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PubMed1999

Selective cloning of peanut allergens, including profilin and 2S albumins, by phage display technology.

BACKGROUND: Peanut kernels contain many allergens able to elicit IgE-mediated type 1 allergic reactions in sensitized individuals. Sera from sensitized patients recognize variable patterns of IgE-binding proteins. The identification of the IgE-binding proteins of peanut extract would faciliate improvement of diagnostic and immunotherapeutic approaches as well as development of sensitive test systems for the detection of hidden peanut allergens present as additives in various industrial food products and the investigation of their stability during processing of food products. METHODS: We applied the pJuFo cloning system based on the phage surface display of functional cDNA expression products to clone cDNAs encoding peanut allergens. Sera (n = 40) of peanut-allergic individuals were selected according to case history, radioallergosorbent test and immunoblot analysis to demonstrate IgE binding towards the newly identified recombinant allergens. RESULTS: In addition to the known allergens Ara h 1 and Ara h 2 we were able to identify four allergens with estimated molecular weights of 36, 16, 14.5 and 14 kDa. Three of them formally termed Ara h 4, Ara h6 and Ara h 7 show significant sequence similarities to the family of seed storage proteins and the fourth (Ara h 5) corresponds to the well-known plant allergen profilin. Immunoblotting of the six expressed recombinant allergens with 40 patients sera shows 14 individual recognition patterns and the following frequency of specific IgE binding: Ara h 1 was recognized by 65%, Ara h 2 by 85%, Ara h 4 by 53%, Ara h 5 by 13%, Ara h 6 by 38% and Ara h 7 by 43% of the selected sera. CONCLUSIONS: All of the selected peanut-positive sera can detect at least one of the six identified recombinant allergens which can be used to establish individual patients' reactivity profiles. A comparison of these profiles with the clinical data will possibly allow a further insight into the relationship between clinical severity of the symptoms and specific IgE levels towards the six peanut allergens.

2S Albumins, Plant↗
PubMed1976

[Aspects to birth control (author's transl)].

From 1964, the year with the highest new born rate since 1945, until 1972, the number of births in the BRD was reduced for 34%. Simultaneously, the birth rate of women between 20 and 30 years was decreased for a third. Presently, the average age of half of the women who deliver their first or second child is over 30 years. While on the one hand there are investigations on the practical experiences which are hidden behind the obvious "one child effect", it would be, on the other hand, dangerous, to lay out a demographic "production policy" which shows no interest in economy. In birth-control, biotic-private individual foundations are variable elements; social values, however, are non individual objectives [corrected] with temporal relatively great constancy. The splitting of these elements is, in the 20th century, tracing back with violent actuality to the original big line of Malthus and Darwin, which is to maintain sufficient scope for nourishment and reproduction to the human world with its vegetable and animal life. This concerns industrial and development countries as well. The challenge is to line out acceptable ideas for the solution of the Circulus vitiosus, based on statistical data, on socio-philosophic understandings which have to be worked out yet and on common sense.

Age Factors↗
PubMed1994

Heart signal recognition by Hidden Markov Models: the ECG case.

Wave recognition in ECG signals by Hidden Markov Models (HMMs) relies on the stationary assumption for the set of parameters used to describe ECG waves. This approach seems unnatural and consequently generates severe errors in practice. A new class of HMMs called Modified Continuous Variable Duration HMMs is proposed to account for the specific properties of the ECG signal. An application of the latter, coupled with a multiresolution front-end analysis of the ECG is presented. Results show these methods can increase the performance of ECG recognition compared to classical HMMs.

Artificial Intelligence↗
PubMedDate not supplied

Neural networks provide superior description of Giardia lamblia inactivation by free chlorine.

Use of conventional models to describe data on microbial inactivation during disinfection suffers from limitations with respect to flexibility and direct quantitative incorporation of water quality variables. This paper develops an approach to analysis of such data using neural networks (NNs). Using the data on free chlorine inactivation of Giardia lamblia previously reported, it was found that the use of an NN with a single hidden layer and four hidden neurons provided a superior (better) fit to the data with a reduced number of model parameters when compared to the fitting of this data using a conventional approach. Therefore, the use of NN models should be considered in the future assessment of microbial inactivation during disinfection. Incorporation of additional facets of the disinfection process, such a disinfectant decay, needs to be considered in subsequent development of this approach.

