Assessment of the histological characteristics of coronary arterial plaque with severe calcification.

BACKGROUND: Several studies have shown that rotational atherectomy (RA) is associated with higher rates of the slow-flow phenomenon and that ablated particles may be the possible cause. Intravascular ultrasound (IVUS) has an intrinsic limitation in assessing plaque morphology behind the calcification because of acoustic shadowing. Therefore, the purpose of this study was to investigate plaque characteristics behind severe calcification by histological examination. METHODS AND RESULTS: One hundred eight coronary arterial segments from 40 human cadavers (24 males, 16 females, mean age 74+/-7 years) were examined. Serial images of IVUS were obtained and 18 severe calcified lesions were collected. Experienced observers quantitatively analyzed the lesions by computerized planimetry for fibrous, fibrofatty, calcification, and necrotic tissue area. Histologically, 15 of 18 severely calcified lesions (83%) had an extensive necrotic tissue containing large numbers of cholesterol crystals and microcalcifications; 16 of same 18 severely calcified lesions (89%) had fibrofatty tissue as well as calcification. The necrotic tissue occupied 14+/-13% and fibrofatty tissue occupied 13+/-11% of severely calcified lesions. CONCLUSION: Necrotic core and fibrofatty tissue components "hidden" behind calcification might cause emboli-induced thrombus formation and distal flow disturbance during RA.     

An infant with multiple cavernous angiomas presenting with frequent epileptic seizures - detection of epileptic focus by magnetoencephalography

We report on a six-year-old girl with frequent partial seizures secondary to multiple cavernous angiomas (CAs) since the age of 17 months. MRI showed two CAs in the left parietal and right frontal lobes. Ictal scalp video EEG demonstrated complex partial seizures of left hemispheric origin, indicating that the left parietal CA was the epileptogenic lesion. Ictal SPECT showed extensive hyper-perfusion in the left frontal and parietal lobes, indicating the left hemispheric focus. Magnetoencephalography (MEG) showed clustered equivalent current dipoles of interictal spikes in the left parietal cortex adjacent to the left parietal CA. We performed lesionectomy of the left parietal CA at 19 months old. The patient became seizure-free for four years. Postoperative MEG yielded no residual interictal spikes. Our study suggests that early surgical intervention of CA may prevent from further development of epileptic seizures. MEG can identify both the epileptogenic zone and lesion underlying the multiple CAs in the infants with catastrophic partial seizures.     

Histopathological predictor for regional lymph node metastasis in gastric cancer

Regional lymph node metastasis in gastric cancer is a definitive indicator of the patient’s prognosis. The goal of this study was to identify the predictors for lymph node metastasis among all the possible histopathological parameters, especially by conducting an objective discrimination of the lymphatic and blood vessels. A total of 210 resected primary gastric cancers with or without lymph node metastasis were evaluated based on the conventional histopathological parameters together with immunohistochemistry using antisera-recognizing lymphatic endothelial hyaluronan receptor-1 (LYVE-1), von Willebrand factor, and lymphangiogenesis promoter vascular endothelial growth factor-C (VEGF-C) antibodies. A multivariate regression analyses of the results indicated that only lymphatic invasion was a significant independent predictor of lymph node metastasis at any stage of cancer invasion. VEGF-C expression was partially related to lymph node metastasis in early gastric cancer. The identification of lymphatic invasion by LYVE-1 antibody is therefore useful to predict regional lymph node metastasis in gastric cancer.     

Capture of bacteria by flexible carbon nanotubes

Capture of bacteria with flexible carbon nanotubes (CNTs) was done in vitro. Bundles of single-walled carbon nanotubes (SWCNTs) or multi-walled carbon nanotubes (MWCNTs) was mixed with Streptococcus mutans. Precipitation assays and colony-forming unit formation assays showed free S. mutans in the solution was significantly decreased by the addition of the CNTs. Observation of the precipitate by scanning electron microscopy showed bacterial adhesion to CNTs. It has been shown that CNTs of different diameters have significantly different effects on the precipitation efficiency, and the manners in which they capture the cells are different. We found that MWCNTs (diameter of approximately 30 nm) had the highest precipitation efficiency, which was attributable to both their adequate dispersibility and aggregation activity. From observations by scanning electron microscopy, bundles of SWCNTs and thin MWCNTs (diameter of approximately 30 nm), which were moderately flexible, were easily wound around the curved surface of S. mutans. Bare CNTs having high adhesive ability could be useful as biomaterials, e.g., as tools for the elimination of oral pathogens at the nano-level.     

