Identification of histological markers for malignant glioma by genome-wide expression analysis: dynein, α-PIX and sorcin

Glioblastoma multiforme (GBM), the most malignant class of glial neoplasm (grade IV in WHO criteria), carries the worst clinical prognosis among primary brain tumors in adults. To identify a set of genes involved in the tumorigenesis of GBM, we evaluated expression profiles of GBM tissues from 11 patients using a cDNA microarray representing 25,344 human genes. By comparing the profiles with those of normal brain tissue, we identified a number of differentially expressed genes: 54 with increased expression and 45 with reduced expression in GBMs. Semi-quantitative RT-PCR experiments with 6 of those genes confirmed higher expression of DNCH2, ARHGEF6, NPM1 and SRI and lower expression of NRGN and TM4SF2 in GBM tumors. Immunohistochemical staining for 3 of the respective gene products, dynein (product of DNCH2), -PIX (product of ARHGEF6), and sorcin (product of SRI) indicated that this technique might be useful for histological grading of glial tumors. To establish criteria for this diagnostic approach, we scored glial tumor tissues of different histological grades according to the staining results; the scores were significantly higher in anaplastic astrocytomas and GBMs than in diffuse astrocytomas or normal brain tissues. These findings indicated that levels of these three proteins might serve as histological markers for malignant glioma classification.     

Teeth contacting habit as a contributing factor to chronic pain in patients with temporomandibular disorders

Many different factors are known to cause and perpetuate the symptoms of temporomandibular disorders (TMD). However, the roles of parafunctional factors have not been clearly elucidated. We found one of these habits in the clinical setting. This parafunctional habit involves daily light touching of the upper and lower teeth, when the mouth is closed. We named this habit Teeth Contacting Habit (TCH). [OBJECTIVES] To investigate the following hypotheses: 1) TCH is associated with perpetuation of chronic pain of TMD patients; 2) TCH is associated with other behavioral factors. [METHODS] Two hundred and twenty-nine TMD outpatients with chronic pain were analyzed with multivariate logistic regression models. [RESULTS] TCH was found in 52.4% of patients. Patients with TCH and pain lasting for more than four months were less likely to experience improvements in pain at the first visit (OR = 1.944, p = 0.043). Other factors associated with TCH were as follows: unilateral chewing (OR = 2.802) and involvement in a precision job (OR = 2.195). [CONCLUSION] TCH can prolong TMD pain and is associated with other behavioral factors.     

Use of Angiotensin II Stress Pulsed Tissue Doppler Imaging to Evaluate Regional Left Ventricular Contractility in Patients with Hypertrophic Cardiomyopathy

There is controversy concerning whether contract-ility in the nonhypertrophied region of the left ventricular (LV) wall is impaired or normal in patients with hypertrophic cardiomyopathy (HCM). Global LV systolic function decreases with increases in afterload in this disease. This study was performed to identify abnormalities in regional LV contractility along the long and short axes in the setting of HCM with the use of angiotensin II (AT-II) stress pulsed tissue Doppler imaging (PTDI). Angiotensin II was administered intravenously to patients with asymmetric septal hypertrophy (HCM group, n = 21) and age-matched normal volunteers (N group, n = 12). We then measured the percent LV fractional shortening (%FS) and end-systolic circumferential LV wall stress by M-mode echocardiography, LV ejection fraction (LVEF) by 2-dimensional echocardiography, and time-velocity integral (TVI) of LV outflow velocity by pulsed Doppler echocardiography. The peak first and second systolic LV wall motion velocities along the long (L-Sw(1) and L-Sw(2)) and short (S-Sw(1) and S-Sw(2)) axes were measured in the LV posterior wall and ventricular septum with the use of PTDI. The end-systolic circumferential LV wall stress at baseline was significantly lower in the HCM group. The L-Sw(1) and L-Sw(2) for the posterior wall were significantly lower in the HCM group, but the S-Sw(1) and S-Sw(2) for the posterior wall and ventricular septum were similar in the two groups. The %FS, LVEF, TVI, and systolic PTDI variables along both axes for the posterior wall decreased significantly, and end-systolic circumferential LV wall stress increased significantly at AT-II doses of 0.005 or 0.010 microg/kg per minute in the HCM group. No significant changes were found in either group in the systolic PTDI variables (except for L-Sw(1)) for the ventricular septum with AT-II infusion. Contractility along the long and short axes of the nonhypertrophied LV wall is easily impaired with increases in afterload in patients with HCM, resulting in a decrease in global LV systolic function. We found AT-II stress PTDI to be a safe and useful technique for evaluating the regional LV systolic function in this disease.     

Clinical presentation and treatment of aneurysms associated with basilar artery fenestration

Aneurysms associated with a fenestrated basilar artery are rare, and treatment strategies have yet to be established. A direct surgical approach to the basilar artery is challenging because the surrounding anatomy is complex. We retrospectively compared the clinical features and treatment outcomes of eight patients (seven female, one male) with aneurysms associated with a fenestrated basilar artery after clipping or coil embolisation and reviewed the literature. Of the eight aneurysms, four were ruptured; seven aneurysms were located at the proximal part of the basilar artery and one aneurysm was located at the middle of the basilar artery. Six aneurysms were surgically treated. Four aneurysms were embolised with Guglielmi detachable coils, two aneurysms were clipped via the transcondylar or temporopolar approach, and two aneurysms were not treated. All six surgically treated patients had good outcomes. We found that both coil embolisation and direct clipping to treat aneurysms associated with a fenestrated basilar artery have advantages and disadvantages. To obtain favourable outcomes, the selected treatment modality must consider the patient's age and clinical condition, the aneurysm size and shape, the direction of the dome, the relationship with perforators, and the neurosurgeon's expertise.     

