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Biomedical subjects

K Mizuguchi

Publications and source records attributed to K Mizuguchi.

At least 55 records · Page 3Linked to original sources

HOMSTRAD: a database of protein structure alignments for homologous families.

We describe a database of protein structure alignments for homologous families. The database HOMSTRAD presently contains 130 protein families and 590 aligned structures, which have been selected on the basis of quality of the X-ray analysis and accuracy of the structure. For each family, the database provides a structure-based alignment derived using COMPARER and annotated with JOY in a special format that represents the local structural environment of each amino acid residue. HOMSTRAD also provides a set of superposed atomic coordinates obtained using MNYFIT, which can be viewed with a graphical user interface or used for comparative modeling studies. The database is freely available on the World Wide Web at: http://www-cryst.bioc.cam. ac.uk/-homstrad/, with search facilities and links to other databases.

Aspartic Acid Endopeptidases↗

Long-term benefits of internal thoracic artery-coronary artery bypass in Japanese patients.

OBJECTIVES: This study sought to determine the effects of grafting the internal thoracic artery (ITA) to the left anterior descending coronary artery (LAD) on long-term (10-year) survival, the cardiac death-free rate, and on the cardiac event-free rate in Japanese patients. BACKGROUND: The use of ITA grafts has been reported to enhance postoperative survival and to decrease the occurrence of cardiac events in the Western literature. However, the survival benefits in Japanese patients, who may have different prognoses with coronary artery disease and a different fate of a saphenous vein graft, have not yet been determined. SUBJECTS AND METHODS: A total of 954 consecutive patients who underwent coronary artery bypass graft operations (CABG) during the last 12 years at the Nara Medical University were followed and evaluated. Of these, 713 patients underwent ITA-CABG to at least the LAD (ITA group), and 241 patients received a saphenous vein graft (SVG) to the LAD (SVG group). At the time of operation, no significant difference was found between these two groups in age, sex ratio left ventricular ejection fraction, left ventricular end-diastolic pressure, cardiac index, incidence of unstable angina, or in the necessity for an emergency operation. However, those patients who received ITA-CABG had significantly higher incidences of diabetes mellitus, hyperlipidemia, and left main coronary artery disease. RESULTS: The 10-year cumulative graft patency rate for the LAD was 23% higher in the ITA group (90.3%) compared to the SVG group (67.0%), (p < .0001). Despite increased preoperative risk factors, patients in the ITA group showed significant improvements in their 5- and 10-year cumulative survival rates as well as in their cardiac death-free and event-free rates. Furthermore, this study demonstrated that ITA grafts improved the prognoses of patients with diabetes mellitus or left ventricular dysfunction and lowered both the long-term postoperative cardiac-death rate and the cardiac-event rate. CONCLUSIONS: The use of ITA grafts was effective in improving both the postoperative survival and cardiac event-free rates, and should be recommended in patients with diabetes mellitus or left ventricular dysfunction. ITA grafting to the LAD should be a routine operation in almost all categories of such patients.

Aged↗

Difference in acetylcholine-induced nitric oxide release of arterial and venous grafts in patients after coronary bypass operations.

OBJECTIVES: In vivo investigation of nitric oxide release in coronary bypass grafts has not been reported. We studied acetylcholine-induced nitric oxide release in vivo of coronary bypass grafts and vasomotor responses to acetylcholine of grafted coronary arteries in patients after coronary bypass grafting. METHODS: We examined 24 internal thoracic artery grafts and 16 saphenous vein grafts in 39 patients. The mean ages of the patients were 65 years for the arterial grafts and 68 years for the venous grafts. Nitric oxide was measured as the plasma nitrite level by the Griess reaction. Before and after intragraft acetylcholine infusion (5 microg), blood was sampled from the distal end of the graft, and angiograms were taken and analyzed by cine-densitometry. RESULTS: The plasma nitrite concentration after stimulation with acetylcholine compared with the control value was 134%+/-52% at 4 minutes (p=0.05) and 184%+/-107% at 6 minutes (p=0.01) in the arterial grafts; in the venous grafts these values were 101%+/-24% at 4 minutes (p=0.96) and 108%+/-36% at 6 minutes (p=0.69). Low-dose acetylcholine dilated the coronary arteries supplied by arterial grafts by 6.3%+/-16.6% whereas coronary arteries supplied by venous grafts were reduced by 9.8%+/-11.8% in diameter and the vasoactive responses were different (p=0.01). CONCLUSIONS: In vivo internal thoracic artery grafts had more endothelium-derived nitric oxide release in response to acetylcholine than did saphenous vein grafts after coronary bypass grafting.

