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PubMed1996

[Role of hepatitis C virus in porphyria cutanea tarda hepatopathy].

BACKGROUND: Porphyria cutanea tarda has been classically considered as an acquired disorder due to the exerted influence of several factors (such as viral infections) on its fenotipic expression. The aim of the present study has been focussed on the prevalence analysis and the hepatotoxic role of the hepatitis C virus (HCV). PATIENTS AND METHODS: By means of a second generation ELISA test, serum antibodies against hepatitis C virus was studied in 132 patients with porphyria cutanea tarda. The polymerase chain reaction (PCR) was assayed in 55 cases to detect serum viral RNA. A liver biopsy was performed in 93 cases. RESULTS: The 64.4% of the studied patients were seropositive and PCR for HCV was positive in the 83% out of the 55 studied cases. The group of 19 patients suffering from familial porphyria cutanea tarda showed a similar prevalence to the group of 113 patients with sporadic porphyria (47.3% vs 67.2%). In 82% out of the total cases, risk factors for HCV infection were not found. In seropositive cases, both transaminases were more frequently altered than in seronegative ones. The univariant study was not able to demonstrate the relationship between seropositivity, and transaminases, urinary porphyrins alcohol consumption, frequency of antibodies against hepatitis B virus, relevance of the histological hepatic damage or incidence of porphyria relapses. Nevertheless, a multivariant analysis on 93 patients with liver biopsy showed that the risk to suffer from severe liver disease increases 2.8 times in seropositive patients, 3.13 times in those presenting high levels of serum ferritin and 9.25 times in patients up to 65 years old. CONCLUSIONS: The frequent hepatitis C virus infection in patients with porphyria cutanea tarda must be considered as a precipitating factor for the disease and as an aggravating factor of its associated liver damage.

Adult↗

PubMed2006

Molecular dynamics simulations of the enzyme Cu, Zn superoxide dismutase.

The enzyme Cu, Zn superoxide dismutase (Cu,Zn-SOD) is a ubiquitous oxireductase, which is responsible for the cellular defense against oxidative stress caused by the high toxicity of the superoxide radical, and has been also linked to some cases of familiar amyotrophic lateral sclerosis. In the present study a set of molecular mechanics parameters for the active site of Cu,Zn-SOD has been derived. Afterward, an extensive molecular dynamics simulation has been carried out in an aqueous environment. The obtained results shed a further light on the structural flexibility of the backbone, where the active site is nested, and the solvation shell occupancy. The relatively small backbone deviation, shown by a root-mean-square deviation below 1.0 A, confirms the accuracy of the parameters. The solvent shell analysis has shown that the first solvation shell is located at about 5 A from the copper ion, generating an empty cavity with enough space to accommodate the superoxide radical. The low residence time means that a high permutation rate of water molecules in both solvation shells is consistent with the efficiency of this catalytic mechanism. Hybrid studies using ONIOM methodologies can now be done to evaluate the mechanistic implications of the explicit inclusion of the whole system.

Computer Simulation↗

PubMed1988

Generational variability in the patterns of motor activity circadian rhythm in the rats.

Motor activity circadian rhythm of 32 rats belonging to three consecutive generations of rats from a laboratory strain, has been studied. This rhythm has been registered from the day of weaning (at 21 days) to at least 30 days after. The pattern of this rhythm has been analyzed by means of a Fourier analysis, by which the daily power spectrum of each rat was obtained. Based on the mean power spectrum of each animal, the variance among the different families and generations has been calculated. Results show that the variance increases in a statistically significant way with the succeeding generations. It can be suggested that in the third generation, the characteristics of the progenitors are dispersed, confirming the genetic character of the rhythm and suggesting a multigenic character for the transmission of the circadian rhythm of motor activity.

Animals↗

PubMed2001

[Study on the reaction mechanism and application of eldest amine basic dye with nitrite].

