Automatic correction of artifact from single-trial event-related potentials by blind source separation using second order statistics only.

Event-related potentials (ERP) are in general masked by various kinds of artifacts. To attenuate the effects of artifacts, various schemes have been introduced, such as epoch rejection, electro-oculogram (EOG) regression and independent component analysis (ICA). However, none of the existing techniques can automatically remove various kinds of artifacts from a single ERP epoch. EOG regression cannot handle artifacts other than ocular ones. ICA incorporating higher order statistics (HOS) normally requires data with large number of time samples in order that the solution is robust. In this paper we blindly separate the multi-channel ERP into source components by estimating the correlation matrices of the data. Since only second order statistics (SOS) is involved, the process performs well at the single epoch level. Automatic artifact identification is performed in the source domain by introducing objective criteria for various artifacts. Criteria are based on time domain signal amplitude for blink and spurious peak artifact, scalp distribution of signal power for eye movement artifact and power distribution of frequency components for muscle artifact. The correction procedure can be completed by removing the identified artifactual sources from the raw multi-channel ERP.

Endothelium-dependent hyperpolarization and relaxation resistance to N(G)-nitro-L-arginine and indomethacin in coronary circulation.

OBJECTIVE: It is controversial whether endothelium-dependent relaxation resistance to inhibitors of nitric oxide (NO) and prostacyclin synthases is completely attributed to endothelium-derived hyperpolarizing factor (EDHF). This study examined NO release and K+ channels involved in endothelium-dependent relaxation and hyperpolarization resistance to N(G)-nitro-L-arginine (L-NNA) and indomethacin in coronary arteries with emphasis on the microarteries. METHODS: NO release, isometric force, and membrane potential of porcine coronary arteries were measured using a NO-specific electrode, wire myograph, and microelectrode, respectively. RESULTS: In large arteries pretreated with indomethacin, bradykinin (BK) evoked a rise in [NO] from 5.5+/-2.4 nM to 105.0+/-19.6 nM and hyperpolarization. L-NNA treatment significantly reduced the BK-stimulated rise in [NO] to 32.1+/-11.3 nM but did not affect the hyperpolarization. In the presence of indomethacin and L-NNA, U46619 contracted and depolarized (from -51+/-3 mV to -30+/-4 mV) vascular smooth muscle in microarteries. The addition of BK produced dose-dependent relaxation (maximal: 70.2+/-5.7%) and repolarization (membrane potential: -50+/-4 mV). Oxyhemoglobin eliminated indomethacin and L-NNA-resistance rise in [NO] but not relaxation (42.3+/-4.4%) and repolarization (-40+/-2 mV) by BK. Tetraethylammonium, charybdotoxin, and iberiotoxin partially decreased the BK-induced responses. Apamin alone did not affect the relaxation by BK; however, in combination with charybdotoxin it almost completely abolished the BK-induced relaxation and hyperpolarization. CONCLUSIONS: In porcine coronary arteries, both EDHF and NO contribute to BK-induced relaxation resistance to indomethacin and L-NNA. Large conductance Ca2+-activated K+ channels (BK(Ca)) may play an important role in mediating the BK-induced responses and small conductance Ca2+-activated K+ channels might function as 'backup' mechanisms when BK(Ca) is curtailed.

The roles played by crucial free radicals like lipid free radicals, nitric oxide, and enzymes NOS and NADPH in CCl(4)-induced acute liver injury of mice.