Acetylcholine↗

Getting knotted: a model for the structure and activation of Spätzle.

Sequence analyses show that Spätzle, the Drosophila melanogaster Toll-receptor ligand, shows striking similarity to nerve growth factor and coagulogen. Comparative modelling suggests that Spätzle adopts a cystine-knot fold and forms a dimer that contains a single, intermolecular disulphide bridge. Proteolytically cleaved Spätzle could therefore dimerize and activate the Toll receptor by inducing receptor dimerization.

Amino Acid Sequence↗

JOY: protein sequence-structure representation and analysis.

MOTIVATION: JOY is a program to annotate protein sequence alignments with three-dimensional (3D) structural features. It was developed to display 3D structural information in a sequence alignment and to help understand the conservation of amino acids in their specific local environments. RESULTS: : The JOY representation now constitutes an essential part of the two databases of protein structure alignments: HOMSTRAD (http://www-cryst.bioc.cam.ac.uk/homstrad ) and CAMPASS (http://www-cryst.bioc.cam.ac. uk/campass). It has also been successfully used for identifying distant evolutionary relationships. AVAILABILITY: The program can be obtained via anonymous ftp from torsa.bioc.cam.ac.uk from the directory /pub/joy/. The address for the JOY server is http://www-cryst.bioc.cam.ac.uk/cgi-bin/joy.cgi. CONTACT: kenji@cryst.bioc.cam.ac.uk

Amino Acid Sequence↗

Primary localized amyloidosis of the ureter.

Localized amyloidosis of the ureter is a relatively rare condition. We report a case of primary localized ureteral amyloidosis. A 66-year-old man was referred to our hospital complaining of right flank pain and gross hematuria. From the right hydronephrosis and irregular margin of the right lower ureter seen on the anterograde pyelography, we could not rule out a right ureteral malignancy. Total nephroureterectomy was performed and histologic examination showed ureteral amyloidosis. Amyloid was classified immunohistochemically as Alambda type. After all examinations for secondary or systemic amyloidosis were negative, primary localized amyloidosis of the ureter was confirmed.

Aged↗

Impact of percutaneous transluminal coronary angioplasty on coronary bypass surgery--changes in the patient profile during the past decade.

As percutaneous transluminal coronary angioplasty has become an increasingly common procedure replacing coronary artery bypass grafting (CABG), the clinical profile of the patients referred for CABG has changed markedly. A retrospective study of the changes in the clinical profile and surgical outcome of patients who underwent CABG during the past 10 years was conducted. Between March 1982 and February 1996, 1010 patients underwent isolated CABG at Nara Medical University. The first 100 consecutive patients who underwent CABG in 1984-85 (group 1) were compared with the first 100 consecutive patients who underwent CABG in 1994-95 (group 2). Preoperative risk increased significantly during the decade with respect to patient age (p<0.001), the presence of diabetes mellitus (p=0.048), the number of diseased vessels (p<0.001), left main trunk disease (p=0.008), the presence of aortic or peripheral vascular disease (p=0.032),and the need for emergency surgery (p=0.013). Operative procedures have become more complicated with respect to the number of total and arterial grafts, duration of the aortic cross-clamp and cardiopulmonary bypass. Hospital mortality for elective CABG has not changed (2%) and the overall mortality has not increased significantly (from 2% to 3%) during the decade. In conclusion, although the preoperative risks have increased and more complicated procedures are required, CABG continues to be performed safely with low mortality rates.

Aged↗

Successful treatment of intraoperative pulmonary tumor embolism from renal cell carcinoma.

During left nephrectomy in a 35-year-old woman with a left renal cell carcinoma extending into the inferior vena cava (IVC) and right atrium, cardiac arrest occurred. Immediate transesophageal echocardiography demonstrated that the event was caused by a pulmonary tumor embolism. Emergent cardiopulmonary bypass (CPB) was established and the tumors in the pulmonary arteries were successfully removed. The left nephrectomy was completed. The patient recovered in the intensive care unit without any neurological deficit. A postoperative pulmonary perfusion scintigram showed no defect in the pulmonary circulation. Transesophageal echocardiography was useful for making a rapid diagnosis of an intraoperative pulmonary embolism originating from a tumor of the IVC or right atrium.

