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S Naito

Publications and source records attributed to S Naito.

At least 73 records · Page 4Linked to original sources

[Strategy for post coronary artery bypass grafting in patients with bypass graft stenosis: comparison of percutaneous transluminal coronary angioplasty for the native coronary artery, internal mammary artery and saphenous vein graft].

OBJECTIVES: The strategy for post coronary artery bypass grafting (CABG) was investigated in patients with graft stenosis. METHODS: The study included 123 post-CABG patients with graft stenosis. The patients were divided into three groups according to target vessels; saphenous vein graft (SVG; n = 72), internal mammary artery (IMA; n = 21) and native coronary artery (n = 30). Furthermore, SVG lesions were divided into proximal anastomosis (n = 23), body (n = 40) and distal anastomosis (n = 9). The procedural success rate and late patency rate were compared between the three groups. Furthermore, the relationships between pre percutaneous transluminal coronary angioplasty (PTCA) percentage diameter stenosis, procedural success rate and late patency rate were evaluated. RESULTS: Procedural success rate was similar in the three groups, but late patency rate was higher in the IMA group. Procedural success rate and late patency rate were significantly lower in proximal anastomoses compared to other sites of SVG stenoses, IMA group and native coronary artery group (p < 0.05). Totally occluded native coronary artery lesions had a high procedural success rate compared with occluded IMA and SVG lesions, but the late patency rate was not higher. Procedural success rate showed no significant difference for 75-99% stenotic lesions, but the late patency rate was significantly higher in the IMA group (p < 0.05). Patients in the stenting group had a greater late patency rate compared with the balloon angioplasty group. There was no significant difference in late patency rate between the IMA group and SVG group. CONCLUSIONS: Late patency rate of the IMA is higher than that of the native coronary artery. SVG with proximal anastomosis and severe stenosis shows a significantly lower late patency rate than the native coronary artery. Therefore, PTCA should be considered for the native coronary artery in the absence of chronic total occlusion.

Aged↗

Protein structure-based de novo design and synthesis of aldose reductase inhibitors.

Aldose reductase has been implicated in the etiology of diabetic complications. Due to the limited number of currently available drugs for the treatment of diabetic complications, we have carried out a structure-based de novo design and synthesis in an attempt to identify new aldose reductase inhibitors. With the LEGEND program, we have designed 200 chemical structures that fit into the ligand binding site of the crystal structure of the enzyme. After their visual inspection and assessment of synthetic feasibility, four compounds were chosen to be synthesized. These compounds were all found to have reasonable inhibitory activities (IC50 = 17-91 microM), indicating the first successful generation of nonpeptide drug leads that have been obtained using a rational de novo design approach.

Aldehyde Reductase↗

Angiostatin generation by cathepsin D secreted by human prostate carcinoma cells.

Angiostatin, a potent endogenous inhibitor of angiogenesis, is generated by cancer-mediated proteolysis of plasminogen. The culture medium of human prostate carcinoma cells, when incubated with plasminogen at a variety of pH values, generated angiostatic peptides and miniplasminogen. The enzyme(s) responsible for this reaction was purified and identified as procathepsin D. The purified procathepsin D, as well as cathepsin D, generated two angiostatic peptides having the same NH(2)-terminal amino acid sequences and comprising kringles 1-4 of plasminogen in the pH range of 3.0-6.8, most strongly at pH 4.0 in vitro. This reaction required the concomitant conversion of procathepsin D to catalytically active pseudocathepsin D. The conversion of pseudocathepsin D to the mature cathepsin D was not observed by the prolonged incubation. The affinity-purified angiostatic peptides inhibited angiogenesis both in vitro and in vivo. Importantly, procathepsin D secreted by human breast carcinoma cells showed a significantly lower angiostatin-generating activity than that by human prostate carcinoma cells. Since deglycosylated procathepsin D from both prostate and breast carcinoma cells exhibited a similar low angiostatin-generating activity, this discrepancy appeared to be attributed to the difference in carbohydrate structures of procathepsin D molecules between the two cell types. The seminal vesicle fluid from patients with prostate carcinoma contained the mature cathepsin D and procathepsin D, but not pseudocathepsin D, suggesting that pseudocathepsin D is not a normal intermediate of procathepsin D processing in vivo. The present study provides evidence for the first time that cathepsin D secreted by human prostate carcinoma cells is responsible for angiostatin generation, thereby causing the prevention of tumor growth and angiogenesis-dependent growth of metastases.

