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PubMedDate not supplied

Top-down modulation of early sensory cortex.

Data from nine previous studies of human visual information processing using positron emission tomography were reanalyzed to contrast blood flow responses during passive viewing and active discriminations of the same stimulus array. The analysis examined whether active visual processing (i) increases blood flow in medial visual regions early in the visual hierarchy and (ii) decreases blood flow in auditory and somatosensory cortex. Significant modulation of medial visual regions was observed in six of nine studies, indicating that top-down processes can affect early visual cortex. Modulations showed several task dependencies, suggesting that in some cases the underlying mechanism was selective (e.g. analysis-or feature-specific) rather than non-selective. Replicable decreases at or near auditory Brodmann area (BA) left 41/42 were observed in two of five studies, but in different locations. Analyses that combined data across studies yielded modest but significant decreases. Replicable decreases were not found in primary somatosensory cortex but were observed in an insular region that may be a somatosensory association area. Decreases were also noted in the parietal operculum (perhaps SII) and BA 40. These results are inconsistent with a model in which the precortical input to task-irrelevant sensory cortical areas is broadly suppressed.

Auditory Cortex↗
PubMed2005

Subtle sequence variation among MHC class I locus products greatly influences sensitivity to HCMV US2- and US11-mediated degradation.

Human cytomegalovirus (HCMV) interferes with cellular immune responses by modulating surface expression of MHC class I molecules. Here, we focused on HCMV-encoded unique short (US) 2 and US11, which bind newly synthesized MHC class I heavy chains (HCs) and support their dislocation into the cytosol for subsequent degradation by proteasomes. Not all MHC class I locus products are equally sensitive to this down-modulation. The aim of this study was to identify which domains, and ultimately which residues, are responsible for the resistance or sensitivity of MHC class I molecules to US2- and US11-mediated down-regulation. We show that, besides endoplasmic reticulum-lumenal regions, the C-terminus of class I molecules represents an important determinant for allele specificity in US11-mediated degradation. HLA-E becomes sensitive to US11-mediated down-regulation when its cytoplasmic tail is extended. Interestingly, this only requires two additional residues, lysine and valine, at its C-terminus. For US2, the MHC class I allele specificity is largely determined by a small region at the junction of the alpha2/alpha3 domain of the HC. It is quite remarkable that minor changes, in only four residues, can completely revert the sensitivity of naturally US2-resistant HLA-E molecules. With this study we provide better insights into the features underlying the selectivity in MHC class I down-regulation by US2 and US11.

Alleles↗
PubMed1990

Application of a new method of pattern recognition in DNA sequence analysis: a study of E. coli promoters.

An algorithm from the pattern recognition theory 'generalized portrait' was used to find a distinguishing vector (scoring matrix) for E. coli promoters. We have attempted to solve three closely linked problems: (i) the selection of significant features of the signal; (ii) subsequent multiple alignment and (iii) calculation of the vector coordinates. Promoters with known strength have been successfully ranked in the correct order using this vector. We demonstrate the use of this method in predicting the location of promoters. A revised consensus promoter sequence is also presented.

Algorithms↗
PubMed1992

An assessment of neural network and statistical approaches for prediction of E. coli promoter sites.

We have constructed a perceptron type neural network for E. coli promoter prediction and improved its ability to generalize with a new technique for selecting the sequence features shown during training. We have also reconstructed five previous prediction methods and compared the effectiveness of those methods and our neural network. Surprisingly, the simple statistical method of Mulligan et al. performed the best amongst the previous methods. Our neural network was comparable to Mulligan's method when false positives were kept low and better than Mulligan's method when false negatives were kept low. We also showed the correlation between the prediction rates of neural networks achieved by previous researchers and the information content of their data sets.

Base Sequence↗
PubMed2005

Modulation of ADAR1 editing activity by Z-RNA in vitro.

RNA editing by A-to-I modification has been recognized as an important molecular mechanism for generating RNA and protein diversity. In mammals, it is mediated by a family of adenosine deaminases that act on RNAs (ADARs). The large version of the editing enzyme ADAR1 (ADAR1-L), expressed from an interferon-responsible promoter, has a Z-DNA/Z-RNA binding domain at its N-terminus. We have tested the in vitro ability of the enzyme to act on a 50 bp segment of dsRNA with or without a Z-RNA forming nucleotide sequence. A-to-I editing efficiency is markedly enhanced in presence of the sequence favoring Z-RNA. In addition, an alteration in the pattern of modification along the RNA duplex becomes evident as reaction times decrease. These results suggest that the local conformation of dsRNA molecules might be an important feature for target selectivity by ADAR1 and other proteins with Z-RNA binding domains.

Adenosine Deaminase↗
PubMed2005

Coming up for air: experts, employers, and workers in campaigns to compensate silicosis sufferers in Britain, 1918-1939.