Mice were administered a single dose of carbon tetrachloride (CCl(4)) to induce acute liver injury. We found that lactate dehydrogenase (LDH) and glutamic pyruvic transaminase (GPT) levels in serum, as well as the level of thiobarbituric acid reaction substances (TBARS) in liver homogenate increased significantly in a manner both dose dependent and time dependent after CCl(4) administration. Such results suggest that the liver is susceptible to CCl(4) treatment and that lipid peroxidation is associated with CCl(4)-induced liver injury. The spin-trapping electron paramagnetic resonance (EPR) method was used to detect nitric oxide (NO) level in liver. The chemiluminescence method was also employed to measure the NO(2)(-)/NO(3)(-) concentration in serum. The NO levels in liver tissues and NO(2)(-)/NO(3)(-) concentration in serum were found to decrease significantly both in a dose-dependent manner and in time course after CCl(4) treatment. The nitric oxide synthase (NOS) II activity in the liver, in contrast, was found to increase significantly. Our study suggests that not only should the expression of NOS be analyzed but NO organ and blood concentration must be measured in the study of diseases involving nitric oxide. L-arginine treatment had no significant effect on the liver function of CCl(4)-treated mice. It was found that NO donor sodium nitroprusside (SNP; 50 or 100 microg/kg) treatment resulted in decreases of LDH, GPT, and TBARS levels, leading to a protective effect on CCl(4)-treated mice. On the other hand, N(G)-nitro-L-arginine methyl ester (L-NAME, 100 or 300 mg/kg) treatment caused more severe liver damage. Moreover, we have found in an in vitro EPR study that SNP could scavenge lipid peroxyl radical LOO&z.rad;. The above results together suggest that NO may protect CCl(4)-induced liver injury through scavenging lipid radical, inhibiting the lipid peroxidation chain reaction. On the basis of our analysis, we put forth two explanations for the stated discrepancy between NOS II and NO production: (i) NO was used up gradually in terminating lipid peroxidation and (ii) NADPH was depleted (on the basis of correlation evidence only).

Maternal cold inducible RNA binding protein is required for embryonic kidney formation in Xenopus laevis.

We cloned a major isoform of Xenopus homologue of cold inducible RNA binding protein (CIRP), XCIRP-1. XCIRP-1 was neither cold inducible nor essential for cell division during early embryonic development. Suppression of XCIRP-1 dose dependently produced tailbuds with deformations of the brain and internal organs. The defects were XCIRP-1 specific as they could be rescued by sense transcript. Suppression of XCIRP-1 also disrupted the morphogenetic migration of the C3 blastomeres (lineaged to become the embryonic kidney, the pronephros). In animal cap explants, depletion of XCIRP-1 inhibited activin/retinoic acid induced expressions of pronephros related Xlim-1 and WT1 genes. These results suggest that XCIRP-1 is required for the specification and morphogenetic lineage migration of the pronephros.

Characterization of human and mouse peroxiredoxin IV: evidence for inhibition by Prx-IV of epidermal growth factor- and p53-induced reactive oxygen species.

The aim of this study was to identify and characterize human and mouse Prx-IV. We identified mouse peroxiredoxin IV (Prx-IV) by virtue of sequence homology to its human ortholog previously called AOE372. Mouse Prx-IV conserves an amino-terminal presequence coding for signal peptide. The amino acid sequences of mature mouse and human Prx-IV share 97.5% identity. Phylogenetic analysis demonstrates that Prx-IV is more closely related to Prx-I/-II/-III than to Prx-V/-VI. Previously, we mapped the mouse Prx-IV gene to chromosome X by analyzing two sets of multiloci genetic crosses. Here we performed further comparative analysis of mouse and human Prx-IV genomic loci. Consistent with the mouse results, human Prx-IV gene localized to chromosome Xp22.135-136, in close proximity to SAT and DXS7178. A bacterial artificial chromosome (BAC) clone containing the complete human Prx-IV locus was identified. The size of 7 exons and the sequences of the splice junctions were confirmed by PCR analysis. We conclude that mouse Prx-IV is abundantly expressed in many tissues. However, we could not detect Prx-IV in the conditioned media of NIH-3T3 and Jurkat cells. Mouse Prx-IV was specifically found in the nucleus-excluded region of cultured mouse cells. Intracellularly, overexpression of mouse Prx-IV prevented the production of reactive oxygen species induced by epidermal growth factor or p53. Taken together, mouse Prx-IV is likely a cytoplasmic or organellar peroxiredoxin involved in intracellular redox signaling.

Catalase and peroxiredoxin 5 protect Xenopus embryos against alcohol-induced ocular anomalies.

