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PubMed2001

Attentional and neuromotor deficits in ADHD.

In order to classify attention-deficit-hyperactivity disorder (ADHD) in 11-year-old children, the role of specific attentional and motor deficits was examined. Participants comprised 22 children with ADHD (19 male, 3 female; median age 11 years, range 8.8 to 13.5 years) and 20 control children (17 male, 3 female; median age 10.6 years, range 8.2 to 12.6 years). Neuromotor assessment indicated that while both groups needed more time to complete finger compared to hand movements, this increase was more pronounced in children with ADHD. Reaction-time testing with continuous-force recording identified both motor and attentional deficits in children with ADHD. Longer intervals between force onset and force peak, and higher rate of responses with multiple force peaks (particularly in the bilateral condition) revealed specific deficits in the speed and quality of their motor output. Increase in errors and variability of force onsets indicated attentional deficits. Prediction analysis indicated that force-onset variability contributed significantly to group classification which was 85.7% correct. Neither neuromotor assessment nor specific motor deficits contributed significantly to classification, indicating that pure motor-speed measures play a minor role in characterizing ADHD in this age range.

Adolescent↗
PubMed1984

Biological markers for endogenous depression in series and parallel.

Several authors have shown that endogenous depressed patients have biological abnormalities which exist to a lesser extent in nonendogenous depressives and in normals, and have suggested that these biological abnormalities may be used as markers to classify depressed patients as endogenous or nonendogenous. We have investigated several of these biological abnormalities, and have explored the diagnostic classifications based on individual markers and on two or more markers in combination. The evaluation of combinations of diagnostic tests requires different statistical techniques than does the evaluation of single tests, and we discuss two such techniques: stepwise multiple regression and contingency table analysis. We report here our results with the dexamethasone suppression test (DST), EEG studies of sleep, and the amphetamine-stimulated release of growth hormone separately and in combination. The amphetamine-stimulated release of growth hormone was not diagnostically useful.

Amphetamine↗
PubMed2001

Resolution of multiple green fluorescent protein color variants and dyes using two-photon microscopy and imaging spectroscopy.

The imaging of living cells and tissues using laser-scanning microscopy is offering dramatic insights into the spatial and temporal controls of biological processes. The availability of genetically encoded labels such as green fluorescent protein (GFP) offers unique opportunities by which to trace cell movements, cell signaling or gene expression dynamically in developing embryos. Two-photon laser scanning microscopy (TPLSM) is ideally suited to imaging cells in vivo due to its deeper tissue penetration and reduced phototoxicity; however, in TPLSM the excitation and emission spectra of GFP and its color variants [e.g., CyanFP (CFP); yellowFP (YFP)] are insufficiently distinct to be uniquely imaged by conventional means. To surmount such difficulties, we have combined the technologies of TPLSM and imaging spectroscopy to unambiguously identify CFP, GFP, YFP, and redFP (RFP) as well as conventional dyes, and have tested the approach in cell lines. In our approach, a liquid crystal tunable filter was used to collect the emission spectrum of each pixel within the TPLSM image. Based on the fluorescent emission spectra, supervised classification and linear unmixing analysis algorithms were used to identify the nature and relative amounts of the fluorescent proteins expressed in the cells. In a most extreme case, we have used the approach to separate GFP and fluorescein, separated by only 7 nm, and appear somewhat indistinguishable by conventional techniques. This approach offers the needed ability to concurrently image multiple colored, spectrally overlapping marker proteins within living cells.

Algorithms↗
PubMed1998

In vivo differentiation of astrocytic brain tumors and isolated demyelinating lesions of the type seen in multiple sclerosis using 1H magnetic resonance spectroscopic imaging.

We used computer pattern recognition of proton magnetic resonance spectroscopic image data to differentiate between brain tumors and large, isolated, demyelinating lesions of the type seen in multiple sclerosis. Leave-one-out linear discriminant analyses correctly classified resonance profiles from five acute demyelinating lesions, 20 low-grade astrocytomas, 22 anoplastic astrocytomas, and 24 glioblastomas. Classification of nonacute lesions will require further development, as the metabolic profiles of demyelinating lesions evolve over time.

Adult↗
PubMed1989

[Phenotypic analysis of human T-cell lymphoma with reference to cell differentiation and morphological classification].

