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Biomedical subjects

M Schwartz

Publications and source records attributed to M Schwartz.

At least 19 recordsLinked to original sources

Distribution of anomalous exponents of natural images.

Recent studies of correlations of intensity in databases of natural images revealed a remarkable property. The two point correlations are described in terms of power law behavior, with an exponent which seems to be robust. In the present Letter we consider the statistical meaning of that result. We study many individual images of one of the databases considered. We find that the same law characterizing the correlations in the whole database governs also images randomly chosen from that database, with one essential difference. The exponent characterizing each image is specific and differs from the exponent characterizing the whole database. The distribution of single image exponents has been measured and found to exhibit a rather heavy tail. The database exponent cannot, thus, be considered as a statistical representative of a single image exponent. Possible reasons for the diversity in image exponents are discussed.

Journal Article↗

Fragile sites are preferential targets for integrations of MLV vectors in gene therapy.

Following gene therapy of SCID-X1 using murine leukemia virus (MLV) derived vector, two patients developed leukemia owing to an activating vector integration near the LMO2 gene. We found that these integrations reside within FRA11E, a common fragile site known to correlate with chromosomal breakpoints in tumors. Further analysis showed that fragile sites attract a nonrandom number of MLV integrations, shedding light on its integration mechanism and risk-to-benefit ratio in gene therapy.

Cells, Cultured↗

Tissue specific distribution of the 3243A->G mtDNA mutation.

BACKGROUND: The 3243A-->G is a common pathogenic mitochondrial DNA (mtDNA) point mutation causing a variety of different phenotypes. Segregation of this mutation to different tissues during embryonic life and postnatally is still enigmatic. OBJECTIVE: To investigate the tissue distribution of this mutation. METHODS: In 65 individuals from nine families segregating the 3243A-->G mutation, the mutation load (% mutated mtDNA) was determined in various tissues. Mutation load was measured in two to four cell types--blood leucocytes, buccal cells, skeletal muscle cells, and urine epithelial cells (UEC)--derived from all three embryogenic germ layers. RESULTS: There was a significant correlation among mutation loads in the four tissues (r = 0.80-0.89, p<0.0001). With blood serving as reference, the mutation load was increased by 16% in buccal mucosa, by 31% in UEC, and by 37% in muscle. There were significant differences between the mitotic tissues blood, buccal mucosa, and UEC (p<0.0001), but no difference between UEC and muscle. Using the present data as a cross sectional investigation, a negative correlation of age with the mutation load was found in blood, while the mutation load in muscle did not change with time; 75% of the children presented with higher mutation loads than their mothers in mitotic tissues but not in the post-mitotic muscle. CONCLUSIONS: There appears to be a uniform distribution of mutant mtDNA throughout the three germ layers in embryogenesis. The significant differences between mutation loads of the individual tissue types indicate tissue specific segregation of the 3243A-->G mtDNA later in embryogenesis.

Adolescent↗

Comparative anatomy of gall development on Gypsophila paniculata induced by bacteria with different mechanisms of pathogenicity.

Galls induced on Gypsophila paniculata by Pantoea agglomerans pv. gypsophilae (Pag) and Agrobacterium tumefaciens (At), bacteria with different mechanisms of pathogenicity, were compared morphologically and anatomically. The pathogenicity of Pag is dependent on the presence of an indigenous plasmid that harbors hrp gene cluster, genes encoding Hop virulence proteins and biosynthetic genes for auxin (IAA) and cytokinins (CKs), whereas that of At involves host transformation. The Pag-induced gall was rough, brittle and exhibited limited growth, in contrast to the smooth, firm appearance and continuous growth of the At-induced gall. Anatomical analysis revealed the presence of cells with enlarged nuclei and multiple nucleoli, giant cells and suberin deposition in Pag that were absent from At-induced galls. Although circular vessels were observed in both gall types, they were more numerous and the vascular system was more organized in At. An aerenchymal tissue was observed in the upper part of the galls. Ethylene emission from Pag galls, recorded 6 days after inoculation, was eight times as great as that from non-infected controls. In contrast, a significant decrease in ethylene production was observed in Gypsophila cuttings infected with Pag mutants deficient in IAA and CK production. The results presented are best accounted for by the two pathogens having distinct pathogenicity mechanisms that lead to their differential recognition by the host as non-self (Pag) and self (At).

Caryophyllaceae↗

Molecular dynamics study of translational and rotational diffusion in liquid ortho-terphenyl.

