The Ser19Stop single nucleotide polymorphism (SNP) of human PHYHIPL affects the cerebellum in mice.

The HapMap Project is a major international research effort to construct a resource to facilitate the discovery of relationships between human genetic variations and health and disease. The Ser19Stop single nucleotide polymorphism (SNP) of human phytanoyl-CoA hydroxylase-interacting protein-like (PHYHIPL) gene was detected in HapMap project and registered in the dbSNP. PHYHIPL gene expression is altered in global ischemia and glioblastoma multiforme. However, the function of PHYHIPL is unknown. We generated PHYHIPL Ser19Stop knock-in mice and found that PHYHIPL impacts the morphology of cerebellar Purkinje cells (PCs), the innervation of climbing fibers to PCs, the inhibitory inputs to PCs from molecular layer interneurons, and motor learning ability. Thus, the Ser19Stop SNP of the PHYHIPL gene may be associated with cerebellum-related diseases.

Comprehensive Profiling of Gene Expression in the Cerebral Cortex and Striatum of BTBRTF/ArtRbrc Mice Compared to C57BL/6J Mice.

Mouse line BTBR T+ Iptr3 tf /J (hereafter referred as to BTBR/J) is a mouse strain that shows lower sociability compared to the C57BL/6J mouse strain (B6) and thus is often utilized as a model for autism spectrum disorder (ASD). In this study, we utilized another subline, BTBRTF/ArtRbrc (hereafter referred as to BTBR/R), and analyzed the associated brain transcriptome compared to B6 mice using microarray analysis, quantitative RT-PCR analysis, various bioinformatics analyses, and in situ hybridization. We focused on the cerebral cortex and the striatum, both of which are thought to be brain circuits associated with ASD symptoms. The transcriptome profiling identified 1,280 differentially expressed genes (DEGs; 974 downregulated and 306 upregulated genes, including 498 non-coding RNAs [ncRNAs]) in BTBR/R mice compared to B6 mice. Among these DEGs, 53 genes were consistent with ASD-related genes already established. Gene Ontology (GO) enrichment analysis highlighted 78 annotations (GO terms) including DNA/chromatin regulation, transcriptional/translational regulation, intercellular signaling, metabolism, immune signaling, and neurotransmitter/synaptic transmission-related terms. RNA interaction analysis revealed novel RNA-RNA networks, including 227 ASD-related genes. Weighted correlation network analysis highlighted 10 enriched modules including DNA/chromatin regulation, neurotransmitter/synaptic transmission, and transcriptional/translational regulation. Finally, the behavioral analyses showed that, compared to B6 mice, BTBR/R mice have mild but significant deficits in social novelty recognition and repetitive behavior. In addition, the BTBR/R data were comprehensively compared with those reported in the previous studies of human subjects with ASD as well as ASD animal models, including BTBR/J mice. Our results allow us to propose potentially important genes, ncRNAs, and RNA interactions. Analysis of the altered brain transcriptome data of the BTBR/R and BTBR/J sublines can contribute to the understanding of the genetic underpinnings of autism susceptibility.

Comparative gene expression analysis of the engulfment and cell motility (ELMO) protein family in the mouse brain.

