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At least 1,081 records · Page 60Linked to original sources
PubMed2003

Hodgkin lymphoma and Epstein-Barr virus (EBV): no evidence to support hit-and-run mechanism in cases classified as non-EBV-associated.

The Epstein-Barr virus (EBV) is associated with a proportion of Hodgkin lymphoma (HL) cases, and this association is believed to be causal. The aetiology of cases lacking EBV in the tumour cells (EBV HRS-ve), which make up the majority of cases in western countries, is obscure. It has been suggested that EBV may also cause these tumours by using a hit-and-run mechanism. Support for this idea comes from the finding that most young adult patients, who are likely to have a good immune response to EBV, have EBV HRS-ve HL. We investigated this possibility using a combined serologic and molecular approach. Analysis of EBV seroprevalence rates in an epidemiologic study of young adult HL revealed that cases with EBV HRS-ve HL were more likely to be EBV-seronegative than controls. Furthermore, additional studies clearly showed that some HL patients have never been infected by EBV. Quantitative PCR was used to look for the presence of deleted EBV genomes in a series of adult cases with both EBV HRS+ve and HRS-ve HL. Subgenomic fragments were detected in equimolar proportions. This study, therefore, found no evidence to support the idea that a hit-and-run mechanism involving EBV plays a role in the pathogenesis of HL.

Adolescent↗
PubMed2001

Kinetics of cytokine expression in melanoma metastases classifies immune responsiveness.

Production of cytokines (CKs) in the tumor micro-environment may modulate tumor-host interactions. However, pre-clinical models often provide conflicting data and there is no established role for CKs as modulators of the natural or treatment-related behavior of tumors. Serial sampling by fine-needle aspirates (FNAs) of identical metastases from patients affected with metastatic melanoma and undergoing IL-2-based vaccination allowed prospective measurement of IL-10, TGF-beta1, TGF-beta2 and IFN-gamma transcriptional levels assessed by quantitative real-time PCR. Thus, it was possible to prospectively document the expression of markers relevant to a given treatment and follow at the same time the clinical outcome of the lesions left in place. Eight of 27 metastatic lesions completely regressed in response to the treatment and 1 demonstrated >50% shrinkage. These regressions occurred after the follow-up FNA had been obtained. IL-10 transcript was differentially expressed in pre-treatment FNA of responding lesions (t-test p(2) = 0.002). During treatment, INF-gamma transcript levels significantly increased in regressing compared to non-regressing lesions (t-test p(2) = 0.03). These data suggest that the pre-treatment CK profile of the tumor micro-environment may determine clinical responsiveness to immune therapy. Furthermore, temporal changes in CK expression during treatment might describe the biological characteristics of an effective immune response.

Cytokines↗
PubMed1992

Calcium antagonists can be classified using in vitro toxicity and potency indices.

The toxicity of eleven calcium antagonists from different chemical families was determined in rat hepatocyte primary cultures. The calcium antagonist potency of the same compounds was also determined in isolated rabbit aortic rings contracted with high K+. The hepatocytotoxicity of the calcium antagonists was not directly linked to blockade of voltage-operated calcium channels, since there was no correlation between the rank order of hepatotoxicity and that for calcium antagonist potency. The toxicity and calcium antagonist potency of each calcium antagonist examined were used to calculate an in vitro therapeutic index value for each compound. It was observed that therapeutic indices fell into three distinct groups and we therefore propose that the in vitro therapeutic index can be used to subclassify the calcium antagonist group of drugs. The proposed classification corresponds very closely with one already suggested by Spedding on pharmacological grounds. In conclusion, the in vitro therapeutic index may provide a useful tool in the characterization and subclassification of novel calcium antagonist compounds.

Animals↗
PubMed2005

Time-resolved autofluorescence spectroscopy for classifying normal and premalignant oral tissues.

BACKGROUND AND OBJECTIVES: Time-resolved autofluorescence spectroscopy has been used for effectively distinguishing normal tissues from precancers and cancers in various organs. The aim of this study was to find out the possibility of using time-resolved autofluorescence spectroscopy to differentiate normal oral mucosa (NOM) from oral premalignant lesions including verrucous hyperplasia (VH), epithelial hyperplasia (EH), and epithelial dysplasia (ED). STUDY DESIGN/MATERIALS AND METHODS: Time-resolved autofluorescence spectra at 633 nm under 410-nm excitation were recorded for 15 VH, 9 EH, 14 ED, and 38 NOM samples. The two-component lifetimes of the obtained curves were calculated, and a Fisher's discriminant analysis (FDA) was employed for distinguishing these tissue samples. RESULTS: After two-component lifetimes for all samples being calculated, a two-dimensional scatter plot was developed, in which 76 oral tissue samples were separated into three groups by FDA. With a leave-one-out method, the FDA algorithm gave an accuracy rate of 93% for ED, of 75% for VH and EH, and of 100% for NOM samples. In addition, all oral premalignant lesions (including VH, EH, and ED) could be distinguished from NOM samples by this FDA algorithm. CONCLUSIONS: We conclude that time-resolved autofluorescence spectroscopy at 633 nm under 410-nm excitation, based on two-component lifetime calculation and FDA, is a very sensitive technique for in vivo diagnosis of oral premalignant lesions. .