PURPOSE: To study the molecular mechanisms underlying alcohol-induced ocular anomalies in Xenopus embryos. METHODS: Xenopus embryos were exposed to various concentrations (0.1%-0.5%) of alcohol, and the subsequent effects in eye development and in eye marker gene expression were determined. To investigate the role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in fetal alcohol syndrome (FAS)-associated ocular injury, two antioxidant enzymes, catalase and peroxiredoxin 5, were overexpressed in the two blastomeres of the two-cell stage Xenopus embryos. RESULTS: Exposure of Xenopus embryos to alcohol during eye development produced marked gross ocular anomalies, including microphthalmia, incomplete closure of the choroid fissure, and malformation of the retina in 40% of the eyes examined. In parallel, alcohol (0.1%-0.5%) dose dependently and significantly reduced the expression of several eye marker genes, of which TBX5, VAX2, and Pax6 were the most vulnerable. Overexpression of catalase and of cytosolic and mitochondrial peroxiredoxin 5 restored the expression of these alcohol-sensitive eye markers and significantly decreased the frequency of ocular malformation from 39% to 21%, 19%, and 13% respectively. All these enzymes reduced alcohol-induced ROS production, but only peroxiredoxin 5 inhibited RNS formation in the alcohol-treated embryos. CONCLUSIONS: The results suggest that oxidative and nitrosative stresses both contribute to alcohol-induced fetal ocular injury.

Plasma nitric oxide level in heart failure secondary to left ventricular diastolic dysfunction.

Nitric oxide (NO) is a free radical that is elevated in the plasma of patients with systolic heart failure. However, its relation to diastolic function is unknown. This study investigated the relation between the level of stable end-products of plasma NO (NOx level) and diastolic function in patients with heart failure. We performed echocardiographic Doppler studies in 76 patients (mean age of 66 +/- 10 years, 75% men) with congestive heart failure. Left ventricular (LV) diastolic dysfunction was classified as either a restrictive (RFP) or nonrestrictive filling pattern (non-RFP). Same day venous total nitrite plus nitrate levels were measured by chemiluminscence. Both patients with isolated diastolic heart failure (ejection fraction >50%) (77 +/- 9 micromol/L, n = 33) and systolic failure (ejection fraction < or = 50%) (115 +/- 17 micromol/L, n = 43) had significantly higher plasma NOx levels than controls (37 +/- 2 micromol/L, both p <0.001). RFP coexists mostly in patients with systolic heart failure (15 of 18), and these patients had a higher NOx level than patients with systolic failure and a non-RFP (n = 28) (163 +/- 35 vs 88 +/- 16 micromol/L, p <0.05). Patients who were not on oral nitrate drugs had insignificant lower plasma NOx levels than those on regular nitrate therapy, although it was still higher than controls. Plasma NOx level did not correlate with LV ejection fraction. Stepwise multiple regression analysis confirmed that the presence of RFP was the only independent predictor of NOx, and hence NO production. Plasma NOx level is elevated in patients with isolated diastolic heart failure. In addition, in patients with LV systolic failure, the severity of LV diastolic dysfunction determines the amount of NO production.

Induction of apoptosis by hexamethylene bisacetamide is p53-dependent associated with telomerase activity but not with terminal differentiation.

The present study investigated the relationships amongst apoptosis, terminal differentiation and telomerase activity in human colon carcinoma cells. We found that hexamethylene bisacetamide (HMBA) induced apoptosis in human colon carcinoma LoVo cells harbouring wild-type p53 but not in SW1116 cells harbouring mutant p53. HMBA reduced telomerase activity in both colon carcinoma cells but it did not induce differentiation in the colon carcinoma cells. Taken together, our results suggest that HMBA can induce apoptosis via a p53-dependent pathway, but apoptosis and terminal differentiation may be separately regulated in LoVo cells. Inhibition of telomerase activity may activate apoptosis through a p53-dependent mechanism.

Free radical EPR spectroscopy analysis using blind source separation.

