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Biomedical subjects

Y Misawa

Publications and source records attributed to Y Misawa.

At least 19 recordsLinked to original sources

Functional analysis of the regulatory requirements of B-Raf and the B-Raf(V600E) oncoprotein.

The BRAF(V600E) mutation is found in approximately 6% of human cancers and mimics the phosphorylation of the kinase domain activation segment. In wild-type B-Raf (B-Raf(wt)), activation segment phosphorylation is thought to cooperate with negative charges within the N-region for full activation. In contrast to Raf-1, the N-region of B-Raf is constitutively negatively charged owing to the presence of residues D447/D448 and the phosphorylation of S446. Therefore, it has been suggested that this hallmark predisposes B-Raf for oncogenic activation. In this study, we demonstrate that neutralizing mutations of these residues (in particular S446 and S447), or uncoupling of B-Raf from Ras-guanine 5'-triphosphate (GTP), strongly reduce the biological activity of B-Raf in a PC12 cell differentiation assay. We also confirm that S365 is a 14-3-3 binding site, and determine that mutation of this residue rescues the impaired biological activity of B-Raf proteins with a neutralized N-region, suggesting that the N-region opposes a 14-3-3-mediated transition into an inactive conformation. However, in the case of B-Raf(V600E), although complete N-region neutralization resulted in a 2.5-fold reduction in kinase activity in vitro, this oncoprotein strongly induced PC12 differentiation or transformation and epithelial-mesenchymal transition of MCF-10A cells regardless of its N-region charge. Furthermore, the biological activity of B-Raf(V600E) was independent of its ability to bind Ras-GTP. Our analysis identifies important regulatory differences between B-Raf(wt) and B-Raf(V600E) and suggests that B-Raf(V600E) cannot be inhibited by strategies aimed at blocking S446 phosphorylation or Ras activation.

14-3-3 Proteins↗

[Patient-prosthesis mismatch after aortic valve replacement; tolerable lower limit of indexed effective orifice area].

This study was aimed at determining the tolerable lower limit of the indexed effective orifice area (EOAI) to prevent patient-prosthesis mismatch (PPM). Echocardiography was performed in 87 consecutive patients who underwent aortic valve replacement (AVR). EOAI was estimated for each type and size of prosthesis and used to define PPM as moderate if >0.65 cm2/ m2 and < or = 0.85 cm2/m2, and severe if < or = 0.65 cm/m2. Aortic valve pressure gradients, left ventricular dimensions, and outcome (in-hospital and 1-year) were analyzed in the presence or absence of abnormal gradients (> or = 40 mmHg) to assess the influence of a small valve (19 mm or less labeled size). Severe PPM was found in 23% of all patients, and 50% of the severe PPM patients had an abnormal gradient. There was 1 death and 1 brain damage from ventricular fibrillation because of severe PPM in the abnormal gradient group with a small valve. In PPM patients with a small valve, EOAI (0.61 +/- 0.04 vs 0.69 +/- 0.07) and preoperative interventricular septal thickness (IVST : 16.4 +/- 2.6 mm vs 13.5 +/- 1.5 mm) were significantly different between abnormal and normal gradient groups. An EOAI > or = 0.69 appeared to be tolerable in patients with a lower level of hypertrophy (IVST < 16 mm).

Aged↗

[Late pseudoaneurysm formation after patch angioplasty of coarctation of the aorta; report of a case].

We report a case of a 13-year-old boy presenting with pseudoaneurysm associated with a knitted Dacron patch used to repair a coarctation of the aorta. At the age of 3 months, he had undergone patch angioplasty for a coarctation of the aorta, which develops following patent ductus arteriosus division at 2 months of age. He was treated by distal aortic arch replacement using 16 mm woven Dacron tube graft in an end-to-end fashion with open proximal anastomosis under deep hypothermic circulatory arrest. The aneurysm was in the aortic wall opposite the patch graft. There was no evidence of infection or dilatation of the patch graft. This case illustrates that repair of aortic coarctations with Dacron patches cannot be recommended.

