 fmole/mg protein, P less than 0.05), whereas the Kd value was in a similar range in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1992

Immunoglobulin G Fc fragment-binding proteins in Mycoplasma salivarium cells.

Cell proteins of Mycoplasma salivarium were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to membranes, then examined for reactivity with human IgG molecules, the Fc fragment of human IgG, and concanavalin A (ConA). Multiple protein bands bound IgG, and most of them also bound ConA. One (corresponding to a molecular mass of 90 kDa) of the IgG- and ConA-binding bands intensely interacted with the Fc fragment of IgG. The reactivity of proteins eluted from the band with the Fc fragment, tested by dot-blotting and ELISA, was inhibited (90%) by pre-incubation with IgG and to a lesser extent (50%), with IgM. Thus, M. salivarium contained a cellular protein with a molecular mass of 90 kDa, that bound the Fc fragment of human IgG.

Bacterial Proteins↗
PubMed1992

Experimental study in a rabbit model of ischemia-reperfusion lung injury during cardiopulmonary bypass.

Adult white rabbits were subjected to 2 hours of partial cardiopulmonary bypass (flow rate 90 ml/min/kg) at 32 degrees C, and unilateral pulmonary artery occlusion was used to simulate total cardiopulmonary bypass in the lung subjected to arterial occlusion, with the other side used as the control lung. The lung subjected to arterial occlusion was reperfused by one of the following methods: (1) by whole blood (WB group), (2) by leukocyte-depleted blood (LD group), and (3) by whole blood with protease inhibitor (nafamostat mesilate, FUT group), expecting its anticomplement action. In the fourth group, the lung was inflated with oxygen during pulmonary artery occlusion followed by whole blood reperfusion (OXY group). As a result, lungs subjected to pulmonary artery occlusion showed significant decreases in tissue concentrations of adenosine triphosphate and regional tissue blood flow during cardiopulmonary bypass. Furthermore, recovery of adenosine triphosphate was depressed in the WB group and recovery of regional tissue blood flow in the WB and OXY groups. Ultrastructural findings in alveolar epithelial cells and capillary endothelial cells showed worsening at reperfusion in only the WB group. Transpulmonary gradients of C5a and leukocyte showed significant increases at reperfusion in the WB and OXY groups. Alveolar-arterial oxygen difference was significantly higher in the WB group than in the others. Results indicate that complete cessation of pulmonary artery flow in normothermic cardiopulmonary bypass may cause ischemia of the lung followed by reperfusion injuries with the no-reflow phenomenon, with possible involvement of activation of leukocytes and complement.

Adenosine Triphosphate↗
PubMed1992

[The pulmonary venous obstruction following repair with absorbable sutures in total anomalous pulmonary venous drainage--a case report].

A 4-month-old boy with infracardiac type of total anomalous pulmonary venous drainage (TAPVD) who underwent anastomosis between left atrium and common pulmonary vein at age of one month with absorbable suture of polydioxanone (PDS), was suffered from pulmonary venous obstruction (PVO). The ostia of pulmonary veins were stenosed severely. The histological findings showed that there were inflammatory changes and fibrosis around PDS suture. These findings suggested that PDS would cause inflammatory change of tissues around, which might be occurred following repair of TAPVD.

Anastomosis, Surgical↗
PubMed1991

Site-directed mutagenesis of the beta subunit of tryptophan synthase from Salmonella typhimurium. Role of active site glutamic acid 350.

To investigate the functional role of glutamic acid 350 in the active site of the beta subunit of tryptophan synthase from Salmonella typhimurium, we have replaced this residue by glutamine or alanine by use of site-directed mutagenesis. The mutant alpha 2 beta 2 complexes were expressed, purified, crystallized, and characterized by spectroscopic and kinetic studies with several substrates. We find large alterations in the substrate and reaction specificity of each mutant form of the alpha 2 beta 2 complex. Since the two mutant enzymes are virtually inactive in reactions with L-serine but are active in reactions with beta-chloro-L-alanine, glutamic acid 350 may facilitate the beta-elimination of the weak hydroxyl leaving group of L-serine. The mutant alpha 2 beta 2 complexes are more active than the wild type enzyme in the beta-elimination reaction with beta-chloro-L-alanine. These enzymes are irreversibly inactivated by beta-chloro-L-alanine, whereas the wild type enzyme is not. These altered properties may result from a change in the conformation of the active site, from a change in the orientation of the coenzyme relative to active site residues, or from a change in the solvent accessibility of the active site. The alteration in the active site may enhance the release of amino acrylate from the Schiff base intermediate by hydrolysis or by transamination.

Amino Acids↗
PubMed1991

Effect of a cyclic adenosine monophosphate phosphodiesterase inhibitor, DN-9693, on myocardial reperfusion injury.