The recognition of the dichotomy of the immune system was a first step in differentiating between a humoral and cellular immune response. This distinction was to be of fundamental importance in the subsequent demonstration of distinct compartments in the lymphatic cell system. Animal studies and investigations on humans with congenital immune defects soon made it possible to differentiate between functionally different cell compartments in lymphatic tissue even on morphological grounds. This formed the basis for the subdivision of lymphatic tissue into B- and T-cell areas. A multiplicity of morphologically highly varied lymphatic neoplasias confronted this clear division. In principle, there are two possible explanations for the morphological and immunological heterogeneity of neoplasias: 1. The variety of lymphatic neoplasias is an expression of a dedifferentiation of cells in which neither the morphological picture nor the immunological properties of the stem cells are expressed. 2. Lymphatic neoplasias represent stages of "arrested" differentiation in the normal cell development. The present study attempts to demonstrate the distribution and development of normal T lymphocytes by analysis of their morphology and antigen constellation. The knowledge thus gained should then make it possible to define the neoplasias of the T-cell system. Thirty-six monoclonal antibodies were employed in addition to standard enzyme-histochemical methods for demonstration of cell antigens; some of the monoclonal antibodies were developed especially for this purpose. The study included normal tissue and samples from 148 lymphomas and leukemias of the T-cell system. Subdivision of the various entities was based on morphology, which enabled us to make a direct distinction between the morphologically defined entity and its corresponding phenotype. These phenotypic analyses of malignant T-cell lymphomas were conducted in pursuit of 3 basic goals: 1. To catch T-cell neoplasias in the full variety of their phenotypical spectrum by using assorted T-cell properties. 2. To bring these varied entities into a sequence corresponding to normal cell differentiation by correlating the neoplasias to normal cell compartments. 3. To determine the extent to which neoplastic equivalents exist for normal T cells with varied phenotypes and/or functional properties. A clear morphological subdivision of the T-cell neoplasias is already possible: 1. lymphoblastic lymphomas and leukemias; 2. peripheral or mature cell T-cell lymphomas. The lymphoblastic lymphomas and leukemias have until now been characterized primarily according to their positivity for the enzyme TdT. The T-lymphoblastic lymphomas and leukemias we analysed phenotypically shared the constant features of CD7 antigen expression, whereas other T-cell features showed a clear variability.

Adolescent↗
PubMed1992

Effect of nondifferential misclassification on estimates of odds ratios with multiple levels of exposure.

Nondifferential misclassification of exposure status with a dichotomous exposure will produce biased estimates of odds ratios such that the misclassified odds ratio is always biased toward the null value. However, when an exposure classification has more than two levels, empirical data indicate that the direction of bias is less predictable. Analysis of an algebraic model of multi-level exposure misclassification reveals that all odds ratios based on the misclassified data are constrained between the nonmisclassified odds ratio for the most extreme category and the inverse of this value. This implies that the misclassified odds ratio for the most extreme exposure level will be biased toward the null but that odds ratios for intermediate levels of exposure could be biased away from the null value. Further, the amount of bias depends not only on the misclassification rates but also on the distribution of subjects across exposure levels. If it is assumed that misclassification is likely to occur only between adjacent categories, the range of possible misclassified odds ratios is reduced but is still sufficient to permit serious distortion of an exposure-response relation. In general, biases away from the null occur only for intermediate levels of exposure. Reversal of an exposure-response relation is more likely to occur when misclassification rates are high (especially between nonadjacent levels) and when the number of exposure levels is low.

Bias↗
PubMed1997

Genomic deletions in the BRCA1, BRCA2 and TP53 regions associate with low expression of the estrogen receptor in sporadic breast carcinoma.

Sporadic breast carcinoma is associated with multiple genetic alterations. The clinical relevance of these alterations, however, needs further clarification. In the present study we analyzed 266 spontaneously arising breast carcinomas for allelic losses in the BRCA1 and TP53 regions on chromosome 17, the BRCA2 region on chromosome 13, the ATM (mutated in ataxia-telangiectasia) region on chromosome 11 and on the chromosomal arms 7q and 16q. In addition the following clinical and pathological parameters were evaluated: age at diagnosis, tumor size, presence or absence of regional and distant metastases, hormone-receptor status, histopathological classification and tumor grading. The analysis of genetic and clinical observations revealed significant associations: absence of expression of the estrogen receptor was linked to a high rate of allelic losses of markers in the BRCA1, TP53 and BRCA2 regions. Expression of the progesterone receptor coincided with allelic loss on the long arm of chromosome 16. High-grade malignant lesions and ductal differentiation were frequently associated with allelic losses in the proximal portion of chromosome 17q. The accumulation of multiple allelic deletions was linked to high-grade malignant tumors, to tumor size, and to loss of expression of the estrogen receptor. Our data point to a relationship between clinically relevant prognostic factors and specific genomic deletions in the BRCA1, BRCA2 and TP53 region.