Adolescent↗

[Ascending aortic aneurysm following aortic valve replacement due to aortitis syndrome; report of a case].

A 60-year-old woman had previously undergone aortic valve replacement for aortic regurgitation. As the aortic wall was elastic hard, inflammatory change was suspected; therefore, we undertook a partial biopsy of the ascending aortic wall and the intraoperative pathological specimens were compatible with aortitis syndrome. As there was no active inflammatory change, she was diagnosed as inactive aortitis syndrome and steroid therapy was not applied. Seven years later, a follow-up computed tomography (CT) showed an ascending aortic aneurysm of 65 mm in diameter. Aortic root replacement was planned based on a clinical diagnosis of an aneurysm of the ascending aorta. The patient was discharged without complication 21 days after surgery. It is possible that an inactive stage of aortitis may lead to late dilatation of the ascending aorta; therefore, careful postoperative follow-up is necessary in such cases.

Aorta↗

Onychomycosis caused by Fusarium proliferatum.

Fusarium infections in humans are usually opportunistic, but the fungus sometimes infects healthy persons, causing keratomycosis or onychomycosis. Onychomycosis is usually caused by F. solani or F. oxysporum. We report the first two cases of onychomycosis caused by F. proliferatum, and discuss methods of diagnosis and effective treatment. Nail samples from the two patients were examined by direct microscopy, cultured, and identified morphologically and genetically as F. proliferatum. Both patients were treated successfully with oral itraconazole, even though the minimum inhibitory concentration of itraconazole was relatively high in Patient 1. This is the first report of F. proliferatum as an agent of onychomycosis. Itraconazole may be effective in the treatment of onychomycosis caused by F. proliferatum.

Antifungal Agents↗

[Cardiac papillary fibroelastomas: report of 2 cases].

We report 2 cases of cardiac papillary fibroelastomas in adults. Case 1: A 61-year-old man was admitted because echocardiography showed a 1 cm pedunculated papillary tumor in the left atrium. In an operation, it was located in the left atrium near the mitral valve and was resected along with a 5 mm margin of endocardium. Case 2: A 60-year-old woman had a 1 cm mobile tumor in the right ventricle near the tricuspid valve located by echocardiography in a preoperative examination of a ventricular septal defect. In an operation, a pedunculated tumor located in the right ventricle was resected. In these 2 cases, histopathology showed the tumor to be a papillary fibroelastoma. Almost all cardiac papillary fibroelastoma are closely related to the cardiac valve, but in these cases, the tumors were located in the left atrium, and the right ventricle, respectively, which is quite rare.

Cardiac Surgical Procedures↗

[Spinal cord ischemia after surgery for arch and aortic valve replacement with elephant trunk for plural thoracic aneurysms].

A 62-years old man had plural aneurysms from the aortic arch to the descending aorta. Y-grafting had been performed twice for an abdominal aortic aneurysm. We performed the first operation which involved aortic valve and arch replacement under deep hypothermia with selective cerebral perfusion. During the operation, hemodynamics was stable, but after the operation he developed paraplegia due to ischemic change in the spinal cord. It was considered that the cause of the ischemia might have been the changing of the blood supply to the spinal cord. In patients with severe atherosclerosis, the blood supply for the spinal cord needs to be very strictly determined.

Aorta, Thoracic↗

[Ischemic left ventricular free wall rupture followed by ventricular septal perforation].

A 78-year-old woman underwent coronary angiography because of acute onset of anterior chest pain, disclosing total occlusion of the left anterior descending artery. After this she fell into circulatory collapse. As a subsequent chest computed tomography (CT) revealed pericardial effusion, she was transferred to our hospital. At operation, an oozing lesion was found on the left ventricular anterior wall near the apex. Under extracorporeal membrane oxygenation, the bleeding was completely controlled by applying fibrin glue sheets. On the thirteenth day after operation, a new systolic murmur appeared with hemodynamic deterioration. Echocardiographic examination revealed ventricular septal perforation, and she underwent reoperation. The ventricular septal perforation was recognized on the apical anterior wall. It was repaired by an infarction exclusion method. The postoperative course was uneventful. Although ischemic ventricular double rupture is a very rare complication, patients who have risk factors for cardiac rupture need to be intensively followed up.

