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PubMed2000

Three-dimensional blind deconvolution of SPECT images.

Thanks to its ability to yield functionally rather than anatomically-based information, the three-dimensional (3-D) SPECT imagery technique has become a great help in the diagnostic of cerebrovascular diseases. Nevertheless, due to the imaging process, the 3-D single photon emission computed tomography (SPECT) images are very blurred and, consequently, their interpretation by the clinician is often difficult and subjective. In order to improve the resolution of these 3-D images and then to facilitate their interpretation, we propose herein to extend a recent image blind deconvolution technique (called the nonnegativity support constraint-recursive inverse filtering deconvolution method) in order to improve both the spatial and the interslice resolution of SPECT volumes. This technique requires a preliminary step in order to find the support of the object to be restored. In this paper, we propose to solve this problem with an unsupervised 3-D Markovian segmentation technique. This method has been successfully tested on numerous real and simulated brain SPECT volumes, yielding very promising restoration results.

Algorithms↗
PubMedDate not supplied

Using small numbers of subjects in fMRI-based research.

The preceding speculations may not sound very novel to some ears. Indeed, when I started to describe the above ideas to any fMRI researcher who has been involved in the field for a substantial number of years, their response is invariably a comment to the effect that, "Oh yes, we are doing something like that right now in our lab." What I think they mean, of course, is that sometime in the uncertain future they might run all their own existing tasks on a few subjects, if they can get around to it and if they can find the software for some of those earlier tasks. The heart (and hard parts) of the present speculation would be creating a repository of (publicly available) interesting tasks and creating software to embody neuropsychological models and the associated imaging data. At the risk of completely losing my audience, it is the image presented in Isaac Asimov's novel Second Foundation for integrating theory and information across many different sources that is the true challenge.

Algorithms↗
PubMedDate not supplied

Surfing the brain.

Explore the source record for details and available documents.

Algorithms↗
PubMed2004

Denoising functional MR images: a comparison of wavelet denoising and Gaussian smoothing.

We present a general wavelet-based denoising scheme for functional magnetic resonance imaging (fMRI) data and compare it to Gaussian smoothing, the traditional denoising method used in fMRI analysis. One-dimensional WaveLab thresholding routines were adapted to two-dimensional (2-D) images, and applied to 2-D wavelet coefficients. To test the effect of these methods on the signal-to-noise ratio (SNR), we compared the SNR of 2-D fMRI images before and after denoising, using both Gaussian smoothing and wavelet-based methods. We simulated a fMRI series with a time signal in an active spot, and tested the methods on noisy copies of it. The denoising methods were evaluated in two ways: by the average temporal SNR inside the original activated spot, and by the shape of the spot detected by thresholding the temporal SNR maps. Denoising methods that introduce much smoothness are better suited for low SNRs, but for images of reasonable quality they are not preferable, because they introduce heavy deformations. Wavelet-based denoising methods that introduce less smoothing preserve the sharpness of the images and retain the original shapes of active regions. We also performed statistical parametric mapping on the denoised simulated time series, as well as on a real fMRI data set. False discovery rate control was used to correct for multiple comparisons. The results show that the methods that produce smooth images introduce more false positives. The less smoothing wavelet-based methods, although generating more false negatives, produce a smaller total number of errors than Gaussian smoothing or wavelet-based methods with a large smoothing effect.

Algorithms↗
PubMed1997

Molecular cloning of the gene for mouse leukotriene-C4 synthase.

