Toshiya Tokui

CYTOSKELETAL REARRANGEMENTS AND TRANSCRIPTIONAL ACTIVATION OF C-FOS SERUM RESPONSE ELEMENT BY RHO-KINASE

The small GTPase Rho is implicated in cytoskeletal rearrangements including stress fiber and focal adhesion formation and in the transcriptional activation of c-fosserum response element. In vitro, Rho-kinase, which is activated by Rho, phosphorylates not only myosin light chain (MLC) (thereby activating myosin ATPase) but also myosin phosphatase, thus inactivating myosin phosphatase. Rho-kinase is involved in the formation of stress fibers and focal adhesions in fibroblasts. Here we show that the expression of constitutively active Rho-kinase increased the level of MLC phosphorylation. The activity of Rho-kinase was necessary for maintaining the vinculin-containing focal adhesions, whereas organized actin stress fibers were not necessary for this. The microinjection of constitutively active Rho-kinase into fibroblasts induced the formation of focal adhesions to some extent under the conditions where organized actin stress fibers were disrupted. The expression of constitutively active Rho-kinase also stimulated the transcriptional activity of c-fos serum response element. These results suggest that Rho-kinase has distinct roles in divergent pathways downstream of Rho, which include MLC phosphorylation leading to stress fiber formation, focal adhesion formation, and gene expression.

EVIDENCE THAT SER-82 IS A UNIQUE PHOSPHORYLATION SITE ON VIMENTIN FOR CA2+-CALMODULIN-DEPENDENT PROTEIN KINASE II

We identified the sites on vimentin that are phosphorylated by Ca2(+)-calmodulin-dependent protein kinase II (CaM-kinase II). Sequential analysis of the purified phosphopeptides demonstrated that the sites are -Thr-Arg-Thr-Tyr-Ser(PO4)38-Leu-Gly-Ser-Ala- and -Val-Arg-Leu-Leu-Gln-Asp-Ser(PO4)82-Val-Asp-, which are located within the amino-terminal head domain of vimentin. For Ser-82 but not Ser-38, the proposed CaM-kinase II recognition amino acid sequence (Arg-X-X-Ser/Thr) was not found. Studies with a series of synthetic peptide analogs corresponding to Ser-82 and its surrounding amino acid sequence indicate that Asp-84 acts as an essential substrate specificity determinant for the Ser-82 phosphorylation by CaM-kinase II. The CaM-kinase II recognition site may be more extensive than heretofore determined.

Ca2+-Calmodulin-dependent protein kinase II phosphorylates various types of non-epithelial intermediate filament proteins

We have investigated the actions of Ca2(+)-calmodulin (CaM)-dependent protein kinase II on various types of non-epithelial intermediate filament proteins, vimentin, desmin, glial fibrillary acidic protein (GFAP) and neurofilament triplet proteins. Most of these filament proteins could serve as substrates. The effects of phosphorylation on the filamentous structure of vimentin were investigated in sedimentation experiments and by using electron microscopy. The amount of unassembled vimentin increased linearly with increased phosphorylation. However, the extent of the effect of phosphorylation on the potential to polymerize was also affected by the MgCl2 concentration, under conditions for reassembly. The actions of Ca2(+)-CaM-dependent protein kinase II on non-epithelial intermediate filaments under physiological conditions are given attention.

Pulmonary leiomyosarcoma extending into left atrium or pulmonary trunk: complete resection with cardiopulmonary bypass☆☆☆★★★

Primary pulmonary leiomyosarcoma is a rare tumor. Few cases have been treated surgically because of its rapid invasion into the pulmonary trunk or heart and tendency toward massive intrapulmonary metastases. We report the cases of two patients with leiomyosarcoma originating in a pulmonary artery or vein that involved the pulmonary trunk or left atrium, both of whom underwent complete surgical resection with cardiopulmonary bypass (CPB). Since their operations, these patients have shown no evidence of recurrent tumor. PATIENT 1. A 72-year-old woman with persistent cough, chest pain, and hemoptysis was referred to our hospital for evaluation and treatment of presumed pulmonary thromboembolism. An angiogram revealed filling defects in the pulmonary trunk, absence of filling of the left main pulmonary artery, and decreased arterial filling in the left lung. A biopsy specimen was obtained from a tumor in the left main pulmonary artery by means of a suction catheter, and the pathologic diagnosis of sarcoma was made. Computed tomography disclosed a mass occluding the left main pulmonary artery and densely filling pulmonary artery branches. Median sternotomy was performed and CPB was applied. The left pulmonary veins were ligated and the left main pulmonary artery was incised. A large tumor completely filled the left main pulmonary artery. Extension of the incision into the pulmonary trunk disclosed that the tumor invaded its wall laterally on the left. The portion of tumor located in the left main pulmonary artery and pulmonary trunk, including the left main pulmonary artery and the left lateral wall of the trunk, was excised. Direct suture closure of the pulmonary trunk was carried out and CPB was terminated. The left main bronchus was transected and left pneumonectomy was completed. Fig. 1 shows the resected left lung and pulmonary artery. Tumor in the main pulmonary artery extended intraluminally into its branches. The tumor was diagnosed histologically with the aid of immunohistochemical stainFrom the Department of Thoracic and Cardiovascular Surgery, Mie University, School of Medicine, Tsu, Japan.

