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PubMed2005

The effect of maternal and grandmaternal age in benign and high temperature environments.

Maternal age is known to be of importance for the fitness of the offspring. Few studies have, however, been able to analyse this phenomenon as an isolated effect without confounding effects through genetic variation. This difficulty can be circumvented by working with parthenogenetic organisms. We investigated the effect of maternal and grandmaternal age on wing traits, pupal survival and developmental instability (DI) in both a benign and a high temperature environment using two different parthenogenetic strains of Drosophila mercatorum. Both the maternal and grandmaternal age was found to influence all the traits. Two opposing factors seem to shape the effects of maternal age. Senescence in older mothers leads to a reduction in offspring fitness, whereas, plastic responses lead to more competitive and stress resistant offspring from older mothers. The relative importance of these factors is trait specific and is influenced by environmental factors. DI is mostly influenced by senescence whereas wing sizes are influenced mostly by plastic responses towards higher competition. This means that any analysis of fitness should take age composition of at least two generations into account.

Aging↗

PubMed2001

Genotyping of NAD(P)H:quinone oxidoreductase (NQO1) in a panel of human tumor xenografts: relationship between genotype status, NQO1 activity and the response of xenografts to Mitomycin C chemotherapy in vivo(1).

Pharmacogenetic analysis of polymorphisms in drug metabolizing enzymes is currently generating considerable interest as a means of individualizing patient therapy. Recent studies have suggested that patients that are homozygous for a polymorphic variant (a C to T transition at position 609 of the cDNA sequence) of the enzyme NAD(P)H:quinone oxidoreductase (NQO1) may be resistant to Mitomycin C (MMC). Genotyping of a panel of 54 human tumor xenografts by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), classified tumors as wild type (40/54), heterozygotes (11/54), and homozygous mutants (3/54). Previously, 37 of these tumors had been characterized in terms of their response to MMC in vivo, and in this study, a further nine tumor xenografts have been characterized in terms of their response to MMC. No correlation could be found between the NQO1 polymorphic status of xenografts and their response to MMC in vivo. In terms of genotype/phenotype relationships, NQO1 activity in tumors genotyped as wild type, heterozygotes, and homozygous mutants were 311.1 +/- 421.9 (N = 40), 76.9 +/- 109.5 (N = 11), and 0.2 +/- 0.17 (N = 3) nmol/min/mg, respectively. Genotyping of patients may provide a useful initial step in identifying patients who are unlikely to benefit from quinone-based chemotherapy. In the case of MMC, however, the work presented here demonstrates that genotyping of individuals with respect to NQO1 is unlikely to be beneficial in terms of predicting tumor responses to MMC.

Animals↗

PubMed1997

Mercury in two fish species from the Paraná river floodplain, Paraná, Brazil.

Total mercury concentrations were measured in dorsal muscle tissue of two edible fish species, Prochilodus scrofa 'curimba' and Pseudoplatystoma corruscans 'pintado', respectively detritivorous and carnivorous. Fish species were sampled monthly between February 1993 and January 1994 and bimonthly between April 1994 and February 1995 in three subsystems of Paraná river' system (Ivinhema River/Lake Patos; Baía River/Lake Guaraná and Paraná River/Cortado Channel), between Paraná and Mato Grosso do Sul. Total mercury was determined by HNO3/H2SO4/V2O5 digestion, SnCl2 reduction, and vapour generation method analysis (CGCH 900), adapted to Atomic Absorption Spectrometer (CGAA 7000 ABC). The mean mercury concentrations varied from 82.0 to 310.5 ng g(-1) and from 68 to 294.4 ng g(-1) in 'curimbas' and 'pintados', respectively. Mercury level increases in sexually mature 'curimbas'. Mercury values detected do not exceed the prevailing criteria for issuance of fish consumption advisories (< 500 ng g(-1)).

Journal Article↗

PubMed1998

Lung and heart dose volume analyses with CT simulator in radiation treatment of breast cancer.