Adult↗
PubMed1980

Myelopoiesis in immunologically classified subgroups of childhood acute lymphocytic leukemia.

Soft agar culture studies of 43 immunologically characterized patients with childhood acute lymphocytic leukemias (ALL) are presented. The immunologic subsets studied include "null"-cell, pre-B-cell, and T-cell leukemias. Abnormal myelopoiesis, including high peripheral blood and low marrow, colony-forming cell numbers, low colony-stimulating activity, and normal maturation of colony-forming cells in vitro was noted in each group as previously described for immunologically uncharacterized ALL. We conclude that immunologic subsets of childhood lymphoblastic leukemia cause similar abnormalities of myelopoiesis. Lack of differences in growth characteristics among immunologic subsets of ALL make it impossible to use this tissue culture technique in subclassification of these leukemic disorders.

Adolescent↗
PubMed2007

Meiotic competence and acetylation pattern of UV light classified mouse antral oocytes after meiotic arrest with isobutylmethylxanthine.

Chromatin transformation from a diffused or NSN configuration to a compacted or SN shape that forms a ring around the nucleolus is regarded as one of the modifications necessary for successful embryonic development. But the process of the transformation is poorly understood. In this study we cultured mouse antral oocytes under meiotic arrest with IBMX for periods between 3 and 24 hr. We observed the chromatin status of the oocytes before and after culture under UV illumination. We reported here that the NSN configured oocytes transformed temporally through an intermediate form into the SN configuration while under meiotic arrest in vitro. Meiotic rate was improved in the NSN oocytes after the meiotic arrest but decreased in the SN oocytes. We also reported that chromatin of both the NSN and SN oocytes was acetylated and the two groups underwent the same pattern of H4/K5 deacetylation during meiotic maturation. We hypothesized that the transformation of mouse oocyte from the NSN to SN type may be time rather than oocyte size specific and the abrupt deacetylation of NSN oocyte during spontaneous maturation may explain its poor meiotic and developmental competence.

1-Methyl-3-isobutylxanthine↗
PubMed2003

Analysis of genetic alterations, classified according to their DNA ploidy pattern, in the progression of colorectal adenomas and early colorectal carcinomas.

DNA aneuploidy is a biological marker of the oncogenic potential of colorectal adenomas. The accumulation of genetic alterations of cancer-related genes is also essential for colorectal carcinogenesis. However, it is unclear whether there is any relationship between these genetic alterations and the DNA ploidy of colon tumour cells in the progression of colorectal adenomas and early colorectal carcinomas. Here we have studied the DNA ploidy state and genetic alterations occurring in colorectal tumours using the crypt isolation technique. Crypts isolated from a total of 106 colorectal tumors (adenoma, 93; early carcinoma, 13) were examined using a combination of flow cytometric analysis of DNA content, polymerase chain reaction-microsatellite assay, and single-strand conformation polymorphism assay for evidence of chromosomal allelic imbalance (AI; 17p; 5q; 18q) or p53 gene mutation. In addition, we examined microsatellite instability (MSI) with BAT 26 primer sets. DNA multiploidy was infrequently detected in colorectal adenomas (15.1%), in contrast to early carcinomas (46.2%). There was a significant difference in the incidence of AI of chromosome 18q between diploid adenomas and aneuploid populations of multiploid adenomas (18.1% vs 57.1%, p = 0.0043). Mutation of p53 was also found more frequently in aneuploid populations of early multiploid colorectal carcinomas than in early diploid colorectal carcinomas (66.7% vs 0%, p = 0.021). MSI was found in only 2 of 93 adenomas, with no MSI detected in early colorectal cancers. The two MSI-positive adenomas were diploid. We subdivided multiploid adenomas into two groups: those with a low or a high DNA index (DI). The incidence of genetic alterations of high-DI adenomas did not differ from those of low-DI adenomas. Allelic imbalance involving loci on chromosome 18q and mutations of p53 seems to be associated with the progression of diploidy to multiploidy in colorectal tumours. On the other hand, MSI may be associated with the development of some diploid tumours. In addition, the incidence of genetic alterations in the colorectal adenomas that we examined appears to be independent of the tumour's DNA index.

