First reported case of Staphylococcus condimenti infection associated with catheter-related bacteraemia.

We report a case of a patient who experienced a catheter-related bloodstream infection caused by Staphylococcus condimenti, which was first isolated from soy sauce mash. This is the first reported case of human infection. Although blood culture isolates and the catheter tip tube did not reveal coagulase or clumping factor, false-positive results were obtained from latex agglutination tests for clumping factor and protein A due to self-agglutination. Care is needed when performing only latex agglutination test without a coagulase test. Further studies are needed to determine the pathogenic potential of S. condimenti based on appropriate identification.

[Ascending aorta-abdominal aorta bypass for a patient with renal hypertension induced by aortitis syndrome; report of a case].

A 58-year-old woman was admitted to our institute. Aortitis syndrome was diagnosed when she was 39 years old. She developed intractable hypertension several years prior, and a computed tomography (CT) scan showed severe calcified stenosis of the descending aorta. The ankle brachial pressure index of the right leg was 0.70 and that of the left leg was 0.63. Plasma renin activity was 4.8 ng/ml/h. Ascending aorta-abdominal aorta bypass grafting was scheduled. The operation was successfully performed under partial cardiopulmonary bypass to control arterial blood pressure. An implanted graft was 14 mm in diameter. The postoperative ankle brachial pressure index of the right leg was 1.07 and that of the left leg was 1.03. Postoperative plasma renin activity was 0.2 ng/ml/h, and three-dimensional CT revealed that the implanted graft was patent. Postoperatively, hypertension was well controlled without medication.

[Integrated coronary artery bypass strategy prevents urgent pump conversion during off-pump coronary artery bypass grafting].

Urgent pump conversion during off-pump coronary artery bypass (OPCAB) results in high morbidity and mortality. We retrospectively evaluated if the peri-operative integrated strategy prevents this lethal event in our 400 consecutive OPCAB operations. The patients with preoperative cardiogenic shock and/or ventricular arrhythmias underwent on-pump coronary artery bypass grafting (CABG). All other patients (99% of total CABG) were scheduled to undergo OPCAB (n=400). Prophylactic intraaortic balloon pumping (IABP) was applied to the patients with critical (>95%) left main trunk stenosis or low (<0.35) left ventricular ejection fraction. All the patients received the deep pericardial suture, apex-traction device, suction-type stabilizer, test-clamp of target coronary arteries by micro bulldog clamp, and intra-coronary shunts. Intra-operative IABP was applied in the case of sustained ST-segment change and/or elevated pulmonary artery pressure. Pump conversion was indicated for the patients with ventricular fibrillation and/or cardiogenic shock. Two patients (0.5%) had pump conversion due to ventricular arrhythmia and sustained hypotension, respectively. These pump conversion did not result in hospital mortality. Three hospital deaths (0.7%) occurred due to non-cardiac causes. The integrated strategy using prophylactic or intra-operative IABP in OPCAB produce a low pump conversion rate even during an early period of surgeon's learning curve.

Novel oligosaccharide has suppressive activity against human leukemia cell proliferation.

Various oligosaccharides containing galactose(s) and one glucosamine (or N-acetylglucosamine) residues with beta1-4, alpha1-6 and beta1-6 glycosidic bond were synthesized; Galbeta1-4GlcNH(2), Galalpha1-6GlcNH(2), Galalpha1-6GlcNAc, Galbeta1-6GlcNH(2), Galbeta1-4Galbeta1-4GlcNH(2) and Galbeta1-4Galbeta1-4GlcNAc. Galalpha1-6GlcNH(2) (MelNH(2)) and glucosamine (GlcNH(2)) had a suppressive effect on the proliferation of K562 cells, but none of the other saccharides tested containing GlcNAc showed this effect. On the other hand, the proliferation of the human normal umbilical cord fibroblast was suppressed by none of the saccharides other than GlcNH(2). Adding Galalpha1-6GlcNH(2) or glucosamine to the culture of K562 cell, the cell number decreased strikingly after 72 h. Staining the remaining cells with Cellstain Hoechst 33258, chromatin aggregation was found in many cells, indicating the occurrence of cell death. Furthermore, all of the cells were stained with Galalpha1-6GlcNH-FITC (MelNH-FITC). Neither the control cells nor the cells incubated with glucosamine were stained. On the other hand, when GlcNH-FITC was also added to cell cultures, some of them incubated with Galalpha1-6GlcNH(2) were stained. The difference in the stainability of the K562 cells by Galalpha1-6GlcNH-FITC and GlcNH-FITC suggests that the intake of Galalpha1-6GlcNH(2) and the cell death induced by this saccharide is not same as those of glucosamine. The isolation of the Galalpha1-6GlcNH(2) binding protein was performed by affinity chromatography (melibiose-agarose) and LC-MS/MS, and we identified the human heterogeneous ribonucleoprotein (hnRNP) A1 (34.3 kDa) isoform protein (30.8 kDa). The hnRNP A1 protein was also detected from the eluate(s) of the MelNH-agarose column by the immunological method (anti-hnRNP-A1 and HRP-labeled anti-mouse IgG (gamma) antibodies).

[Repair of paravalvular leak after a third mitral valve replacement].