NVT molecular dynamics simulations were performed on liquid o-terphenyl as a function of temperature in the range 320-480 K. Computed translational diffusion coefficients displayed the non-Arrhenius behavior expected of a fragile glass-forming liquid and were in good, semiquantitative agreement with experimental results. Rotational correlation functions calculated for various vectors within the molecule exhibited a very short time (0-1 ps) initial decay, followed by a reversal, which corresponds to free reorientation within the "solvent" cage prior to collision with a wall. Rotational correlation times of three orthogonal vectors fixed on the central benzene were close to equal at all temperatures, indicating nearly isotropic overall molecular reorientation. The average correlation times exhibited a non-Arrhenius temperature dependence and were in very good agreement with experimental values derived from 2D and 1H NMR relaxation times. Correlation times of vectors located on the lateral phenyl rings were used to calculate the "spinning" internal rotation diffusion coefficients, which were approximately twice as great as the overall rotational diffusion constants, indicating rapid internal rotation of the phenyl side groups over wide ranges of angle in the liquid.

Computer Simulation↗

Naturally conceived twins with monochorionic placentation have the highest risk of fetal loss.

OBJECTIVE: The aim of this study was to estimate the rate of fetal loss in dichorionic (DC) and monochorionic (MC) twin pregnancies stratified according to zygosity and method of conception. METHODS: In a prospective multicenter observational study women with a twin pregnancy had an ultrasound scan before 14 + 6 weeks' gestation in order to determine chorionicity. The fetal loss rate, the perinatal, neonatal and infant mortality rates and the frequency of very preterm labor were estimated for the different types of twin. RESULTS: Among the 495 pregnancies (421 DC and 74 MC) 229 (46%) were conceived naturally and 266 (54%) by assisted reproduction (AR). Outcome data for 945 liveborn babies were obtained. The spontaneous miscarriage rate before 24 weeks' gestation was 10.9% (7/64) among naturally conceived MC compared to 3.0% (5/165) for naturally conceived DC twins (P < 0.05). For twins conceived by AR the corresponding figures were 0% (0/10) and 0.4% (1/256). The odds ratio (OR) for very preterm birth-before 28 weeks' gestation-was 4.2 for MC twins compared to DC twins. The relative risk of fetal loss or death among DC twins was 20% of the risk for MC twins. CONCLUSION: The risk of fetal loss, very preterm delivery and neonatal/infant death is significantly higher among twins with MC compared to DC placentation. Twins conceived by AR have a much lower risk of MC placentation. The risk of losing one or both twins seems higher among naturally conceived twins compared to twins conceived by AR, despite the fact that the maternal age was higher among the mothers of the AR twins.

Adult↗

Linking environmental and economic sustainability in establishing standards for wastewater re-use in Israel.

Israel is one of the world's leaders in agricultural re-use of wastewater, currently re-using over 60% of produced wastewater. The effects of arid climate, intensive irrigated agriculture and limited water resources make re-use necessary to conserve fresh water for domestic use. Quality standards for wastewater re-use are needed to protect public health and prevent environmental and agricultural damage. This paper examines the environmental and economic sustainability of the proposed upgrade of wastewater quality standards. A tertiary treatment standard was proposed, but has not been approved due to objections from local authorities and farmers. An upgrade will require higher treatment costs, which will be divided between farmers and local authorities through the pricing of the wastewater. Farmers oppose the upgrade because they will not be able to pay higher prices for wastewater, which they use to irrigate low-profit crops. If the price is too high, these farmers may be forced out of business and a substantial reduction in cultivated lands may result. If the price is too low, the poorer local authorities may not be able to comply with the standards, and may discharge improperly treated wastewater, causing environmental damage. A successful policy balances the needs for environmental protection with the economic realities of farmers and local authorities and may require compensation for local authorities or farmers in order to achieve maximum environmental protection.

Agriculture↗

Changes in coping style following traumatic brain injury and their relationship to productivity status.

The use of maladaptive coping strategies following traumatic brain injury (TBI) is known to be associated with increased depression and a lower productivity status. What is not known is whether coping behaviours change following TBI and if they do change whether these changes account for significant variance in outcome. Seventy-three significant others of TBI survivors were recruited at the time their friend/family member was injured and followed prospectively. They reported on their friend/family member's pre-injury and 6-month coping behaviours using the Coping with Health Injuries and Problems Scale. The use of emotional pre-occupation coping (p = .02) increased significantly and approached significance for distraction coping(p = .08). These changes in coping also accounted for significant variance (22%, p = .02) in productivity status over and above that accounted for by demographics and injury severity. Whether maladaptive coping changes can be prevented with a view to improving outcomes is a question that now needs to be explored.