Engulfment and cell motility (ELMO) proteins bind to Dock180, a guanine nucleotide exchange factor (GEF) of the Rac family, and regulate GEF activity. The resultant ELMO/Dock180/Rac module regulates cytoskeletal reorganization responsible for the engulfment of apoptotic cells, cell migration, and neurite extension. The expression and function of Elmo family proteins in the nervous system, however, are not yet fully understood. Here, we characterize the comparative gene expression profiles of three Elmo family members (Elmo1, Elmo2, and Elmo3) in the brain of C57BL/6J mice, a widely used inbred strain, together with reeler mutant mice to understand gene expression in normal laminated brain areas compared with abnormal areas. Although all three Elmo genes showed widespread mRNA expression over various mouse tissues tested, Elmo1 and Elmo2 were the major types expressed in the brain, and three Elmo genes were up-regulated between the first postnatal week (infant stage) and the third postnatal week (juvenile, weaning stage). In addition, the mRNAs of Elmo genes showed distinct distribution patterns in various brain areas and cell-types; such as neurons including inhibitory interneurons as well as some non-neuronal cells. In the cerebral cortex, the three Elmo genes were widely expressed over many cortical regions, but the predominant areas of Elmo1 and Elmo2 expression tended to be distributed unevenly in the deep (a lower part of the VI) and superficial (II/III) layers, respectively, which also changed depending on the cortical areas and postnatal stages. In the dentate gyrus of the hippocampus, Elmo2 was expressed in dentate granule cells more in the mature stage rather than the immature-differentiating stage. In the thalamus, Elmo1 but not the other members was highly expressed in many nuclei. In the medial habenula, Elmo2 and Elmo3 were expressed at intermediate levels. In the cerebellar cortex, Elmo1 and Elmo2 were expressed in differentiating-mature granule cells and mature granule cells, respectively. In the Purkinje cell layer, Elmo1 and Elmo2 were expressed in Purkinje cells and Bergmann glia, respectively. Disturbed cellular distributions and laminar structures caused by the reeler mutation did not severely change expression in these cell types despite the disturbed cellular distributions and laminar structures, including those of the cerebrum, hippocampus, and cerebellum. Taken together, these results suggested that these three Elmo family members share their functional roles in various brain regions during prenatal-postnatal development.

Perioperative management for iatrogenic aortocoronary dissection during percutaneous coronary intervention.

Aortocoronary dissection is a rare but serious complication. We report the case of a 72-year-old female with angina. Percutaneous coronary intervention was performed for right coronary artery disease. Manipulation of the guiding catheter led to aortocoronary dissection. A drug-eluting stent was immediately implanted in the right coronary ostium to seal the entry of the dissection. Computed tomography (CT) showed ascending aortic dissection. The patient was observed without surgery. CT performed the following day and showed the contrast in the false lumen which had disappeared. Clinicians are more likely to avoid surgical treatment if stenting successfully seals the entry of the coronary dissection.

Unique Technique for Open Surgical Repair after Failed Endovascular Aneurysm Repair with Proximal Anastomoses.

Endovascular aortic aneurysm repair (EVAR) has revolutionized the management of abdominal aortic aneurysms (AAAs), with lower perioperative morbidity and mortality compared to conventional surgical repair. However, late secondary re-interventions after EVAR are still needed before aneurysm rupture in many cases. A patient with impending rupture of an AAA associated with a type I endoleak 7 years after EVAR who was successfully treated with a unique technique of fixation of the proximal aortic neck taking into account the structure of the stent graft is reported. This technique offers a safe solution to late open conversion after failed EVAR.

Difficult preoperative diagnosis in a case of rapidly progressive carcinomatous pericarditis.

A 54-year-old woman initially diagnosed with stage IIIb squamous cell carcinoma of the uterine cervix was treated with chemotherapy and radiation therapy. After 8 months, she developed dyspnea, leg edema, pleural effusion, pericardial effusion, and liver congestion. Her cardiac ejection fraction was normal and cardiomegaly was not evident. Metastatic carcinomatous pericarditis or pleurisy was suspected, but laboratory findings, including tumor markers, were normal. She was transferred to our hospital for the repair a cardiac injury caused by a pericardial drainage procedure. Emergency surgery was performed for the misplaced drainage catheter in the right atrium and for an abnormal mass in her right and left atria. The clinical diagnosis of carcinomatous pericarditis was made; however, her condition rapidly deteriorated, and she died 6 days postoperatively. At autopsy, metastasis was identified in a large area of the pericardium and myocardium.

Molecular prevalence and genetic diversity of bovine Theileria orientalis in Myanmar.

