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Biomedical subjects

Y Sawa

Publications and source records attributed to Y Sawa.

At least 163 records · Page 9Linked to original sources

Saccular aneurysm in the right-sided aortic arch: a successfully corrected case.

We report the surgical treatment of a rare case of true aortic aneurysm in a right-sided aortic arch. A 49-year-old female patient with obstructive respiratory problems demonstrated a true aneurysm with a diameter of 58 mm located at the right-sided aortic arch between the right carotid artery and right subclavian artery. Surgery was successfully performed by replacing the arch including the aneurysm with a prosthetic graft. The positions of true aneurysms in the right-sided aortic arch can be divided into two subtypes: first, the transverse arch between the right carotid artery and right subclavian artery, and second, the base of the subclavian artery, the Kommerell's diverticulum. The region is informative for consideration of the surgical approach toward aneurysms of this entity.

Angiography, Digital Subtraction↗

In vivo transfection of cis element "decoy" against nuclear factor-kappaB binding site prevents myocardial infarction.

The transcriptional factor nuclear factor-kappaB (NFkappaB) plays a pivotal role in the coordinated transactivation of cytokine and adhesion molecule genes that might be involved in myocardial damage after ischemia and reperfusion. Therefore, we hypothesized that synthetic double-stranded DNA with high affinity for NFkappaB could be introduced in vivo as "decoy" cis elements to bind the transcriptional factor and to block the activation of genes mediating myocardial infarction, thus providing effective therapy for myocardial infarction. Treatment before and after infarction by transfection of NFkappaB decoy, but not scrambled decoy, oligodeoxynucleotides before coronary artery occlusion or immediately after reperfusion had a significant inhibitory effect on the area of infarction. Here, we report the first successful in vivo transfer of NFkappaB decoy oligodeoxynucleotides to reduce the extent of myocardial infarction following reperfusion, providing a new therapeutic strategy for myocardial infarction.

Animals↗

Prevention of graft coronary arteriosclerosis by antisense cdk2 kinase oligonucleotide.

Graft coronary arteriosclerosis, which limits the long-term survival of allograft recipients, is characterized by diffuse intimal thickening composed of proliferative smooth muscle cells. We observed that messenger RNA of the cell cycle regulatory enzyme cyclin-dependent kinase (cdk) 2 kinase, which mediates smooth muscle cell proliferation, was elevated in the thickened intima of coronary arteries of murine heterotopic cardiac allografts. We studied the effects of antisense phosphorothioate oligodeoxynucleotide (ODN) against this enzyme using gene transfer mediated by a hemagglutinating virus of Japan (HVJ)-liposome complex intraluminally delivered to inhibit the intimal hyperplasia. At 30 days after transplantation, antisense cdk2 kinase ODN treatment had dramatically inhibited neointimal formation in the allografts. Expression of vascular cell adhesion molecule-1 was also suppressed by antisense cdk2 kinase. However, these effects were not observed in the sense or scrambled ODN-treated allografts. Thus, an intraluminal administration of antisense ODN directed to a specific cell cycle regulatory gene can inhibit neointimal formation after cardiac transplantation.

Animals↗

Survival of grafts of genetically modified cardiac myocytes transfected with FITC-labeled oligodeoxynucleotides and the beta-galactosidase gene in the noninfarcted area, but not the myocardial infarcted area.

Since one of the attractions of gene therapy in the heart is the implantation of genetically modified cultured cells, we employed genetically modified myocytes transfected with FITC-labeled oligodeoxynucleotides (ODN) and beta-galactosidase gene in this study, to investigate the cellular localization and fate of grafted myocytes in the heart. In addition, we examined the feasibility of myocytes grafting into a myocardial infarction model. Delivery of FITC-labeled ODN with the HVJ-liposome method resulted in sustained fluorescence as compared to direct transfer of 'naked' ODN. Interestingly, implantation of cardiac myocytes transfected with FITC-labeled ODN ex vivo by the HVJ-liposome method resulted in sustained fluorescence for at least 1 week in the noninfarcted area, whereas little fluorescence was detected in the area of infarction. This observation was confirmed by measurement of fluorescence, which showed significantly higher levels in the noninfarcted area than the infarcted area. Positive staining for beta-galactosidase protein was also clearly observed 7 days after grafting of transfection of the beta-galactosidase gene, while no staining was detected in grafted myocytes in control rats. Survival of implanted genetically modified cardiac myocytes in the noninfarcted, but not infarcted area, provides new information for the local delivery of recombinant molecules to the heart using gene therapy.