In this paper, we propose a novel approach for electron paramagnetic resonance (EPR) mixture spectra analysis based on blind source separation (BSS) technique. EPR spectrum of a free radical is often superimposed by overlapping spectra of other species. It is important and challenging to accurately identify and quantify the 'pure' spectra from such mixtures. In this study, an automated BSS method implementing independent component analysis is used to extract the components from mixed EPR spectra that contain overlapping components of different paramagnetic centers. To apply this method, there is no requirement to know the component spectra or the number of components in advance. The method is applied to analyze free radical EPR spectra which are collected from standard chemical system, cultured cell suspense, and ex vivo rat kidneys by spin trapping EPR technique. Results show that the BSS method proposed here is capable of identifying the component EPR spectra from mixtures with unknown compositions. The BSS technique can offer powerful aids in resolving spectral overlapping problems in general EPR spectroscopy analysis.

Overexpression of BMP-2/4, -5 and BMPR-IA associated with malignancy of oral epithelium.

The aim of the present study was to determine the relationships between bone morphogenetic proteins (BMPs), BMP receptor type IA and carcinogenesis of oral epithelium. A retrospective study was performed on material obtained from oral mucosa, including nine cases of normal mucosa (NB), eight cases of nonspecific chronic inflammation (NCI), seven cases of hyperkeratosis (HK), five cases of squamous cell papilloma (SCP), 29 cases of squamous cell carcinoma (SCC) with various grades of differentiation and 10 cases of epithelium adjacent to carcinoma (EAC). Six cases of NB from hard palate (NHP) were chosen as a control group. The benign groups consisted of NCI, HK and SCP. The antibodies against BMP-2/4, -5, receptor BMPR-IA and purified bovine BMP (bBMP-McAb) were utilised using an immunocytochemical method. The results demonstrated that the immunostaining of BMP-2/4, BMP-5, BMPR-IA and bBMP-McAb was weak and not consistent in normal and benign groups. The immunoreactivity level was independent of the clinical and pathological grading of SCC. All cases of SCC showed positive staining for BMP-2/4, BMP-5, BMPR-IA and bBMP-McAb except for three cases and one case of SCC which negatively stained for BMP-2/4 and BMP-5, respectively. The staining intensity and proportion of the positively stained cells were markedly increased in SCC when compared with that of the normal and benign groups except for EAC. The metastatic carcinoma cells in lymph nodes were strongly and positively stained for BMP-2/4 and BMP-5 when compared with the primary lesions. Our results indicate that there was an overexpression of BMP-2/4, BMP-5, bBMP-McAb and BMPR-IA in the high-risk premalignant and malignant lesions of oral epithelium. Our findings suggest that BMP-2/4 and BMP-5 but not BMPR-IA might be involved in the metastasis of oral carcinoma cells.

Alpha rhythm and alpha-like activity in coma.

A normal waking EEG was obtained on a 22 year old man four days prior to cardiopulmonary arrest. Three days after resuscitation the EEG showed the pattern of alpha-like activity while the patient remained in deep coma. Since the EEGs were recorded by the same technician using the same 16 channel electroencephalograph and montages, it is possible to compare in the same individual these alpha-frequency activities before and after arrest. The alpha-like activity of coma does not resemble the waking alpha rhythm in amplitude, frequency, spatial distribution, variability and reactivity.

Salivary adenoid cystic carcinoma. Features of an intra-abdominal metastasis.

An adenoid cystic carcinoma of salivary gland origin metastasized to the abdomen four years after the initial diagnosis. It showed heavy uptake of Ga-67 citrate and hypervascularity. The clinical and pathologic features are discussed. Gallium scan and arteriography (usually external carotid artery injection) may prove helpful in the early diagnosis and management in the various phases of the disease.

Removal of hydrophobic dyestuff from dyeing wastewater by photo-sensitization process.