Adult↗

Comparative rest and exercise hemodynamics of allograft and prosthetic valves in the aortic position.

BACKGROUND: Allograft aortic valve replacement has gained widespread acceptance. However, there is little information about in vivo allograft valve function at rest and during exercise. METHODS: Cardiac catheterization was performed to measure hemodynamic variables at rest and during supine bicycle exercise in 44 patients who had had aortic valve replacement using allograft valves or Bicer or St. Jude Medical prosthetic valves 19 to 27 mm in diameter. Sixteen patients received an allograft valve; 17, a Bicer valve; and 11, a St. Jude Medical valve. There were no significant differences between the three groups in age, body surface area, left ventricular end-systolic and end-diastolic volume indices, exercise cardiac index, exercise heart rate, or work load achieved. Left ventricular and ascending aortic pressures were measured simultaneously according to the transseptal method. RESULTS: The mean pressure gradient was generally higher for the Bicer and St. Jude Medical valves than for the allograft valves, both at rest and during exercise. Significant differences were obtained in patients with small-sized valves (21 and 23 mm); pressure gradients were higher in the prosthetic valve groups. In patients with large-sized prosthetic valves (25 mm), there were no significant differences between the three groups at rest and during exercise. However, there was no pressure gradient at all for allograft valves. CONCLUSIONS: Exercise cardiac catheterization confirms that the allograft aortic valve is an ideal substitute from the hemodynamic aspect, particularly in patients with a small aortic root and in those who perform strenuous exercise.

Aortic Valve↗

Effects of ethyl-all-cis-5,8,11,14,17-icosapentaenoate (EPA-E), pravastatin and their combination on serum lipids and intimal thickening of cuff-sheathed carotid artery in rabbits.

The anti-arteriosclerotic effects of ethyl all-cis-5, 8, 11, 14, 17-icosapentaenoate (EPA-E), pravastatin and their combination in cuff-treated rabbits were investigated. EPA-E at 600 mg/kg, pravastatin at 50 mg/kg or their combination was orally administered once daily for 5 weeks, and each of the animals was sheathed with a cuff on the carotid artery 2 weeks after the beginning of drug administration. EPA-E, pravastatin and their combination significantly reduced serum total cholesterol compared to the control group. EPA-E also potently reduced serum triglyceride, while pravastatin only slightly reduced it. The combination of these two agents had the most potent effect on the level of serum triglyceride. Serum phospholipids were also reduced by these treatments in a similar fashion. At the end of treatment, diffuse intimal thickening was observed in the cuff-covered region in all animals in the control group, and the intima/media area ratio in this group was 0.293 +/- 0.038. Treatment with EPA-E alone tended to prevent the intimal thickening, and the intima/media area ratio was 0.209 +/- 0.058 (p = 0.094). This ratio was 0.287 +/- 0.048 (p = 0.902) when pravastatin was administered alone, indicating that it had no significant effect on intimal thickening. The ratio was 0.175 +/- 0.041 (p = 0.042) when both EPA-E and pravastatin were administered, indicating that this combination had a significant inhibitory effect on intimal thickening in the cuff-sheathed region. These findings suggest that combined treatment with EPA-E and pravastatin is more effective than respective monotherapies in lowering serum lipids and/or preventing an intimal thickening as events of atherogenesis.

Animals↗

[Effects of ulinastatin on experimental ulcerative colitis in rats].

We examined the effect of ulinastatin in comparison with prednisolone (PSL) and salazosulfapyridine (SASP), well-known drugs for ulcerative colitis (UC), on two experimental UC models induced by dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNB) in rats. Ulinastatin at the doses of 3000 approximately 10,000 units/kg/day (i.v.) significantly ameliorated the formation of erosion and infiltration of inflammatory cells in colonic mucosa in DSS-induced rat UC models. Moreover, ulinastatin at the dose of 10,000 units/kg/day (i.v.) significantly suppressed inflammation with ulcer in the colonic mucosa in TNB-induced rat UC models. PSL at the dose of 1 mg/kg/day (p.o.) also was as effective as ulinastatin on the above two UC models, while SASP at the dose of 100 mg/kg/day (p.o.) was less effective than ulinastatin and PSL. In addition, ulinastatin inhibited the activities of elastase and cathepsin G from human leukocytes, and it suppressed TNF alpha, IL-8 and superoxide production by rat macrophages and rabbit leukocytes in vitro. These results suggest that the suppression of inflammatory mediators produced by leukocytes is involved in the mechanism of the anti-UC action of ulinastatin.