Adenoma↗
PubMed1993

Gastric intestinal metaplasia type III cases are classified as low-grade dysplasia on the basis of morphometry.

The aim of this study was to try to place gastric intestinal metaplasia, type III (type III IM) in the stepwise chain of events from atrophic gastritis to cancer. A number of dysplastic, periulcer regenerative, and type III IM lesions were qualitatively diagnosed (and graded) blindly and independently by several pathologists. These lesions were further analysed by means of quantitative parameters, with the aim of differentiating dysplastic from regenerative changes. Inconsistencies between the qualitative and quantitative classification (about 7 per cent of cases) were eliminated and homogeneous groups (low-grade dysplasia, high-grade dysplasia, regenerative changes) were obtained. These cases were taken as the gold standard against which type III IM was compared. The results indicate that the great majority (91.4 per cent) of cases of type III IM fulfil the nuclear and architectural criteria for low-grade dysplasia.

Adult↗
PubMed2007

Systematic comparison of catalytic mechanisms of hydrolysis and transfer reactions classified in the EzCatDB database.

Catalytic mechanisms of 270 enzymes from 131 superfamilies, mainly hydrolases and transferases, were analyzed based on their enzyme structures. A method of systematic comparison and classification of the catalytic reactions was developed. Hydrolysis and transfer reactions closely resemble one another, displaying common mechanisms, single displacement, and double displacement. These displacement mechanisms might be further subclassified according to the type of catalytic factors and nucleophilic substitution involved. Several types of catalytic factors exist: nucleophile, acid, base, stabilizer, modulator, cofactors. Nucleophilic substitution might be categorized as S(N)1/S(N)2 (or dissociative/associative) reactions. The classification indicates that some mechanisms favor particular types of catalytic factors. In hydrolyses of amide bonds and phosphoric ester bonds, mechanisms with single displacement tend to use inorganic cofactors such as zinc and magnesium ions as important catalysts, whereas those with double displacement frequently do not use such cofactors. In contrast, hydrolyses of O-glycoside bond rarely use such cofactors, with one exception. The trypsin-like hydrolytic reaction, which is catalyzed by the classic catalytic triad comprising serine/histidine/aspartate, can be considered as a "super-reaction" because it is observed in at least three nonhomologous enzymes, whereas most reactions are singlets without any nonhomologous enzymes. By dividing complex reactions into several reactions, correlations between active site structures and catalytic functions can be suggested. This classification method is applicable to other reactions such as elimination and isomerization. Furthermore, it will facilitate annotation of enzyme functions from 3D patterns of enzyme active sites. The classification is available at http://mbs.cbrc.jp/EzCatDB/RLCP/index.html.

Binding Sites↗
PubMed2005

Bayesian sample-size determination for inference on two binomial populations with no gold standard classifier.

We consider the impact of test properties on the required sample size for the Bayesian design problem for comparing two proportions with error-prone data. Specifically, we examine four cases: a single diagnostic test and two independent diagnostic tests, both when the test properties are identical across populations and when they differ. Interval-based and moment-based sample-size determination criteria are contrasted using Monte Carlo simulation methods. We consider an application in which Strongyloides infections are compared in two populations.

Animals↗
PubMedDate not supplied

An application of kappa-type analyses to interobserver variation in classifying chest radiographs for pneumoconiosis.

We investigated interobserver variation between three physician readers in the independent classification of chest radiographs from 1771 taconite workers for pneumoconiosis. We analysed variation with a general methodology for the analysis of categorical data, and quantified interobserver agreement in terms of kappa-type statistics. The results revealed considerable variation in the profusion of opacities reported by each observer. This was especially so for the earliest radiographic changes, but variation also occurred with the small number of films in the series showing category 2 pneumoconiosis or over. Variation in the classification of profusion of small opacities was greater in films of poor quality, and also increased with the length of time between taking and reading the film (film age). We could not account for the effect of film age by controlling for film quality, as subjectively assessed by the readers.

Epidemiologic Methods↗
PubMed2002

Classifying class I and class II compounds by hydrophobicity and hydrogen bonding descriptors.