A new cyclic adenosine monophosphate phosphodiesterase inhibitor, DN-9693, was examined to see whether myocardial reperfusion injury could be reduced in a setting of cardioplegic arrest through its antiaggregation effect on leukocytes. Isolated rabbit heart models with whole blood perfusion were used, and 18 hearts were divided into three groups according to the reperfusion method: control (G-1, n = 5), DN-9693 (G-2, n = 7), and leukocyte depletion (G-3, n = 6). The hearts were subjected to 120 minutes of cold global ischemia under crystalloid cardioplegia followed by 30 minutes of reperfusion. A dose of 20 micrograms.kg-1.min-1 of DN-9693 was administered in G-2, and a leukocyte removal filter was used in G-3 during reperfusion. Ultrastructural changes in mitochondrial injuries, intracellular edema, and capillary injuries of the myocardium showed worse changes in G-1 than in G-2 and G-3. Under microscopic study, the intracapillary leukocyte count was significantly higher in G-1 than in G-2 and G-3. Recovery of rate-pressure product, left ventricular developed pressure, and coronary flow were significantly better in G-2 and G-3 than in G-1. There were no significant differences between G-2 and G-3 for all these indices. These results indicate that reperfusion with leukocyte-depleted blood attenuates reperfusion myocardial injury and DN-9693 has a comparable myocardial protective effect with possible inhibition of leukocyte aggregation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Experimental evaluation of myocardial protective effect of prostacyclin analog (OP-41483) as an adjunct to cardioplegic solution.

A stable prostacyclin analog (OP-41483) was evaluated for myocardial protective effect against global ischemia with the use of cardioplegia. Isolated canine hearts (n = 25) were exposed to 60 minutes of warm (37 degrees C) global ischemia after the arrest by crystalloid cardioplegia. Prostaglandin analog was given in three different ways: preadministration (700 ng/kg body weight per minute) before ischemia for 30 minutes (group I, n = 5), given as a component of cardioplegic solution (600 ng/ml, group II, n, = 6), and post-administration (25 ng/kg body weight per minute) during reperfusion for 30 minutes (group III, n = 7). During reperfusion, coronary sinus blood flow, 6-keto-prostaglandin F1 alpha in coronary sinus blood, and myocardial oxygen consumption were measured during reperfusion. As a result, groups II and III showed significantly better global left ventricular function (developed pressure, maximum dP/dt, and diastolic compliance) than the control group (without prostaglandin analog, n = 7) and group I. Myocardial oxygen consumption at reperfusion (1 minute) was significantly larger in group II than in the control group. 6-keto-prostaglandin F1 alpha flux was significantly larger in group II than in the other three groups during reperfusion. The results indicated that prostaglandin analog has a beneficial effect on myocardial protection under global ischemia with cardioplegia, particularly when used as a component of cardioplegic solution and also during reperfusion. The mechanism may relate to the cytoprotective effect (including protection of endothelium with enhanced endogenous prostacyclin production at reperfusion and also to the modulation of reperfusion per se.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Shy-Drager syndrome. Effect of fludrocortisone and L-threo-3,4-dihydroxyphenylserine on the blood pressure and regional cerebral blood flow.

In nine cases of Shy-Drager syndrome, the changes in blood pressure and cerebral blood flow on sitting up from a supine position were studied. The influence of fludrocortisone, a synthetic mineralocorticoid, and L-threo-3,4-dihydroxyphenylserine (DOPS), a precursor of norepinephrine, on these changes was examined. On sitting up, the regional cerebral blood flow (rCBF) measured by Xe133 inhalation showed a tendency to decrease. Fludrocortisone reduced the fall of the mean blood pressure significantly. DOPS reduced the fall of both the diastolic blood pressure and rCBF significantly.

Administration, Oral↗
PubMed1990

[Clinical analysis of the patients with delayed sternal closure following open heart surgery].

Thirteen patients with successful or unsuccessful delayed sternal closure (DSC) after open heart surgery were reviewed. The indications of DSC were cardiac dilatation in 12 patients and intractable bleeding in one. Patients were divided into two groups as follows: Group A of 7 patients with mediastinum being sealed by prosthetic material, and Group B of 6 patients with primary skin closure by mobilized skin-flap. Postoperative complications and prognosis were compared between these two groups. There were 6 long term survivors. In group A, there were 4 deaths, 2 from low output syndrome (LOS) and 2 from sepsis due to mediastinitis. In group B, 2 died of LOS and 1 died of multiple organ failure, while no patients developed mediastinitis. In patients with unsuccessful DSC, mainly due to poor hemodynamics, there found no tendencies of decrease in CVP and LAP levels and no reduction in the amount of catecholamine dosage prior to attempted DSC. In conclusion, 1) mediastinal isolation with primary skin closure seemed more effective for preventing mediastinitis than coverage with prosthetic materials, 2) DSC was possible when there were hemodynamic improvements with decrease in CVP and LAP levels, and reduction in catecholamine dosage, and 3) plastic surgical technique was useful for primary skin closure.

Aged↗
PubMed1989

Effects of reserpine on dopamine metabolite in the nucleus accumbens and locomotor activity in freely moving rats.

The effect of reserpine (2 mg/kg i.p.) on both locomotor activity and the turnover of dopamine metabolite in the rat nucleus accumbens was estimated by using an activity monitor (Animex) and by in vivo brain microdialysis. Three to five hours after reserpine administration locomotor activity was reduced and there was a concomitant increase in the level of the dopamine metabolite, homovanillic These findings suggest that depletion of dopamine from the nucleus accumbens may result in decreased locomotor activity. The data support the notion that dopamine in this tissue contributes to the control of locomotion.