Theileria orientalis is a causative agent of benign theileriosis in cattle and distributed in mainly Asian countries. In the present study, we examined the prevalence of T. orientalis infection by PCR based on the major piroplasm surface protein gene (MPSP) sequences in cattle in Myanmar, followed by phylogenetic analysis of the MPSP genes. The MPSP gene was amplified in 258 of 713 (36.2%) cattle blood DNA samples collected from five cities in different geographical regions of Myanmar. Phylogenetic analysis of MPSP sequences from 54 T. orientalis-positive DNA samples revealed the presence of six allelic genotypes, including Types 1, 3, 4, 5, 7, and N-3. Types 5 and 7 were the predominant types detected. Sequences of the MPSP genes detected in Myanmar were closely related to those from Thailand, Vietnam or Mongolia. These findings suggest that movement of animals carrying T. orientalis parasites between Southeast Asian countries could be a reason for the similar genotype distribution of the parasites in Myanmar.

[Succesful case of open heart surgery in a dialysis patient with infectious endocarditis and severe bone marrow suppression: report of a case].

We report a case of infectious endocarditis due to Corynebacterium species. The patient was 71-yearold man, who was on dialysis and had tracheostomy preoperatively. He went to the hospital complaining of dyspnea. He was diagnosed with congestive heart failure and treated after admission. His respiratory condition was exacerbated and he was intubated. Respiratory management prolonged over 2 weeks. Tracheostomy was performed. One month after admission, cardiac echo showed massive aortic valve regurgitation and vegetation of aortic valve. The patient was transferred to our hospital to undergo operation for aortic valve regurgitation and infectious endocarditis. In our hospital, labo data showed severe bone marrow suppresssion with white blood cell(WBC)1,700/µl, red blood cell(RBC)259×104/µl, platelet(PLT) 5.0×104/µl. Aortic valve replacement was performed. Because the patient had tracheostomy, we incised sternal bone in a T shape to avoid mediastinitis. After operation, patient recovered well and left hospital 48th day after the operation.

[Prevention of cerebral infarction in thoracic endovascular aneurysm repair(TEVAR) of distal aortic arch aneurysms; left subclavian artery balloon technique].

Thoracic endovascular aneurysm repair(TEVAR) has been applied more and more frequently to an atherosclerotic distal aortic arch aneurysm. Even if the procedure is successful, extensive cerebral infarction might occur, especially in the left vertebral artery area. We therefore devised a new method to prevent embolic events using a thrombectomy catheter with an end hole, which was placed at the origin of the letf subclavian artery via the radial artery. This simple left subclavian artery balloon technique not only prevents cerebral embolism in the left vertebral artery system, but also provides a position marker under X-ray, and enables tight compaction of the embolization coils.

Modified reduction aortoplasty with external reinforcement of the ascending aortic aneurysm caused by giant cell arteritis treated as polymyalgia rheumatica.

A 74-year-old Japanese woman was referred to our hospital for surgical repair of an ascending aortic aneurysm and severe aortic valve regurgitation. She had received low dose steroid treatment for 6 years due to a diagnosis of the polymyalgia rheumatica (PMR), and no signs of inflammation were detected serologically. Modified reduction aortoplasty with external prosthetic support of the ascending aorta was performed following uneventful aortic valve replacement under cardiopulmonary bypass. The macroscopic view of the ascending aortic wall showed the diffuse spotty medial defects. The pathological interpretation of the aneurysmal wall was giant cell arteritis (GCA). Because PMR is intimately associated with GCA, physicians should be aware of the development of thoracic aortic aneurysm even in the course of PMR. Reduction aortoplasty is simple and may not be precluded from the treatment option for the aortic dilatation associated with giant cell arteritis.

The results of the enclose II proximal anastomotic device in 178 off-pump coronary artery bypass surgeries.

OBJECTIVE: Enclose II is a new device for proximal coronary artery bypass anastomoses. We evaluated the safety and effectiveness of Enclose II in patients who underwent off-pump coronary artery bypass grafting (CABG). METHODS: Enclose II was used for isolated off-pump CABG in 178 patients at six heart centers between October 2005 and December 2009. The preoperative characteristics of the patients, complications related to Enclose II, and early graft patency rates were examined. RESULTS: A total of 222 proximal anastomoses were performed in 178 patients using Enclose II. Forty-four of these patients had two proximal anastomoses using this device. New cerebral infarction that arose in two patients (1.1%) was not related to Enclose II. No aortic injury occurred. The graft patency rate was 96.4% at 1 year after surgery. CONCLUSIONS: Enclose II is a safe and useful assist device for proximal anastomoses in patients undergoing off-pump CABG.