In this paper, the reaction of eldest amine basic dye with nitrite in hydrochloric acid medium by ultraviolet-visible spectrometry, electrochemistry analysis, Fourier transform infrared spectrometer and nuclear magnetic resonance was studied systematically. The reaction of its structure and effect was preliminarily understood. It is realized that there is diazotization-coupling or diazo-reaction mechanism, generating triazene or diazo-compound. It has magnificent meaning for perfecting, applying this kind of basic dye and instituting a ultraviolet-visible spectrometry or electrochemistry analysis new method of measuring nitrite.

Amines↗

PubMed1980

Accuracy of methods for calculating cerebral blood flow from intracarotid xenon-133 injection.

The accuracy of the three commonly used methods, the initial slope analysis, the stochastic analysis, and the compartmental analysis, for calculating mean cerebral blood flow from xenon-133 clearance curves was studied with the use of computer-generated and real curves. The accuracy of calculation was affected by the cutoff time of the curve, by the level of the compartmental blood flows to white and gray matter and by the ratio of these flow levels, by the relative weight of gray matter, and by the choice of the method of calculation. None of the methods was clearly superior to the others. Each had its own defects that render it more or less suitable for different situations. All three methods generally overestimated mean cerebral blood flow. This overestimation was greater the lower the flow. A curve-fitting index was devised which can be used to check the validity of the bicompartmental model when using compartmental analysis. This same index can provide, though not always, an estimate of the error in the calculation of mean cerebral blood flow when an optimization method is used.

Cerebrovascular Circulation↗

PubMed1992

Automated detection and quantification of venous beading using Fourier analysis.

Venous beading associated with diabetic retinopathy is currently assessed by means of subjective comparison to standard photographs from the modified Airlie House classification scheme. We describe a computerized grading scheme for venous beading. The algorithm, based on Fourier analysis of vessel width measurements, generates a venous beading index (VBI) for digitized colour fundus photographs. Colour photographs of local vessel segments about 1200 microns in length were evaluated by experienced graders. A comparison between the VBI and subjective grading showed good agreement. The mean VBI values across the four levels of clinical grading were significantly different (p = 0.000). Multiple comparison testing indicated that the VBI was able to significantly differentiate between all four categories except the "questionable" (grade 1) category (p < 0.05). We also found that progression of venous beading can be followed with the VBI. The results indicate that further development of automated grading of venous beading is warranted.

Algorithms↗

PubMed1990

Psychologic health of women: a phenomenologic study of women's inner strength.

This article describes a phenomenologic research study of psychologic health--the inner strength of women. The research objective was to identify and to describe the meanings, qualities, and structures of the lived experiences of inner strength for women. Nine women were selected who acknowledged and articulated their subjective experience of inner strength. Data were generated using unstructured, in-depth, face-to-face interviews. Data analysis incorporated the methods of Colaizzi, van Manen, and Spiegelberg. The results revealed nine essential themes that add to the cumulative knowledge base of psychologic health by generating new meanings of the nature and essences of inner strength from female perspectives.

Adult↗

PubMed2003

Student generated learning objectives: extent of congruence with faculty set objectives and factors influencing their generation.

CONTEXT: A problem-based learning strategy is used for curriculum planning and implementation at the Arabian Gulf University, Bahrain. Problems are constructed in a way that faculty-set objectives are expected to be identified by students during tutorials. Students in small groups, along with a tutor functioning as a facilitator, identify learning issues and define their learning objectives. PURPOSE: We compared objectives identified by student groups with faculty-set objectives to determine extent of congruence, and identified factors that influenced students' ability at identifying faculty-set objectives. METHOD: Male and female students were segregated and randomly grouped. A faculty tutor was allocated for each group. This study was based on 13 problems given to entry-level medical students. Pooled objectives of these problems were classified into four categories: structural, functional, clinical and psychosocial. Univariate analysis of variance was used for comparison, and a p > 0.05 was considered significant. RESULTS: The mean of overall objectives generated by the students was 54.2%, for each problem. Students identified psychosocial learning objectives more readily than structural ones. Female students identified more psychosocial objectives, whereas male students identified more of structural objectives. Tutor characteristics such as medical/non-medical background, and the years of teaching were correlated with categories of learning issues identified. CONCLUSION: Students identify part of the faculty-set learning objectives during tutorials with a faculty tutor acting as a facilitator. Students' gender influences types of learning issues identified. Content expertise of tutors does not influence identification of learning needs by students.