Recently, photochemical reaction became more important in view of using UV in textile dyeing wastewater treatment processes, in which neither chemical sludges nor toxic residues are left in the treated effluent. The photodegradation of hydrophobic dye (Palanil Yellow 5R, PY-5R) in the presence of acetone, which performs as a solvent and/or a photo-sensitizer, was investigated in this study. The results demonstrated that photochemical reaction in the presence of acetone could rapidly and effectively enhance color removal at a wavelength of 253.7 nm. The photodegradation follows pseudo first-order decay. The rate constants and decay quantum yields of dye degradation by UV depend on the solution pH and solvent system, (i.e., acetone to water ratio). The photosensitization of the disperse dye was found to be optimized at pH 9 and in 0.5 (v:v) acetone-water ratio.

Degradation kinetics of reactive dye by UV/H2O2/US process under continuous mode operation.

Degradation of a dye, C. I . Reactive Red 120, in dyeing waatewater by the process o UV/H2O2/US was studied with a bench-scale reactor under the continuous mode of operation. The effects of dyeing wastewater flow rate and the feeding rate of an oxidant, H2O2, on the color removal efficiency of the process were investigated. The significance of ultrasonic (US) combined with UV irradiation was also investigated and the performances of the process on color removal were evaluated. The results showed that the decoloration process followed a pseudo first-order kinetic model and the UV light is the most significant factor on dye removal. Besides, at higher flow rates, incomplete color removal was observed due to relatively insufficient irradiation time (low degradation rate). In order to achieve a higher degradation rate, the feeding rate of H2O2 should be increased.

Recent advances in the treatment of colon cancer.

Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Although surgical resection is still the only treatment capable of curing colon cancer, adjuvant therapy continues to play an important role in preventing recurrence and metastasis. In recent years remarkable progress has been made in the treatment of colon cancer. This review discusses recent advances in adjuvant therapy for colon cancer, including chemotherapy, immunotherapy, antiangiogenic therapy and apoptosis induction. In the meantime, molecular therapy is also elucidated in the above methods. All these new advances will provide new promises for patients of colon cancer.

Gene selection for brain cancer classification.

With the introduction of microarray, cancer classification, diagnosis and prediction are made more accurate and effective. However, the final outcome of the data analyses very much depend on the huge number of genes with relatively small number of samples present in each experiment. It is thus crucial to select relevant genes to be used for future specific cancer markers. Many feature selection methods have been proposed but none is able to classify all kinds of microarray data accurately, especially on those multi-class datasets. We propose a one-versus-one comparison method for selecting discriminatory features instead of performing the statistical test in a one-versus-all manner. Brain cancer is chosen as an example. Here, 3 types of statistics are used: signal-to-noise ratio (SNR), t-statistics and Pearson correlation coefficient. Results are verified by performing hierarchical and k-means clustering. Using our one-versus-one comparisons, best performance accuracies of 90.48% and 97.62% can be obtained by hierarchical and k-means clustering respectively. However best performance accuracies of 88.10% and 80.95% can be obtained respectively when using one-versus-all comparison. This shows that one-versus-one comparison is superior.

An Improved Method for Discriminating ECG Signals using Typical Nonlinear Dynamic Parameters and Recurrence Quantification Analysis in Cardiac Disease Therapy.

The discrimination of ECG signals using nonlinear dynamic parameters is of crucial importance in the cardiac disease therapy and chaos control for arrhythmia defibrillation in the cardiac system. However, the discrimination results of previous studies using features such as maximal Lyapunov exponent (λmax) and correlation dimension (D2) alone are somewhat limited in recognition rate. In this paper, improved methods for computing λmaxand D2are purposed. Another parameter from recurrence quantification analysis is incorporated to the new multi-feature Bayesian classifier with λmaxand D2so as to improve the discrimination power. Experimental results have verified the prediction using Fisher discriminant that the maximal vertical line length (Vmax) from recurrence quantification analysis is the best to distinguish different ECG classes. Experimental results using the MIT-BIH Arrhythmia Database show improved and excellent overall accuracy (96.3%), average sensitivity (96.3%) and average specificity (98.15%) for discriminating sinus, premature ventricular contraction and ventricular flutter signals.