PURPOSE: Radiation pneumonitis and cardiac effects are directly related to the irradiated lung and heart volumes in the treatment fields. The central lung distance (CLD) from a tangential breast radiograph is shown to be a significant indicator of ipsilateral irradiated lung volume. Retrospective analysis of the pattern of dose volume of lung and heart with actual volume data from a CT simulator in the treatment of breast cancer is presented with respect to CLD. METHODS AND MATERIALS: The heart and lung volumes in the tangential treatment fields were analyzed in 108 consecutive cases (52 left and 56 right breast) referred for CT simulation. All patients in this study were immobilized and placed on an inclined breast board in actual treatment setup. Both arms were stretched over head to avoid collision with the scanner aperture. Radiopaque marks were placed on the medial and lateral borders of the tangential fields. All patients were scanned in spiral mode with slice width and thickness of 3 mm each, respectively. The lung and heart structures as well as irradiated areas were delineated on each slice and respective volumes were accurately measured. The treatment beam parameters were recorded and the digitally reconstructed radiographs (DRRs) were generated for the measurement of the CLD and analysis. RESULTS: Using CT data the mean volume and standard deviation of left and right lungs were 1307.7+/-297.7 cm3 and 1529.6+/-298.5 cm3, respectively. The magnitude of irradiated volume in left and right lung is nearly equal for the same CLD that produces different percent irradiated volumes (PIV). The left and right PIV lungs are 8.3+/-4.7% and 6.6+/-3.7%, respectively. The PIV data have shown to correlate with CLD with second- and third-degree polynomials; however, in this study a simple straight line regression is used to provide better confidence than the higher order polynomials. The regression lines for the left and right breasts are very different based on actual CT data. The slopes of regression lines for the left and right lung are 0.6%/mm and 0.5%/mm, respectively which is statistically different with thep value of 0.01. A maximum heart PIV of >3.0% is observed in 80% of the patients. The heart PIV is inversely correlated with gantry angle and weakly correlated with CLD. CONCLUSIONS: The CT-simulator provides accurate volumetric information of the heart and lungs in the treatment fields. The lung PIV is directly correlated to the CLD (0.6%/mm and 0.5%/mm for the left and right lungs). Left and right lungs have different volumes and hence, different regression lines are recommended. An additional 12% lung volume could be irradiated in the supraclavicular field. Heart volume is not correlated with the CLD. The heart PIV is associated to the beam angle. Heart volume may not be accurately visualized in a tangential radiograph; however, this can be easily seen in a DRR with contour delineation and can be minimized with proper beam parameters iteratively with a virtual simulator. Lung and heart PIV along with dose volume histograms (DVH) are essential in reducing pulmonary and cardiac complications.

Adult↗

PubMed1988

Distinct cloned class II MHC DNA binding proteins recognize the X box transcription element.

The class II (Ia) major histocompatibility complex (MHC) antigens are a family of integral membrane proteins whose expression is limited to certain cell types. A pair of consensus sequences, X and Y, is found upstream of all class II genes, and deletion of each of these sequences eliminates expression of transfected genes. Furthermore, the absence of a specific X box binding protein in patients with severe combined immunodeficiency disease whose cells lack class II suggests an important role for these proteins in class II regulation. Here, the cloning of two lambda gt11 complementary DNAs encoding DNA binding proteins (murine X box binding proteins lambda mXBP and lambda mXBP-2) is reported. Both phage-encoded fusion proteins bind specifically to the X box of the A alpha, but not to E alpha or E beta class II genes. These two independent isolates do not cross-hybridize. The lambda mXBP complementary DNA hybridizes to two RNA species, 6.2 and 3.0 kilobases in mouse, that are expressed in both Ia positive and Ia negative cells. By means of DNA blot analysis with the lambda mXBP complementary DNA insert and probes generated from each end of this complementary DNA insert, lambda mXBP was found to arise from a multigene family. These data illustrate the high degree of complexity in the transcriptional control of this coordinately regulated gene family.

