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Evaluation of sleep using ambulatory skin potential recording: differences between morning and evening type.

In order to validate the evaluation of sleep using cassette type ambulatory skin potential measurement system (C-SPA), sleep duration variables extracted from 24 h recordings were compared between two groups (16 of the intermediate type and 16 of the evening type) with different sleep-wake habits rated by Morningness and Eveningness Questionnaires (MEQ). Compared with the intermediate type, the evening type subjects go to bed and get up later, have difficulty in falling asleep and more frequently awaken during sleep. Thus, the sleep variables by C-SPA provide valuable information about duration of sleep and differentiate the sleep-wake habits.

Activity Cycles↗

Association between human IgM autoantibodies and kappa chain allotypes.

The relationship between the immunoglobulin kappa light chain allotypes and autoantibodies was studied in a series of seven human monoclonal kappa-bearing IgM antibodies with Rheumatoid Factor (RF) activity, two IgM anti-low density lipoprotein (LDL) antibodies, and one IgM anti-intermediate filament (IF) antibody. Residues at amino acid positions 153 and 191 related to the Km allotypes in human kappa chains were determined by an HPLC tryptic fingerprint and corroborated by amino acid sequence analysis. All the autoantibodies shared similar variable regions derived from the V kappa IIIb gene(s). The seven RF and the anti-IF were associated with the Km(3) constant region allotype whereas the two anti-LDL were associated with the Km(1,2) allotype. Thus, monoclonal autoantibodies showed the same Km allotypic distribution as the normal population. However, although the number of samples is small, it seems likely that a preferential association may exist between particular V kappa genes and Km alleles in the generation of autoantibodies with different specificities.

Amino Acid Sequence↗

Ferredoxin:thioredoxin Reductase: Disulfide Reduction Catalyzed via Novel Site-specific [4Fe-4S] Cluster Chemistry.

Thioredoxin-mediated light regulation in plant chloroplasts involves a unique class of disulfide reductases that catalyze disulfide reduction in two one-electron steps using a [2Fe-2S] ferredoxin as the electron donor and an active site comprising a [4Fe-4S] cluster and a redox-active disulfide. This review summarizes structural and spectroscopic studies of ferredoxin:thioredoxin reductase (FTR) and a chemically modified form, termed NEM-FTR, which provides a stable analog of the one-electron reduced catalytic intermediate. Detailed spectroscopic characterization of FTR and NEM-FTR using absorption, EPR, electron-nuclear double resonance, variable-temperature magnetic circular dichroism, resonance Raman and Mössbauer spectroscopies indicate that the one-electron reduced catalytic intermediate involves two-electron disulfide reduction coupled with one-electron cluster oxidation of a [4Fe-4S](2+) cluster to yield a unique type of S= 1/2 [4Fe-4S](3+) cluster with two cysteine residues ligated at a specific Fe site. The results provide the basis for a novel mechanism for disulfide cleavage in two one-electron steps involving site-specific [4Fe-4S] cluster chemistry. A similar mechanism is proposed for direct [4Fe-4S]-mediated cleavage of the CoM-S-S-CoB heterodisulfide in methanogenic archaea by heterodisulfide reductases.

Journal Article↗

Antibodies to intermediate filaments in polymyalgia rheumatica and giant cell arteritis: a sequential study.

Serum specimens from 35 patients with polymyalgia rheumatica and giant cell arteritis (PMR/GCA) were obtained sequentially at variable time intervals up to a year from onset of disease. These were tested for antibodies to intermediate filaments by indirect immunofluorescence using HEp2 cells as substrate. Twenty four of 35 (68%) patients' sera at onset of disease were positive at an anti-intermediate filament antibody (AIFA) titre of greater than 1/40 compared with three outs of 19 (15%) control sera. AIFA were predominantly of IgM class, and there was no significant change in AIFA titres on follow up despite clinical remission of disease.

Autoantibodies↗

Design of artificial neural network and its applications to the analysis of alcoholism data.

Artificial neural networks were applied to the alcoholism data to reveal nonlinear relationships between intermediate phenotypes, marker identity-by-descent sharing, and the affection status. A variable number of hidden units were considered to achieve a balance between the minimal mean-squared error and over-fitting of the data. The predictability of the affection status based on intermediate phenotype information (event-related potential 300, monoamine oxidase, and gender) was 65% to 75%, and sensitivity/specificity ranged around 50% to 80%. The IBD approach succeeded in identifying the same marker as previous studies, but also found additional peaks.

