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PubMed2001

Pathogen filtration, heterogeneity, and the potable reuse of wastewater.

Filtration is commonly employed in water and wastewater treatment to remove particles and reduce the concentration of microbial pathogens. All physical models of packed-bed filtration are based on a proportional relationship between particle removal per unit depth of bed and the local particle concentration, dC/dz = -C/l, where l is the filtration length scale. Although l is known to vary with time and filter depth for heterogeneous suspensions or "dirty" beds, this paper demonstrates that the filtration rates of even seemingly monodisperse particle suspensions under clean-bed filtration conditions cannot be described with a single filtration length scale. A new model is derived for particle filtration that accounts for heterogeneity at two different spatial scales. Heterogeneity at the scale of the pathogen and/or collector (microscale heterogeneity) leads to a slow power-law decay of contaminant concentration with distance, instead of the fast exponential decay predicted by the standard model. Heterogeneity at the filter scale (macroscale heterogeneity) provides another level of complexity that can be evaluated once microscale heterogeneity effects are characterized. This model for microscale and macroscale heterogeneous particle filtration is verified by filtration experiments on a recombinant analogue of the waterborne pathogen Norwalk virus.

Filtration↗
PubMed1997

Gastrointestinal drug absorption: is it time to consider heterogeneity as well as homogeneity?

The current analysis of gastrointestinal absorption phenomena relies on the concept of homogeneity. However, drug dissolution, transit and uptake in the gastrointestinal tract are heterogeneous processes since they take place at interfaces of different phases under variable stirring conditions. Recent advances in physics and chemistry demonstrate that the geometry of the environment is of major importance for the treatment of heterogeneous processes. In this context, the heterogeneous character of in vivo drug dissolution, transit and uptake is discussed in terms of fractal concepts. Based on this analysis, drugs are classified in accordance with their gastrointestinal absorption characteristics into two broad categories i.e. homogeneous and heterogeneous. The former category includes drugs with satisfactory solubility and permeability which ensure the validity of the homogeneous hypothesis. Drugs with low solubility and permeability are termed heterogeneous since they traverse the entire gastrointestinal tract and therefore are more likely to exhibit heterogeneous dissolution, transit and uptake. The high variability of whole bowel transit and the unpredictability of conventional dissolution tests for heterogeneous drugs are interpreted on the basis of the fractal nature of these processes under in vivo conditions. The implications associated with the use of strict statistical criteria in bioequivalence studies for heterogeneous drugs are also pointed out.

Area Under Curve↗
PubMedDate not supplied

Subcellular heterogeneity of mitochondrial function and dysfunction: evidence obtained by confocal imaging.

Beyond their fundamental role in energy metabolism, mitochondria perform a great variety of other important functions (e.g. in Ca2+ homeostasis, apoptosis, thermogenesis, etc.), thus suggesting their region-specific specializations and intracellular heterogeneity. Although mitochondrial functional heterogeneity has been demonstrated for several cell types, its origin and role under physiological and, in particular, pathophysiological conditions, where the extent of heterogeneity may significantly increase, remain to be elucidated. The present work thus investigated the static and dynamic heterogeneity of mitochondria and mitochondrial function in various cell types in which mitochondria may cope with specific functions including cardiomyocytes, hepatocytes and some cultured carcinoma cells. Modern confocal and two-photon fluorescent microscopy was used for the investigation and direct imaging of region-specific mitochondrial function and heterogeneity. Analysis of the autofluorescence of mitochondrial flavoproteins in hepatocytes and carcinoma cells permitted significant intracellular heterogeneity of mitochondrial redox state to be demonstrated. Comparative homogeneity and clear colocalization of mitochondrial flavoproteins, membrane potential and calcium-sensitive probes were observed in both isolated cardiomyocytes and permeabilized myocardial fibers. After ischemia reperfusion, however, or under conditions of substrate deprivation, significant heterogeneity of all these parameters was detected. Some methodological issues, mechanistic aspects, possible metabolic consequences of mitochondrial functional heterogeneity and its impact under pathological conditions are discussed.

Animals↗
PubMed1991

Model of kinetic behavior of deoxyglucose in heterogeneous tissues in brain: a reinterpretation of the significance of parameters fitted to homogeneous tissue models.