Animals↗

PubMed2005

Using unsupervised learning with independent component analysis to identify patterns of glaucomatous visual field defects.

PURPOSE: Clustering by unsupervised learning with machine learning classifiers was shown to segment clusters of patterns in standard automated perimetry (SAP) for glaucoma in previous publications. In this study, unsupervised learning by independent component analysis decomposed SAP field patterns into axes, and the information represented by these axes was evaluated. METHODS: SAP fields were used that were obtained with the Humphrey Visual Field Analyzer (Carl Zeiss Meditec, Dublin, CA) from 189 normal eyes and 156 eyes with glaucomatous optic neuropathy (GON) determined by masked review with stereoscopic optic disc photographs. The variational Bayesian independent component analysis mixture model (vB-ICA-mm) partitioned the SAP fields into the most informative number of clusters. Simultaneously, the model learned an optimal number of maximally independent axes for each cluster. RESULTS: The most informative number of clusters in the SAP set was two. vB-ICA-mm placed 68.6% of the eyes with GON in a cluster labeled G and 98.4% of the eyes with normal optic discs in a cluster labeled N. Cluster G optimally contained six axes. Post hoc analysis of patterns generated at -1 SD and +2 SD from the cluster G mean on the six axes revealed defects similar to those identified by experts as indicative of glaucoma. SAP fields associated with an axis showed increasing severity, as they were located farther in the positive direction from the cluster G mean. CONCLUSIONS: vB-ICA-mm represented the SAP fields with patterns that were meaningful for glaucoma experts. This process also captured severity in the patterns uncovered. These findings should validate vB-ICA-mm as a data-mining technique for new and unfamiliar complex tests.

Artificial Intelligence↗

PubMed2005

Patterns of inheritance in familial ALS.

We investigated 185 families with ALS for evidence of anticipation and mitochondrial inheritance. Although initial analysis demonstrated significant anticipation of age at death between generations in patients with familial ALS, further analysis demonstrated features of regression to the mean, suggesting that the perceived differences are the result of bias. In addition, there was no evidence of an effect of preferential maternal inheritance, which would have supported transmission of mitochondrial DNA mutations.

Age Distribution↗

PubMed1999

Quantitation of vital bleaching by computer analysis of photographic images.

BACKGROUND: The authors investigated the use of computer processing of photographic images to monitor changes in tooth brightness after nightguard vital bleaching, or NGVB. METHODS: Photographs of shade guides and clinical cases (patients' teeth) were taken on 35-millimeter film with electronic flash illumination and processed commercially. A slide scanner was used to digitize images as red, green and blue, or RGB, files, with constant brightness, contrast and linearity settings; the images were then analyzed with commercial software. Relevant image components (that is, teeth or shade guide tabs) were separated, and histograms of various numerical color descriptors were generated for each image component. RESULTS: Analysis of shade tab images showed that the mean pixel intensity for the RGB blue channel, or MPIb, was the most satisfactory brightness descriptor, with clear sequential MPIb increments from lighter to darker shades in each series of colors (A through D) and close correlation with the manufacturer's brightness scale (r = .83). Mathematical analysis of MPIb data for shade tabs in the same image yielded a brightness index that was reproducible and correlated well with the manufacturer's brightness scale. Sequential measurements of this index in three subjects whose teeth were bleached with carbamide peroxide for 14 days correlated well with assessments made by visual shade guide comparisons. CONCLUSIONS: The authors conclude that computer analysis of digitized photographic images with internal color controls provides an index of tooth brightness that is reproducible from image to image. CLINICAL IMPLICATIONS: A brightness index derived from computer analysis of digitized photographic images may be useful for monitoring the effectiveness of NGVB.

Carbamide Peroxide↗

PubMed2006

The pier abutment: a review of the literature and a suggested mathematical model.