Animals↗

[Preventive effects of eicosapentaenoic acid (EPA) on cholesterol gallstone formation in hamsters].

Polyunsaturated fatty acids (PUFA) regulate various biological functions and are involved in a variety of diseases. Eicosapentaenoic acid (20:5, EPA), one of the omega-3 PUFA, has been reported a number of actions including suppression of platelet aggregability and decrease in serum lipids and is well known to be useful in preventing the atherosclerotic diseases. In this paper, we demonstrated that highly purified ethyl eicosapentaenoate (EPA-E) prevents cholesterol (CH) gallstone formation in hamster model. Repeated administration of EPA-E to animals fed a lithogenic diet for 6 weeks decreased the incidences of both CH crystal and CH gallstone formations in gallbladder bile. Contrary, bezafibrate, one of fibric acid derivative which were reported to increase CH saturation index (CSI) in bile, significantly increased the incidences of CH crystal and gallstone formations. EPA-E did not affect the CSI, but markedly increased biliary phospholipid concentration. In the same model, ethyl palmitate (16:0), ethyl oleate (18:1), ethyl linolate (18:2, omega-6) and ethyl arachidonate (20:4, omega-6) had no effects both on biliary lipids composition and CH gallstone formation. These result suggest the benefit of EPA-E in the prevention of CH gallstone.

Animals↗

[Extended aortoplasty for supravalvular aortic stenosis with Williams syndrome].

We report a male case of supravalvular aortic stenosis associated with Williams syndrome requiring surgery at age 11. At 5 years of age, this boy presented with a harsh systolic heart murmur and was diagnosed as having a supravalvular aortic stenosis. In association with mental retardation, elfin face and bilateral inguinal hernias, he was diagnosed as a Williams syndrome confirmed by the chromosomal analysis revealing the deletion of 7q11.23. The pressure gradient across the stenotic lesion of the ascending aorta, which had been 35 mmHg at age 5, progressed to 80 mmHg at age 11 years. Extended aortoplasty was performed using a patch of 20 mm Hemashield graft prosthesis. Postoperative cardiac catheterization confirmed that the pressure gradient in the ascending aorta completely disappeared following surgery.

Aorta↗

[Coronary artery bypass grafting in patients over 70 years old].

We examined the outcome of CABG in 157 patients aged over 70 years. The average age was 72.7 +/- 2.4 years: the number of the diseased vessels, 2.5 +/- 0.7/pt; the mean preoperative LVEF, 0.55 +/- 0.17 and the number of patients with left main trunk disease, 40 (26%). The mean number of bypass grafts was 2.8 +/- 0.8/pt. In 131 patients (83.4), left internal thoracic artery (LITA) was used to bypass the left anterior descending artery (LAD). The postoperative hospital mortality rate was 6.4%. After 10 years of follow-up, the actuarial survival rate and cardiac event-free rate were 73.6% and 88.9%, respectively calculated by the Kaplan-Meier method. A comparison of the long-term results of CABG with and without ITA grafting, showed no statistical difference with respect to actuarial survival rate. However, the cardiac event-free rate was improved by using an ITA graft (92.4% with an ITA vs 77.3% without an ITA, p = 0.047). This result suggested that the use of ITA in patients over 70 years old reduced the incidence of postoperative cardiac events without increasing the operative risk.

Age Factors↗

Increased risk of coronary artery bypass grafting for left ventricular dysfunction with dilated left ventricle.