Breast Neoplasms↗
PubMed2005

Phylogenetic analysis of the main neutralization and hemagglutination determinants of all human adenovirus prototypes as a basis for molecular classification and taxonomy.

Human adenoviruses (HAdV) are responsible for a wide spectrum of diseases. The neutralization epsilon determinant (loops 1 and 2) and the hemagglutination gamma determinant are relevant for the taxonomy of HAdV. Precise type identification of HAdV prototypes is crucial for detection of infection chains and epidemiology. epsilon and gamma determinant sequences of all 51 HAdV were generated to propose molecular classification criteria. Phylogenetic analysis of epsilon determinant sequences demonstrated sufficient genetic divergence for molecular classification, with the exception of HAdV-15 and HAdV-29, which also cannot be differentiated by classical cross-neutralization. Precise sequence divergence criteria for typing (<2.5% from loop 2 prototype sequence and <2.4% from loop 1 sequence) were deduced from phylogenetic analysis. These criteria may also facilitate identification of new HAdV prototypes. Fiber knob (gamma determinant) phylogeny indicated a two-step model of species evolution and multiple intraspecies recombination events in the origin of HAdV prototypes. HAdV-29 was identified as a recombination variant of HAdV-15 (epsilon determinant) and a speculative, not-yet-isolated HAdV prototype (gamma determinant). Subanalysis of molecular evolution in hypervariable regions 1 to 6 of the epsilon determinant indicated different selective pressures in subclusters of species HAdV-D. Additionally, gamma determinant phylogenetic analysis demonstrated that HAdV-8 did not cluster with -19 and -37 in spite of their having the same tissue tropism. The phylogeny of HAdV-E4 suggested origination by interspecies recombination between HAdV-B (hexon) and HAdV-C (fiber), as in simian adenovirus 25, indicating additional zoonotic transfer. In conclusion, molecular classification by systematic sequence analysis of immunogenic determinants yields new insights into HAdV phylogeny and evolution.

Adenovirus Infections, Human↗
PubMed2007

Nosology and classification of genetic skeletal disorders: 2006 revision.

The objective of the paper is to provide the revision of the Nosology of Constitutional Disorders of Bone that incorporates newly recognized disorders and reflects new molecular and pathogenetic concepts. Criteria for inclusion of disorders were (1) significant skeletal involvement corresponding to the definition of skeletal dysplasias, metabolic bone disorders, dysostoses, and skeletal malformation and/or reduction syndromes, (2) publication and/or MIM listing, (3) genetic basis proven or very likely, and (4) nosologic autonomy confirmed by molecular or linkage analysis and/or distinctive diagnostic features and observation in multiple individuals or families. Three hundred seventy-two different conditions were included and placed in 37 groups defined by molecular, biochemical and/or radiographic criteria. Of these conditions, 215 were associated with one or more of 140 different genes. Nosologic status was classified as final (mutations or locus identified), probable (pedigree evidence), or bona fide (multiple observations and clear diagnostic criteria, but no pedigree or locus evidence yet). The number of recognized genetic disorders with a significant skeletal component is growing and the distinction between dysplasias, metabolic bone disorders, dysostoses, and malformation syndromes is blurring. For classification purposes, pathogenetic and molecular criteria are integrating with morphological ones but disorders are still identified by clinical features and radiographic appearance. Molecular evidence leads to confirmation of individual entities and to the constitution of new groups, but also allows for delineation of related but distinct entities and indicates a previously unexpected heterogeneity of molecular mechanisms; thus, molecular evidence does not necessarily simplify the Nosology, and a further increase in the number of entities and growing complexity is expected. By providing an updated overview of recognized entities with skeletal involvement and of the underlying gene defects, the new Nosology can provide practical diagnostic help, facilitate the recognition of new entities, and foster and direct research in skeletal biology and genetic disorders.

Bone Diseases↗
PubMed1999

Signal to noise analysis of multiple color fluorescence imaging microscopy.