Many clinicians consider the prosthetic restoration of missing posterior teeth by means of a 5-unit fixed partial denture with a pier abutment a non-favorable situation. The present article assesses the validity of the pier abutment by means of a critical review of the literature and mathematical analysis of the forces generated within a fixed partial denture of this design. Few studies are available, and none substantiate the theory that the pier abutment serves as a fulcrum. A mathematical model suggests that debonding may occur in the anterior abutment, but not due to the teetering of the fixed partial denture around the pier abutment.

Algorithms↗

PubMed2005

Unsupervised learning with independent component analysis can identify patterns of glaucomatous visual field defects.

PURPOSE: We previously reported the use of clustering by unsupervised learning with machine learning classifiers to segment clusters of patterns in standard automated perimetry (SAP) for glaucoma. In this study, the process of unsupervised learning by independent component analysis decomposed SAP field patterns into axes, and the information represented by these axes was evaluated. METHODS: SAP fields were obtained with the Humphrey Visual Field Analyzer on 189 normal eyes and 156 eyes with glaucomatous optic neuropathy (GON) determined by masked review with stereoscopic optic disc photos. The variational Bayesian independent component analysis mixture model (vB-ICA-mm) partitioned the SAP fields into the most informative number of clusters. Simultaneously, it learned an optimal number of maximally independent axes for each cluster. RESULTS: The most informative number of clusters was two. vB-ICA-mm placed 68.6% of the SAP fields from eyes with GON in a cluster labeled G and 98.4% of the fields from eyes with normal optic discs in a cluster labeled N. Cluster G optimally contained six axes. Post hoc analysis of patterns generated at -1 SD and +2 SD from the cluster G mean on the six axes revealed defects similar to those identified by experts as indicative of glaucoma. SAP fields associated with an axis showed increasing severity as they were located farther in the positive direction from the cluster G mean. CONCLUSIONS: vB-ICA-mm represented the SAP fields with patterns that were meaningful for glaucoma experts. This process also captured severity in the patterns uncovered. These findings should validate vB-ICA-mm as a data mining technique for new and unfamiliar complex tests.

Artificial Intelligence↗

PubMed1982

Brain damage among mentally disordered sex offenders.

The incidence and nature of structural brain dysfunction was investigated in a pilot study sample of individuals currently assigned the Nebraska Penal Code designation of mentally disordered sexual offender. It was hypothesized that the sexual offenders would show a significantly higher incidence of dysfunction than a psychosocially normal group as evidenced by computed tomography scan measures, regional cerebral blood flow, and neuropsychological instruments. The hypothesis was tested by two different methods. One method used a 160 by 160 printout of density numbers generated by computer from computed tomography scans administered to the sexual offenders. The second method used mean blood flow data generated from a Harshaw TASC-5 Regional Cerebral Blood Flow analysis system. Additionally, the Luria-Nebraska Neuropsychological Test Battery was administered as a measure of the behavioral correlates of brain dysfunction. Preliminary analyses indicate that 50% of the sexual offenders tested showed brain dysfunction as demonstrated by decreased density measures, decreased blood flow, and performance deficits on the Luria Battery. The implications of these findings, if confirmed, are substantial on issues of criminal responsibility, sentencing, treatment, and rehabilitation of the sex offender. Case reports of the patients studied are presented.

Adult↗

PubMed2002

Measurements of wave speed and reflected waves in elastic tubes and bifurcations.

Wave intensity analysis is a time domain method for studying waves in elastic tubes. Testing the ability of the method to extract information from complex pressure and velocity waveforms such as those generated by a wave passing through a mismatched elastic bifurcation is the primary aim of this research. The analysis provides a means for separating forward and backward waves, but the separation requires knowledge of the wave speed. The PU-loop method is a technique for determining the wave speed from measurements of pressure and velocity, and investigating the relative accuracy of this method is another aim of this research. We generated a single semi-sinusoidal wave in long elastic tubes and measured pressure and velocity at the inlet, and pressure at the exit of the tubes. In our experiments, the results of the PU-loop and the traditional foot-to-foot methods for determining the wave speed are comparable and the difference is on the order of 2.9+/-0.8%. A single semi-sinusoidal wave running through a mismatched elastic bifurcation generated complicated pressure and velocity waveforms. By using wave intensity analysis we have decomposed the complex waveforms into simple information of the times and magnitudes of waves passing by the observation site. We conclude that wave intensity analysis and the PU-loop method combined, provide a convenient, time-based technique for analysing waves in elastic tubes.