Animals↗

Functional and phenotypical activation of leucocytes in inflamed human colonic mucosa.

Infiltrating leucocytes are activated to generate reactive oxygen species or to produce several molecules in inflamed colonic mucosa. To clarify the phenotypical and functional properties of activating cells in colitic mucosa, 23 patients with ulcerative colitis and 13 controls were studied using a combined method for determining in situ nitroblue tetrazolium reducing activity and immunohistochemical characterization. Antibodies 25F9 (anti-macrophage), EG2 (anti-eosinophil cationic protein), MAC387 (anti-calprotectin, expressed by activated myeloid-histiocytes lineage), and MAC-1 (anti-CD11b) were used. The proportion of EG2, calprotectin, and CD11b-positive cells were significantly increased in inflamed mucosa. The proportion of EG2, calprotectin, and CD11b-positive cells significantly correlated with the histological degree of inflammation. Proportion of EG2-positive cells but not calprotectin nor CD11b-positive cells was significantly correlated with nitroblue tetrazolium reducing activity. Aggregated cells reducing nitroblue tetrazolium seen in severely inflamed mucosa were found to be EG2 positive. Most of the calprotectin-positive cells were 25F9 negative. In addition to activation of neutrophils and macrophages, eosinophil activation has been shown to be involved in inflamed colonic mucosa.

Adolescent↗

Biocompatibility of heparin-coated circuits in pediatric cardiopulmonary bypass.

In this study, we evaluated the biocompatibility of heparin-coated circuits in pediatric cardiopulmonary bypass (CPB). Eight patients were divided into 2 groups: the control group (Group C) and heparin-coated group (Group H). In Group H, CPB circuits, including the arterial pump, oxygenator, and cannulas were heparin-coated. Before, during, and after CPB, blood samples were obtained to assess the platelet counts (Plat), alpha 2-plasmin plasminogen inhibitor complex (PIC), thrombin-antithrombin III complex (TAT), C3 activation products (C3a), interleukin (IL)-6, IL-8, and polymorphonuclear neutrophil leukocyte (PMN) elastase. There was no significant difference in Plat, PIC, or TAT between groups. Group H showed significantly low levels of C3a (during and after CPB), PMN elastase (during CPB), and IL-6 (after CPB). These data demonstrated that in pediatric CPB, heparin-coated CPB circuits reduced the activation of complements and the production of PMN elastase and IL-6, suggesting the superior biocompatibility of the heparin-coated circuits.

Anticoagulants↗

[David's operation for aortic regurgitation associated with annulo-aortic ectasia].

A 54-year-old man with AR due to AAE underwent the replacement of ascending aorta by sparing an aortic valve (David operation). Under cardiopulmonary bypass, the aneurysmal aorta and the all three sinuses of valsalva were excised, leaving 5 mm of arterial wall attached to the aortic valve. The aortic valve was reimplanted inside a Dacron graft (28 mm Hemashield) which was calculated by aortic valve leaflet height as well as from the size of LVOT. The patient has survived the operative procedure and showed uneventful recovery. We believe this new procedure preserving the native aortic valve is useful for preventing from some complications associated with an artificial heart valve and improvement of QOL of patient.

Aorta↗

Hydroxylation of ent-kaurenoic acid to steviol in Stevia rebaudiana Bertoni--purification and partial characterization of the enzyme.

The diterpenoic compound steviol (ent-kaur-16-en-13-ol-19-oic acid) is the aglycone of sweet glycosides accumulated in Stevia rebaudiana Bertoni. This compound is the hydroxylated form of ent-kaurenoic acid (ent-kaur-16-en-19-oic acid; ent-KA). The hydroxylation of ent-KA to form steviol requiring NADPH and molecular oxygen was detected in stroma prepared from S. rebaudiana Bertoni. The enzyme was purified from leaf extract to apparent homogeneity with a molecular mass of 39 kDa. Taken together with the value of 160 kDa estimated for native enzyme, this suggested that the hydroxylating enzyme is a homotetramer. The N-terminal sequence was determined through 20 residues. The pH optimum was 7.5-7.8. Apparent Km values were 11.1 microM for ent-KA and 20.6 microM for NADPH. Its visible absorption spectrum suggested that the enzyme was flavoprotein. The stoichiometric relationship between the formation of steviol and the utilization of ent-KA and cofactors confirmed the equation ent-KA + NADPH + H(+) + O2-->steviol + NADPH(+) + H2O.

