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Biomedical subjects

S Kawada

Publications and source records attributed to S Kawada.

At least 19 recordsLinked to original sources

Coagulation factor X activating enzyme from Russell's viper venom (RVV-X). A novel metalloproteinase with disintegrin (platelet aggregation inhibitor)-like and C-type lectin-like domains.

We determined the complete amino acid sequence of RVV-X, the blood coagulation factor X activating enzyme, isolated from Russell's viper venom and studied structure-function relationships. RVV-X (M(r) 79,000) consists of a disulfide-bonded two-chain glycoprotein with a heavy chain of M(r) 59,000 and a light chain of heterogeneous M(r) 18,000 (LC1) and 21,000 (LC2). These chains were separated after reduction and S-pyridylethylation, and the isolated major component LC1 was used for sequence analysis. The heavy chain consists of 427 residues containing four asparagine-linked oligosaccharides, and its entire sequence was similar to that of the high molecular mass hemorrhagic protein, HR1B, isolated from the venom of Trimere-surus flavoviridis. The heavy chain contains three distinct domains, metalloproteinase, disintegrin (platelet aggregation inhibitor)-like and unknown cysteine-rich domains. On the other hand, light chain LC1 consists of 123 amino acid residues containing one asparagine-linked oligosaccharide and shows sequence homology similar to that found in the so-called C-type (Ca(2+)-dependent) lectins. Therefore, RVV-X is a novel metalloproteinase containing a mosaic structure with distintegrin-like, cysteine-rich, and C-type lectin-like domains. RVV-X potently inhibits collagen- and ADP-stimulated platelet aggregations, probably via its distintegrin-like domain, although this domain does not contain the Arg-Gly-Asp sequence which is conserved in various venom distintegrins and which is thought to be one of the interaction sites for platelet integrins. Our findings also indicate that snake venom factor IX/factor X-binding protein with a C-type lectin structure (Atoda, H., Hyuga, M., and Morita, T. (1991) J. Biol. Chem. 266, 14903-14911) inhibits RVV-X-catalyzed factor X activation; hence, the light chain of RVV-X probably participates in recognizing some portion of the zymogen factor X.

Amino Acid Sequence

[Extended aortic reconstruction for dissecting aneurysm of the aorta].

While lifesaving palliative surgery may be selected for dissecting aneurysm of the aorta, extended reconstructive surgery has been advocated as a more curative procedure. We performed a variety of extended reconstructive surgeries, for example, replacement of the ascending aorta and the aortic arch, subtotal replacement of the thoracic aorta, replacement of the entire descending thoracic aorta and replacement of the entire descending aorta in 20 cases of dissecting aneurysm of the aorta. However, the operative mortality remained high as 35%, and the operative procedures have not yet to be standardized. We believe that it is extremely important to strive for much greater improvement in the operative results by correct selection of the operative indications, and by improving the operative techniques and patient management during surgery.

Adult

[A modified technique in total cavopulmonary connection].

We have used an alternative technique in Total Cavopulmonary Connection without using any prosthetic material. The technique is a modification of Senning operation in which a flap of right atrial wall is used to create a tunnel between inferior vena cava and superior vena cava. We used this modified technique in two cases, and they showed excellent postoperative convalescence.

Blood Vessel Prosthesis

Induction of mammalian DNA topoisomerase I and II mediated DNA cleavage by saintopin, a new antitumor agent from fungus.

Saintopin is an antitumor antibiotic recently discovered in mechanistically oriented screening using purified calf thymus DNA topoisomerases. Saintopin induced topoisomerase I mediated DNA cleavage comparable to that of camptothecin, and topoisomerase II mediated DNA cleavage equipotent to those of 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) or 4'-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-beta-D-glucopyranoside) (VP-16). Treatment of a reaction mixture containing saintopin and topoisomerase I or II with either elevated temperature (65 degrees C) or higher salt concentration (0.5 M NaCl) resulted in a substantial reduction in DNA cleavage, suggesting that the topoisomerase I and II mediated DNA cleavage induced by saintopin is through the mechanism of stabilizing the reversible enzyme-DNA "cleavable complex". Consistent with the cleavable complex formation with both topoisomerases, saintopin inhibited catalytic activities of both topoisomerase I and topoisomerase II. The DNA cleavage intensity pattern induced by saintopin with topoisomerase I was different from that by camptothecin. A difference in cleavage pattern was also detected between saintopin and m-AMSA or VP-16 in topoisomerase II mediated DNA cleavage. DNA unwinding assay using T4 DNA ligase showed that saintopin is a weak DNA intercalator like m-AMSA. Thus, saintopin represents a new class of antitumor agent that can induce both mammalian DNA topoisomerase I and mammalian DNA topisomerase II mediated DNA cleavage.

Amsacrine

Induction of a heat-stable topoisomerase II-DNA cleavable complex by nonintercalative terpenoides, terpentecin and clerocidin.