[The property and applications of the photovoltaic solar panel in the region of diagnostic X-ray].

In this study, the sensitivity in the diagnostic X-ray region of the single crystalline Si photovoltaic solar panel, which is expected to grow further, was measured by using an X-ray tube. The output voltage of the solar panel was clearly proportional to the tube voltage and a good time response in the irradiation time setting of the tube was measured. The factor which converts measured voltage to irradiation dose was extracted experimentally using a correction filter to investigate the ability of the solar panel as a dose monitor. The obtained conversion factors were N(S) = 13 ± 1[µV/µSv/s] for the serial and N(P) = 58 ± 2[µV/µSv/s] for the parallel connected solar panels, both with the Al 1 mm + Cu 0.1 mm correction filter, respectively. Therefore, a good dose dependence of the conversion factor was confirmed by varying the distance between the X-ray tube and the solar panel with that filter. In conclusion, a simple extension of our results pointed out the potential of a new concept of measurements using, for example, the photovoltaic solar panel, the direct dose measurement from X-ray tube and real time estimation of the exposed dose in IVR.

A newly designed holder for grafts with four side branches used in total arch replacement.

Grafts with four presewn side branches have proven very useful for total aortic arch replacement worldwide. However, the four side branches often obscure the surgeon's view of the distal anastomotic site. Thus, we designed a holder for this graft, which sheaths and hides the graft body and branches, allowing the surgeon a better view of the distal anastomosis. By using this device, distal anastomosis can be achieved early and quickly without obstruction of the surgeon's view, resulting in reduced cardiac ischemic time in aortic arch surgery.

Injury to the tricuspid valve and membranous atrioventricular septum caused by huge calcified right ventricular myxoma: report of a case.

A 64-year-old female, admitted because of severe dyspnea on exertion and facial edema, showed echocardiographic findings of a large tumor in the right ventricle (RV). Echocardiography revealed a cardiac mass extending from the RV across the tricuspid valve into the right atrium, synchronized with the cardiac cycle, and severe tricuspid regurgitation was apparent. The mass was removed under cardiopulmonary bypass. It measured 7 x 5 x 5 cm with diffuse superficial calcification and arose from the posterior wall of the RV, just under the tricuspid valve ring, with a short pedicle. During the same procedure, after the successful excision of the tumor, small atrial and ventricular septal defects were found that had been caused by the tumor and these were closed directly. The tricuspid valve was repaired with valvuloplasty, chordoplasty and annuloplasty. The microscopic findings were of typical myxoma; however, a right ventricular myxoma protruding into the right atrium is exceedingly rare.

Pathogenetic significance of myxomatous degeneration in fenestration-related massive aortic regurgitation.

BACKGROUND: Aortic valvular regurgitation has several mechanisms and the present study investigated its clinicopathological correlations with aortic valve fenestration. METHODS AND RESULTS: Six male patients with massive regurgitation and enlarged fenestrations or ruptured fenestrated fibrous cords underwent aortic valve replacement. The clinicopathological features showed many similarities. Four cases had family histories of aortic regurgitation. All six patients showed moderate to severe myxomatous degeneration of the aortic valve and enlargement of aortic annulus. Four patients had 1-2 ruptured fibrous cords, located at the right coronary cusp. Echocardiographic examinations showed an abnormal fibrous cord attached to the prolapsing cusp in 3 cases with ruptured fenestrated valve and detailed examination by transesophageal echocardiography showed an intact fenestrated fibrous cord at the commissure in 1 case. CONCLUSION: Extensively fenestrated cusps with an enlarged aortic annulus because of myxomatous degeneration can cause chronic regurgitation or sudden deterioration after rupture of the fibrous cord. There is an increasing incidence of fenestration-related aortic regurgitation in the Japanese population. An important pathogenetic factor in male patients is myxomatous degeneration of the aortic cusp and annulus.