Aged↗

[Sinus of Valsalva dilatation after replacement of the ascending aorta and aortic valve].

A 52-year-old woman, height, 149 cm; weight, 40 kg, was admitted because of anterior chest discomfort and palpitations. There was no family history of Marfan syndrome. She had undergone replacement of the ascending aorta and aortic valve 10 years prior for DeBakey II aortic dissection. Postoperative pathological examination of the resected aortic wall revealed cystic medionecrosis. Computed tomography(CT) 4 years after the surgery showed moderate enlargement of the preserved sinuses of Valsalva, and CT 10 years after the surgery showed enlargement of the sinus. She consented to a reoperation. The prostheses were explanted, and the aortic root was replaced with a composite graft. The right coronary artery ostium was completely closed, and no graftable portions of the distal right coronary artery were detected. Thus, the left coronary artery alone was reimplanted. The patient required extracorporeal membrane oxygenation for 10 days postoperatively, after which she recovered fully without complications. This case may indicate that the complete aortic root should be replaced during initial surgery of the ascending aorta or aortic valve in patients with potential risk of sinus of Valsalva dilatation.

Aortic Dissection↗

[Reconstruction of aortic branches after total aortic replacement in Marfan syndrome; report of a case].

A 34-year-old man with Marfan syndrome finished to replace the total aorta in consecutive 4 operations for 7 years. Two years later, he was diagnosed as bilateral common iliac artery aneurysms and performed a reconstruction of both arteries in September 7, 1998. Then 2 years later, innominate artery was dilated and Y-type grafting was performed in March 14, 2001. Now we have a scheduled operation for celiac artery aneurysm. In patients with Marfan syndrome, aortic dissection and aneurysms are common complications, but progressive dilatations of aortic branches are rear. Regular follow-up is important even though total aortic replacement was completed.

Adult↗

Synthesis and antibacterial activity of acylides (3-O-acyl-erythromycin derivatives): a novel class of macrolide antibiotics.

Introduction of an acyl group to the 3-O-position of erythromycin A derivatives instead of L-cladinose led to a novel class of macrolide antibiotics that we named "acylides". The 3-O-nitrophenylacetyl derivative TEA0777 showed significantly potent activity against not only erythromycin-susceptible Gram-positive pathogens but also inducibly macrolides-lincosamides-streptogramin B (MLS(B))-resistant Staphylococcus aureus and efflux-resistant Streptococcus pneumoniae. These results indicated that acylides have potential as next-generation macrolide antibiotics.

Animals↗

Platelet activation and aggregation during normothermic cardiopulmonary bypass.

OBJECTIVE: The usefulness of heparin-bonded circuits under normothermic cardiopulmonary bypass has not been elucidated. We studied platelet activation and aggregation differences between heparin-bonded and nonheparin-bonded circuits in patients undergoing surgery involving normothermic cardiopulmonary bypass. METHODS: Eight patients underwent coronary artery bypass grafting with non heparin-bonded circuits (controls) and 7 the same with heparin-bonded circuits (heparin group). Heparin bonding was applied to the blood contact surface of our system, including the oxygenator and connecting tubes. Patient body temperature was kept between 36 and 37 degrees C. Beta-thromboglobulin and platelet factor 4 were measured before, during, and after cardiopulmonary bypass, and platelet aggregation was evaluated by laser-light scattering. RESULTS: Changes in beta-thromboglobulin and platelet factor 4 during and after cardiopulmonary bypass were similar in both groups. Small particle formation was the primary aggregate induced during and after cardiopulmonary bypass in both groups, and serial changes in particle formation up to 24 hours after cardiopulmonary bypass were similar in both groups. CONCLUSIONS: Our results indicate that in 2-3 hours of normothermic cardiopulmonary bypass, heparin-bonded circuits are similar to nonheparin-bonded ones in platelet compatibility.