Angiostatins↗

Immunohistochemical expression of Ets-1 transcription factor and the urokinase-type plasminogen activator is correlated with the malignant and invasive potential in meningiomas.

BACKGROUND: The Ets-1 transcription factor has been proposed to play an important role in the invasive process of tumor cells through the induction of urokinase-type plasminogen activator (u-PA). METHODS: Because meningiomas are potentially invasive tumors, irrespective of their malignancy grades, the authors immunohistochemically investigated Ets-1 and u-PA expression in tissues obtained from 50 benign (16 meningotheliomatous, 14 fibrous, 13 transitional, 6 angiomatous, and 1 microcystic), 4 atypical, and 6 anaplastic meningiomas and correlated their results with the malignancy and invasive potential. RESULTS: Ets-1 protein was expressed in 19 of the benign meningiomas (38%)whereas 31 (62%) were u-PA positive. The percentage of positive cells frequently was < 50%. In contrast, Ets-1 and u-PA expression was observed in all 4 atypical (100%) and all 6 anaplastic (100%) cases, respectively. The proportion of cells positive for Ets-1 and u-PA frequently were > or = 50%. A significant difference was observed between Ets-1 and u-PA expression in benign and high grade meningiomas (P < 0.0001). Moreover, Ets-1 expression was found to correlate significantly with u-PA positivity in meningiomas (P < 0.0001). Twenty-one of 60 meningioma cases (35%) showed infiltration either to the brain, dura mater, or bone. Eighteen of these 21 cases (85.7%) were positive for Ets-1 and u-PA. Ets-1 and u-PA positivity was found to correlate well with the invasive phenotype in meningiomas (P < 0.001). CONCLUSIONS: The findings of the current study support the possibility that the Ets-1 transcription factor, through u-PA induction, may be involved in the invasive process in meningiomas.

Blotting, Western↗

TOM1, an Arabidopsis gene required for efficient multiplication of a tobamovirus, encodes a putative transmembrane protein.

Host-encoded factors play an important role in virus multiplication, acting in concert with virus-encoded factors. However, information regarding the host factors involved in this process is limited. Here we report the map-based cloning of an Arabidopsis thaliana gene, TOM1, which is necessary for the efficient multiplication of tobamoviruses, positive-strand RNA viruses infecting a wide variety of plants. The TOM1 mRNA is suggested to encode a 291-aa polypeptide that is predicted to be a multipass transmembrane protein. The Sos recruitment assay supported the hypothesis that TOM1 is associated with membranes, and in addition, that TOM1 interacts with the helicase domain of tobamovirus-encoded replication proteins. Taken into account that the tobamovirus replication complex is associated with membranes, we propose that TOM1 participates in the in vivo formation of the replication complex by serving as a membrane anchor.

Amino Acid Sequence↗

The role of ABI3 and FUS3 loci in Arabidopsis thaliana on phase transition from late embryo development to germination.

Arabidopsis abi3 and fus3 mutants are defective in late embryo development and their embryos show precocious growth. To understand the function and role of ABI3 and FUS3, we analyzed expression patterns of genes which were normally activated during late embryo development and germination in these mutants. Using the differential display method, both upregulated and downregulated genes were observed in immature siliques of the abi3 fus3 double mutant. Four clones having more abundant expression in the abi3 fus3 double mutant than in wild type were isolated. These genes were activated during wild-type germination, suggesting that some genes that are activated during wild-type germination are precociously activated in the abi3 fus3 mutant during late embryo development. Also, genes that were activated during wild-type germination were isolated and their expression patterns during late embryo development in the wild type and in abi3, fus3, and abi3 fus3 mutants were analyzed. Sixteen such clones were found, and 11 of these showed derepression or precocious activation of gene expression in the mutants. These results indicate that ABI3 and FUS3 negatively regulate a particular set of genes during late embryo development. We also showed that immature fus3 siliques accumulated one-third of the wild-type level of abscisic acid (ABA), but mature fus3 siliques accumulated ABA at a level comparable to that in the wild type. The possible mechanisms of controlling developmental timing in late embryo development as well as collaborative and distinct roles of ABI3 and FUS3 are discussed.