Expression of PD-1, PD-L1, and PD-L2 in the liver in autoimmune liver diseases

OBJECTIVES: PD-L1 (also B7-H1) and PD-L2 (also B7-DC) are ligands for programmed death-1 (PD-1), which is a member of the CD28/B7 superfamily of costimulatory molecules and plays an inhibitory role on the periphery. Impaired regulation of this system may cause disruption to self-tolerance leading to autoimmunity; however, the role of these molecules in the liver is unknown. Therefore, we examined the expression of PD-1, PD-L1, and PD-L2 in the liver in autoimmune liver diseases. METHODS: We examined the liver expression of these molecules in autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) with no previous medical treatment using immunohistochemical staining and real-time PCR, and compared with chronic hepatitis type C (CHC) as a control. RESULTS: Although PD-1, PD-L1, and PD-L2 were expressed in the liver in AIH, PBC, as well as CHC, the expressions were relatively lower in PBC. In AIH, despite more severe inflammation than in CHC, the expression of these molecules was not greater than in CHC, and when compared with the relative expression of PD-L1, PD-L2 was lower in AIH. PD-L1 and PD-L2 expressions were well correlated with the level of IFN-gamma; however, relatively decreased induction for PD-L1 and PD-L2 by IFN-gamma was observed in AIH or PBC than in CHC. CONCLUSION: Modulation of PD-1/PD-L1 and PD-L2 systems may play a role in the development of autoimmune liver diseases.     

Early onset West syndrome with cerebral hypomyelination and reduced cerebral white matter

Numerous numbers of pre-, peri- and postnatal damages cause West syndrome in early infancy, however, etiology in many cases are not still elucidated despite intensive biochemical and neuroradiologic investigations. We described four patients having early onset epileptic encephalopathy with severe hypomyelination and reduction in cerebral white matter. The clinical symptoms of these patients are impaired visual attention, acquired microcephaly, spastic tetraplegia, profound psychomotor delay and infantile spasms since early infancy. All patients had striking hypomyelination of cerebrum, reduced volume of white matter and cortical atrophy on MRI. Serial MRI investigations in three patients showed absence of myelination of the white matter. On EEG, one patient revealed suppression-burst and other three had hypsarrhythmia. Despite having intractable seizures, no patient showed deterioration of neurological development. The group of these findings is mimicking to clinical manifestations of 3-phosphoglycerate dehydrogenase deficiency, and has some overlap with progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) like syndrome, however it is not compatible with these two conditions. The findings observed in our patients can be regarded as a new clinical condition associated with early onset West syndrome.     

Vacuum-assisted closure for pediatric post-sternotomy mediastinitis: are low negative pressures sufficient?

We present 3 cases of pediatric post-sternotomy mediastinitis treated by a vacuum-assisted closure (VAC). The patients 2 girls, aged 6 months and 10 months, and a 2-year-old boy. The onset of infection was at 9, 14, and 32 postoperative days. The culture examination detected coagulase-negative Staphylococci strains in 2 cases, and Staphylococcus aureus in 1 case. A VAC was performed at -50 mm Hg for 10, 12, and 7 days. The wounds were closed without vascularized soft tissue. A VAC under a low negative pressure is a useful and safe procedure for the management of pediatric post-sternotomy mediastinitis.     

Highly sensitive upregulation of apolipoprotein A-IV by peroxisome proliferator-activated receptor alpha (PPARalpha) agonist in human hepatoma cells

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a key regulator in hepatic lipid metabolism and a potential therapeutic target for dyslipidemia. However, in humans hepatic PPARalpha-regulated genes remain unclear. To investigate the effect of PPARalpha agonism on mRNA expressions of lipid metabolism-related genes in human livers, a potent PPARalpha agonist, KRP-101 (KRP), was used to treat the human hepatoma cell line, HepaRG cells. KRP did not affect AOX or L-PBE, which are involved in peroxisomal beta-oxidation. KRP increased L-FABP, CPT1A, VLCAD, and PDK4, which are involved in lipid transport or oxidation. However, the EC(50) values (114-2500 nM) were >10-fold weaker than the EC(50) value (10.9 nM) for human PPARalpha in a transactivation assay. To search for more sensitive genes, we determined the mRNA levels of apolipoproteins, apoA-I, apoA-II, apoA-IV, apoA-V, and apoC-III. KRP had no or little effect on apoA-I, apoC-III, and apoA-II. Interestingly, KRP increased apoA-IV (EC(50), 0.99 nM) and apoA-V (EC(50), 0.29 nM) with high sensitivity. We identified apoA-IV as a PPARalpha-upregulated gene in a study using PPARalpha siRNA. Moreover, when administered orally to dogs, KRP decreased the serum triglyceride level and increased the serum apoA-IV level in a dose-dependent manner. These findings suggest that apoA-IV, newly identified as a highly sensitive PPARalpha-regulated gene in human livers, may be one of the mechanisms underlying PPARalpha agonist-induced triglyceride decrease and HDL elevation.