Clinical evaluation of a silicone coated hollow fiber oxygenator.

In this article, the clinical experience with a cardiopulmonary bypass (CPB) using a newly developed hollow fiber oxygenator with an ultra-thin layer of silicone is reported. A comparative study of biocompatibility between the new oxygenator and a heparin coated oxygenator is also described. The CPB was performed with a silicone coated oxygenator, Mera Excelung Binding Prim HPO 15 H-C (Group I, n = 6) or Binding Prim HPO 25 H-C (Group II, n = 10) (Senko Medical Instrument Mfg., Tokyo, Japan). Air could be vented through the silicone coated hollow fibers, and it was easy to prime the circuits. The CPB duration was 101 ± 37 min and 170 ± 64 min for Groups I and II, respectively. There were no deaths and no complications from CPB. Partial arterial pressure of O2 levels 60 minutes after the start of CPB were 529 ± 28 mm Hg and 529 ± 28 mmHg for Group I and II, respectively. of Co. levels 60 min after the start

Upside down use of Gore Excluder or Cook Zenith Legs

PurposeEndovascular aneurysm repair is becoming increasingly popular. This technical note describes the usefulness of the upside-down technique of Gore Excluder or Cook Zenith legs.MethodsFour patients with iliac or abdominal aortic aneurysms were treated. Three patients with isolated iliac artery aneurysms and one patient with an abdominal aortic aneurysm, in which the neck diameters were unfit for commercially available stent-grafts, were treated using an Excluder or a Zenith leg in an upside-down technique.ResultsThe aneurysms were completely excluded and no endoleak occurred. There were no serious adverse events.ConclusionsThe upside-down technique using an Excluder leg or a Zenith leg is both feasible and effective.

Less Invasive Therapy using Endovascular Stent Graft Repair and Video-Assisted Thoracoscopic Surgery for Ruptured Acute Aortic Dissection

We report a 75-year-old man with a ruptured acute thoracic aortic dissecting hematoma treated using endovascular stent grafting and video-assisted thoracoscopic surgery. This less invasive therapy is a good therapeutic option even in ruptured acute aortic dissections, particularly given the difficulty of surgery.

Aggregatibacter aphrophilus infective endocarditis confirmed by broad-range PCR diagnosis: A case report

Highlights • Case of infective endocarditis caused by a rare pathogen, Aggregatibacter aphrophilus is presented.• Aggregatibacter aphrophilus can’t be detected by common culture methods.• Br-PCR testing is a useful tool to identify pathogens of culture negative endocarditis.• Serum PR3-ANCA can be positive in Aggregatibacter aphrophilus endocarditis.

Retrograde Ascending Dissection After Thoracic Endovascular Aortic Repair Combined With the Chimney Technique and Successful Open Repair Using the Frozen Elephant Trunk Technique

The chimney technique can be combined with thoracic endovascular aortic repair (TEVAR) to both obtain an appropriate landing zone and maintain blood flow of the arch vessels. However, surgical repair becomes more complicated if retrograde type A aortic dissection occurs after TEVAR with the chimney technique. We herein report a case involving a 73-year-old woman who developed a retrograde ascending dissection 3 months after TEVAR for acute type B aortic dissection. To ensure an adequate proximal sealing distance, the proximal edge of the stent graft was located at the zone 2 level and an additional bare stent was placed at the left subclavian artery (the chimney technique) at the time of TEVAR. Enhanced computed tomography revealed an aortic dissection involving the ascending aorta and aortic arch. Surgical aortic repair using the frozen elephant trunk technique was urgently performed. The patient survived without stroke, paraplegia, renal failure, or other major complications. Retrograde ascending dissection can occur after TEVAR combined with the chimney technique. The frozen elephant trunk technique is useful for surgical repair in such complicated cases.

Coronary artery bypass grafting after radiation therapy for lung cancer

Radiation therapy has been a common treatment modality for many malignant tumors, including lung cancer. Coronary artery disease can be an adverse effect of chest irradiation as well as other major coronary risk factors. Coronary artery bypass grafting in such patients is difficult due to the presence of extensive radiation-induced mediastinal fibrosis. Here, we describe a successful case of surgical treatment for left main of coronary artery occlusion after radiation therapy for advanced lung cancer.