Leukotriene C4 (LTC4) synthase (LTC4S), an integral membrane protein, catalyzes the conjugation of leukotriene A4 with reduced glutathione to form LTC4, the biosynthetic parent of the additional cysteinyl leukotriene metabolites. An XmnI-digested fragment of a P1 clone from a 129 mouse ES library contained the full-length gene of 2.01 kb for mouse LTC4S. The mouse LTC4S gene is comprised of 5 exons of 122, 100, 71, 82 and 241 nucleotides, with intron sizes that range from 76 nucleotides to 937 nucleotides. The intron/exon boundaries are identical to those of the human genes for LTC4S and 5-lipoxygenase-activating protein (FLAP). Primer extension demonstrated a single transcription-initiation site 64 bp 5' of the ATG translation-start site. Nucleotide sequencing of 1.2 kb of the 5' flanking region revealed multiple putative sites for activating protein-2, CCAAT/enhancer-binding protein, and polyoma virus enhancer-3. Fluorescent in situ hybridization mapped the mouse LTC4S gene to mouse chromosome 11, in a region containing the genes for interleukin 13 and granulocyte/macrophage-colony-stimulating factor, and orthologous to the chromosomal location of 5q35 for the human LTC4S gene. Thus, the mouse LTC4S gene is similar in size, intron/exon organization and chromosomal localization to the human LTC4S gene. Recent mutagenic analysis of the conjugation function of human LTC4S has identified R51 and Y93 as critical for acid and base catalysis of LTA4 and reduced glutathione, respectively. A comparison across species for proteins that possess LTC4S activity reveals conservation of both of these residues, whereas R51 is absent in the FLAP molecules. Thus, within the glutathione S-transferase superfamily of genes, alignment of specific residues allows the separation of LTC4S family members from their most structurally similar counterparts, the FLAP molecules.

Amino Acid Sequence↗
PubMed1995

Costimulation requirement for AP-1 and NF-kappa B transcription factor activation in T cells.

The transcriptional activity of the IL-2 promoter requires T-cell costimulation delivered by the TCR and the auxiliary receptor CD28. Several transcription factors participate in IL-2 promoter activation, among which are AP-1-like factors and NF-kappa B. Protein phosphorylation has an important role in the regulation of these two factors: (1) it induces the transactivating capacity of the AP-1 protein c-Jun; and (2) it is involved in the release of the cytoplasmic inhibitor, I kappa B, from NF-kappa B, allowing translocation of the latter into the nucleus. We have recently shown that both phosphorylation processes require T-cell costimulation. Furthermore, in activated T cells, the kinetics of the two phosphorylation events are essentially similar. According to our results, however, the kinases responsible for the two processes are distinct entities. Whereas TPCK inhibits phosphorylation of I kappa B and, consequently, activation of NF-kappa B, it markedly enhances the activity of JNK, the MAP kinase-related kinase that phosphorylates the transactivation domain of c-Jun. We, therefore, propose the activation scheme presented in FIGURE 3 for T-cell costimulation. Costimulation results in the activation of a signaling pathway that leads to the simultaneous induction of the two transcription factors, AP-1 and NF-kappa B. Integration of the signals generated by TCR and CD28 engagement occurs along this pathway, which then bifurcates to induce I kappa B phosphorylation and NF-kappa B activation on the one hand, and JNK activation and c-Jun phosphorylation on the other. We are currently engaged in defining where the two signals integrate along the AP-1/NF-kappa B pathway.

Antibodies↗
PubMedDate not supplied

An algorithm for three-dimensional visualization of radiation therapy beams.

A computer algorithm to display radiation beams superimposed on three-dimensional (3-D) views of patient anatomy has been developed. It may be implemented as a postprocessing step to existing software for 3-D presentation and display. The algorithm takes as input a shaded 3-D view (reconstructed, for example, from computed tomography scans), together with the associated depth map, and generates as output an enhanced 3-D view highlighting in color the visible points which lie within the projected beam outlines. The algorithm is independent of the method used to generate the 3-D view (surface or volume rendering techniques may be used) and is independent of beam shape (beams may be modified with shielding blocks). It is not restricted to external surfaces and will correctly show radiation beams projected onto cut-away views of internal organs. The method is illustrated by application to a tangential pair for breast malignancy, using 3-D views generated with volume rendering software.

Algorithms↗
PubMed1990

Epitopes functional in neutralization of varicella-zoster virus.

By competition neutralization assay using monoclonal antibodies (MAbs) to varicella-zoster virus (VZV) glycoproteins (gps), we attempted to determine the topographical relationship of epitopes which are functional in VZV neutralization. MAbs against gpI interfered moderately to strongly with neutralization of MAbs against gpIII, and one antigenic domain with two distinct epitopes was identified on gpIII. Competition neutralization assays performed with MAbs to gpI revealed at least three distinct antigenic domains: the first contained two complement-dependent neutralizing epitopes; the second contained five complement-dependent neutralizing, overlapping epitopes and one nonneutralizing, nonoverlapping epitope; and the third contained one complement-enhanced neutralizing epitope. Competition neutralization assays performed with MAbs to gpIV showed one antigenic domain with two distinct epitopes which competed with nonneutralizing gpI MAbs. gpII did not interfere with neutralization of gpI, gpIII, or gpIV. Our data suggest that neutralizing and nonneutralizing MAbs can interfere with the action of viral neutralization either by inhibition or by enhancement. This report describes the epitope mapping of VZV gps by a functional biological assay.