Terpentecin and clerocidin, microbial terpenoides, have been known to be potent antitumor antibiotics. However, the critical biochemical target of these terpenoides has not been identified. Our present studies, using purified mammalian topoisomerase II, have shown that terpentecin and clerocidin induce topoisomerase II-mediated DNA cleavage in vitro with comparable potency to that of demethylepipodophyllotoxin ethylidene-beta-D-glucoside. These terpenoides produced a similar DNA cleavage pattern which is distinctly different from those generated in the presence of the known topoisomerase poisons, demethylepipodophyllotoxin ethylidene-beta-D-glucoside and 4'-(9-acridinylamino)methanesulfon-m-anisidide. Brief heating at 65 degrees C, which abolishes completely the cleavable complex with demethylepipodophyllotoxin ethylidene-beta-D-glucoside, of the reaction mixture containing these terpenoides resulted in slight reduction in DNA cleavage. Thus, differently from other topoisomerase II-active antitumor agents, terpentecin and clerocidin induce formation of a cleavable complex which is stable for heat or salt treatments. The lack of significant DNA binding or intercalation activity of terpentecin and clerocidin suggests that topoisomerase II is a cellular target for these drugs.

Anti-Bacterial Agents

[Early and late operative results of simultaneous aortic valve and ascending aorta replacement].

Thirty-four patients of ascending aortic aneurysm associated with aortic regurgitation were treated with simultaneous aortic valve and ascending aorta replacement utilizing composite graft, until December 1990. Twenty-four patients of the group were diagnosed as Marfan's syndrome and 17 had aortic dissection. For the operative procedure, Bentall's technique were employed in 25 patients and other modifications in nine. Operative death was observed in three cases (8.8%) due to low output syndrome, caused by coronary ostium abnormality, all in Marfan's syndrome. Late death was observed in six including 2 hospital deaths of cerebro-vascular disturbance and sepsis. Other causes of death were rupture of residual aneurysm (in 3) and LOS at reoperation (in 1). Hospital survivors remarkably improved in NYHA class and in cardiac size. Actuarial survival in 3, 5, 7, and 10 years were 78%, 72%, 72%, and 62% respectively. Therefore, surgical result of composite graft technique in our institution proved to be reasonable as others. However, long term result of the procedure should be carefully evaluated, because of the anatomical and histopathological peculiarity of the disease.

Adult

Induction of mammalian DNA topoisomerase II dependent DNA cleavage by antitumor antibiotic streptonigrin.

Streptonigrin, a nonintercalative antitumor antibiotic, induced mammalian topoisomerase II dependent DNA cleavage in vitro. The cleavage activity of streptonigrin was comparable to that of demethylepipodophyllotoxin ethylidene-beta-D-glucoside at a low concentration (less than or equal to 10 microM) but one-third lower at a higher concentration (greater than 250 microM). Exposure of a reaction mixture containing streptonigrin, DNA, and topoisomerase II to an elevated temperature (65 degrees C) resulted in substantial reduction in DNA cleavage, suggesting that the mechanism of the topoisomerase II dependent DNA cleavage induced by streptonigrin was through the formation of a cleavage complex previously reported for topoisomerase II poisons such as 4'-(9-acridinylamino) methanesulfon-m-anisidide and epipodophyllotoxins.

DNA

Induction of mammalian topoisomerase II dependent DNA cleavage by nonintercalative flavonoids, genistein and orobol.

Two isoflavones, genistein (4',5,7-trihydroxyisoflavone) (1) and orobol (5,7,3',4'-tetrahydroxyisoflavone) (2) induced mammalian topoisomerase II dependent DNA cleavage in vitro. The cleavage activities of 1 and 2 were comparable to those of known antitumor agents with topoisomerase II dependent DNA cleavage activity such as 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) and demethylepipodophyllotoxin ethylidene-beta-D-glucoside (VP-16). Two flavones, fisetin (3,7,3',4'-tetrahydroxyflavone) (3) and quercetin (3,5,7,3',4'-pentahydroxyflavone) (4) showed topoisomerase II dependent DNA cleavage activity with similar potentials to that of Adriamycin. Addition of salt (0.5 M NaCl) to the reaction mixture containing genistein and topoisomerase II resulted in a great reduction of DNA cleavage, suggesting that the mechanism of the topoisomerase II dependent DNA cleavage induced by flavonoids is through the cleavable complex formation as seen with m-AMSA and VP-16. DNA unwinding assay using mammalian topoisomerase I showed that both 1 and 2 did not intercalate into DNA but both 3 and 4 intercalated like m-AMSA. Other structurally related flavonoids could not induce topoisomerase II dependent DNA cleavage, indicating that the restricted structures of flavonoids were required for the cleavage activity.

Amsacrine

A tuberculous pseudoaneurysm of the thoracic aorta presenting as massive hemoptysis--a case of successful surgical treatment.