Animals↗
PubMed2004

[Quality of life in unipolar depressive and bipolar affective patients].

OBJECTIVE: To assess subjective quality of life (QOL) of subjects with unipolar depressive and bipolar affective disorders. METHODS: 153 consecutive psychiatric in-patients were assessed with standardized interviews. Prior to discharge QOL was assessed with WHOQOL-bref. With the help of multivariate statistics, the effect of illness and biographical factors on four domains of QOL (physical health, psychological, social relationships and environment) was analyzed. RESULTS: 103 patients suffered from unipolar depression, 51 from bipolar affective disorder (30 fulfilled criteria for a mixed or pure manic episode). With the exception of the domain environment for (mixed) manic patients, all patients reported lower QOL in all domains than was reported for the general population according to the German test manual. Multivariate analyses revealed that the chosen variables explained between 11.1 % (social relationships) and 33.6 % (psychological) of the variance of the QOL domains. The domains "psychological" and "environment" were first of all explained by the presence of a (mixed) manic episode, while the best variable to predict "physical health" was presence of comorbid neurotic disorder. The depression score had little additional effects on QOL. CONCLUSIONS: We found little support that the QOL domains of the WHOQOL-bref in affective disorder are only hidden depression scores, as has been argued before. Therefore, QOL could be an interesting construct to better understand differences between subjective evaluation and (supposedly) objective psychopathology in bipolar affective disorders.

Adult↗
PubMed1999

Statistical physics and physiology: monofractal and multifractal approaches.

Even under healthy, basal conditions, physiologic systems show erratic fluctuations resembling those found in dynamical systems driven away from a single equilibrium state. Do such "nonequilibrium" fluctuations simply reflect the fact that physiologic systems are being constantly perturbed by external and intrinsic noise? Or, do these fluctuations actually, contain useful, "hidden" information about the underlying nonequilibrium control mechanisms? We report some recent attempts to understand the dynamics of complex physiologic fluctuations by adapting and extending concepts and methods developed very recently in statistical physics. Specifically, we focus on interbeat interval variability as an important quantity to help elucidate possibly non-homeostatic physiologic variability because (i) the heart rate is under direct neuroautonomic control, (ii) interbeat interval variability is readily measured by noninvasive means, and (iii) analysis of these heart rate dynamics may provide important practical diagnostic and prognostic information not obtainable with current approaches. The analytic tools we discuss may be used on a wider range of physiologic signals. We first review recent progress using two analysis methods--detrended fluctuation analysis and wavelets--sufficient for quantifying monofractual structures. We then describe recent work that quantifies multifractal features of interbeat interval series, and the discovery that the multifractal structure of healthy subjects is different than that of diseased subjects.

Biophysical Phenomena↗
PubMed2004

Fold-specific substitution matrices for protein classification.

MOTIVATION: Methods that focus on secondary structures, such as Position Specific Scoring Matrices and Hidden Markov Models, have proved useful for assigning proteins to families. However, for assigning proteins to an attribute class within a family these methods may introduce more free parameters than are needed. There are fewer members and there is less variability among sequences within a family. We describe a method for organizing proteins in a family that exhibits up to an order of magnitude reduction in the number of parameters. The basis is the log odds ratio commonly used to measure similarity. We adapt this to characterize the sequence dissimilarities that give rise to attribute differentiation. This leads to the definition of Class Attribute Substitution Matrices (CLASSUM), a dual of the BLOSUM. RESULTS: The method was applied to classify sequences hierarchically in the lambda and kappa subgroups of the immunoglobulin superfamily. Positions conferring class were identified based on the degree of amino acid variability at a position. The CLASSUM computed for these positions classified better than 90% of test data correctly compared with 35-50% for BLOSUM-62. The expected value for a random matrix is 14%. The results suggest that family-specific data-derived substitution matrices can improve the resolution of automated methods that use generic substitution matrices for searching for and classifying proteins.

Algorithms↗
PubMed1985

Variability of genetic load with changing socio-cultural environment.