Antibodies, Monoclonal↗
PubMed2002

Effect of in vivo nitrate tolerance on hypersensitivity to NO donors after NO-synthase blockade.

Animals treated with nitric oxide synthase (NOS) inhibitors exhibit marked hypersensitivity to the blood pressure lowering effects of exogenous nitric oxide (NO) donors. We used this model as a sensitive index to evaluate the relative importance of reduced biotransformation of glyceryl trinitrate (GTN) to NO in the development of nitrate tolerance. NOS-blockade hypertension using N(G)-nitro-L-arginine methyl ester (L-NAME) caused a marked enhancement of the mean arterial pressure (MAP) decrease mediated by GTN in nontolerant rats. However, even large doses of GTN were unable to change the MAP in GTN-tolerant, NOS-blockade hypertensive animals. In contrast, the MAP responses to the spontaneous NO donor sodium nitroprusside (SNP) were completely unaltered in either tolerant rats or tolerant NOS-blockade hypertensive animals, indicating that NO-dependent vasodilatory mechanisms remain intact despite the development of GTN tolerance. The MAP-lowering effects of GTN in NOS-blockade hypertensive animals were restored 48 h after cessation of chronic GTN exposure. These alterations in the pharmacodynamic response to GTN during tolerance development and reversal were associated with parallel changes in the pattern of GTN metabolite formation, suggesting that the activity of one or more enzymes involved in nitrate metabolism was altered as a consequence of chronic GTN exposure. These findings suggest that the vasodilation resulting from the vascular biotransformation of GTN to NO (or a closely related species) is severely compromised in nitrate-tolerant animals, and that although other mechanisms may contribute to the vascular changes observed following the development of GTN tolerance, decreased GTN bioactivation is likely the most important.

Animals↗
PubMed1999

Changes in resistance vessels during hemorrhagic shock and resuscitation in conscious hamster model.

The unanesthetized hamster dorsal skinfold preparation was used to monitor diameters and blood flow rates in resistance arteries (small arteries, A0: diameter, 156 +/- 23 micrometers) and capacitance vessels (small veins, V0: 365 +/- 64 micrometers), during 45 min of hemorrhagic shock at 40 mmHg mean arterial pressure (MAP) and resuscitation. A0 and V0 vessels constricted significantly to 52 and 70% of the basal values, respectively, whereas precapillary arterioles (A1-A4, 8-60 micrometers) and collecting venules (VC-VL, 26-80 micrometers) did not change or tended to dilate. Blood flow rates in the microvessels declined to <20% of the basal values. Resuscitation with shed autologous blood (SAB) showed incomplete recovery of A0 and V0 diameters even 2 h after resuscitation (71 +/- 14% and 81 +/- 18%, respectively, of basal value), whereas other vessels did not change significantly. The behavior of A0 diameter coincided with the incomplete recovery of blood flow rates in all the vessels (ca. 50%) according to Poiseuille's law, and the incomplete recovery of functional capillary density (ca. 75%). Resuscitation with 8% human serum albumin in saline (HSA) tended to show higher levels of A0 constriction and A4 dilation and lowered blood flow rates. Resuscitation with SAB restored tissue PO2 27 +/- 10 mmHg after 2 h, which was near control levels (28 +/- 5 mmHg), whereas resuscitation with HSA caused tissue PO2 to remain significantly depressed (6 +/- 2 mmHg), and flow rates were significantly lower than resuscitation with SAB. These results indicate that response of the A0 vessels is the crucial determinant of blood flow in the observed area. The constriction of A0 may help sustain MAP, and constriction of V0 may enhance blood redistribution from the skin to the vital organs under the hypotensive condition.

Animals↗
PubMed2001

AT(1) receptor blockers prevent sympathetic hyperactivity and hypertension by chronic ouabain and hypertonic saline.