Adaptation, Psychological↗

Molecular dynamics study of anisotropic translational and rotational diffusion in liquid benzene.

Equilibrium NPT and NVT molecular dynamics simulations were performed on liquid benzene over an extended range of temperature (from 260 to 360 K) using the COMPASS force field. Densities and enthalpies of vaporization (from cohesive energy densities) were within 1% of experiment at all temperatures. tumbling and spinning rotational diffusion coefficients, D(perpendicular) and D(parallel), computed as a function of temperature, agreed qualitatively with the results of earlier reported experimental and computational investigations. Generally, it was found that D(parallel)/D(perpendicular) approximately 1.4-2.5 and the activation energy for tumbling was significantly greater than for spinning about the C6 axis [Ea(D(perpendicular)) = 8.1 kJ mol(-1) and Ea(D(parallel)) = 4.5 kJ mol(-1)]. Calculated translational diffusion coefficients were found to be in quantitative agreement with experimental values at all temperatures [deviations were less than the scatter between different reported measurements]. In addition, translational diffusion coefficients were computed in the molecule-fixed frame to yield values for Dxy (diffusion in the plane of the molecule) and Dz (diffusion perpendicular to the plane). It was found that the ratio Dxy/Dz approximately 2.0, and that the two coefficients have roughly equal activation energies. This represents the first atomistic molecular dynamics study of translational diffusion in the molecular frame.

Journal Article↗

A computational study of the thermochemistry of bromine- and iodine-containing methanes and methyl radicals.

Bromo- and iodomethanes and the corresponding halogenated methyl radicals have been investigated by ab initio methods. Geometries and vibrational frequencies were derived with quadratic configuration interaction methods at the QCISD/6-311G(d,p) level of theory, and energies via QCISD(T)/6-311+G(3df,2p). Core electrons were represented with relativistic effective potentials. Anharmonicity of the out-of-plane bending modes in the methyl radicals was taken into account by numerical integration of the Schrödinger equation with potentials derived from relaxed scans of these modes. The results are in good accord with experimental data where available. Thermochemistry derived via isodesmic reactions referenced to CH3, CH4, and monohalomethanes yields excellent accord with new experiments on dihalomethanes and provides recommendations for the more poorly characterized tri- and tetrahalomethanes and halomethyl radicals. For the methanes CH2Br2, CHBr3, CBr4, CH2I2, CHI3, CI4, CH2BrI, CHBr2I, and CHBrI2 we compute DeltafH degrees (298) values of 4.3, 51.6, 110.6, 108.1, 208.5, 321.3, 56.8, 104.8, and 157.1 kJ mol(-1), respectively. For the methyl radicals CH2Br, CHBr2, CBr3, CH2I, CHI2, CI3, CHBrI, CBr2I, and CBrI2 we compute DeltafH degrees (298) values of 166.6, 191.7, 224.0, 217.2, 290.4, 369.1, 241.6, 320.8, and 272.3 kJ mol(-1), respectively. Recommended confidence limits are +/-3 kJ mol(-1) per Br or I atom. Trends in these values and the corresponding C-H bond strengths are discussed and compared with prior experiments, empirical estimation schemes, and ab initio calculations.

Journal Article↗

[Risk factors for community acquired pneumonia (CAP). A systematic review].

BACKGROUND AND OBJECTIVE: Community acquired pneumonia (CAP) is the most frequent mortal infectious disease in the western industrial countries. So far no detailed information about incidence, pathogenetic agents, medical service and risk factors existed within Germany. This article reviews international studies, which identified risk factors for CAP. METHOD: The MEDLINE database search comprised 743 articles from 1966 to December 2003. Ten published studies analysing risk factors for CAP were included in this study. RESULTS: Age, gender, smoking and chronic lung diseases ranged among the leading risk factors. Other variables, like medication, dangerous substances, alcohol or sociodemographic factors have so far been insufficiently proved. CONCLUSION: Comparable data concerning CAP in Germany are currently inadequate. In order to improve the data situation, in 2002, the Community Acquired Pneumonia NETwork (CAPNET) was established. CAPNET assembles and soon intends to publish detailed information about incidence and risk factors of Community Acquired Pneumonia.

Adolescent↗

Macrophages and dendritic cells treatment of spinal cord injury: from the bench to the clinic.