Brainstem encephalitis (rhombencephalitis) due to Listeria monocytogenes: case report and review.

Listerial brainstem encephalitis is a rare disease. Only 62 cases have been reported previously; all were in adults, only 8% of whom were immunosuppressed. The disease has a characteristic biphasic course: a nonspecific prodrome of headache, nausea or vomiting, and fever lasting for several days is followed by progressive asymmetrical cranial-nerve palsies, cerebellar signs, hemiparesis or hypesthesia, and impairment of consciousness. Neck stiffness was initially present in only 55% of the cases described thus far. Studies of cerebrospinal fluid often revealed only mild abnormalities. Cultures of cerebrospinal fluid and blood were positive in 41% and 61% of cases, respectively. Respiratory failure occurred in 41% of cases. Initial computed tomography of the brain often gave normal results; magnetic resonance imaging better demonstrated brainstem abnormalities. Overall mortality was 51%. All untreated patients died. When treatment with ampicillin or penicillin was initiated early, the rate of survival was > 70%; however, neurological sequelae developed in 61% of survivors.

Acute hypoxia elevates nitric oxide generation in rat carotid body in vitro.

In acute hypoxia, the release of nitric oxide (NO) produced in rat carotid body is unclear. The concentration of NO was measured electrochemically with a Pt/Nafion/Pd-IrOx/POAP-modified electrode placed on the surface of isolated carotid bodies superfused with bicarbonate-buffer saline at 35 degrees C. In hypoxia, the concentration of NO in the carotid body was increased by 17+/-2 nM. The amount of NO release during hypoxia was augmented by increasing the number of carotid bodies surrounding the electrode and also in the presence of L-arginine. In addition, the hypoxia-induced elevation of NO was abolished by pretreatment with a nitric oxide synthase (NOS) inhibitor, L-N(G)-nitroarginine methylester (L-NAME). The results suggest that endogenous NO production in the carotid body increases during hypoxia. Electrophysiological measurement of single fiber activity in the sinus nerve revealed that L-NAME treatment enhances the afferent discharge in response to hypoxia. This confirms that the hypoxia-induced elevation of NO suppresses the carotid chemoreceptor response to hypoxia. Taken together, it is concluded that acute hypoxia increases NO generation in the rat carotid body, and that the elevated levels of NO suppress carotid chemoreceptor activity during hypoxia. Hence, NO may play an active inhibitory role in the control of carotid chemoreceptor activity during hypoxia.

Direct observation of trapping and release of nitric oxide by glutathione and cysteine with electron paramagnetic resonance spectroscopy.

While the biosynthesis of nitric oxide (NO) is well established, one of the key issues that remains to be solved is whether NO participates in the biological responses right after generation through biosynthesis or there is a "secret passage" via which NO itself is trapped, transported, and released to exert its functions. It has been shown that NO reacts with thiol-containing biomolecules (RSH), like cysteine (Cys), glutathione (GSH), etc., to form S-nitrosothiols (RSNOs), which then release nitrogen compounds, including NO. The direct observation of trapping of NO and its release by RSNO has not been well documented, as most of the detection techniques measure the content of NO as well as nitrite and nitrate. Here we use spin-trapping electron paramagnetic resonance (EPR) technique to measure NO content directly in the reaction time course of samples of GSH and Cys ( approximately mM) mixed with NO ( approximately microM) in the presence of metal ion chelator, which pertains to physiological conditions. We demonstrate that NO is readily trapped by these thiols in less than 10 min and approximately 70-90% is released afterward. These data imply that approximately 10-30% of the reaction product of NO does not exist in the free radical form. The NO release versus time curves are slightly pH dependent in the presence of metal ion chelator. Because GSH and Cys exist in high molar concentrations in blood and in mammalian cells, the trapping and release passage of NO by these thiols may provide a mechanism for temporal and spatial sequestration of NO to overcome its concentration gradient-dependent diffusion, so as to exert its multiple biological effects by reacting with various targets through regeneration.