Sympathetic hyperactivity and hypertension caused by chronic treatment with ouabain or sodium-rich artificial cerebrospinal fluid (aCSF) can be prevented by central administration of an angiotensin type 1 (AT(1)) receptor blocker. In the present study, we assessed whether, in Wistar rats, chronic peripheral treatment with the AT(1) receptor blockers losartan and embusartan can exert sufficient central effects to prevent these central effects of ouabain and sodium. Losartan or embusartan (both at 100 mg x kg(-1) x day(-1)) were given subcutaneously once daily. Ouabain (50 microg/day) was infused subcutaneously, and sodium-rich aCSF (1.2 M Na(+), 5 microl/h) was infused intracerebroventricularly, both by osmotic minipump for 13-14 days. The mean arterial pressure (MAP) at rest and in response to air stress and intracerebroventricularly injection of guanabenz (75 microg/7.5 microl), ANG II (30 ng/3 microl), and ouabain (0.5 microg/2 microl) were then measured. In control rats, chronic treatment with ouabain subcutaneously and hypertonic saline intracerebroventricularly both increased baseline MAP by 20-25 mmHg and enhanced twofold the pressor responses to air stress and depressor responses to the alpha(2)-adrenoceptor agonist guanabenz. Simultaneous treatment with losartan or embusartan fully prevented hypertension, maintained normal responses to air stress and guanabenz, and attenuated pressor responses to acute intracerebroventricular injection of ANG II and ouabain. We concluded that peripheral administration of losartan as well as embusartan can cause sufficient central effects to prevent the sympathetic hyperactivity and hypertension induced by chronic peripheral ouabain and central sodium.

Air Movements↗
PubMed1998

Effect of continuous negative-pressure breathing on skin blood flow during exercise in a hot environment.

To assess the impact of continuous negative-pressure breathing (CNPB) on the regulation of skin blood flow, we measured forearm blood flow (FBF) by venous-occlusion plethysmography and laser-Doppler flow (LDF) at the anterior chest during exercise in a hot environment (ambient temperature = 30 degreesC, relative humidity = approximately 30%). Seven male subjects exercised in the upright position at an intensity of 60% peak oxygen consumption rate for 40 min with and without CNPB after 20 min of exercise. The esophageal temperature (Tes) in both conditions increased to 38.1 degreesC by the end of exercise, without any significant differences between the two trials. Mean arterial pressure (MAP) increased by approximately 15 mmHg by 8 min of exercise, without any significant difference between the two trials before CNPB. However, CNPB reduced MAP by approximately 10 mmHg after 24 min of exercise (P < 0.05). The increase in FBF and LDF in the control condition leveled off after 18 min of exercise above a Tes of 37.7 degreesC, whereas in the CNPB trial the increase continued, with a rise in Tes despite the decrease in MAP. These results suggest that CNPB enhances vasodilation of skin above a Tes of approximately 38 degrees C by stretching intrathoracic baroreceptors such as cardiopulmonary baroreceptors.

Adult↗
PubMed2005

A robust algorithm for copy number detection using high-density oligonucleotide single nucleotide polymorphism genotyping arrays.

We have developed a robust algorithm for copy number analysis of the human genome using high-density oligonucleotide microarrays containing 116,204 single-nucleotide polymorphisms. The advantages of this algorithm include the improvement of signal-to-noise (S/N) ratios and the use of an optimized reference. The raw S/N ratios were improved by accounting for the length and GC content of the PCR products using quadratic regressions. The use of constitutional DNA, when available, gives the lowest SD values (0.16 +/- 0.03) and also enables allele-based copy number detection in cancer genomes, which can unmask otherwise concealed allelic imbalances. In the absence of constitutional DNA, optimized selection of multiple normal references with the highest S/N ratios, in combination with the data regressions, dramatically improves SD values from 0.67 +/- 0.12 to 0.18 +/- 0.03. These improvements allow for highly reliable comparison of data across different experimental conditions, detection of allele-based copy number changes, and more accurate estimations of the range and magnitude of copy number aberrations. This algorithm has been implemented in a software package called Copy Number Analyzer for Affymetrix GeneChip Mapping 100K arrays (CNAG). Overall, these enhancements make CNAG a useful tool for high-resolution detection of copy number alterations which can help in the understanding of the pathogenesis of cancers and other diseases as well as in exploring the complexities of the human genome.