Government regulation of dangerous trades and the compensation of those injured by their work remains a matter of considerable debate among medical historians. Trade unions have frequently been criticized for pursuing financial awards for their members rather than demanding improvements in health and safety at the workplace. This article examines the neglected subject of silicosis injuries in Britain from the time when the first legislation was passed for compensation of those suffering from the harmful affects of silica dust in 1918 to the outbreak of war in 1939, when a major new study was under way which would transform the scientific understanding and the legal compensation of those who were diagnosed as being ill with pneumoconiosis. It is argued that in framing legislation from compensation, politicians and their civil servants sought to retain the legal framework created in 1897-1906 and developed a model of industrial insurance which depended to a large extent on a co-operative relationship with leading employers. Medical scientists identified silica as a uniquely hazardous agent in workers' lung disease, which emphasizing the specialist knowledge required for its diagnosis. One remarkable feature of the selective compensation schemes devised after 1918 was the reliance on geological rather than pathological evidence to prove compensation rights as well as strict employment limits on those eligible to claim. only the campaigning of labour organizations and persistent evidence of lung disease among anthracite coal miners led to a significant relaxation of compensation rules in 1934 and the fresh scientific investigation which transformed the medical understanding of respiratory illness among industrial workers.

Coal Mining↗
PubMed1997

Rheumatic manifestations of inherited diseases.

In this paper the rheumatic features of a selection of inherited diseases are reviewed. Further evidence has been reported strengthening the association between hypercholesterolemia and Achilles tendinous xanthomatosis, although the clinical manifestations of hyperlipidemic arthropathy remain poorly understood. Osteonecrosis of the femoral head is demonstrated to have a good functional prognosis in children and adolescents with Gaucher's disease. Magnetic resonance imaging of the liver may prove to be useful in monitoring enzyme replacement in Gaucher's disease because it correlates with the presence of avascular necrosis. A case of cervical myelopathy in Hunter's disease is also presented.

Genetic Diseases, Inborn↗
PubMedDate not supplied

An evaluation of the effectiveness of CT vs. other imaging modalities in the diagnosis of atypical renal masses.

A retrospective review of 34 patients undergoing nephrectomy for suspected renal malignancy was undertaken to evaluate the effectiveness of computed tomography (CT), ultrasound, arteriography, and cyst puncture in providing a definitive preoperative diagnosis of benign vs. malignant renal abnormality. The predictive value of a test suggesting malignancy was 88% for angiography, 86% for ultrasound, 71% for cyst puncture, and 80% for CT. The predictive value of a test suggesting no malignancy for non-CT imaging modalities was poor. The predictive value of renal CT increased to 96%, when three or more characteristics are present which suggest the lesion is not a simple, benign renal cyst. Using these criteria all malignancies were identified, and all but one benign lesion excluded. Unusual lesions that have equivocal or indeterminate diagnostic studies and only one or two noncystic CT features should undergo selective exploration rather than radical nephrectomy.

Adult↗
PubMed1994

Inhibition of signal Ca2+ in dog coronary arterial vascular muscle cells by Ro 40-5967.

The effects of Ro 40-5967, a chemically novel Ca2+ channel antagonist, were examined on K(+)- and norepinephrine (NE)-stimulated intracellular free Ca2+ concentrations in dog coronary artery vascular muscle cells (VMC). Intracellular Ca2+ activity increases stimulated by NE or K+ were measured by shuttered, low-intensity illumination with the fluorescent Ca2+ indicator fluo3 in single myovascular cells < or = 2 days after isolation. Pretreatment of VMC for 5 min with 10 microM Ro 40-5967 significantly reduced intracellular Ca2+ activity increase on exposure to 100 mM K+ in both subsarcolemmal (SSL) and central regions during K+ depolarization, similar to actions of diltiazem. More impressively, Ro 40-5967 (but not diltiazem) also reduced intracellular Ca2+ activity during stimulation with 100 nM NE to basal level at both peripheral and central regions. Prevention of Ca2+ increases, especially those caused by release from central Ca2+ stores, during NE stimulation is an unusual property for a Ca2+ antagonist, as shown by the contrast with diltiazem, which did not significantly attenuate Ca2+ increases during NE stimulation. Another Ro 40-5967 feature was vascular selectivity; i.e., Ro 40-5967 had only a minor effect on contraction frequency of rat myocardial cells while significantly inhibiting spontaneous contractions of rat spontaneously active VMC. In comparison, diltiazem and verapamil potently inhibited both vascular and cardiac muscle spontaneous contractions. The decidedly stronger actions of Ro 40-5967 as compared with those of benzothiazepine or phenylalkylamine on NE-stimulated Ca2+ increases, together with less action on cardiac pacemakers, are differences that appear to distinguish Ro 40-5967 from other Ca2+ antagonists.