Tuberculous aneurysms of the aorta need early diagnosis and prompt surgical intervention because if untreated, they lead to severe consequences. We report herein, a case of a 63 year old woman who underwent successful resection of a tuberculous pseudoaneurysm which had ruptured into the left upper lobe of the lung after a punch biopsy, performed under bronchoscopy, had caused severe bleeding. Subsequent CT and MRI examinations suggested a fistula between the mass and the aorta and proved useful in establishing the diagnosis of a pseudoaneurysm. We wish to emphasize the need for bronchoscopy to be done carefully because of the risk of inducing massive hemoptysis.

Aorta, Thoracic

[Two cases of obstructive jaundice due to extrahepatic carcinoma of the bile duct with marked response to daily oral administration of etoposide].

Two cases of obstructive jaundice due to cancer of extrahepatic bile duct were treated with a combination chemotherapy combined with etoposide. The first case was a 81-year-old male and the second case was a 62-year-old female who introduced to this hospital because of jaundice and admitted. Cholangiography was performed and diagnosed cancer of the extrahepatic bile duct. Daily oral administration of etoposide (25mg/day) added to other immunochemotherapy was carried out. The cholangiography via PTCD tube revealed a passage of obstruction of the choledochus. These data suggest that a combination chemotherapy including oral administration of etoposide was effective in these two cases.

Administration, Oral

[Torsion after left lower lobectomy and cerebral infarction following the re-exploratory thoracotomy: a case report].

A 38-year-old man had a left lower lobectomy for pulmonary carcinoid. Following the operation, torsion of the left residual upper lobe occurred. Re-explosive thoracotomy was performed on the second postoperative day. The left upper lobe showed a clockwise 180-degree rotation. Pneumonectomy was not done. After the re-thoracotomy, the patient developed right hemiplegia. Head CT showed a cerebral infarction due to the thrombus of pulmonary vein that was released after the repair of the torsion.

Adult

[Improvement of heart failure after intracardiac operation for tetralogy of Fallot by transcatheter embolization of major aortopulmonary collateral arteries].

A two-year-and-ten-month-old female with tetralogy of Fallot with major aortopulmonary collateral arteries (MAPCAs) developed a persistent heart failure after an intracardiac repair. Angiograms revealed four MAPCAs originating from the upper portion of the descending thoracic aorta and draining into the left pulmonary artery, one MAPCA from the inferior phrenic artery into bilateral pulmonary arteries, and remaining one from the left subclavian artery into left pulmonary artery. Three of these MAPCAs were occluded by transcatheter embolization by the use of the steal coil. The heart failure was improved dramatically by this treatment.

Aorta

[Fontan-type operation in a 14-month-old patient with tricuspid atresia who had [I, D, D], pulmonary atresia and right pulmonary artery stenosis].

A 14-month-old male with tricuspid atresia who had [I, D, D], pulmonary atresia, right pulmonary stenosis and a Blalock-Taussig shunt successfully underwent a Fontan-type operation accomplished by making a direct right atrial-pulmonary arterial connection with a Gore-Tex roof patch. The patient had an uneventful postoperative course without development of the heart failure.

Heart Atria

[Pathological findings of the aortic wall at the site of ligation against the rigid rings of an intraluminal graft for acute DeBakey type I aortic dissection].

A ringed intraluminal graft has been utilized in the surgical treatment for dissecting aneurysm since 1978. Histological findings of the aortic wall long after surgery, however, have not been described in detail, and concern remains about possible pressure necrosis at the point of encirclement. The following report is for a case of acute type I aortic dissection which required the use of an intraluminal surgical graft in a patient who died eight months postoperatively of a disease unrelated to previous surgical management. The pathological findings at autopsy were as follows. At the site of circumferential ligations around the aorta, 1) discontinuity of the elastic fibers in the media was found only at the outer surface, 2) there was no compression necrosis in the outer half of the media, although a dark shade of elastic fibers was recognized, 3) there were no pathological changes in the inner half of the media. In addition, complete repair of the intimal tear as well as closure of the false lumen replaced by collagen fibers was confirmed histologically in the whole length of aorta where the intraluminal graft had been placed. We conclude that concerns about the fragility of the aortic wall at the site of circumferential ligation, the migration of prosthesis, and the formation of thrombi is alleviated by these pathological observation.

Acute Disease

[A case of mediastinal cystic lymphangioma--case reports and review of the literature in Japan].

A 15-year-old woman was admitted to our hospital with complaints of left anterior chest pain and an abnormal shadow on her chest X-ray film. At the left thoracotomy, a large cyst (20.5 x 15 x 3 cm) was located in the left anterior mediastinum and contained translucent yellow fluid. Histological diagnosis was cystic lymphangioma. Mediastinal cystic lymphangioma is very rare among mediastinal tumors. Altogether 32 cases of mediastinal cystic lymphangioma including our case were collected from the Japanese literature and reviewed.

Adolescent