The successful development of quantitative structure-activity relationships (QSARs) and the prediction of toxicity based on QSARs depend on the correct classification of the mechanism of toxic action of chemical compounds. The toxicity mechanism of a compound can be determined by a few existing methods, such as studying the chemical structure of the compound for certain substructures and assigning a mechanism accordingly. However, these methods are less reliable for compounds with complex structures and are usually complicated. A novel descriptor-based method employing a multivariate statistical technique--discriminant analysis--was developed in this study for the classification of class I and class II compounds. The discriminating variables used in discriminant analysis were the hydrophobicity descriptor log(K(ow)) and the hydrogen bonding descriptors E(LUMO), E(HOMO), Q(+), and Q(-). Because only numerical values of these descriptors are required for this method, which can be calculated, no additional experimental work was required for the toxicity mechanism classification of new compounds. A nonlinear discriminant function was generated that could not be expressed explicitly. Assessing the predicting ability of the discriminant function by the cross-validation method showed that a low total error rate, 4.2% was achieved.

Environmental Pollutants↗
PubMed1996

Statistical methods in the Fourier domain to enhance and classify images.

A mathematical model, for which rigorous methods of statistical inference are available, is described and techniques for image enhancement and linear discriminant analysis of groups are developed. Since the gray values of neighboring pixels in tomographically produced medical images are spatially correlated, the calculations are carried out in the Fourier domain to insure statistical independence of the variables. Furthermore, to increase the power of statistical tests the known spatial covariance was used to specify constraints in the spectral domain. These methods were compared to statistical procedures carried out in the spatial domain. Positron emission tomography (PET) images of alcoholics with organic brain disorders were compared by these techniques to age-matched normal volunteers. Although these techniques are employed to analyze group characteristics of functional images, they provide a comprehensive set of mathematical and statistical procedures in the spectral domain that can also be applied to images of other modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI).

Aged↗
PubMed1997

An ECG classifier designed using modified decision based neural networks.

In this paper, a neural network based generalized software system is presented for automatic analysis of electrocardiograms (ECGs). The proposed system is capable of intuitively diagnosing the disease from the ECG using the knowledge acquired from the training. A modified decision based neural network which converges in a finite amount of time is employed. The training procedure used automatically varies the size of the network. The system is capable of being trained even without an expert's supervision. The physician can correct the network as and when a misclassification occurs, thus making the system less error-prone as time passes. The proposed system has been tested using an ECG data base representing different cardiological conditions such as bundle branch blocks and infarctions. The system is capable of detecting different types of arrhythmias also.

Algorithms↗
PubMed1996

Counting and classifying attractors in high dimensional dynamical systems.

Randomly connected Boolean networks have been used as mathematical models of neural, genetic, and immune systems. A key quantity of such networks is the number of basins of attraction in the state space. The number of basins of attraction changes as a function of the size of the network, its connectivity and its transition rules. In discrete networks, a simple count of the number of attractors does not reveal the combinatorial structure of the attractors. These points are illustrated in a reexamination of dynamics in a class of random Boolean networks considered previously by Kauffman. We also consider comparisons between dynamics in discrete networks and continuous analogues. A continuous analogue of a discrete network may have a different number of attractors for many different reasons. Some attractors in discrete networks may be associated with unstable dynamics, and several different attractors in a discrete network may be associated with a single attractor in the continuous case. Special problems in determining attractors in continuous systems arise when there is aperiodic dynamics associated with quasiperiodicity of deterministic chaos.

Animals↗
PubMed2003

Development of a mathematical method for classifying and comparing tree architecture using parameters from a topological model of a trifurcating botanical tree.

This paper describes a model for the topological mapping of trifurcating botanical trees. The model was based on a system of modular units that represented the interconnectivity of shoot meristems (terminal segments) and internodes (internal segments) within whole plant canopies, organized with increasing centrifugal ordering. The model was capable of describing the dynamics of plant growth as expressed by changes in topological parameters over time. Preliminary calculations for experimental trees indicated that the model represents growth in a biologically sound manner. Methods are described for the calculation of the architecture parameters size, size-complexity, structural complexity, and tree asymmetry index (TAI). Parameter calculations were based on the mathematical principles developed for the classification of bifurcating dendrite trees, and were designed to both extract structural information, and to enable statistical comparison between trees of different size. Parameters were mathematically adjusted for trifurcation, and appeared to be able to represent quantitatively the architectural properties of tree structures. In addition to the calculation of the TAI for trifurcating trees, new methods were developed to enable comparisons to be made of the architectural complexity of trifurcating trees of differing size. These were based on the principle of the pair-wise comparison of the mean centrifugal order number (MCON) with respect to segments against highest order number. We argue and illustrate that this principle can be more informative than that of pair-wise comparison of the MCON against tree degree (topological size). Further improvements to this method were made by examining branching points (vertices) rather than segments (links) to calculate the MCON.

Models, Biological↗