MEMBRANOUS GLOMERULONEPHRITIS ASSOCIATED WITH ACTIVE LIVER CIRRHOSIS BOTH INVOLVED BY HBs ANTIGEN

This is a case report of a 35-year-old female who showed a relatively short clinical course of severe liver cirrhosis and proteinuria. On light microscopical studies of autopsy material, besides active postnecrotic type liver cirrhosis, typical membranous glomerulonephritis was found. Immunofluorescent study disclosed not only clustered HBsAg (hepatitis type B surface antigen) in occasional hepatic cells but also beaded granular type deposition of HBsAg, IgG, IgM, IgA and complement G_s along renal glomerular basement membrane (GBM). Electron microscopical study disclosed multiple particulated material in occasional inclusion bodies of hepatic cells and in subepithelial and subendothelial dense deposits along the GBM. Enzymatic immunoelectron microscopical study confirmed these particles especially along the GBM being HBsAg themselves. It was concluded that HBsAg-Ab (antibody) complex was the pathogenetic factor responsible for the glomerular change of this particular case. Although HBsAg and Ab were examined to be negative in serum throughout the patient's clinical course, the possibility of the presence of circulating HBsAg-Ab complex in serum was discussed.     

Coronary revascularization with arterial conduits collateral to the lower limb

A 62-year-old man with left main coronary artery disease had coronary artery bypass grafting. Angiography disclosed total occlusion of the left common iliac artery. The left internal thoracic artery and the left inferior epigastric artery were well developed as collateral pathways to the left external iliac artery. With concomitant femoro-femoral crossover bypass, these two large arterial conduits were harvested and grafted to the coronary artery.     

Development of Terumo implantable left ventricular assist system (T-ILVAS) with a magnetically suspended centrifugal pump

The research group of Terumo, NTN, and the Setsunan University have been developing an implantable left ventricular assist system (T-ILVAS) featuring a centrifugal blood pump with a magnetically suspended impeller (MSCP). The present study describes recent progress in the development of the T-ILVAS, focusing on ex vivo and in vivo evaluations of the prototype MSCP. The MSCP is composed of four parts: a magnetic bearing, an impeller, a housing, and a DC burshless motor. The impeller is suspended by a magnetic bearing, thus providing contact-free rotation of the impeller inside the pump. The prototype MSCP was placed paracorporeally in three sheep and implanted intrathoracically in two sheep to evaluate its long-term durability and nonthrombogenicity. One sheep implanted ex vivo with the paracorporeal MSCP (Model I) survived for 864 days without any mechanical failure or thromboembolic complications, and with negligible hemolysis. The implantable Model II pump was evaluated ex vivo in two sheep and intrathoracically implanted in one sheep. These experiments were terminated 70, 79, and 17 days after implantation due to mechanical failure caused by blood leakage through the intrahousing connector of the Model II pump. However, there was no intradevice thrombus formation in any of the retrieved pumps. The dual connector system was then introduced to the Model II pump (the modified Model II), and the pump was intrathoracically implanted in a sheep. The sheep survived for more than 14 months without major complications, and the study is being continued. The preliminary chronic animal experiments demonstrated improved durability and nonthrombogenicity of the MSCP, with a low hemolysis rate for up to 864 days. Thus, the MSCP has significant potential for longterm application as an implantable circulatory assist system. Further developments toward a totally implantable system, including an implantable controller and a transcutaneous energy/information transfer system, are under way.     

Super long-term surviving two renal grafts with severe arteriolosclerosis and glomerulosclerosis

Two long-term renal transplant survivors, for about 20 yr, with unusual histological features in the allograft kidney are reported. In both cases, marked hyalinosis was observed in the arterioles of the transplanted kidney, despite never having been administered cyclosporine or tacrolimus. The cause remains unknown at the present time, but we think that the changes could be multifactorial in origin, including due to aging of the graft, hypertension, hyperlipidemia and chronic rejection. We conclude that histological analysis of the allograft kidney must be performed in long-term renal transplant survivors, in order to understand the histological changes in the chronic phase after kidney transplantation and to predict the prognosis of the graft.     

Infective Endocarditis from Furuncle with Meningitis Complication Caused by Methicillin-resistant Staphylococcus aureus

Infective endocarditis (IE) may be acquired in the community as community-acquired (CA) IE or in the healthcare setting. In Japan, cases of CA-methicillin-resistant Staphylococcus aureus (MRSA) infection as skin infection have been increasing. CA-MRSA strains, including the USA300 clone, have higher pathogenicity and are more destructive to tissue than healthcare-associated MRSA strains because of the toxins they produce, including arginine-catabolic mobile element (ACME) and Panton-Valentine leukocidin (PVL). However, only a few IE cases induced by USA300 have been reported. We herein report a 64-year-old man who developed CA-IE from a furuncle caused by USA300 MRSA producing PVL and ACME, which resulted in complications of meningitis.