Arabidopsis↗

Molecular analysis of mechanisms regulating drug sensitivity and the development of new chemotherapy strategies for genitourinary carcinomas.

The emergence of drug-resistant tumors during treatment remains one of the major obstacles in cancer chemotherapy. Overexpression of P-glycoprotein encoded by the multidrug resistance 1 (MDR1) gene or multidrug resistance-associated protein (MRP) (or both) and decreased expression of DNA topoisomerase II are responsible for expression of the multidrug resistance (MDR) phenotype. The expression of P-glycoprotein is also often observed in untreated cancers showing spontaneous MDR, such as renal cell carcinoma. Regarding cisplatin resistance, decreased cisplatin accumulation, an increase in cisplatin detoxification by glutathione-related enzymes or metallothionein (or both), and increased repair of DNA damage are all considered to play an important role. The combination of reversal agents targeting such drug resistance markers may be a way to improve the outcome of chemotherapy. Regarding the presently available reversal agents, however, clinically relevant chemosensitizing doses cannot be given to humans without inducing significant toxicity. The development of new agents that reverse drug resistance without causing significant toxicity and their clinical application based on the mechanisms regulating drug sensitivity may therefore be a potentially effective new treatment strategy for genitourinary carcinomas.

Drug Resistance, Multiple↗

Does repeated balloon inflation during coronary angioplasty induce ischemic tolerance? Analysis based on regional work.

It has been reported that repeated brief balloon inflation during coronary angioplasty (PTCA) alleviates myocardial dysfunction. However, it has also been reported that PTCA does not induce ischemic tolerance. Six patients with stable angina pectoris were recruited for this study. They were scheduled for PTCA to a significant stenosis of the proximal left anterior descending artery (LAD). All patients had single-vessel coronary artery disease without angiographic evidence of collateral circulation and with normal wall motion. After the stenosis of LAD was dilated by a 30-s inflation, 60 s of balloon inflation was performed five times at 60-s intervals. Left ventricular regional work was determined in the first and fifth inflations, and the data were compared. Regional work of the interventricular septum decreased immediately after the balloon inflation (the first inflation: 5.3 +/- 1.0 --> 0.6 +/- 0.2 mJ/cm3; fifth inflation; 5.3 +/- 1.0 --> 0.6 +/- 0.3 mJ/cm3) and no statistically significant differences were found between the first and fifth inflations. After balloon deflation, the time required for the recovery of regional work was 30s in the fifth inflation, compared with 40 s in the first inflation (at 30 s after deflation, first inflation: 3.6 +/- 1.3 mJ/cm3; fifth inflation: 5.2 +/- 1.2 mJ/cm3). Although repeated balloon inflation did not change the amount of reduction in regional work, it improved the postischemic recovery of regional work. These results suggest ischemic tolerance.

Aged↗

Overexpression of Ets-1 transcription factor in angiosarcoma of the skin.

Angiosarcoma of the skin is a rare malignant tumor which is slow-growing but highly aggressive and often recurs following surgery and/or radiation therapy, finally metastasizing to the regional lymph nodes. The ets-1 protooncogene is shown to be transcribed in endothelial cells during angiogenesis in granulation tissue and in malignant cells during tumor invasion. Furthermore, it can regulate the expression of metalloproteinase genes such as collagenase-1 (MMP-1), stromelysin (MMP-3) and urokinase-type plasminogen activator (uPA). In this study we investigated the ets-1 and MMP-1 expression in 7 angiosarcomas of the skin, compared with 7 hemangiomas and 7 granuloma pyogenicums of the skin, which are well known as benign vascular diseases. The ets-1 and MMP-1 mRNAs and their proteins were overexpressed in all angiosarcomas tested, and the localization of MMP-1 expression corresponded to that of ets-1. On the other hand, they were weakly or not at all expressed in hemangiomas and granuloma pyogenicums. These results suggest that the constitutive overexpression of ets-1 might be closely related with the malignant progression of angiosarcoma, possibly through the up-regulation of the transcription of MMP-1.