Arteries↗

PubMed1990

Spectral analysis of blood pressure and heart rate in conscious rats: effects of autonomic blockers.

We investigated the fluctuations which underly the spontaneous variability of blood pressure and heart rate in conscious rats. Intrafemoral blood pressure was computed to generate evenly spaced signals (systolic, diastolic, mean blood pressure, heart rate) at 200 ms intervals. This equidistant sampling allowed a direct spectral analysis using a Fast Fourier Transform algorithm. Systolic blood pressure and heart rate exhibited low-frequency oscillations (Mayer waves, 20-605 mHz) and a high- frequency oscillation related to respiration (1855 mHz). The respiratory fluctuations in heart rate were almost abolished by vagal blockade (atropine). Heart rate fluctuations in the low-frequency regime were diminished by vagal blockade or cardiac sympathetic blockade (atenolol). The respiratory frequency fluctuations in systolic blood pressure were markedly increased by alpha-sympathetic blockade (prazosin). In contrast, the low-frequency oscillations in systolic blood pressure were reduced by alpha-sympathetic blockade. These data indicate that in conscious rats: (1) the heart rate oscillation with respiration is vagally mediated; (2) the heart rate fluctuation in the low-frequency range is jointly mediated by beta-sympathetic and parasympathetic activities; (3) the respiratory oscillation in systolic blood pressure depends on fluctuations in cardiac output and is normally counteracted by the sympathetic tone; (4) the low-frequency oscillations in systolic blood pressure reflect the sympathetic activity to the resistance vessels.

Animals↗

PubMed2001

Microarray-based genetics of cardiac malformations.

One of the most revolutionary approaches in human genomics is DNA microarray technology. Latest developments have brought this technology to a widespread use. In this paper we discuss its usefulness especially for the study of the genetic component in congenital heart disease as a model of multifactorial disease and the possible clinical applications in the near future. Malformations of the heart and blood vessels account for the largest number of human birth defects. The susceptibility of the heart to developmental anomalies reflects the complexity of the morphogenetic events responsible for the heart formation. The genetics of congenital heart disease points to the existence of powerful disease modifiers. Tissue analysis of gene expression with cDNA microarrays provides a measure of transcriptional or posttranscriptional regulation. Large-scale partial sequencing of cDNA libraries generating expressed sequence tags is an effective means of discovering novel genes and characterizing transcription patterns in different organs and tissues. The qualitative and quantitative analysis of genes expressed in cardiac tissue by means of comparison of expression patterns related to the normal and to the pathological tissue may be of great importance for the study of cardiac pathologies. The variation in phenotypic penetrance and severity suggests that if we can identify high-risk individuals, a reduction in infant morbidity might be possible by altering environmental or maternal factors.

Gene Expression Profiling↗

PubMed2006

Analysis of lecithin-cholesterol mixtures using Raman spectroscopy.

FT-Raman spectroscopy has been used to investigate interactions between lecithin and cholesterol. Raman spectra of lecithin show multiple peaks which can be classified into three regions: hydrophobic chain, interfacial, and headgroup regions. Binary lipid mixtures (1:1, w/w, lecithin:cholesterol) were prepared by physical mixing, granulation, coprecipitation, hydration and heating (65 degrees C), and heating (120 degrees C). Regardless of the preparation method, no changes in the spectra were observed in the hydrophobic region. A shift in the wavenumber of the choline methyl asymmetric stretching mode was observed when the samples were prepared by coprecipitation, hydration and heating (65 degrees C), and heating (120 degrees C). This may indicate a modification of phospholipids in the headgroup region in these samples. The difference in degrees of frequency shift (physical mixing approximately granulation<coprecipitation approximately hydration and heating (65 degrees C)<heating (120 degrees C)) suggests that different levels of hydrogen bonding may have occurred in mixtures prepared with these methods. Multivariate analysis utilizing partial least squares regression based on selected wavenumber ranges was applied for the quantitative analysis of the amount of lecithin in lipid mixtures. Calibration models from physical mixing and heating (120 degrees C) exhibited lower R2 and root mean square error of cross validation (RMSECV) values compared to the other models suggesting lower sample homogeneity for these preparation methods. Low values of the mean absolute residues and mean Mahalanobis distances imply that the calibration model generated from physical mixing samples may be appropriate for quantitative analysis of lecithin in lipid mixtures prepared by any of the other techniques.