Alcoholism↗

Identification of severe coronary artery disease using simple clinical parameters.

The purpose of our study was to examine the ability of clinical and resting electrocardiographic variables to provide useful estimates of the probability of three-vessel or left-main coronary artery disease. The study group consisted of 680 patients with symptomatic coronary artery disease who underwent exercise equilibrium radionuclide angiography and coronary angiography within 6 months. Sixteen clinical and electrocardiographic variables were examined by logistic regression analysis. The independently predictive variables were then used to develop convenient graphic estimates of the probability of three-vessel or left-main disease and to classify patients into high-risk (greater than 35%), intermediate-risk (15-35%), or low-risk (less than 15%) groups. Five variables were independently predictive of left-main or three-vessel disease: age, typical angina, diabetes, gender, and both history and electrocardiographic evidence of a prior myocardial infarction. A single graph was constructed that displayed the probability of severe coronary artery disease as a function of a five-point cardiac risk scale, which incorporated these variables. Two hundred sixty-two patients (39% of the study group) were classified as high risk; 127 of these patients (48%) had three-vessel or left-main disease. An additional 96 patients were classified as low risk; nine of these patients (9%) had three-vessel or left-main disease. Five clinical variables that were obtained on an initial patient assessment can provide useful estimates of the likelihood of severe coronary disease.

Coronary Angiography↗

The distribution of positive psychosis-like symptoms in the population: a latent class analysis of the National Comorbidity Survey.

OBJECTIVE: Previous research has suggested that psychosis is better described as a continuum rather than a dichotomous entity. This study aimed to describe the distribution of positive psychosis-like symptoms in the general population by means of latent class analysis. METHOD: Latent class analysis was used to identify homogeneous sub-types of psychosis-like experiences. Multinomial logistic regression models were used to interpret the nature of the latent classes, or groups, by estimating the associations with demographic factors, clinical variables, and experiences of traumatic events. RESULTS: The best fitting latent class model was a four-class solution: a psychosis class, a hallucinatory class, an intermediate class, and a normative class. The associations between the latent classes and the demographic risk factors, clinical variables, and experiences of traumatic events showed significantly higher risks for the psychosis class, the hallucinatory class, and the intermediate class compared to the normative class. Furthermore there appeared to be a grading in the magnitude of the odds ratios: the odds ratios for the psychosis group were generally higher than those for the hallucinatory class, and the odds ratios for the hallucinatory class were generally higher than those for the intermediate class. CONCLUSIONS: The latent class analysis showed that psychosis-like symptoms at the population level could be best explained by four groups that appeared to represent an underlying continuum.

Adolescent↗

A morphometric method to discriminate normal from dysplastic/carcinoma in situ squamous epithelium in the human esophagus.

The possibility to differentiate normal squamous epithelium from dysplastic/cis in the human esophagus by means of quantitative morphometry was investigated in surgical specimens from 31 consecutive patients. The epithelium was divided into three equal zones, and a total of 186 areas was investigated. Of all variables employed, the interzonal variation between the three epithelial layers was the one showing the highest degree of efficiency (95%) in discriminating normal esophageal epithelium from dysplastic/cis lesions. Nuclear density, nuclear area, nuclear irregularity, nuclear parallelity and nuclear ovality were the most efficient discriminatory individual morphological variables. A 100% sensitivity in discriminating normal squamous epithelium from dysplastic/cis through morphometric evaluation was achieved by considering nuclear area in the superficial zone, nuclear perpendiculairty in the intermediate zone, nuclear density in the total epithelial thickness and interzonal variation of these variables. On the other hand, the specificity in discriminating dysplasia/cis lesions from normal squamous epithelium was only 96.8%. This was due to the fact that one case, by visual impression considered as dysplasia, was morphometrically recorded as normal. The view of that case showed that our initial visual impression of a dysplastic lesion proved to be erroneous, and today that case would be recorded as a reactive lesion due to chronic inflammation.

Analysis of Variance↗

A structural comparison of tryptic fragments of three types of intermediate filaments.