Amino Acid Sequence↗

Leukocyte depletion attenuates reperfusion injury in patients with left ventricular hypertrophy.

BACKGROUND: Reperfusion injury can occur after a long period of aortic cross-clamping in patients with left ventricular hypertrophy during open-heart surgery, even with the most up-to-date techniques of myocardial protection. In the present study, we examined whether leukocyte depletion as an adjunct to terminal blood cardioplegia (LDTC) attenuates reperfusion injury in patients with left ventricular hypertrophy (LV mass, >300 g; left ventricular end-systolic volume index, >100 mL/m2) in a group of 30 patients undergoing aortic valve replacement. METHODS AND RESULTS: We used basic cold potassium crystalloid cardioplegic solution. Terminal blood cardioplegic solution (TC) or LDTC was accomplished by mixing a cold potassium crystalloid cardioplegic solution with warm arterial blood obtained through cardiopulmonary bypass and administered to the aortic root for the first 10 minutes of reperfusion. During delivery of LDTC, warm arterial blood was passed through a leukocyte-removal filter. Patients were randomized into one of three groups for reperfusion: whole blood (WB) (n=10), TC (n=10), and LDTC (n=10). Left ventricular biopsies were obtained before ischemia, at the end of ischemia, and 15 minutes after reperfusion. Semiquantitative scoring for ultrastructural alterations indicated that the LDTC group achieved significantly better recoveries of both scores at reperfusion for myocyte damage and for endothelial cell damage of capillaries than did the WB and TC groups. The LDTC group had significantly fewer neutrophils adhering to endothelial cells at reperfusion and a lower level of malondialdehyde derived from myocardium than did the WB and TC groups. Regarding the clinical data, the LDTC group had a lower maximum creatine kinase-MB, a higher percentage of spontaneous defibrillation, a lower pulmonary capillary wedge pressure, and a lower requirement for dopamine that did the WB group, whereas the TC group failed to do better than the WB group. CONCLUSIONS: These results demonstrate that leukocyte-depleted reperfusion is potentially beneficial as an adjunct to terminal cardioplegia during cardiac surgery to attenuate reperfusion injury in patients with left ventricular hypertrophy.

Adult↗

Repair of postinfarction ventricular septal defect on a beating heart.

Two elderly patients with postinfarction ventricular septal defect underwent repair by endocardial patch with infarct exclusion on a beating heart under normothermic cardiopulmonary bypass with ultra-short-acting beta-blocker infusion. Their hemodynamic states soon recovered, and postoperative angiographic studies showed improvement of cardiac function and no residual shunt. Ultra-short-acting beta-blocker has the potential to facilitate safe repair of postinfarction ventricular septal defect on a beating heart, and this operative approach can be beneficial for myocardial protection.

Adrenergic beta-Antagonists↗

Attenuation of cardiopulmonary bypass-derived inflammatory reactions reduces myocardial reperfusion injury in cardiac operations.

In cardiac operations endopeptidase (protease) inhibitor may be beneficial in reducing myocardial injury when administered in the cardiopulmonary bypass prime. Nafamostat mesilate was evaluated in 20 patients who underwent coronary artery bypass grafting. The patients were divided into a control group (n = 10) and a nafamostat group (n = 10). Nafamostat (2 mg/kg per hour) was continuously given during cardiopulmonary bypass in the nafamostat group. The age, number of grafts, cardiopulmonary bypass time, and aortic crossclamp time were similar between groups. In the control group, neither tumor necrosis factor-alpha nor interleukin-1 levels showed any significant change during cardiopulmonary bypass, whereas interleukin-6 and interleukin-8 levels, percent expression of adhesion molecule (CD18) on neutrophils, and CH50 assay results increased significantly during cardiopulmonary bypass. As compared with the control group, the nafamostat group showed significantly lower levels of interleukin-6 (123 +/- 57 versus 40 +/- 22 pg/ml, respectively) and interleukin-8 (96 +/- 13 versus 66 +/- 14 pg/ml, respectively). The nafamostat group showed a significantly lower difference of CH50 assay results and malondialdehyde levels between coronary sinus blood and arterial blood and peak values of creatine kinase MB (43 +/- 12 IU/L versus 19 +/- 6 IU/L) during the postoperative course compared with findings in the control group. These results demonstrated that inflammatory reactions induced by cardiopulmonary bypass had adverse effects on myocardial recovery after aortic crossclamping and that nafamostat mesilate given during cardiopulmonary bypass appeared to reduce myocardial reperfusion injury by attenuating such inflammatory reactions. Attenuation of inflammatory reactions of cardiopulmonary bypass should be considered in the strategy of myocardial protection.