Bahrain↗

PubMed2001

Terminologia anatomica: considered from the perspective of next-generation knowledge sources.

This report examines the semantic structure of Terminologia Anatomica, taking one page as an example. The focus of analysis is the meaning imparted to an anatomical term by virtue of its location within the structured list. Terminologia's structure, expressed through hierarchies of headings, varied typographical styles, indentations, and an alphanumeric code, implies specific relationships among the terms embedded in the list. Together, terms and relationships can potentially capture essential elements of anatomical knowledge. The analysis focuses on these knowledge elements and evaluates the consistency and logic in their representation. Most critical of these elements are class inclusion and part-whole relationships. Since these are implied, rather than explicitly modeled, by Terminologia, the use of the term list is limited to those who have some knowledge of anatomy; computer programs are excluded from navigating through the terminology. Assuring consistency in the explicit representation of anatomical relationships would facilitate adoption of Terminologia as the anatomical standard by the various controlled medical terminology (CMT) projects. These projects are motivated by the need to computerize the patient record, and their aim is to generate machine-understandable representations of biomedical concepts, including anatomy. Because of the lack of a consistent and explicit representation of anatomy, each of these CMTs has generated its own anatomy model. None of these models is compatible with any other, yet each is consistent with textbook descriptions of anatomy. The analysis of the semantic structure of Terminologia Anatomica leads to some suggestions for enhancing the term list in ways that would facilitate its adoption as the standard for anatomical knowledge representation in biomedical informatics.

Anatomy↗

PubMed1998

A multiway 3D QSAR analysis of a series of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-methoxybenzamides.

Recently, the multilinear PLS algorithm was presented by Bro and later implemented as a regression method in 3D QSAR by Nilsson et al. In the present article a well-known set of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-methoxybenzamides, with affinity towards the dopamine D2 receptor subtype, was utilised for the validation of the multilinear PLS method. After exhaustive conformational analyses on the ligands, the active analogue approach was employed to align them in their presumed pharmacologically active conformations, using (-)-piquindone as a template. Descriptors were then generated in the GRID program, and 40 calibration compounds and 18 test compounds were selected by means of a principal component analysis in the descriptor space. The final model was validated with different types of cross-validation experiments, e.g. leave-one-out, leave-three-out and leave-five-out. The cross-validated Q2 was 62% for all experiments, confirming the stability of the model. The prediction of the test set with a predicted Q2 of 62% also established the predictive ability. Finally, the conformations and the alignment of the ligands in combination with multilinear PLS, obviously, played an important role for the success of our model.

Algorithms↗

PubMedDate not supplied

Base deficit and alveolar-arterial gradient during resuscitation contribute independently but modestly to the prediction of mortality after burn injury.

The main determinants of mortality after burn injury that can be measured on admission include age, total burn size (% burn), and inhalation injury (INHAL). Other variables, measured during resuscitation, may provide additional information about injury severity. We assessed the utility of early arterial blood gas (ABG) data in predicting mortality after burn injury. Data were limited to samples obtained during the first 2 days after burn injury and to those obtained during high-frequency percussive ventilation. Mean values for each patient's ABG data were calculated; subsequent analysis used these derived variables. Logistic regression analysis (LRA) was used to generate a mortality predictor using burn, age (as a cubic age score, AGE), and INHAL. LRA was then repeated with the ABG variables. A total of 162 patients were included. By univariate analysis, death was associated with increased alveolar-arterial gradient (AaDO2), AGE, % burn, full-thickness burn size, INHAL, and with decreased pH and base excess. LRA of % burn, AGE, INHAL, and full-thickness burn size retained the first three variables. The addition of ABG data demonstrated that mean burn excess and mean AaDO2 also contributed independently to mortality. However, there was no difference in accuracy (86%) between the two equations. By Kaplan Meier analysis, AaDO2 but not BE predicted earlier death in those who died. Measured during resuscitation, metabolic acidosis (ie, a base deficit) and oxygenation failure (ie, increased AaDO2) contributed independently, but modestly, to ultimate mortality after burn injury. The inclusion of these variables did not improve predictive accuracy. Whether therapies targeted at these endpoints would improve outcome is unknown.