We have compared tryptic fragments of three types of intermediate filaments, emphasizing structural characteristics as seen in the electron microscope. Variable, long alpha-helical rod fragments were found to be similar for keratin, neurofilaments and desmin filaments. Short rod fragments from keratin and neurofilaments appeared similar when observed by electron microscopy. Short rod fragments were not seen in desmin filament digests. In addition to these elongated particles, globular fragments, which have not been described previously, were obtained from all three types of intermediate filaments. These globular fragments were characterized by gel filtration and electron microscopy, and compared to globular proteins of known size using both methods. The diameter was about 6 nm and the molecular weight was estimated to be 50 000-60 000. These globular particles may comprise the short, nonhelical regions from several IF protein subunits, which are clustered into an interface in the intact filament or protofilaments.

Animals↗

Bovine corneal opacity and permeability test: an in vitro assay of ocular irritancy.

Most of the published in vitro tests of ocular irritancy investigate a single parameter, generally cytotoxicity, using different cell types in culture. Although good correlations with in vivo data have been reported by some investigators, many of these studies examined only limited classes of products, mainly surfactants and cosmetic ingredients. To predict the irritant potential of compounds in development and process intermediates (which include a wide variety of chemical classes with variable physical characteristics), an assay which would allow great flexibility was needed. A recently published model of corneal opacity was appropriate for this purpose and therefore investigated. The method was substantially modified and extended to study, in the same assay, two important components of irritation, i.e., opacity and permeability. For opacity alone, values obtained for 44 common chemicals showed a correlation of r = 0.73 with published in vivo data. However, compounds like sodium lauryl sulfate and some medium-chain alcohols gave false-negative results, apparently because they produced destruction of corneal epithelium. Such an effect was quantified by the measure of corneal permeability to fluorescein, and changes observed were found to be consistent with the known irritant potential of the compounds. In combination, the measurement of these two endpoints thus appeared to be sufficient to accurately predict ocular irritancy. This was further verified with 15 process intermediates. In short, the bovine corneal opacity and permeability assay allows investigation of two important components of eye irritation, in a one-day experiment, using an ocular tissue. It represents a useful approach to assess ocular irritation at least for our needs.

Animals↗

"Essential noise" - enhancing variability of informational constraints benefits movement control: a comment on Waddington and Adams (2003).

This commentary proposes a dynamical systems perspective to re-interpret data from a group of international soccer players demonstrating that wearing textured insoles in soccer boots enhanced tactile information from the sole of the foot and increased movement discrimination capacity in ankle inversion sensitivity tests to levels similar to those in barefoot conditions. Theoretical arguments on the functional role of variability induced in the sensorimotor system by textured insoles, acting as a form of "essential noise" to enhance the accuracy of foot positioning are presented. It seems that, far from interfering with motor performance, variability can actually enhance perception of information to support motor performance. The addition of intermittent, intermediate levels of noise in a perceptual motor context may benefit performers by helping them to pick up information signals from background structure. Movement system variability is conceived as noise induced resonance benefiting the pick up of information to regulate behaviour. Variability can be functional in practical programmes to offset negative effects of losses in sensory sensitivity through ageing, disease, illness, or injury.

Ankle Joint↗

Subtle imitation behaviour in convenience samples of normal, demented, and currently depressed elderly subjects.

BACKGROUND: The clinical significance of imitation behaviour (IB) is unclear. The aim of this study was to investigate the prevalence of subtle naïve and obstinate IB in convenience samples of normal elderly, demented, and depressed subjects. METHOD: Subtle IB was assessed using a protocol constructed ad hoc in 146 patients, consecutively referred to a memory clinic having received an ICD-10 diagnosis of either dementia or depression, and in 241 healthy subjects. The prevalence of IB in the three groups was determined and the association with possible demographic, cognitive, and non-cognitive variables analysed. RESULTS: Subtle naïve IB was frequent in the elderly with dementia, intermediate in the depressed, and rare in the normal elderly except that the latter frequently stretched out their arms. Obstinate IB never occurred in the normal elderly. IB was predicted by none of the variables used. LIMITATIONS: The groups included were convenience samples with the depressed being a small group precluding further distinction of depressive subtypes. CONCLUSION: Although naïve IB is a frequent clinical feature in the demented, it also accompanies depressive disorders in the elderly. It can be observed as context-specific IB in the normal elderly. Obstinate IB does not occur in the normal elderly.