The failure of the spinal cord to recover after injury has been associated with the immune privilege mechanism that suppresses immune activity throughout the central nervous system. Primed macrophages and dendritic cells were shown to promote neurological recovery in preclinical models of spinal cord injury. A cell therapy consisting of autologous incubated macrophages is now being tested on spinal cord injury patients in clinical trials.

Animals↗

Protective autoimmunity: interferon-gamma enables microglia to remove glutamate without evoking inflammatory mediators.

Glutamate in excessive amounts is a major contributor to neuronal degeneration, and its removal is attributed mainly to astrocytes. Traumatic injury to the central nervous system (CNS) is often accompanied by disappearance of astrocytes from the lesion site and failure of the remaining cells to withstand the ensuing toxicity. Microglia that repopulate the lesion site are the usual suspects for causing redox imbalance and inflammation and thus further exacerbating the neurotoxicity. However, our group recently demonstrated that early post-injury activation of microglia as antigen-presenting cells correlates with an ability to withstand injurious conditions. Moreover, we found that T cells reactive to CNS-specific self-antigens protected neurons against glutamate toxicity. Here, we show that antigen-specific autoimmune T cells, by tailoring the microglial phenotype, can increase the ability of microglia-enriched cultures to remove glutamate. This T-cell-mediated effect could not be achieved by the potent microglia-activating agent lipopolysaccharide (LPS), but was dose-dependently reproduced by the Th1 cytokine interferon (IFN)-gamma and significantly reduced by neutralizing anti-IFN-gamma antibodies. Under the same conditions, IFN-gamma had no effect on cultured astrocytes. Up-regulation of glutamate uptake induced by IFN-gamma activation was not accompanied by the acute inflammatory response seen in LPS-activated cultures. These findings suggest that T cells or their cytokines can cause microglia to adopt a phenotype that facilitates rather than impairs glutamate clearance, possibly contributing to restoration of homeostasis.

Animals↗

Patient defined dichotomous end points for remission and clinical improvement in ulcerative colitis.

BACKGROUND AND AIMS: Ulcerative colitis disease activity indices offer good statistical power but small changes in these indices may not be clinically important. There are no validated definitions of remission or of significant improvement for these indices. The use of clinically important end points would strengthen the validity of study outcomes. Our aims were to identify objective end points in standard disease activity indices for remission and for improvement in ulcerative colitis. METHODS: Sixty six consecutive patients with ulcerative colitis provided information about remission status and their disease activity. At a return visit 1-14 months later, these patients provided information about the change in their disease activity, and non-invasive indices were measured. RESULTS: Specific objective end points for determining remission with four standard indices and a quality of life instrument were determined (St Mark's <3.5, ulcerative colitis disease activity index <2.5, simple clinical colitis activity index (SCCAI) <2.5, Seo <120, and inflammatory bowel disease quality of life index (IBDQ) >205). These cut offs also identified patients who met a regulatory definition of remission. Specific objective end points for clinical improvement in two non-invasive indices and a quality of life instrument were determined with good sensitivity and specificity (SCCAI decrease >1.5, Seo decrease >30, IBDQ increase >20). CONCLUSIONS: We found specific cut off values for disease activity indices that identify patients who have significantly improved or achieved remission in an objective, sensitive, and specific manner. These cut offs should help in the interpretation of the outcomes of clinical trials in ulcerative colitis.

Adult↗

How does fluoride affect dentin microhardness and mineralization?

Fluoride (F) has been a useful instrument in caries prevention. However, only limited data exist on the effect of its long-term use on dentin mineralization patterns and microhardness. The objective of this study was to evaluate the influence of tooth F concentration ([F]) and dental fluorosis (DF) severity on dentin microhardness and mineralization. We collected 137 teeth in Montreal and Toronto, Canada, and Fortaleza, Brazil, where optimum or suboptimum levels of water F were 0.2 ppm, 1 ppm, and 0.7 ppm, respectively. Teeth were analyzed for DF severity, dentin [F], enamel [F], dentin microhardness, and dentin mineralization. Dentin [F] correlated with DF severity; enamel [F] correlated with dentin microhardness and dentin mineralization; DF severity correlated with dentin microhardness. Genetic factors (e.g., DF severity) and environmental factors (e.g., tooth [F]) influenced the mechanical properties (microhardness) of the teeth, while only the environmental factors influenced their material properties (e.g., mineralization). Fortaleza teeth were harder and less mineralized and presented higher dentin [F] values. Montreal teeth presented lower levels of DF when compared with both Toronto and Fortaleza teeth.

Adolescent↗