Animals↗
PubMed1989

Immunoelectron microscopic localization of actin in normal and cholestatic rat hepatocytes.

The immunoelectron microscopic localization of actin in hepatocytes was studied in normal, common bile duct-ligated, and phalloidin treated rats. We used the low temperature embedding procedure with Lowicryl K4M and protein A-gold technique was applied to demonstrate the localization of actin. The tissues embedded in Lowicryl K4M at low temperature provided good preservation of ultrastructure and antigenicity of actin. In control rats bile canaliculi were clearly visualized and most of the gold particles were observed on the bile canalicular microvilli, at the pericanalicular ectoplasm, at the cell border, and on the sinusoidal microvilli. In common bile duct-ligated rats and phalloidin treated rats, pericanalicular ectoplasm was thickened and many gold particles were seen there.

Actins↗
PubMed1989

Evaluation of prostacyclin analogue OP-41483 as an adjunct to crystalloid cardioplegia in infants and children.

A chemically stable prostacyclin analogue (PGI2-A, carbacyclin, OP-41483) was evaluated as an adjunct to potassium cardioplegia in infants (n = 13) and children (n = 32), in whom the current potassium cardioplegia may be limited in its effects. PGI2-A was added in a dose of 300 micrograms/L to the potassium cardioplegic solution. Postoperatively, peak levels of the myocardial-specific isoenzyme of creatine kinase (MB-CK) were compared for the PGI2 group and a control group (n = 65). In patients 1 year of age or older (n = 32 and 49 for the PGI2 and control groups, respectively), the MB-CK level was significantly lower in the PGI2 group only when compared between the subgroups with an aortic cross-clamp time of 120 minutes or more (n = 9 and 10; MB-CK level, 35.2 +/- 15.6 vs 68.3 +/- 32.4 IU/L;p less than 0.05). In patients less than 1 year of age, in whom aortic cross-clamp times were generally less than 120 minutes, the MB-CK level was also lower in the PGI2-A group than in the control group (n = 13 and 16; MB-CK level, 33.6 +/- 14.3 vs 61.6 +/- 36.3 IU/L;p less than 0.05). Infants less than 6 months of age (n = 18) underwent ultrastructural assessment of left ventricular myocardial biopsy specimens, and the PGI2-A group showed better results in mitochondrial and intracellular edema scores. This clinical trial showed beneficial effects of PGI2-A used with crystalloid potassium cardioplegia in infants and children.

Adolescent↗
PubMed1989

Analysis of acute and chronic heart failure in view of hepatic oxygen supply-demand relationship using hepatic venous oxygen saturation.

The adequacy of hepatic circulation in terms of oxygen supply-demand relation was assessed by measuring hepatic venous oxygen saturation (Shvo2) in patients. Among those with congenital cardiac lesions (n = 11), Shvo2 during the early postoperative period was markedly low as less than 20% in Fontan operation group (n = 5) with subsequent clinical findings of acute hepatic dysfunction. Significant correlations were found between Shvo2 values early after surgery and subsequent peak values in serum hepatic enzymes. Serum total bilirubin and prothrombin time started to deteriorate when Shvo2 became below 30%. Cardiac index, hepatic perfusion pressure and mixed venous oxygen saturation showed positive linear correlations with Shvo2, and central venous pressure (CVP) with an inverse relation. In chronic valvular disease (n = 28), those with NYHA class IV patients showed lower Shvo2 (average; 47.4%) at cardiac catheterization than the others (class-I; 66.4%, class-II; 63.9%, p less than 0.05). These results indicate that Shvo2 monitoring appears to be useful to assess the hepatic perfusion in terms of oxygen supply-demand relation in acute and chronic heart failure, and Shvo2 of 30% seems to be a critical level.

Adult↗
PubMed1989

[Extended aortic arch anastomosis for aortic coarctation in neonate and early infancy--experience in 5 patients].

The aortic coarctation (CoA) was repaired with extended aortic arch (AA) anastomosis in 5 consecutive patients, 2 in neonate and 3 in infancy, ranging in age from 3 to 106 days. The associated lesions were ventricular septal defect in 2, atrial septal defect in 2 and complete atrioventricular canal in 1. Patent ductus was found in 4 and prostaglandin E1 was required in 2 with response in 1 patient. The AA was hypoplastic in 2 patients with arch to descending aorta diameter ratio below 0.5. The CoA repair was performed as the first procedure in all. The primary anastomosis was possible in all between AA and the descending aorta without undue tension after removal of the all ductus tissue and extensive mobilization of the aorta. Aortic clamp time was 28 minutes in average. The intraoperative pressure gradient after repair across AA was 0 to 10 mmHg (average 4.6 mmHg). All except 1 with preceding hepatic dysfunction tolerated the procedure without complication or operative death. Postoperative evaluation at 1 to 11 months showed no significant pressure gradient between upper and lower extremities. This method appears to be useful for CoA in early infancy particularly when AA is hypoplastic.

Anastomosis, Surgical↗