Adult↗

Antimicrobial activity of gemifloxacin (SB-265805), a newer fluoroquinolone, against clinical isolates of Neisseria gonorrhoeae, including fluoroquinolone-resistant isolates.

Antimicrobial activity of gemifloxacin (SB-265805), a newly developed fluoroquinolone, to Japanese isolates of Neisseria gonorrhoeae was compared with those of various fluoroquinolones, including norfloxacin, ciprofloxacin, tosufloxacin, levofloxacin, sparfloxacin, and trovafloxacin. Among the fluoroquinolones tested, gemifloxacin was most active against N. gonorrhoeae isolates. The MIC90 values of gemifloxacin for 94 N. gonorrhoeae isolated from 1992 through 1993 and 100 isolated from 1996 through 1997 were 0.03 and 0.125 microg/ml, respectively. On the other hand, MIC90 values of the other fluoroquinolone for the 1992-1993 isolates and the 1996-1997 isolates ranged from 0.125 to 2 microg/ml and from 0.5 to 8 microg/ml, respectively. Gemifloxacin was also the most potent fluoroquinolone against 31 ciprofloxacin-resistant isolates with the ciprofloxacin MIC of 1 to 16 microg/ml, for which the gemifloxacin MIC50 and MIC90 values were 0.25 and 2 microg/ml, respectively. Moreover, the activity of gemifloxacin against fluoroquinolone-resistant gonococcal isolates containing multiple amino acid substitutions in both GyrA and ParC proteins was superior to those of the other compounds.

Amoxicillin↗

Demonstration of diastolic and presystolic Purkinje potentials as critical potentials in a macroreentry circuit of verapamil-sensitive idiopathic left ventricular tachycardia.

OBJECTIVES: The purpose of this study was to determine the relation of diastolic and presystolic potentials recorded during verapamil-sensitive idiopathic left ventricular tachycardia (ILVT) to reentry circuit. BACKGROUND: Successful ablation of verapamil-sensitive ILVT at the zone of slow conduction from which the diastolic potential is recorded has been reported. However, the relationship between the diastolic potential and the reentrant circuit remains a matter of debate. METHODS: Radiofrequency (RF) ablation was performed in 20 patients with verapamil-sensitive ILVT. After identifying the ventricular tachycardia (VT) exit site, we searched for the mid-diastolic potential (P1) during VT. Entrainment followed by RF current application was performed. If the mid-diastolic potential could not be detected, RF current was applied at the VT exit site showing the earliest ventricular activation with a single fused presystolic Purkinje potential (P2). RESULTS: In 15 of 20 patients, both P1 and P2 were recorded during VT from midseptal region. Entrainment pacing captured P1 orthodromically and reset the VT. The interval from stimulus to P1 was prolonged as the pacing rate was increased. Radiofrequency ablation was successfully performed at this site in all 15 patients. After successful ablation, P1 appeared after the QRS complex during sinus rhythm with the identical sequence to that during VT. In the remaining five patients, the diastolic potential could not be detected, and a single fused P2 was recorded only at the VT exit site. Successful ablation was performed at this site in all five patients. CONCLUSIONS: This study demonstrates that P1 and P2 are critical potentials in a circuit of verapamil-sensitive ILVT and suggests the presence of a macroreentry circuit involving the normal Purkinje system and the abnormal Purkinje tissue with decremental property and verapamil-sensitivity.

Adolescent↗

Complications of laparoscopic and retroperitoneoscopic adrenalectomies in 370 cases in Japan: a multi-institutional study.