Animals↗
PubMed1998

Studies of endothelin-converting enzyme in bovine endothelial cells and vascular smooth-muscle cells: further characterization of the biosynthetic process.

Endothelin-1 (ET-1) is synthesized by a number of cell types, including endothelial, epithelial, and smooth muscle cells. Initial biosynthesis occurs as a protein precursor, preproendothelin-1 (preproET-1). This is processed intracellularly to the inactive intermediate big ET-1, which is hydrolyzed by endothelin-converting enzyme (ECE) to generate ET-1, but the precise identity of the physiologically relevant ECE has yet to be confirmed. Although ET-1 is synthesized in the constitutive secretory pathway, many features of the selective processing of proET-1 are comparable to those of peptide hormones. We describe here experimental investigations aimed at defining the regulation of ET-1 synthesis and its relationship to the biosynthesis of ECE.

Animals↗
PubMed2004

Vasopressor agents: old and new components.

PURPOSE OF REVIEW: In settings of cardiac arrest, reestablishing vital organ perfusion plays an important role in initial CPR. As a pharmacologic intervention, vasopressor agents aim to improve aortic diastolic pressure and, consequently, coronary and cerebral perfusion pressures. RECENT FINDINGS: Historically, adrenergic agonists such as epinephrine have been suggested for routine use in CPR. However, epinephrine's efficacy is controversial because of its unfavorable inotropic and chronotropic action. This has prompted research into the use of alternative pressor agents with more promising hemodynamic features; these include selective alpha 2-adrenergic agonists and other nonadrenergic vasoconstrictors such as vasopressin. SUMMARY: In this article, the main traditional and novel adrenergic and nonadrenergic vasopressor drugs are reviewed.

Adrenergic Agents↗
PubMed2004

Watchful waiting and factors predictive of secondary treatment of localized prostate cancer.

PURPOSE: Watchful waiting remains an important treatment option for some patients with localized prostate cancer. We defined the demographic, clinical and outcome features of men selecting watchful waiting as an initial treatment strategy, and determined factors predictive of eventual progression to secondary treatment. MATERIALS AND METHODS: Of 8390 patients diagnosed with prostate cancer from 1990 to 2001 in the Department of Defense Center for Prostate Disease Research Database, 1158 patients chose watchful waiting as initial treatment. The demographic and clinical differences between patients on watchful waiting and those choosing other initial treatments were compared using the chi-square test. Secondary treatment-free survival according to various prognostic factors was plotted using the Kaplan-Meier method and differences were tested using the log rank test. A multivariate Cox proportional hazards regression analysis was performed to determine which factors were independent predictors of secondary treatment. RESULTS: Compared to other patients, those selecting watchful waiting were older, had lower prostate specific antigen (PSA) at diagnosis, and were more likely to have lower stage (cT1) and lower grade (Gleason sum 7 or less) cancers. Age, PSA and clinical stage were all significant and independent predictors of secondary treatment. The relative risk of secondary treatment can be expressed as EXP (-0.034 x age at diagnosis + 0.284 x LOG (diagnostic PSA) + 0.271 x clinical stage T2 + 0.264 x clinical stage T3). CONCLUSIONS: Men who elect watchful waiting as initial management for prostate cancer are older with lower Gleason sums and serum PSA. In these men, age at diagnosis, serum PSA and clinical stage are the most significant predictors of requiring or selecting secondary treatment.

Aged↗
PubMed1990

Human attention: the exclusion of distracting information as a function of real and apparent separation of relevant and irrelevant events.

A leading theory suggests that human vision operates by separate and parallel analysis of each of the simple features of the visual scene; but computation of the identity of objects, which needs combination of these features, is undertaken selectively and only for some parts of the incoming information. It is known that the identity of distracting events affects reaction time only for distractors spatially close to the reaction signal. This suggests that the selection is spatially based; perhaps taking place in the projection areas. Experiments on this topic have, however, normally considered events only at a fixed viewing distance; in this study different viewing distances were employed. It was found that, over the range of conditions used, the ability to exclude irrelevant distractors depended upon the true physical separation and not on the angular separation at the eye of the observer. Hence the 'attention' system must operate at a point later than the computation of true physical location, rather than at the very early stage where angular separation only is available.

Attention↗
PubMed2002

Determinants of loss of mammal species during the Late Quaternary 'megafauna' extinctions: life history and ecology, but not body size.

