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151.
Kanako Sugawara Youichi Tajima Ikuo Kawashima Takahiro Tsukimura Seiji Saito Kazuki Ohno Kunihiko Iwamoto Toshihide Kobayashi Kohji Itoh Hitoshi Sakuraba 《Molecular genetics and metabolism》2009,96(4):233-238
Enzyme enhancement therapy (EET) for Fabry disease involving imino sugars has been developed and attracted interest. It is thought that imino sugars act as pharmacological chaperones for wild-type and mutant α-galactosidases (GLAs) in cells, but the mechanisms underlying the molecular interactions between the imino sugars and the enzyme have not been clarified yet. We examined various kinds of imino sugars and found that galactostatin bisulfite (GBS) inhibited GLA in vitro and increased the enzyme activity in cultured Fabry fibroblasts as in the case of 1-deoxygalactonojirimycin (DGJ). Then, we analyzed the molecular interactions between the imino sugars and recombinant human GLA by means of isothermal titration calorimetry and surface plasmon resonance biosensor assays, and first determined the thermodynamic and binding-kinetics parameters of imino sugar and GLA complex formation. The results revealed that DGJ bound to the enzyme more strongly than GBS, the binding of DGJ to the enzyme protein being enthalpy-driven. In the case of GBS, the reaction was mainly enthalpy-driven, but there was a possibility that entropy-driven factors were involved in the binding. Structural analysis in silico revealed that both the chemicals fit into the active-site pocket and undergo hydrogen bonding with residues comprising the active-site pocket including the catalytic ones. The side chain of GBS was oriented towards the entrance of the active-site pocket, and thus it could be in contact with residues comprising the wall of the active-site pocket. Thermodynamic, kinetic and structural studies should provide us with a lot of information for improving EET for Fabry disease. 相似文献
152.
153.
K Kawachi S Kitamura R Morita T Nishii T Seki S Taniguchi K Inoue 《Journal of the American College of Cardiology》1989,14(2):332-337
Between December 1981 and June 1987, 71 patients underwent aortic valve replacement with a Bicer monostrut tilting disc prosthesis. Clinical results and in vivo function of the artificial valve were assessed. The average age of the 71 patients at the time of operation was 51.3 +/- 11.5 years. The hospital mortality rate was 2.8% (two patients) and there were no further deaths during a mean (+/- SD) follow-up period of 2.4 +/- 1.6 years (range 1 month to 5.5 years) after surgery. There was also no occurrence of thromboembolism or valve dysfunction. Function of the Bicer valve prosthesis was assessed in 17 patients: 5 with a 21 mm valve, 7 with a 23 mm valve and 5 with a 25 mm valve. Examination was performed on average 10.3 +/- 8.1 months after surgery. Valve function was examined at rest and during exercise performed with a bicycle ergometer. Pressure gradients at rest were low: 21 mm valve = 8 mm Hg, 23 mm valve = 3 mm Hg and 25 mm valve = 2 mm Hg; the gradients during exercise were 11, 8 and 8 mm Hg, respectively. The valves had the following effective orifice area at rest: 21 mm valve = 1.54 cm2, 23 mm valve = 4.20 cm2 and 25 mm valve = 3.76 cm2; during exercise, the respective areas were 1.57, 3.48 and 3.01 cm2. These valves are deemed to be sufficiently wide for effective valve function. Aortographic observation indicated mild regurgitation that was within reasonable limits and posed no problem.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
154.
Takahiro Hayashi Masaru Miyataka Akio Kimura Mitsugu Taniguchi Atsuhiro Kurooka Hiroshi Yabushita Takashi Kiyoshima Hajime Nakamura Yutaka Hirano Kinji Ishikawa 《Circulation journal》2005,69(4):420-426
BACKGROUND: Many patients with acute myocardial infarction will still die after admission. Recent trends in hospital mortality were analyzed to identify aspects that need improvement. METHODS AND RESULTS: A total of 1,247 patients admitted to Kinki University School of Medicine within 24 h of the onset of infarction were analyzed between 1975 and 2001. The percentage of patients discharged with 100% occlusion decreased gradually from 31.3% during 1975-1982 to 2.1% during 1998-2001, while those with 50% stenosis or less gradually increased from 12.5% to 82.5% during the same period (trends: p < 0.01). The cardiac death rate was 17.1% in 1975-1982, and 7.7% in 1998-2001, showing a significant decrease with time (p < 0.01). This decrease was particularly marked among those admitted within 6 h of the onset of infarction. Death due to cardiac rupture decreased significantly with time (p < 0.001). In contrast, the non-cardiac death rate, amounting to 2.2% on average, did not decline. CONCLUSIONS: Cardiac deaths due to acute myocardial infarction have decreased markedly of late. However, patients must be admitted within 6 h of the onset of infarction to benefit from this improvement. More effort should be made to improve the general care of patients in order to reduce the incidence of non-cardiac death. 相似文献
155.
156.