Variability in genetic load has been studied against their contrasting socioeconomic and cultural backgrounds in two endogamous populations, namely, the well-off Brahmins and the low income Jalaris of Visakhapatnam, India. The A (genetic and environmental damage) and B (hidden genetic damage) estimates are higher in Jalaris. Decreased A estimates indicate the better medical care in Brahmins; the value of B could be low since many of the deaths in consanguineous families due to infectious diseases are now rarer. The genetic load (B/A ratio) indicates that the average gamete carries 0.057 and 2.123 deleterious genes, respectively, in Brahmins and Jalaris, which, if made homozygous, would kill an individual before reproductive age. The load is 35 times higher in Jalaris; this may be due to their higher inbreeding level. Contrasting socioeconomic differences and meagre medical aid might add another bias towards relatively higher B/A in Jalaris. In general the observed genetic load in both populations are lower than in other studies which may be due to gradual elimination of deleterious genes by continued practice of inbreeding.

Consanguinity↗
PubMed1986

Hypernychthemeral sleep-wake cycle: some hidden regularities.

A patient with a sleep-wake cycle greater than 24 h recorded his sleep-onset and wake times for 4 years. During this time the patient found himself unable to maintain a 24-h sleep-wake schedule. The lengths of his sleep-wake periods (subjective days) and his sleep periods were highly variable. Nonetheless, there were certain unexpected regularities in his sleep-wake data, corresponding to fixed clock hours. Across the 4-year period, there were certain clock hours during which sleep onset and waking were likely to occur and certain clock hours that may be considered forbidden zones for sleep, during which the patient rarely either began or ended a sleep period. It is possible that the unexpected regularities resulted from partial entrainment to external cues or from some residual influence of an endogenous ultradian-regulating mechanism.

Adult↗
PubMed1993

Neural network analysis of ventilation-perfusion lung scans.

A neural network model was constructed to interpret ventilation-perfusion (V/Q) lung scans. This model was trained with data from 100 consecutive V/Q scans with pulmonary angiographic correlation. The network was constructed from 28 input parameters that described various standard V/Q findings, which were fed into a single hidden layer that contained 10-20 nodes. The network output indicated the percentage probability of pulmonary embolism for each set of findings on V/Q scans. This network was then used to classify 28 new scans; the resultant classifications were compared with the rankings of an experienced observer who read the scans without knowledge of the correlative angiographic data. The network with 15 hidden nodes outperformed the experienced observer in prediction of the likelihood of pulmonary embolism in the 28-case test set (P = .039). The neural network has several advantages over current algorithms for interpretation of V/Q scans, including the ability to synthesize many variables into a single conclusion and to learn, or modify itself, at exposure to additional data.

Adult↗
PubMed2006

[A 35-year-old man with aggressive periodontitis].

BACKGROUND: Aggressive and necrotic periodontal diseases may occasionally be associated with undiagnosed systemic diseases and immune deficiencies. We present a 35-year-old man with an undiagnosed hypo-gammaglobulinaemia and severe aggressive periodontitis. MATERIAL AND METHODS: Gingival biopsies and peripheral blood were collected for immunohistochemical and cell culture studies from the patient with aggressive periodontitis, 3 patients with chronic periodontitis and 3 controls. Mast cells and neutrophils were visualised and counted on histological sections. Freshly isolated monocytes were challenged with lipopolysaccharides and supernatants assayed for interleukin (IL)-1beta, IL-8, IL-10, IL-12 and tumour necrosis factor. Analysis of peripheral blood for any hidden systemic diseases was carried out, including blood cell counts and measurement of immunoglobulin levels in serum. RESULTS: The patient had depressed levels of immunoglobulin in serum (IgG: 3.2 g/l, IgA: 0.6 g/l and IgM: 0.4 g/l ) and was diagnosed with common variable immunodeficiency. The inflamed gingiva revealed significantly increased numbers of mast cells and neutrophils. Signs of mast cell degranulation were observed in the aggressive periodontitis patient only, and monocytes secreted significantly more IL-1beta, IL-8, IL-12 and tumour necrosis factor, but less IL-10. INTERPRETATION: Low antibody production concurrent with an obviously increased activity of the innate immune defense with massive release of pro-inflammatory cytokines may partly cause the severe destruction of periodontal tissue as seen in this patient.

Adult↗
PubMedDate not supplied

Oral infections and glycemic control in pregnant type 2 diabetics.