BACKGROUND: Various approaches that were recently developed demonstrate the ability to simultaneously detect all human (or other species) chromosomes by using combinatorial labeling and fluorescence in situ hybridization (FISH). With the growing interest in this field, it is important to develop tools for optimizing and estimating the accuracy of different experimental methods. METHODS: We have analyzed the principles of multiple color fluorescence imaging microscopy. First, formalism based on the physical principles of fluorescence microscopy and noise analysis is introduced. Next, a signal to noise (S/N) analysis is performed and summarized in a simple accuracy criterion. The analysis assumes shot noise to be the dominant source of noise. RESULTS: The accuracy criterion was used to calculate the S/N of multicolor FISH (M-FISH), spectral karyotyping, ratio imaging, and a method based on using a set of broad band filters. Spectral karyotyping is tested on various types of samples and shows accurate classifications. We have also tested classification accuracy as a function of total measurement time. CONCLUSIONS: The accuracy criterion that we have developed can be used for optimizing and analyzing different multiple color fluorescence microscopy methods. The assumption that shot noise is dominant in these measurements is supported by our measurements.

Female↗
PubMedDate not supplied

A complete enumeration and classification of two-locus disease models.

There are 512 two-locus, two-allele, two-phenotype, fully penetrant disease models. Using the permutation between two alleles, between two loci, and between being affected and unaffected, one model can be considered to be equivalent to another model under the corresponding permutation. These permutations greatly reduce the number of two-locus models in the analysis of complex diseases. This paper determines the number of nonredundant two-locus models (which can be 102, 100, 96, 51, 50, or 58, depending on which permutations are used, and depending on whether zero-locus and single-locus models are excluded). Whenever possible, these nonredundant two-locus models are classified by their property. Besides the familiar features of multiplicative models (logical AND), heterogeneity models (logical OR), and threshold models, new classifications are added or expanded: modifying-effect models, logical XOR models, interference and negative interference models (neither dominant nor recessive), conditionally dominant/recessive models, missing lethal genotype models, and highly symmetric models. The following aspects of two-locus models are studied: the marginal penetrance tables at both loci, the expected joint identity-by-descent (IBD) probabilities, and the correlation between marginal IBD probabilities at the two loci. These studies are useful for linkage analyses using single-locus models while the underlying disease model is two-locus, and for correlation analyses using the linkage signals at different locations obtained by a single-locus model.

Animals↗
PubMed2004

Hippocampal changes and white matter lesions in early-onset depression.

BACKGROUND: Hippocampal volume reduction and increased prevalence of subcortical white matter lesions have been reported in late-life depression. We aimed to examine whether total number of subcortical white matter lesions were associated with reduced hippocampal volume in aged female subjects with early-onset depression (< 45 years) and healthy comparison subjects. METHODS: The study included 28 middle-aged and elderly subjects with major depression and 41 age-matched control subjects. Hippocampal, parahippocampal gyrus, and orbitofrontal cortex volumes were determined using manual tracing methods. White matter lesions were rated from T2-weighted MRI scans using a semiquantitative classification scale. RESULTS: After controlling for total brain volume and age, patients had reduced hippocampal volume due to right hippocampal volume decrease (2.84 mL vs. 3.12 mL, F = 16.6, p < .001). Parahippocampal and orbitofrontal volumes did not differ significantly between groups. Multiple linear regression analysis indicated that reduced hippocampal volume did not significantly correlate with total number of subcortical white matter lesions (t = .673, p = .518). CONCLUSIONS: Right hippocampal volume was reduced in aged female early-onset subjects with depression. Total number of subcortical white matter lesions was not associated with the decrease in right hippocampal volume. Our data suggest hippocampal involvement, independent of subcortical white matter lesions, in the neuropathology of early-onset depression.

Age of Onset↗
PubMed2005

A new progressive-iterative algorithm for multiple structure alignment.

MOTIVATION: Multiple structure alignments are becoming important tools in many aspects of structural bioinformatics. The current explosion in the number of available protein structures demands multiple structural alignment algorithms with an adequate balance of accuracy and speed, for large scale applications in structural genomics, protein structure prediction and protein classification. RESULTS: A new multiple structural alignment program, MAMMOTH-mult, is described. It is demonstrated that the alignments obtained with the new method are an improvement over previous manual or automatic alignments available in several widely used databases at all structural levels. Detailed analysis of the structural alignments for a few representative cases indicates that MAMMOTH-mult delivers biologically meaningful trees and conservation at the sequence and structural levels of functional motifs in the alignments. An important improvement over previous methods is the reduction in computational cost. Typical alignments take only a median time of 5 CPU seconds in a single R12000 processor. MAMMOTH-mult is particularly useful for large scale applications. AVAILABILITY: http://ub.cbm.uam.es/mammoth/mult.

Algorithms↗
PubMed1999

Prediction of performance on the RCMP physical ability requirement evaluation.