Acidosis↗

PubMed2000

EEG bands during wakefulness, slow-wave and paradoxical sleep as a result of principal component analysis in man.

Human electroencephalogram (EEG) has been divided in bands established by visual inspection that frequently do not correspond with EEG generators nor with functional meaning of EEG rhythms. Power spectra from wakefulness, stage 2, stage 4 and paradoxical sleep of 8 young adults were submitted to Principal Component Analyses to investigate which frequencies covaried together. Two identical eigenvectors were identified for stage 2 and stage 4: 1 to 8 Hz and 5 to 15 Hz (87.95 and 84.62 % of the total variance respectively). Two eigenvectors were extracted for PS: 1 to 9 Hz and 10 to 15 Hz (81.62% of the total variance). Three eigenvectors were obtained for W: with frequencies between 1 to 7 Hz, 7 to 11 Hz, and 12 to 15 Hz (78.32% of the total variance). Power for all frequencies showed significant differences among vigilance states. These results indicate that slow wave activity can oscillate at higher frequencies, up to 8 Hz, and that spindle oscillations have a wider range down to 5 Hz. No theta band was independently identified, suggesting either that delta and theta oscillations are two rhythms under the same global influence, or that the traditional division of theta band in the human cortical EEG is artificial. Alpha as a band was identified only during wakefulness. Principal component analysis upon spectral densities extracted broad bands different for each vigilance state and from traditional bands, consistent with functional significance of EEG and with frequencies of generators of rhythmic activity obtained in cellular studies in animals.

Adult↗

PubMed1981

Planar curve analysis of three-channel auditory brain stem response: a preliminary report.

Recording of auditory brain stem responses (ABRs) were made in guinea pigs by means of far-field computer averaging from three orthogonal electrode pairs. The 'Y' locations were mouth and nuchal ridge, 'X' locations left and right mastoids, and 'Z' locations vertex and throat. Three-dimensional models were constructed to plot simultaneous points from the three averages in a voltage-voltage-voltage space. In all five animals tested, at least three subsets of sequential data points lie in separate planes. The data points in each plane roughly correspond to waves I to III in the guinea pig ABR as recorded from the vertex-throat electrode pair. The planarity of data points is a new observation and is not predicted from the single-channel recordings. Three-dimensional planes are also found by means of vectorcardiography, which suggests some underlying principle, such as synchrony and homogeneity of anatomical position of the generators. Planar analysis of ABRs may be useful in analyzing and utilizing the additional information obtainable from 'non-standard' electrode pairs.

Acoustic Stimulation↗

PubMed1997

A t-statistic for objective interpretation of comparative genomic hybridization (CGH) profiles.

An objective method for interpreting comparative genomic hybridization (CGH) is described and compared with current methods of interpretation. The method is based on a two-sample t-statistic in which composite test:reference and reference:reference CGH profiles are compared at each point along the genome to detect regions of significant differences. Composite profiles are created by combining CGH profiles measured from several metaphase chromosomes for each type of chromosome in the normal human karyotype. Composites for both test:reference and reference:reference CGH analyses are used to generate mean CGH profiles and information about the variance therein. The utility of the method is demonstrated through analysis of aneusomies and partial gain and loss of DNA sequence in a myeloid leukemia specimen. Banding analyses of this specimen indicated inv (3)(q21q26), del (5)(q2?q35), -7, +8 and add (17)(p11.2). The t-statistic analyses of CGH data indicated rev ish enh (8) and rev ish dim (5q31.1q33.1,7q11.23qter). The undetected gain on 17p was small and confined to a single band (17p11.2). Thus, the t-statistic is an objective and effective method for defining significant differences between test and reference CGH profiles.