Benzamidines↗

Side effects of high-dose interferon therapy for chronic hepatitis C.

BACKGROUND/AIMS: Various side effects have been reported in patients treated with alpha interferon, but their incidence and prognosis remain unknown. METHODS: Nine hundred and eighty-seven patients with chronic active hepatitis C received 6 to 10 MU of alpha interferon per day for 2 weeks and 3 times per week for 22 weeks. Autoantibodies, thyroid function tests, and fasting plasma glucose concentrations were evaluated prior to alpha interferon therapy. RESULTS: Of the 987 patients, 310 were required reduction in the dose of alpha interferon to 3 MU/day or cessation of alpha interferon therapy because of adverse reactions such as flu-like symptoms, leukopenia, and thrombocytopenia. Of the remaining 677, five developed diabetes mellitus, 12 had hyperthyroidism, and six acquired hypothyroidism. Of the 18 with thyroid disorders, five demonstrated antimicrosomal antibodies before therapy. Forty-four patients revealed high or low concentrations of thyroid stimulating hormone at the end of alpha interferon therapy. Three patients developed interstitial pneumonia, one acquired systemic lupus erythematosus-like syndrome, two had autoimmune hepatitis, two developed rheumatoid arthritis, and one developed autoimmune thrombocytopenic purpura. No patients had a history of an autoimmune disorder. One patient experienced sudden hearing impairment and one had retinal detachment. Melena was seen in three patients; two of these cases were compatible with ischemic colitis. Symptoms of depression were seen in 23 patients, and one patient manifested memory loss. CONCLUSION: High-dose alpha interferon therapy induces various adverse effects. Most of the side effects cannot be predicted, but are reversible.

Adult↗

Haemodynamic effects of combined treatment with molsidomine and propranolol on portal hypertension in conscious and unrestrained cirrhotic rats.

We investigated the systemic and splanchnic haemodynamic effects of combined treatment with molsidomine and propranolol on cirrhotic rats. Liver cirrhosis was produced by repeated intraperitoneal injections of thioacetamide. The blood flow of each organ was measured serially using the radioactive microsphere method in the awake state before and after the administration of each agent. Cirrhotic rats received molsidomine (0-.5 mg/kg), propranolol (0.1 or 0.2 mg/min), both agents or placebo. Combination treatment with molsidomine and 0.1 mg/min propranolol significantly reduced portal pressure compared with molsidomine or propranolol alone (21 +/- 4 vs 15 +/- 3 or 11 +/- 2% P < 0.05). Systemic haemodynamic changes with this combined treatment were mild. This combined treatment slightly inhibited the molsidomine-induced decrease in portal vascular resistance (27 +/- 9 vs 31 +/- 6; NS) and markedly inhibited the molsidomine-induced decrease in splanchnic arterial resistance (7 +/- 6 vs 27 +/- 5% P < 0.05). Compared with low-dose propranolol administration, the combined treatment was associated with a significant decrease in portal vascular resistance (27 +/- 9% decrease vs 2 +/- 2% increase; P < 0.001) and a significant decrease in splanchnic arterial resistance (7 +/- 6% decrease vs 5 +/- 4% increase P < 0.05). The combination of molsidomine and high-dose propranolol (0.2 mg/min) caused a marked reduction in portal venous inflow, mean arterial pressure and cardiac index. We conclude that propranolol enhances the molsidomine-induced decrease in portal pressure by splanchnic vasoconstriction in association with a slight decrease in portal vascular resistance. The combination therapy with molsidomine and low-dose propranolol combination had more beneficial and less harmful effects on systemic and splanchnic haemodynamics and thus appears to be a superior method for treating portal hypertension.