A total of 370 laparoscopic adrenalectomies, including 311 transperitoneal (TP) and 59 retroperitoneal (RP) approaches, were performed in nine urologic centers, where the laparoscopic adrenalectomy was first begun independently in Japan, and their affiliated hospitals between January 1992 and September 1996. The clinical diagnoses of those 370 adrenal diseases were primary aldosteronism in 155 patients, Cushing's syndrome in 61. preclinical Cushing's syndrome in 21. pheochromocytoma in 16, nonfunctioning adenoma in 87, complicated cyst in ten, myelolipoma in nine, adrenal cancer in four and other diagnoses in eight (table 1). There was no mortality in this series. Intraoperative complication rate was 33/370 (9%) in total: 26/311(8%) in the TP procedures and 7/59 (12%) in the RP procedures (table 11). Postoperative complication rate was 24/370 (6%) in total: 22/311 (7%) in the TP procedures and 2/59 (3%) in the RP ones (table 111). Conversion rates to open surgery in total, in the TP and in the RP procedures were 13/370 (3.5%), 10/311 (3.2%) and 3/59 (5.1 %). respectively (table IV). Although the RP procedure has a lower morbidity rate compared to the TP procedure, more skill is required to overcome the drawback of the narrow working space and fewer anatomical landmarks.

Adenoma↗

Molecular structure of bacterial endotoxin (Escherichia coli Re lipopolysaccharide): implications for formation of a novel heterogeneous lattice structure.

Analyses of crystals of Escherichia coli Re lipopolysaccharide (LPS) formed after storage in 1% triethylamine indicate that the LPS molecules are assembled to form a monolayered structure consisting of a novel heterogeneous lattice structure, the greater part of which is occupied by one kind of lattice (lattice I), corresponding to the acyl chain portion of lipid A, and the remainder is occupied by the other kind of lattice (lattice II), corresponding to the 3-deoxy-Dmanno-octulosonic acid (dOclA) dimer and the N-acetylglucosamine disaccharide of lipid A. X-ray diffraction reveals that the type of cell is monoclinic (a = 5.53 A, b = 27.2 A, c = 6.47 A, alpha = 90 degrees, beta = 125.8 degrees, gamma = 90 degrees ). Atomic force microscopy shows that crystals consist of multiple layers; the thickness of a layer corresponds to the b-axis value, and two types of surface topographies are visualized. One, regarded as the view onto the acyl chain ends, is two-dimensional arrays of oval bodies that constitute the lattice, with the lattice constants corresponding to the a- and c-axes and the angle of beta (lattice I). The other, regarded as the view onto the dOclA dimers, is two-dimensional arrays of dromedary-back-like bodies that constitute the lattice with axes of 9.0 and 10.7 A and the angle of 65 degrees formed by both axes (lattice II). Based on these results, we present the molecular model of E. coli Re LPS.

Carbohydrate Conformation↗

Involvement of collagen-binding heat shock protein 47 and procollagen type I synthesis in idiopathic pulmonary fibrosis: contribution of type II pneumocytes to fibrosis.

The most common pathologic form of idiopathic pulmonary fibrosis is usual interstitial pneumonia, which is characterized by patchy fibrotic areas, marked increase in the number of fibroblasts and type II pneumocytes, and excessive deposition of extracellular matrix proteins, especially collagen. Heat shock protein 47 is a collagen-binding stress protein and has a specific role in intracellular processing of procollagen molecules as a collagen-specific molecular chaperone. However, its role in the causation of fibrosis in usual interstitial pneumonia is unknown. In this study, we examined the expression of heat shock protein 47 and type I procollagen in 12 patients with usual interstitial pneumonia by immunohistochemistry on sequential sections. Heat shock protein 47 was localized predominantly in alpha-smooth muscle actin-positive myofibroblasts and surfactant protein-A-positive type II pneumocytes in active fibrotic areas of usual interstitial pneumonia. Type I procollagen was also expressed in those cells. In contrast, heat shock protein 47 and type I procollagen were weakly or not at all expressed in myofibroblasts and type II pneumocytes in bronchiolitis obliterans organizing pneumonia and normal lung tissue samples obtained from excised lung cancer tissues. The numbers of heat shock protein 47- and type I procollagen-positive cells to type II pneumocytes or myofibroblasts were significantly higher in usual interstitial pneumonia than in bronchiolitis obliterans organizing pneumonia and normal lung tissue specimens. Our results suggest that myofibroblasts and type II pneumocytes play an important role in the progression of fibrosis through the induction of heat shock protein 47, which regulates the synthesis/assembly of type I procollagen in usual interstitial pneumonia. HUM PATHOL 31:1498-1505.