Arata Tabuchi Ryoji Taniguchi Kanako Takahashi Hirokazu Kondo Mitsunori Kawato Takeshi Morimoto Takeshi Kimura Toru Kita Hisanori Horiuchi 《Circulation journal》2008,72(3):420-426
BACKGROUND: There are few monitoring systems widely used in clinical practice for evaluating the effectiveness of aspirin therapy, so in the present study aspirin's antiplatelet effects we investigated with a whole blood aggregometer using a screen filtration pressure (SFP) method. METHODS AND RESULTS: Thirty-five healthy male volunteers took 100 mg/day aspirin for 14 days. Whole-blood aggregation was analyzed at baseline and on days 7 and 14, using collagen and adenosine diphosphate as the stimuli, and compared with the platelet-rich plasma (PRP) aggregation measured by optical aggregometer. The platelet-aggregation threshold index (PATI) for both methods, which was defined as the putative agonist-concentration giving half-maximal aggregation, and the PRP-maximal aggregation rate were analyzed. The maximal aggregation rate induced by 1.6 mg/L collagen decreased from 85.5% (80.8-92.8) [median (interquartile range)] at baseline to 51.5% (39-63.8) on day 14 (p<0.0001). The PRP-PATI and whole-blood PATI for collagen increased from 0.32 (0.28-0.70) to 1.82 mg/L (1.25-2.89) (p<0.0001) and from 0.28 (0.22-0.3) to 1.06 mg/L (1.01-1.29) (p<0.0001) respectively. CONCLUSIONS: The whole-blood PATI and PRP-PATI for collagen, as well as the maximal PRP aggregation rate, clearly distinguish platelet aggregability before and after aspirin intake. However, whole-blood analysis by the SFP-method is easier to perform, and is a promising method of monitoring aspirin's effects. 相似文献
157.
Pulmonary ventricular outflow reconstruction with a size-reduced cryopreserved pulmonary valve allograft: mid-term follow-up 总被引:1,自引:0,他引:1
Yoshikawa Y Kitamura S Taniguchi S Kameda Y Niwaya K Sakaguchi H 《Japanese circulation journal》2000,64(1):23-26
Surgical reduction of pulmonary allografts is being performed because of the shortage of allografts of suitable size for pediatric use. However, the outcome of size-reduced pulmonary allografts for pulmonary conduits is unknown. In the present study, cryopreserved pulmonary allografts harvested from adults at the time of kidney donation were size-reduced and used in 4 children, 2 with pulmonary atresia and ventricular septal defect and 2 with atrioventricular discordance, pulmonary atresia and ventricular septal defect. They all had undergone right and/or left modified Blalock-Taussig shunt operations with a 5-mm synthetic graft prior to the reparative operations. They underwent definitive repair with a size-reduced cryopreserved pulmonary allograft valved conduit and were followed up for 2-5 years. Postoperative echocardiographic and cineangiographic assessments revealed excellent function of the pulmonary bicuspidalized valves with a minimal pressure gradient and no, or only trivial, regurgitation. Although the long-term result of a cryopreserved bicuspid pulmonary valved conduit remains unknown, the remodeled bicuspid pulmonary allograft conduits showed excellent hemodynamic characteristics in mid-term follow-up and appear to be a reasonable alternative to other types of conduits when an appropriate-sized allograft is not available. 相似文献
158.
159.
Takizawa M Nobuhisa I Igarashi K Ueno M Nakashima K Kitamura T Taga T 《Experimental hematology》2003,31(4):283-289
OBJECTIVE: Definitive hematopoiesis starts in the aorta-gonad-mesonephros (AGM) region during mouse development and remarkably expands in the liver at a later stage of ontogeny. gp130 is a signal transducing receptor component shared by all the IL-6 family cytokines, whose gene ablation in mouse results in the significant reduction in the fetal liver hematopoiesis. The present study aims to evaluate the role of gp130 signaling in the fetal mouse AGM hematopoiesis. METHODS AND MATERIALS: Mouse AGM regions from the wild-type and gp130-deficient mice on embryonic day 11.5 were dissociated and cultured with a mixture of cytokines, including one which activates gp130. Wild-type human gp130 and its mutant constructs were introduced into cultured gp130-deficient AGM cells using retrovirus system. To further analyze gp130 downstream signaling, a dominant-negative mutant of STAT3 was also introduced. RESULTS: The gp130 deficiency in the culture of fetal mouse AGM cells resulted in the failure of the expansion of the c-kit(+), Sca-1(+), and lineage markers(-) population. Such failure was rescued by introduction of a wild-type gp130 expression construct but not its mutant constructs having no ability to activate STAT3. In the normal AGM cell culture, introduction of a dominant-negative form of STAT3 in which Y(705) was changed to phenylalanine suppressed the expansion of hematopoietic cell colonies. CONCLUSION: gp130 plays an indispensable role in the expansion of hematopoietic precursor cells in the fetal mouse AGM. In particular, the activation of STAT3 by gp130 is found to be important in this process. 相似文献