Extinctions of megafauna species during the Late Quaternary dramatically reduced the global diversity of mammals. There is intense debate over the causes of these extinctions, especially regarding the extent to which humans were involved. Most previous analyses of this question have focused on chronologies of extinction and on the archaeological evidence for human-megafauna interaction. Here, I take an alternative approach: comparison of the biological traits of extinct species with those of survivors. I use this to demonstrate two general features of the selectivity of Late Quaternary mammal extinctions in Australia, Eurasia, the Americas and Madagascar. First, large size was not directly related to risk of extinction; rather, species with slow reproductive rates were at high risk regardless of their body size. This finding rejects the 'blitzkrieg' model of overkill, in which extinctions were completed during brief intervals of selective hunting of large-bodied prey. Second, species that survived despite having low reproductive rates typically occurred in closed habitats and many were arboreal or nocturnal. Such traits would have reduced their exposure to direct interaction with people. Therefore, although this analysis rejects blitzkrieg as a general scenario for the mammal megafauna extinctions, it is consistent with extinctions being due to interaction with human populations.

Animals↗
PubMed2004

Some computational and algorithmic developments in computational mechanics of discontinua.

Discontinua simulations are becoming an important part of computational mechanics to the extent that computational mechanics of discontinua is becoming a separate sub-discipline of computational mechanics. Among the most widely used methods of computational mechanics of discontinua are discrete-element methods, combined finite-discrete-element methods and discontinuum deformation analysis methods. A range of key algorithmic procedures is common to most of these methods. These include contact detection, explicit solvers, fracture and fragmentation models, handling of complex geometric considerations when processing interaction in three dimensions (contact kinematics) and fluid coupling. In recent years, there have been major breakthroughs in almost all of these key algorithmic aspects. These include linear contact-detection procedures (NBS, C-grid), discretized contact solutions, fracture and fragmentation solutions, together with fluid pressure driven fracture process and three-dimensional explicit solvers incorporating finite rotations. Many of these breakthroughs have not yet been applied across the full range of relevant discontinuum problems. The major reason for this is that discrete-element method, discontinuum deformation analysis and combined finite-discrete-element method publications are spread over a wide range of specialist journals and conferences. Thus in this paper, the main features of a selection of algorithmic breakthroughs are reviewed for the first time, enabling researchers in different fields to apply these compatible developments to their specific applications.

Journal Article↗
PubMed1983

The purity of auditory memory.

Recent evidence from experiments on immediate memory indicates unambiguously that silent speech perception can produce typically 'auditory' effects while there is either active or passive mouthing of the relevant articulatory gestures. This result falsifies previous theories of auditory sensory memory (pre-categorical acoustic store) that insisted on external auditory stimulation as indispensable for access to the system. A resolution is proposed that leaves the properties of pre-categorical acoustic store much as they were assumed to be before but adds the possibility that visual information can affect the selection of auditory features in a pre-categorical stage of speech perception. In common terms, a speaker's facial gestures (or one's own) can influence auditory experience independently of determining what it was that was said. Some results in word perception that encourage this view are discussed.

Feedback↗
PubMed2000

Skeletal growth estimation using radiographic image processing and analysis.

An automated knowledge-based vision system for skeletal growth estimation in children is reported in this paper. Images were obtained from hand radiographs of 32 male and 25 female children of age 1-16 yr. Phalanx bones were automatically localized and segmented using hierarchical inferences and active shape models, respectively. A number of shape descriptors were obtained from the segmented bone contour to quantify skeletal growth. From these descriptors, a feature vector was selected for a regression model and a Bayesian estimator. The estimation accuracy was 84% for females and 82% for males. This level of accuracy is comparable to that of expert pediatric radiologists, which suggests that the proposed approach has a potential application in pediatric medicine.

Adolescent↗
PubMed2002

HAMMER: hierarchical attribute matching mechanism for elastic registration.

A new approach is presented for elastic registration of medical images, and is applied to magnetic resonance images of the brain. Experimental results demonstrate very high accuracy in superposition of images from different subjects. There are two major novelties in the proposed algorithm. First, it uses an attribute vector, i.e., a set of geometric moment invariants (GMIs) that are defined on each voxel in an image and are calculated from the tissue maps, to reflect the underlying anatomy at different scales. The attribute vector, if rich enough, can distinguish between different parts of an image, which helps establish anatomical correspondences in the deformation procedure; it also helps reduce local minima, by reducing ambiguity in potential matches. This is a fundamental deviation of our method, referred to as the hierarchical attribute matching mechanism for elastic registration (HAMMER), from other volumetric deformation methods, which are typically based on maximizing image similarity. Second, in order to avoid being trapped by local minima, i.e., suboptimal poor matches, HAMMER uses a successive approximation of the energy function being optimized by lower dimensional smooth energy functions, which are constructed to have significantly fewer local minima. This is achieved by hierarchically selecting the driving features that have distinct attribute vectors, thus, drastically reducing ambiguity in finding correspondence. A number of experiments demonstrate that the proposed algorithm results in accurate superposition of image data from individuals with significant anatomical differences.

Aged↗