UNLABELLED: The operative mortality and morbidity in patients with severe left ventricular dysfunction who undergo coronary artery bypass grafting (CABG) remain high. The low ejection fraction is the major risk factor for operative mortality. However, ejection fraction (EF) alone may not necessarily be an accurate predictor of operative mortality. We studied the correlation between indices of left ventricular volume and operative mortality. One thousand patients undergoing isolated coronary bypass operations were divided into three groups according to their preoperative ejection fraction. Fifty patients (group I) had severe left ventricular dysfunction (EF < or = 0.3), 56 patients (group II) had moderately left ventricular dysfunction (0.3 < EF < or = 0.4) and 894 patients (group III) had good left ventricular function (EF > 0.4). We analyzed the relationship between hospital mortality and left ventricular volume in 106 patients with an EF < or = 0.4. RESULTS: Cardiac index was not significantly different among the three groups. The left ventricular end-diastolic pressure (LVEDP) and mean pulmonary artery pressure in groups I an II were higher than those in group III. The left ventricular end-diastolic volume (LVEDV) was 146 +/- 44 ml/m2 in Group I, 112 +/- 31 ml/m2 in Group II and 82 + 30 ml/m2 in Group III, respectively (Group I versus II, p < 0.05, Group I and II versus III, p < 0.01). The left ventricular end-systolic volume (LVESV) was 111 +/- 38 ml/m2 in Group I, 72 +/- 21 ml/m2 in Group II and 30 +/- 14 ml/m2 in Group III, respectively (Group I versus II, p < 0.05, Group I and II versus III, p < 0.01). The LVEDV and LVESV were higher in Group I than in Group II and both in Groups I and II were higher than in Group III. The hospital mortality of any cause before discharge was 8.0% (4/50) in Group I, 3.6% (2/56) in Group II, and 2.0% (18/894) in Group III. The mortality in Group I was higher than that in Group III, but the mortality between Groups I and II was not different. We assessed correlations between large left ventricle with left ventricular dysfunction and operative mortality in 106 patients with ejection fractions of < or = 0.4. The hospital mortality in patients with both under fraction 0.4 and an LVESV > or = 140 ml/m2 was 50% (4/8). This rate was higher than in patients with an LVESV between 80 and 140 ml/m2 (1.8%, 1/55) (p = 0.0006) and an LVESV less than 80 ml/m2 (2.3%, 1/43), (p = 0.0013). The hospital mortality in patients with an LVEDV > or = 200 ml/m2 was 67% (4/6). It was also higher than that in patients with an LVEDV between 200 and 120 ml/m2 (1.7%, 1/58), (p = 0.0001), and an LVEDV less than 120 ml/m2 (2.4%, 1/42), (p = 0.0004). We conclude that patients with a low ejection fraction and an elevated LVESV or LVEDV are at increased risk for hospital death following CABG.

Cardiac Volume↗

[MIDCAB (minimally invasive direct coronary artery bypass) using mini-CABG instruments: a case report].

A 61-year-old man with unstable angina due to complete occlusion of the proximal LAD underwent MIDCAB (left internal thoracic artery (ITA)-left anterior descending artery (LAD) anastomosis), because of active hepatitis and unsuccessful PTCA. The left fourth intercostal mini-thoracotomy (9 cm long) was performed. The left ITA was harvested through the thoracotomy. The left ITA to LAD anastomosis under the beating heart was successfully performed using Mini-CABG instruments (USSC). Postoperative recovery was uneventful and postoperative coronary angiography on the 5th postoperative day revealed a widely patent graft. The patient was discharged on the 8th postoperative day. This device was very useful to perform the MIDCAB procedure.

Angina, Unstable↗

Crystal structure of glutathione synthetase at optimal pH: domain architecture and structural similarity with other proteins.

The crystal structure of Escherichia coli B glutathione synthetase (GSHase) has been determined at the optimal catalytic condition pH 7.5. The most significant structural difference from the structure at pH 6.0 is the movement of the central domain towards the N-terminal domain almost as a rigid body. As a result of this movement, new interdomain and intersubunit polar interactions are formed which stabilize the dimeric structure further. The structure of GSHase at optimal pH was compared with 294 other known protein structures in terms of the spatial arrangements of secondary structural elements. Three enzymes (D-alanine: D-alanine ligase, succinyl-CoA synthetase and the biotin carboxylase subunit of acetyl-CoA carboxylase) were found to have structures similar to the ATP-binding site of GSHase, which extends across two domains. The ATP-binding sites in these four enzymes are composed of two antiparallel beta-sheets and are different from the classic mononucleotide-binding fold. Except for these proteins, no significant structural similarity was detected between GSHase and the other ATP-binding proteins. A structural motif in the N-terminal domain of GSHase has been found to be similar to the NAD-binding fold. This structural motif is shared by a number of other proteins that bind various negatively charged molecules.

Acetyl-CoA Carboxylase↗