Algorithms↗
PubMed1979

Evaluation of myocardial ischemic damage of various ages by computerized transmission tomography. Time-dependent effects of contrast material.

The potential role of computerized transmission tomography (CTT) in the detection and quantitation of acute myocardial ischemic damage was assessed in 42 excised canine hearts at 2 hours, 8 hours, and 48 hours after coronary occlusion. The CTT scan detected by myocardial damage that was 2-48 hours old each time the presence of regional ischemia was confirmed by histochemical straining or epicardial electrocardiographic mapping. Intravenous administration of contrast material enhanced the x-ray attenuation of areas of ischemic damage of 8 and 48 hours duration compared with normal myocardium, but enhanced only normal myocardium in those of 2 hours duration. Volumetric estimation of the extent of damage from the CTT scans in dogs with ischemia of 48 hours duration showed a close linear relationship with the morphometric volume in the absence of contrast material. Quantitation of the area of ischemic damage from the CTT scan after contrast administration resulted in substantial underestimation of the volume of damaged tissue.

Animals↗
PubMed1997

Comparison of effective and ineffective target sites that demonstrate concealed entrainment in patients with coronary artery disease undergoing radiofrequency ablation of ventricular tachycardia.

BACKGROUND: Concealed entrainment has been useful in guiding catheter ablation of monomorphic ventricular tachycardia in patients with coronary artery disease. However, not all sites with concealed entrainment result in successful ablation of the targeted ventricular tachycardia. The purpose of this prospective study was to identify factors at sites that demonstrate concealed entrainment that differentiate effective from ineffective target sites. METHODS AND RESULTS: In 14 consecutive patients with hemodynamically stable monomorphic ventricular tachycardia and coronary artery disease, radiofrequency ablation of 26 ventricular tachycardias was performed. Ablation was attempted at 46 sites that demonstrated concealed entrainment. Twenty-five of the targeted ventricular tachycardias (96%) were successfully ablated. The positive predictive value of concealed entrainment for successful ablation was 54%; it increased to 72% in the presence of a stimulus-QRS interval/ventricular tachycardia cycle length ratio of < or = 70%, to 82% in the presence of a match of the stimulus-QRS and electrogram-QRS interval, and to 89% in the presence of isolated mid diastolic potentials that could not be dissociated from ventricular tachycardia during entrainment. CONCLUSIONS: The positive predictive value of concealed entrainment for identification of successful ablation sites in patients with sustained ventricular tachycardia and coronary artery disease can be significantly enhanced by the presence of associated mapping criteria, particularly an isolated mid diastolic potential that cannot be dissociated from the tachycardia.

Adult↗
PubMed1995

Brain 'ouabain' mediates sympathetic hyperactivity in congestive heart failure.

In congestive heart failure (CHF), endogenous compounds with ouabainlike activity (OLA) may contribute to the maintenance of the circulatory homeostasis by peripheral as well as central effects. In the present study, we assessed changes in peripheral (plasma and left ventricle) and central (pituitary, hypothalamus, pons, and cortex) OLA in two animal models of CHF and determined whether brain OLA mediates sympathetic hyperactivity in CHF. Cardiomyopathic hamsters with their controls were studied at 9 months of age for tissue OLA. Rats were studied 4 weeks after acute coronary artery ligation for tissue OLA and sympathetic activity. In both models, left ventricular end-diastolic pressure was markedly increased. CHF was associated with significant increases in both plasma and tissue OLA in both models. In the brain, the most marked (twofold to threefold) increases occurred in the hypothalamus. In vitro, all OLA measured could be blocked by antibody Fab fragments (Digibind). Conscious rats with CHF showed elevated plasma catecholamines and enhanced responses of mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) to air stress and to intracerebroventricular (ICV) injection of the alpha 2-adrenergic receptor agonist guanabenz compared with sham-operated rats. ICV administration of the Fab fragments did not change resting RSNA or responses to air stress at 1 hour. However, 18 hours after injection of the Fab fragments, resting RSNA levels had significantly decreased compared with the control values, and plasma catecholamine levels had decreased to control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