Aged↗

Variable expression of isotopic discrimination in metabolic flows.

Isotopic discrimination in reaction velocity may affect to a variable extent the estimation of metabolic flow when a metabolic intermediate is catabolized by two pathways with different degrees of discrimination. This was explored in erythrocytes exposed to 14C- or 3H-labelled D-glucose in the absence or presence of menadione. In the absence of menadione, when the pentose phosphate pathway accounted for only 5% of the D-glucose 6-phosphate turnover, the oxidation of C1-protonated or C1-deuterated D-[U-14C]glucose and D-[1-14C]glucose, mixed with the homologous non-radioactive D-[1-1H]glucose or D-[1-2H]glucose, indicated that, relative to the phosphorylation of the hexose, C1-deuterated D-glucose was less efficiently converted to 14CO2 than C1-protonated D-glucose. Moreover, in the absence of menadione, non-deuterated D-[U-14C]glucose and D-[1-14C]glucose were more efficiently oxidized in cells exposed to D-[1-2H]glucose rather than D-[1-1H]glucose. In the presence of menadione, which increased more than ten-fold the flow rate through the pentose phosphate pathway, the phenomenon of isotopic discrimination was either revealed or masked. These data indicate that the phenomenon of isotopic discrimination may indeed affect to a variable extent the estimation of a given metabolic flow.

Animals↗

Advances in satellite remote sensing of environmental variables for epidemiological applications.

Earth-observing satellites have provided an unprecedented view of the land surface but have been exploited relatively little for the measurement of environmental variables of particular relevance to epidemiology. Recent advances in techniques to recover continuous fields of air temperature, humidity, and vapour pressure deficit from remotely sensed observations have significant potential for disease vector monitoring and related epidemiological applications. We report on the development of techniques to map environmental variables with relevance to the prediction of the relative abundance of disease vectors and intermediate hosts. Improvements to current methods of obtaining information on vegetation properties, canopy and surface temperature and soil moisture over large areas are also discussed. Algorithms used to measure these variables incorporate visible, near-infrared and thermal infrared radiation observations derived from time series of satellite-based sensors, focused here primarily but not exclusively on the Advanced Very High Resolution Radiometer (AVHRR) instruments. The variables compare favourably with surface measurements over a broad array of conditions at several study sites, and maps of retrieved variables captured patterns of spatial variability comparable to, and locally more accurate than, spatially interpolated meteorological observations. Application of multi-temporal maps of these variables are discussed in relation to current epidemiological research on the distribution and abundance of some common disease vectors.

Animals↗

[FLuorescence of photoactive bacteriorhodopsin].

Fluorescence characteristics of all-trans-bacteriorhodopsin (BR570), 13-cis-BR (BR560), and the intermediate of the BR cycle (P585) are obtained by measuring variable fluorescence in the course of their phototransformations. The fluorescence spectra (lambda greater than 580 nm) have a maximum at 720, 730 and 740 nm, their respective excitation spectra with a maximum of 578, 565 and 585 nm coincide with the absorption spectra of the three states. The emission quantum yield for P585 is approximately 10(-4) at -62 degrees C and 4 +/- 2 10(-4) for BR560 at -196 degrees C. The effect of sharp increase of BR570 fluorescence quantum yield (from less than or equal to 10(-4) to approximately 10(-3)) under action of light at -196 degrees C (photoactivation or induction of emission) is found which points to the existence of photoprocess parallel to the photoconversion of BR570 into P600 (formula: see text). The emission of BR560 is not photoactivated. The photoactivated state BR570 is not identical with pseudo-BR of Gillbro et al., (1977) which has a maximum in the excitation spectrum at 597 nm. The greater part of the red fluorescence of the membrane belongs to the minor nonphotoactive forms of BR (B578, B630) with relatively high fluorescence yield (greater than or equal to 10(-2) at -196 degrees C). The fluorescence characteristics of BR are discussed in the framework of a scheme in which the existence of an intermediate excited level common for the emission and photoconversion and a ground level common for the initial state and photoproduct is suggested.

Bacteriorhodopsins↗

Editing of non-cognate aminoacyl adenylates by peptide synthetases.