The Royal Canadian Mounted Police use the Physical Ability Requirement Evaluation (PARE) for screening applicants. The purposes of this investigation were to identify those field tests of physical fitness that were associated with PARE performance and determine which most accurately classified successful and unsuccessful PARE performers. The participants were 27 female and 21 male volunteers. Testing included measures of aerobic power, anaerobic power, agility, muscular strength, muscular endurance, and body composition. Multiple regression analysis revealed a three-variable model for males (70-lb bench press, standing long jump, and agility) explaining 79% of the variability in PARE time, whereas a one-variable model (agility) explained 43% of the variability for females. Analysis of the classification accuracy of the males' data was prohibited because 91% of the males passed the PARE. Classification accuracy of the females' data, using logistic regression, produced a two-variable model (agility, 1.5-mile endurance run) with 93% overall classification accuracy.

Adult↗
PubMed1985

Double-judgment psychophysics: problems and solutions.

Many paradigms for comparing identification thresholds with detection thresholds require the observer to make double judgments. We show that these paradigms can produce misleading results because of response biases and attentional shifts. For example, the subject's response bias plus correlated noise can mimic inhibition between channels. Some of these same problems can affect single-judgment paradigms. A detailed analysis of the double-judgment forced-choice paradigm reveals that there are a multiplicity of optimal strategies, some of which enhance identification over detection. Several improved analysis techniques for minimizing the effects of cognitive factors are proposed for both the double-judgment forced-choice paradigm and the double-judgment rating-scale paradigm. A classification scheme for distinguishing different types of interactions and correlations is developed. When the new rating-scale algorithm is applied to the detection of well-separated spatial frequencies, substantial masking but negligible inhibition is found. The rating-scale paradigm is shown to be useful in revealing not only the sensitivity and the interactions of the underlying mechanisms but also the observer's information-processing strategies.

Attention↗
PubMed1999

[Waldenström macroglobulinemia with diffuse large B-cell lymphoma that developed from a different B-cell clone].

A 62-year-old man was given a diagnosis of Waldenström macroglobulinemia (WM) in January 1995. He was treated with melphalan and corticosteroid until January 1996, when he experienced high fever and weight loss. The patient visited a nearby hospital, received a diagnosis of liver abscess, and was referred to our hospital on February 23, 1996. Computed axial tomographic scans demonstrated multiple isodensity masses in the liver, left adrenal region, and right kidney hilum. Needle biopsy specimens of a liver mass revealed infiltration of diffuse large B-cell lymphoma (REAL classification), suggesting that non-Hodgkin's lymphoma supervened WM. Despite multiple cycles of chemotherapy, the lymphoma responded poorly. The patient died of pneumonia and sepsis on May 10, 1996 and an autopsy disclosed broad involvement of liver and spleen with lymphoma. Southern blot analysis of DNA samples obtained from the patient's bone marrow at the time of the initial diagnosis of WM, and later from the needle biopsy specimen of liver mass, displayed different patterns of immunoglobulin heavy chain gene rearrangement. We therefore concluded that in this patient the lymphoma was not a progression of WM, but rather, an independent B-cell malignancy.

B-Lymphocytes↗
PubMed1989

[Social factors and arterial hypertension].

Hypertension in Hungary is classed as a potentially prevalent disease both because of its incidence and social consequences. Its origins can be traced back to environmental, economic and social changes. The aim of our analysis is: -to show the connections between hypertension development and the characteristics of social structure, life style and awareness. -to define social determination of hypertension and to evaluate it in view of applicability in prevention and treatment. Screening examination and sociological data collection was conducted in the 17th district of Budapest in 1982-83 in a random sample of patients between 20-64 years of age. While screening besides blood pressure measurement weight and height were measured, blood sugar content and serum lipid were determined and anamnestic particulars were recorded. Groups of topics of the sociological interview: -characteristics of social stratification and mobility -nutritional habits -smoking habits -leisure time physical activity -characteristics of work performed -social connections -critical personality traits -health care culture The 20-64 population of the 17th district is 39,456. Our analysis concerns 1,600 persons selected on a statistical basis. In the present lecture we analyse the connection between social stratification and life style and hypertension. Systolic and diastolic blood pressures are analysed separately as their biological characteristics are different. In our analysis blood pressure was treated as a continuous variable or was classified as normal marginal or high based on WHO criteria.2+ Systolic blood pressure of the surveyed population shown in Table I. Multiple regression or multivariable discriminant analyses were used to examine factors affecting classification into each group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