Chemistry, Pharmaceutical↗

PubMed1988

Prior antimicrobial therapy and resistance of Enterobacter Citrobacter and Serratia to third generation cephalosporins.

During a 6-month period all inpatients from whom Enterobacter, Citrobacter or Serratia. had been isolated were reviewed and information on selected variables recorded. Two groups, one including 19 patients with organisms resistant to third generation cephalosporins and the other 111 patients with susceptible organisms were compared. In the initial analysis, the mean number of antimicrobials received in the prior 2 months was the variable most strongly associated with isolation of resistant organisms (2.6 +/- 1.5 vs 1.5 +/- 1.6; P = 0.002). When patients who had received no antimicrobials were omitted from the analysis, the mean number of antimicrobials was similar (2.6 +/- 1.5 vs 2.3 +/- 1.5; P = 0.19). Comparisons of antimicrobials received in the prior 2 months showed only cefoxitin (9/70 vs 7/19; P = 0.016) and cefotaxime (4/70 vs 5/19; P = 0.008) to be associated with isolation of resistant organisms. These data suggest that, at our institution, antimicrobial therapy with an extended spectrum cephalosporin is an important risk factor for subsequent acquisition of an organism resistant to third generation cephalosporins.

Cephalosporins↗

PubMed2001

[DNA chip data mining].

DNA chip data routinely contain gene expression levels of thousands of genes and the analysis should be supported by various computational tools. To be brief, the analysis procedure consists of four steps including image scanning, image processing, mathematical interpretation and biological interpretation. In image processing step, we should detect the spots and measure the signals of the spots and the background. In mathematical interpretation step, first of all we should massage the measured signals to make them appropriate for further mathematical analysis. The massaged data could be analyzed by various computational methods especially when the data were generated for multiple samples comparisons. The clustering techniques including hierarchical clustering, k-means clustering, SOTA, SOM are the most popular methods in this step. Various other multivariate statistics and related machine learning techniques are being introduced and applied to DNA chip data analysis recently. And finally the most important step we should tackle is the biological interpretation task. Although the depth of the domain knowledge about the biological situation under which the data were generated is the most important factor to elucidate the biological context, it could be supported by various bioinformatics tools including MEDLINE abstract processing by NLP techniques or genetic network models constructed by Boolean networks algorithms.

Algorithms↗

PubMed2005

A targeted mass spectrometric analysis of phosphatidylinositol phosphate species.

The development of a new mass spectrometric lipid profiling methodology permits the identification of cellular phosphatidylinositol monophosphate/phosphatidylinositol bisphosphate/phosphatidylinositol trisphosphate (PIP/PIP2/PIP3) species that includes the fatty acyl composition. Using electrospray ionization mass spectrometry, we were able to resolve and identify 28 PIP and PIP2 compounds as well as 8 PIP3 compounds from RAW 264.7 or primary murine macrophage cell extracts. Analysis of PIP profiles after agonist stimulation of cells revealed the generation of differential PIP3 species and permitted us to propose a novel means for regulation and specificity in signaling through PIP3. This is the first reported identification of intact, cellular PIP3 by mass spectral analysis. The ability to analyze the fatty acyl chain composition of signaling lipids initiates new venues for investigation of the processes by which specific polyphosphoinositide species mediate.

Animals↗