Animals↗

[The earlier detection of myocardial damage in open heart surgery using serum human heart fatty acid-binding protein].

Human heart fatty acid-binding protein (HH-FABP), which is a low molecular weight protein and abundant in the cytoplasm of myocardial cells, is reported to be released into the circulation shortly after the onset of acute myocardial damage. However, the changes in serum HH-FABP levels in open heart surgery have not been elucidated. To determine whether HH-FABP enables the earlier detection of myocardial damage caused by ischemia-reperfusion in open heart surgery, we measured the serial levels of serum HH-FABP, CK-MB and Troponin T (TnT) at every 15 min for 48 hours after reperfusion in 10 adult patients with coronary artery bypass graft. The serum HH-FABP levels reached the peak within 60 min after reperfusion (mean +/- SD; 49 +/- 7 min), and this was significantly (p < 0.001) earlier than CK-MB (212 +/- 108 min) and TnT (244 +/- 150 min). The peak value of serum HH-FABP had a significant correlation to the peak value of serum CK-MB or TnT (r = 0.815, p = 0.02; r = 0.925, p = 0.0001, respectively). These results indicate that serum HH-FABP enables the earlier detection of myocardial damage than the other markers in the patients with open heart surgery.

Adult↗

[Coronary artery bypass grafting under bradycardia induced by ultra-short acting beta blocker].

From Dec. 1993 to May, 1994, coronary artery bypass grafting (CABG) was performed in 7 patients under bradycardia induced by an ultra-short acting beta blocker (esmolol). The ages ranged from 51 to 68 years. There was one patient with low ejection fraction (EF = 31%) and two patients with porcelain aorta. A tepid temperature was maintained during cardiopulmonary bypass (CPB). A high flow rate of 2.2-2.6 liter/min/m2 was applied to control perfusion pressure above 50 mmHg during CPB. After CPB was started, a high dose of esomolol was added (10-30 mg/kg intravenous bolus followed by a continuous infusion of 1-4 mg/kg/min). Severe bradycardia was achieved by the initial loading of esmolol. The mean heart rate was significantly (p < 0.01) decreased from 78 +/- 12 bpm to 49 +/- 7 bpm by the loading. Altogether, 25 anastomoses (11 ITA, 6 GEA, 8 SVG) were performed to LAD (10), Cx (7) and RCA (8), with an average of 3.6 +/- 0.9 anastomoses/patient. IABP was required for 2 patients postoperatively. There was no operative death, but one hospital death due to aspiration pneumonia 3 months later. Postoperative max CPK-MB was low (17.4 +/- 9.7 IU/L) in 6 patients. The postoperative angiography was performed in all patients with a patency rate of 88%. It was considered that esmolol facilitated CABG under beating heart and this technique is suitable for patients with severe atheromatous disease of the ascending aorta or patients with a low ejection fraction to avoid aortic cross-clamping.

Adrenergic beta-Antagonists↗

[Matured mediastinal teratoma with high levels of tumor markers in cystic fluid].

A 42-year-old woman was admitted to Gifu Municipal Hospital because of an abnormal mediastinal shadow on a chest X-ray film. The serum CA125 level was slightly high 38 U/L, normal: < 35 U/L. Preoperative examination of fluid from a cyst revealed a high level of carcinoembryonic antigen (550 ng/ ml). The tumor resected was 11 x 9 x 5 cm. Microscopic examination revealed a matured teratoma containing pancreatic cells, collagenous tissues, squamous epithelia, and hair follicle-like tissues. Biochemical analysis of the cystic fluid revealed high levels of eight tumor markers: carcinoembryonic antigen, CA125, CA19-9, SLX, Ferritin, NSE TPA, and elastase 1. Samples stained positively for the tumor markers carcinoembryonic antigen CA125, CA19-9, and NSE by ABC immunohistochemical staining. The serum carcinoembryonic antigen levels had decreased to the normal level within two weeks after the surgery. The high levels of tumor markers and materials in the cystic fluid may have been related to the biological characteristics of the various cell components in this matured teratoma.

Adult↗