BACKGROUND: The relationship between diabetes mellitus and infection is bidirectional. Diabetes favors infection, while infections make controlling diabetes much more difficult. The most frequent infections encountered in pregnant diabetics are those of the urinary tract (UTI) and cervicovaginal (CVI) area. Periodontal diseases (PD) and active caries (AC) are infectious diseases frequently found in these cases often remaining as hidden entities of low intensity. The aim of this study was to assess whether there is an association between PD and caries with lack of glycemic control often encountered in pregnant type 2 diabetic women. METHODS: A single skilled researcher performed the periodontal evaluation of PD and AC cases. Glycated alpha hemoglobin (HbA(1c)) over 6.5% was used to diagnose metabolic glucose disturbances. The controlled variables were UTI, CVI and adherence to treatment. The statistical tests used were chi-square adjusted for continuity, analysis of variance, odds ratio with 95% confidence intervals and logistic regression with a significance level of p < 0.05. RESULTS: One hundred twenty-seven type 2 diabetic women were seen during the second trimester of their pregnancies. Mean age was 31.3 years; 55% had lack of glycemic control associated with CVI (chi2 21.07, p < 0.000), PD (chi2 5.72, p < 0.005) and UTI (chi2 13.77, p < 0.000) with therapeutic adherence (TA) (chi2 14.80, p < 0.00). No association was found with AC. The logistic regression results showed that UTI, CIV, PD and TA are associated with lack of glycemic control. CONCLUSIONS: Periodontal diseases may act as "hidden" infections in pregnant diabetics and be associated with lack of glycemic control. This situation should be taken into consideration by healthcare teams in charge of prenatal care.

Adult↗
PubMed1992

The physical exertion factor in compensable work injuries. A hidden flaw in previous research.

Studies of the industrially injured worker invariably suggest that compensation reinforces pain and prolongs disability. These claims may be spurious. Researchers have historically failed to take into account the fact that return to work is partly contingent on the amount of physical labor involved in the job, and that compensation and noncompensation groups differ on this variable in important ways. Patients on compensation are more likely involved in heavy physical exertion on their jobs. In this study, 1,191 workers with low-back pain who were injured on the job were compared with 389 workers who were injured away from work on variables of disability time and pain intensity. To disentangle the effects of physical exertion, four levels ranging from none to heavy were examined. The results suggest that injury on the job operates both independent of level of physical exertion, as well as in interaction with it, to extend the period of disability. Injury on the job is associated with prolonged disability time, irrespective of the type of job performed.

Adult↗
PubMed2004

A hidden markov model derived structural alphabet for proteins.

Understanding and predicting protein structures depends on the complexity and the accuracy of the models used to represent them. We have set up a hidden Markov model that discretizes protein backbone conformation as series of overlapping fragments (states) of four residues length. This approach learns simultaneously the geometry of the states and their connections. We obtain, using a statistical criterion, an optimal systematic decomposition of the conformational variability of the protein peptidic chain in 27 states with strong connection logic. This result is stable over different protein sets. Our model fits well the previous knowledge related to protein architecture organisation and seems able to grab some subtle details of protein organisation, such as helix sub-level organisation schemes. Taking into account the dependence between the states results in a description of local protein structure of low complexity. On an average, the model makes use of only 8.3 states among 27 to describe each position of a protein structure. Although we use short fragments, the learning process on entire protein conformations captures the logic of the assembly on a larger scale. Using such a model, the structure of proteins can be reconstructed with an average accuracy close to 1.1A root-mean-square deviation and for a complexity of only 3. Finally, we also observe that sequence specificity increases with the number of states of the structural alphabet. Such models can constitute a very relevant approach to the analysis of protein architecture in particular for protein structure prediction.

Algorithms↗
PubMed1995

Serological response patterns of melanoma patients immunized with a GM2 ganglioside conjugate vaccine.