Aged↗

Organized thrombus of the tricuspid valve mimicking valvular tumor.

We report on a case of organized thrombus of the tricuspid valve mimicking a valve tumor. Preoperative transesophageal echocardiography showed the mass to have originated from the septal leaflet of the tricuspid valve. A pouch of the tricuspid valve and a ventricular septal defect were observed perioperatively, with the mass attached to the septal leaflet. Histologic examination revealed the mass to be an organized thrombus without tumor components.

Adult↗

Late pericarditis secondary to pericardial patch implantation 25 years prior.

We report a rare case of a 50-year-old man with signs of right heart failure due to localized pericarditis that was secondary to implantation of an artificial pericardial patch 25 years prior following pericardectomy for constrictive pericarditis. The patient's clinical symptoms resolved completely in the 3 years following patch removal.

Humans↗

Systematic status of Hynobius tokyoensis (Amphibia: Urodela) from Aichi Prefecture, Japan: a biochemical survey.

Taxonomic status of a salamander now identified as Hynobius tokyoensis from Aichi Prefecture, Japan, was assessed by allozymic comparisons with its relatives. All three populations of H. tokyoensis from Aichi formed a monophyletic group with populations of H. nebulosus; this group is substantially diverged from a conspecific population from Kanagawa that formed another group with H. lichenatus. In the former group, the population of H. nebulosus from near the type locality was more divergent from the other conspecific populations than were three populations of H. tokyoensis from Aichi. It is quite clear that the salamander from Aichi now identified as H. tokyoensis is genetically much closer to H. nebulosus than to H. tokyoensis from Kanagawa, which is closest geographically to its type locality. This result conforms well to reported results of morphological and genetic studies, and the salamander from Aichi, now called H. tokyoensis, should be identified as H. nebulosus, which is sufficiently diverged from H. tokyoensis to be considered a distinct species.

Algorithms↗

A comparative study of characteristics of current-type and conventional-type cationic bactericides.

We have synthesized new polycationic bactericides, polyloxyethylene(dimethyliminio)trimethylene(dimethyliminio)ethylene dichloridel (OXD) and poly(hexamethyleneguanidine phosphate) (HEP), in order to develop more active but less skin-irritative bactericides. The effects of these bactericides on Pseudomonas aeruginosa, Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, methicillin resistant Staphylococcus aureus (MRSA) and the degree of their irritations on skin were compared with those of a widely used low molecular-weight cationic bactericide, benzalkonium chloride (BAC), and a polycationic bactericide, poly[2-hydroxyethylene(dimethyliminio)methylene chloride] (2HYC). The minimum bactericidal concentration (MBC) of OXD for 10 min contact incubation was 16 microg/ml against P. aeruginosa, E. coli, S. marcescens and K. pneumoniae, and >1000 microg/ml against MRSA. The MBC of HEP for 10 min contact incubation was 16 microg/ml against P. aeruginosa, 32 microg/ml against E. coli and K. pneumoniae, and 64 microg/ml against S. marcescens and MRSA. Itch, edema, erythema, heat, injury, desquamation and keratinization caused by skin irritation were examined in 21 subjects by patch tests. Only one subject treated with OXD experienced edema, and one subject with HEP experienced keratinization. However, BAC caused itch in 3 subjects, edema in 1, erythema in 10 and desquamation in 2, indicating that the incidence of skin irritation of BAC was higher than that of OXD or HEP. OXD and HEP had sterilization ability similar to BAC, however, they were less skin-irritative than BAC. This indicates that OXD and HEP can be used as safe bactericides.

Adult↗