Non-ribosomally formed peptides display both highly conserved and variable amino acid positions, the variations leading to a wide range of peptide families. Activation of the amino acid substrate proceeds in analogy to the ribosomal biosynthetic mechanism generating aminoacyl adenylate and acyl intermediates. To approach the mechanism of fidelity of amino acid selection, the stability of the aminoacyl adenylates was studied by employing a continuous coupled spectrophotometric assay. The apo-form of tyrocidine synthetase 1 (apo-TY1) was used, generating an l-phenylalanyl-adenylate intermediate stabilized by the interaction of two structural subdomains of the adenylation domain. Adenylates of substrate analogues have shown variable and reduced degrees of stability, thus leading to an enhanced generation of pyrophosphate due to hydrolysis and continuous adenylate formation. Discrimination of the non-aromatic amino acids l-Leu and l-Met, or l-Phe analogues such as p-amino- and p-chloro-l-Phe derivatives, as well as the stereospecific selection of l-Phe, is supported by less-stable adenylate intermediates exhibiting elevated susceptibility to hydrolysis. Breakdown of the l-phenylalanyl intermediate utilizing 2'-deoxy-ATP as the nucleotide substrate was significantly enhanced compared with the natural analogue. Apo-TY1 engineered at positions involved in adenylate formation showed variable protection against hydrolysis. The results imply that stability of the aminoacyl intermediates may act as an essential factor in substrate selection and fidelity of non-ribosomal-peptide-forming systems.

Adenosine Monophosphate↗

Relation of heart rate dynamics to the occurrence of myocardial ischemia after coronary artery bypass grafting.

Postoperative myocardial ischemia is a common finding after coronary artery bypass grafting (CABG) and is associated with an adverse short-term clinical outcome. The reasons and pathophysiologic background for the occurrence of ischemia after CABG are not well established. We tested the hypothesis that altered heart rate (HR) behavior precedes the onset of myocardial ischemic episodes in patients after CABG. Time-domain HR variability measurements, along with analysis of Poincaré plots and fractal scaling analysis were assessed in 40 CABG patients from 48-hour postoperative Holter recordings. Twenty patients experienced 195 ischemic episodes during the postoperative course. In the univariate analysis of HR variability measurements of the first postoperative day (POD), the increased ratio between the short-term (SD1) and long-term (SD2) HR variability analyzed from the Poincaré plot and the decreased short- and intermediate-term fractal scaling exponents alpha(1) and alpha(2) were significantly associated with ischemia during the study period (p <0.01, p <0.05, and p <0.05, respectively). In the multivariate model, the increased SD1/SD2 ratio of the first POD was the most powerful independent predictor of all possible confounding variables for the occurrence of postoperative ischemia (corresponding to a change of 0.15 U; odds ratio 2.2 and 95% confidence interval 1.2 to 5.7; p <0.01). Altered HR dynamics have been associated with myocardial ischemic episodes in patients after CABG, suggesting that the autonomic nervous system has an important role in the pathogenesis of myocardial ischemia in the postoperative phase of CABG.

Aged↗

Imaging genomics and response to treatment with antipsychotics in schizophrenia.

Recent important advancements in genomic research have opened the way to new strategies for public health management. One of these questions pertains to how individual genetic variation may be associated with individual variability in response to drug treatment. The field of pharmacogenetics may have a profound impact on treatment of complex psychiatric disorders like schizophrenia. However, pharmacogenetic studies in schizophrenia have produced conflicting results. The first studies examined potential associations between clinical response and drug receptor genes. Subsequent studies have tried to use more objective phenotypes still in association with drug receptor genes. More recently, other studies have sought the association between putative causative or modifier genes and intermediate phenotypes. Thus, conflicting results may be at least in part explained by variability and choice of the phenotype, by choice of candidate genes, or by the relatively little knowledge about the neurobiology of this disorder. We propose that choosing intermediate phenotypes that allow in vivo measurement of specific neuronal functions may be of great help in reducing several of the potential confounds intrinsic to clinical measurements. Functional neuroimaging is ideally suited to address several of these potential confounds, and it may represent a powerful strategy to investigate the relationship between behavior, brain function, genes, and individual variability in the response to treatment with antipsychotic drugs in schizophrenia. Preliminary evidence with potential susceptilibity genes such as COMT, DISC1, and GRM3 support these assumptions.

Antipsychotic Agents↗