Gangliosides, such as GM2, GD2, GD3, and 9-O-acetyl GD3, are receiving attention as targets for antibody-based and vaccine-based therapies of melanoma. GM2 appears to be a particularly immunogenic ganglioside in humans, as indicated by the presence of naturally occurring IgM anti-GM2 antibodies in approximately 5% of humans and the fact that immunization with irradiated GM2-expressing melanoma cells or purified GM2 adherent to bacillus Calmette-Guérin elicits GM2 antibodies of low to moderate titers in a high proportion of vaccinated patients. To develop vaccines that consistently induce high titers of IgM as well as IgG anti-GM2 antibodies, vaccines containing GM2 conjugated to keyhole limpet hemocyanin as the carrier protein and QS-21 as the adjuvant have been constructed. The serological response of vaccinated patients was monitored by ELISA using purified GM2 ganglioside for IgM and IgG anti-GM2 antibodies and for GM2 cell surface-reactive antibodies by immune adherence assays and cytotoxic tests (IgM antibodies) and mixed hemadsorption assays (IgG antibodies). The majority of vaccinated patients developed IgM and IgG antibodies detectable by ELISA. In most cases, the results of IgM ELISA correlated with assays for cell surface-reactive IgM antibodies. This was not true for IgG anti-GM2 antibodies, where strong discrepancies were seen between high titers in ELISA and little or no reactivity in mixed hemadsorption tests for cell surface-reactive antibodies. These IgG antibodies (and the less frequent IgM antibodies that show similar discrepancies) may be directed against GM2 determinants that are buried, hidden, or not present on GM2-expressing target cells. With regard to a major objective of ganglioside vaccines--i.e., generation of cytotoxic antibodies--the GM2-keyhole limpet hemocyanin/QS-21 vaccine is clearly superior to the previously tested GM2/bacillus Calmette-Guérin vaccine. However, variability in patient response and lack of persistence of high-titered IgM cytotoxic antibodies in many patients are problems that remain to be solved.

Adjuvants, Immunologic↗
PubMed2003

Multivariate exploratory tools for microarray data analysis.

The ultimate success of microarray technology in basic and applied biological sciences depends critically on the development of statistical methods for gene expression data analysis. The most widely used tests for differential expression of genes are essentially univariate. Such tests disregard the multidimensional structure of microarray data. Multivariate methods are needed to utilize the information hidden in gene interactions and hence to provide more powerful and biologically meaningful methods for finding subsets of differentially expressed genes. The objective of this paper is to develop methods of multidimensional search for biologically significant genes, considering expression signals as mutually dependent random variables. To attain these ends, we consider the utility of a pertinent distance between random vectors and its empirical counterpart constructed from gene expression data. The distance furnishes exploratory procedures aimed at finding a target subset of differentially expressed genes. To determine the size of the target subset, we resort to successive elimination of smaller subsets resulting from each step of a random search algorithm based on maximization of the proposed distance. Different stopping rules associated with this procedure are evaluated. The usefulness of the proposed approach is illustrated with an application to the analysis of two sets of gene expression data.

Algorithms↗
PubMed2005

Gender and liver fibrosis in chronic hepatitis: the role of iron status.

BACKGROUND: The role of gender in the progression of fibrosis in chronic hepatitis C is still under investigation. AIM: To investigate whether gender affects the progression of liver disease and/or hides other risk factors. METHODS: A prospective series of 121 consecutive patients with chronic hepatitis C underwent liver biopsy. Grading and staging for chronic hepatitis were each evaluated according to Ishak's classification. RESULTS: In univariate and multivariate analysis on the whole group of patients, male gender was not associated either with significant liver fibrosis (Ishak's score > 2) or with cirrhosis (Ishak's score > 4). On the contrary, in univariate analysis on patients aged < or = 50 years, male gender was nearly significantly (P = 0.06) predictive of liver fibrosis, whereas it was not in patients > 50 years. Hepatic iron grading, along with age, was an independent factor associated with fibrosis. Moreover, the values of all the variables which describe iron status were significantly higher in males aged < or = 50 years in comparison with females of the same age. CONCLUSIONS: In chronic hepatitis C, male gender may be predictive of liver fibrosis only in patients aged < or = 50 years. Among fibrogenetic factors hidden by gender, iron status could play a major role.

Adult↗
PubMed2005

Using cellular automata images and pseudo amino acid composition to predict protein subcellular location.

The avalanche of newly found protein sequences in the post-genomic era has motivated and challenged us to develop an automated method that can rapidly and accurately predict the localization of an uncharacterized protein in cells because the knowledge thus obtained can greatly speed up the process in finding its biological functions. However, it is very difficult to establish such a desired predictor by acquiring the key statistical information buried in a pile of extremely complicated and highly variable sequences. In this paper, based on the concept of the pseudo amino acid composition (Chou, K. C. PROTEINS: Structure, Function, and Genetics, 2001, 43: 246-255), the approach of cellular automata image is introduced to cope with this problem. Many important features, which are originally hidden in the long amino acid sequences, can be clearly displayed through their cellular automata images. One of the remarkable merits by doing so is that many image recognition tools can be straightforwardly applied to the target aimed here. High success rates were observed through the self-consistency, jackknife, and independent dataset tests, respectively.

Algorithms↗