Humans↗

PubMedDate not supplied

Estimation of fetal weight by ultrasound.

Birth weight (BW) and log10 birth weight (LBW) are expressed as linear, multilinear, parabolic, and polynomial regression functions of the abdominal circumference (AC), and combinations of fetal index measurements, namely, AC and head circumference (HC); biparietal diameter (BPD) and AC; and BPD, HC, and AC. The relationship of somatic weight and log10 somatic weight to AC was similarly determined. The analysis generated 20 equations whose accuracy in providing BW estimates is compared. Several equations provide BW estimates whose mean percentage deviations from measured BWs do not differ significantly. The deviations, however, have the smallest variance when BW is estimated from the HC and AC either by using a multilinear regression equation or by deriving separate estimates of brain and somatic weights from these index measurements. The role of individual and population differences in fetal anthropometry as causes of error in estimating BW by different methods is discussed. Because HC is a function of both BPD and occipito-frontal diameter (OFD), it is a better brain-size modulus than the commonly used BPD and avoids the errors of underestimation which occur when the BPD is unusually small in cases of dolichocephaly. A comparison of ponderal growth in American and South African fetal populations shows differences throughout most of the gestational range (26-40 wk) analyzed in this study.

Abdomen↗

PubMed2003

A unified statistical and information theoretic framework for multi-modal image registration.

We formulate and interpret several registration methods in the context of a unified statistical and information theoretic framework. A unified interpretation clarifies the implicit assumptions of each method yielding a better understanding of their relative strengths and weaknesses. Additionally, we discuss a generative statistical model from which we derive a novel analysis tool, the auto-information function, as a means of assessing and exploiting the common spatial dependencies inherent in multi-modal imagery. We analytically derive useful properties of the auto-information as well as verify them empirically on multi-modal imagery. Among the useful aspects of the auto-information function is that it can be computed from imaging modalities independently and it allows one to decompose the search space of registration problems.

Algorithms↗

PubMed2005

The 3D structure of the binding pocket of the human oxytocin receptor for benzoxazine antagonists, determined by molecular docking, scoring functions and 3D-QSAR methods.

Molecular docking and 3D-QSAR studies were performed to determine the binding mode for a series of benzoxazine oxytocin antagonists taken from the literature. Structural hypotheses were generated by docking the most active molecule to the rigid receptor by means of AutoDock 3.05. The cluster analysis yielded seven possible binding conformations. These structures were refined by using constrained simulated annealing, and the further ligands were aligned in the refined receptor by molecular docking. A good correlation was found between the estimated deltaG(bind) and the pKi values for complex F. The Connolly-surface analysis, CoMFA and CoMSIA models q2(CoMFA) = 0.653, q2(CoMSA) = 0.630 and r2(pred,CoMFA) = 0.852 , r2(pred,CoMSIA) = 0.815) confirmed the scoring function results. The structural features of the receptor-ligand complex and the CoMFA and CoMSIA fields are in closely connected. These results suggest that receptor-ligand complex F is the most likely binding hypothesis for the studied benzoxazine analogs.

Benzoxazines↗

PubMed1993

Application of Markov chains to linked genes with interference. II. Genotypic selection.

The case of a selfing population and three diallelic loci under genotypic selection is considered. Expressions are obtained for the mean number of times that a process passes through a transient state, for the mean number of generations needed to reach an absorbing state, and for other interesting parameters. The variates under analysis are the coefficient of coincidence, the probabilities of recombination, and the genotypic fitness. The expressions obtained allow the direct computation of the entries of the inverse matrices, avoiding the inverting routines that could present problems of ill-conditioning. Three types of inheritance for fitness are considered in a numerical application: no dominance, complete dominance, and overdominance. Finally, the possible existence of interaction between coincidence and dominance for fitness is analyzed.

Genes, Dominant↗