Actins↗

Biotransformation of the xanthine oxidase inhibitor BOF-4272 and its metabolites in the liver and by the intestinal flora in rat.

1. BOF-4272, (+/-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo[1,5-a]-1,3,5-triazine-4(1H)-one), is a new drug intended for the treatment of hyperuricaemia. 2. This paper describes the detailed biotransformation of BOF-4272 and its metabolites in the liver and by the intestinal flora in rat. 3. Only the sulphoxide metabolite (M6) was detected in plasma in small amounts after the intravenous administration of M4 (hydroxy-BOF-4272) and in culture medium after the addition of M4. 4. Only M3 (the sulphide metabolite of M4) was detected in faeces, and its amount was approximately 50% of the administered dose within 1 day after the intravenous administration of M4. 5. These findings suggest that M4, which is excreted in the bile, is metabolized mainly to M3 (the corresponding sulphide of M4) by the intestinal flora in rat, whereas little M4 is metabolized to the sulphoxide (M6) in the rat liver. 6. M2, which is the demethylated form of BOF-4269, was detected in faeces after the oral administration of BOF-4272 to rat in which the common bile duct was cannulated, suggesting that BOF-4272 is metabolized to BOF-4269 and then to M2 by the intestinal flora. 7. These findings suggest that in rat the sulphoxide of BOF-4272 and its metabolites are demethylated and reduced by the intestinal flora, with other types of biotransformation occurring in the liver.

Animals↗

Laparoscopic adrenalectomy for pheochromocytoma: comparison with open adrenalectomy and comparison of laparoscopic surgery for pheochromocytoma versus other adrenal tumors.

OBJECTIVE: To compare the efficacy of laparoscopic adrenalectomy for pheochromocytoma with that of conventional open adrenalectomy for pheochromocytoma and laparoscopic surgery for other adrenal tumors. PATIENTS AND METHODS: Fifty-four patients with adrenal tumors, including 10 cases of pheochromocytoma, 18 cases of Cushing's syndrome, 20 cases of primary aldosteronism, and 6 cases of nonfunctioning tumors, were evaluated. A historical group of 7 consecutive patients who underwent conventional open adrenalectomy for pheochromocytoma was also studied. RESULTS: Laparoscopic adrenalectomy for pheochromocytoma was successful in 9 of the 10 patients. There was no difference in tumor size, operation time, estimated blood loss, or occurrence of hypertensive episodes during surgery between patients treated with laparoscopic procedures and those treated with open surgery. However, the number of days to first postoperative oral feeding and first ambulation, length of hospitalization, and number of patients requiring parenteral analgesics were significantly smaller after laparoscopic surgery than after open surgery. There was no significant difference in operation time, estimated blood loss, incidence of intraoperative complications, or postoperative recovery between patients who underwent laparoscopic adrenalectomy for pheochromocytoma and those who underwent laparoscopic surgery for other adrenal lesions. CONCLUSIONS: Laparoscopic adrenalectomy does not increase the specific risks associated with surgery for pheochromocytoma. It is a minimally invasive alternative to conventional open adrenalectomy.

Adolescent↗

Post-transcriptional gene silencing in cultured rice cells.

Post-transcriptional gene silencing (PTGS) has been shown to occur in many transgenic dicotyledonous plants. Although transgene silencing has been documented in transgenic monocots, PTGS has been only recently described in monocotyledonous plants. To study PTGS in rice, we generated 25 transgenic rice cell lines in which the 35S-gus gene was stably integrated. In one transgenic cell line, lack of gus expression was shown to be caused by PTGS based on the results of run-on transcription assays. Furthermore, to examine whether reintroduction of the same plasmid DNA into cells in which the gus gene was highly expressed causes the suppression of the gus expression, the gus plasmid was introduced into protoplasts isolated from a high gus-expressing line. Results of the kinetic analysis of the GUS activities in transfected protoplasts indicated that the gus expression in transfected protoplasts was suppressed by the gus plasmid but not by the luc plasmid harboring the 35S-luciferase gene, suggesting that suppression of the gus expression by introduced plasmid DNA was homology-dependent. These results suggest that the transgenic protoplasts may be a useful experimental system to study PTGS in rice and other species.

Cells, Cultured↗