This study reports on a 57-year-old woman who underwent a 3rd mitral valve replacement and presented with complaints of fatigue. Laboratory examination revealed severe hemolytic anemia, and trans-esophageal echocardiography revealed a paravalvular leak (PVL) around the prosthetic valve at the posterior trigone in the mitral position. PVL was regarded as the cause of hemolytic anemia. At surgery, a small tissue defect was detected around the calcified posterior trigone of the mitral annulus with no evidence of infective endocarditis. The mitral PVL was successfully repaired with suture closure of the annular defect. The postoperative course was uneventful: postoperative echocardiography revealed no evidence of PVL, and the hemolytic anemia subsided.

[Therapeutic strategies for acute type A aortic dissection].

We herein present the early and mid-term outcomes of therapeutic strategies for acute type A aortic dissection in our department. Subjects were 75 patients who were admitted to our department from January 2001 to October 2006. A total of 33 patients had thrombosed dissection: emergent surgery was indicated for cases in which the maximal ascending aortic diameter was > or =50 mm or when ulcer-like projection (ULP) was observed in the ascending aorta. Only 1 case of rupture-related death was observed, in a patient who had a maximal ascending aortic diameter of 52 mm and refused surgery. Although 8 patients were converted to surgery during the chronic phase, elective surgery was recommended in all cases. Surgery consisted of entry resection using open distal anastomosis under circulatory arrest at a bladder temperature of 25 degrees C, with antegrade cerebral perfusion into the 3 cervical branches of arch aorta based on bilateral axillary artery. In-hospital mortality of the 62 patients who underwent surgery was low (4.8%) and no dissection-related deaths were reported for the midterm outcomes. In addition, a low rate of cerebral infarction was observed among cases who had residual dissection of the brachiocephalic arteries after surgery. These findings demonstrate the validity of the therapeutic strategies in our department.

Galanin and galanin receptor type 1 suppress proliferation in squamous carcinoma cells: activation of the extracellular signal regulated kinase pathway and induction of cyclin-dependent kinase inhibitors.

Galanin receptor 1 (GALR1) maps to a common region of 18q loss in head and neck squamous cell carcinomas and is frequently inactivated by methylation. To investigate effects of GALR1 and its signaling pathways, we stably expressed hemaglutinin-tagged GALR1 in a human oral carcinoma cell line (UM-SCC-1-GALR1) that expresses no endogenous GALR1. In transfected cells, galanin induced activation of the extracellular-regulated protein kinase-1/2 (ERK1/2) and suppressed proliferation. Galanin stimulation mediated decreased expression of cyclin D1 and increased expression of the cyclin-dependent kinase inhibitors (CKI), p27(Kip1) and p57(Kip2). Pretreatment with the ERK1/2-specific inhibitor U0126 prevented these galanin-induced effects. Phosphatidylinositol 3-kinase (PI3K) pathway activation did not differ in UM-SCC-1-GALR1 and UM-SCC-1-mock cells after galanin treatment. Pertussis toxin and LY294002 inhibition demonstrated that galanin and GALR1 induce ERK1/2 activation via Galphai, not the PI3K pathway-linked to the Gbetagamma subunit. Galanin and GALR1 also inhibit colony formation and tumor growth in vivo. Our results implicate GALR1, a Gi protein-coupled receptor, as a tumor suppressor gene that inhibits cell proliferation via ERK1/2 activation.

[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.

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.

[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.

[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).

[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.

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.

[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.

[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.

[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.

[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.

Fourteen year experience with the omnicarbon prosthetic heart valve.

The Omnicarbon prosthetic valve was implanted in 168 patients (mean age, 53 years); 84 had aortic valve replacement (AVR), 57 had mitral valve replacement (MVR), and 27 had both aortic and mitral valve replacement (DVR). The mean follow-up period was 6.8 years, with a maximum of 13.7 years. Three patients (1.8%) were lost to follow-up. There were 4 (2.4%) early deaths and 26 late deaths. Survival at 10 years was 76% in the AVR and MVR groups, and 85% in the DVR group. Freedom from thromboembolism at 10 years was 94% in the AVR group, 80% in the MVR group, and 92% in the DVR group. Freedom from hemorrhagic complications at 10 years was 86% in the AVR group and 92% in the MVR group. At 10 years, 97% in the AVR group and 96% in the MVR group were free from endocarditis. One patient in the DVR group suffered a paravalvular leak. At 10 years, 97% in the AVR group and 95% in the MVR group had not needed reoperation. Elevation of the postoperative serum lactate dehydrogenase levels were acceptable in the three groups. In conclusion, the Omnicarbon prosthetic valve has shown excellent long-term clinical results.

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.

Synthesis and antibacterial activity of the tricyclic ketolides TE-802 and its analogs.

The novel 6-O-methyl tricyclic ketolides TE-802 and its analogs were synthesized by two successive cyclization reactions, 11,12-cyclic carbamate formation by intramolecular Michael addition and 9,11-diazaheptene ring construction by intramolecular dehydration reaction. These new tricyclic ketolides exhibited good in vitro antibacterial activity against not only erythromycin-susceptible strains but also erythromycin-resistant Staphylococcus aureus and Streptococcus pneumoniae, which are problematic pathogens of nosocomial and community-acquired respiratory tract infections, respectively.