Effects of tissue heterogeneity on regional CMRglc (rCMRglc) calculated by use of the deoxyglucose (DG) method at 45 min following the pulse of DG were evaluated in simulation studies. A theoretical model was developed to describe the kinetics of DG uptake and metabolism in heterogeneous brain tissues. Rate constants were fitted to simulation data for mixed tissue and rCMRglc computed on the basis of this tissue heterogeneity model. The results were compared with those obtained by use of the original model of the DG method for homogeneous tissue, both without (3K model) and with (4K model) a term to describe an apparent loss of deoxyglucose-6-phosphate (DG-6-P). As a direct consequence of tissue heterogeneity, the effective rate constant for phosphorylation of DG, k3*, declined with time. To compensate for the time-changing k3*, estimates of the dephosphorylation rate constant, k4*, were artifactually high when the 4K model was used, even though no dephosphorylation of DG-6-P actually occurred. The present study demonstrates that the finding of a significant k4*, at least within 45 min following a pulse of DG, may not represent dephosphorylation at all, but rather the consequence of measuring radioactivity in a heterogeneous tissue and applying a model designed for a homogeneous tissue. Furthermore, the high estimates of k4* resulted in significant overestimation of rCMRglc. When rCMRglc was computed with the conventional single-scan or autoradiographic method at 45 min after a pulse of DG, the 3K and tissue heterogeneity models yielded values that were within 5% of the true weighted average value for the heterogeneous tissue as a whole. We conclude that the effects of tissue heterogeneity alone can give the appearance of product loss, even when none occurs, and that the use of the 4K model with the assumption of product loss in the 45-min experimental period recommended for the DG method may lead to overestimation of the rates of glucose utilization.

Brain↗
PubMed2006

Resistance against heterogeneous sequential infections: experimental studies with a tapeworm and its copepod host.

Parasite heterogeneity is thought to be an important factor influencing the likelihood and the dynamics of infection. Previous studies have demonstrated that simultaneous exposure of hosts to a heterogeneous mixture of parasites might increase infection success. Here this view is extended towards the effect of parasite heterogeneity on subsequent infections. Using a system of the tapeworm Schistocephalus solidus and its copepod intermediate host, heterogeneity of the tapeworm surface carbohydrates is investigated, i.e. structures that are potentially recognized by the invertebrate host's immune system. With lectin labelling, a significant proportion of variation in surface carbohydrates is related to differences in worm sibships (i.e. families). Tapeworm sibships were used for experimental exposure of copepods to either homogeneous combinations of tapeworm larvae, i.e. worms derived from the same sibship or heterogeneous mixtures of larvae, and copepods were subsequently challenged with an unrelated larva to study re-infection. Contrary to expectation, neither an effect of parasite heterogeneity on the current infection, nor on re-infection were found. The effect of parasitic heterogeneity on host immunity is therefore complex, potentially involving increased cross-protection on the one hand, with higher costs of raising a more heterogeneous immune response on the other.

Animals↗
PubMed2006

Effects of resource heterogeneity on nitrogen translocation within clonal fragments of Sasa palmata: an isotopic (15N) assessment.

BACKGROUND AND AIMS: Clonal fragments of the rhizomatous dwarf bamboo Sasa palmata, which widely predominates in temperate regions of Japan, were grown under heterogeneous resource conditions such as gap understories or nutrient-patchy grassland. Clonal fragments develop multiple ramets with long rhizomes and appear to be physiologically integrated by the translocation of assimilates. The glasshouse experiment reported here was designed to clarify the mechanisms of physiological integration of nitrogen more precisely. METHODS: To assess how resource conditions influence the amount of nitrogen translocation, and which organ acts as the strongest sink, two experiments were conducted that traced movement of 15N label between interconnected pairs of ramets to compare homogeneous and heterogeneous light and soil nitrogen conditions. KEY RESULTS: The amount of 15N translocated to leaves was between 9% and 11% greater in high-N and high-light ramets in the heterogeneous compared with homogeneous treatments. Under heterogeneous soil nitrogen conditions, translocation increased from individual ramets in resource-rich patches to ramets in resource-poor patches, while the reverse was true under heterogeneous light environments, reflecting differences in the positions of leaves that act as the strongest sinks. Neither the mass increments nor the total mass of clonal fragments was significantly affected by heterogeneity of either light or nutrients, possibly because the experimental period was too short for differences to manifest themselves. CONCLUSIONS: This study clearly demonstrated that nitrogen is readily translocated between ramets, particularly under heterogeneous resource conditions. The translocation patterns were governed by functional 'division of labour' mechanisms that resulted in net nitrogen movement from understory sites to gaps, thereby enhancing the carbon acquisition of the whole fragment. Thus, physiological integration may provide benefits for S. palmata when it is growing under heterogeneous conditions in which there are deficits of certain environmental resources.

Data Interpretation, Statistical↗
PubMed1992

Dofetilide, a new class III antiarrhythmic agent, reduces pacing induced heterogeneity of repolarisation in vivo.

OBJECTIVES: The aim was to determine whether dofetilide, a new class III antiarrhythmic agent, could reduce the heterogeneity of repolarisation produced by rapid cardiac pacing and to compare it with quinidine. Increased heterogeneity of repolarisation times may be causally linked to malignant cardiac re-entrant arrhythmias. METHODS: Studies were performed in open chest, artificially ventilated, pentobarbitone anaesthetised beagle dogs of 13 to 15 kg body weight. Myocardial electrocardiograms were simultaneously recorded from 31 electrodes located on the left and right ventricular surfaces of the in situ canine heart. Recordings were obtained over a single cardiac cycle during rapid ventricular pacing at the maximum following frequency. Computer assisted measurements of activation time, activation-repolarisation interval, and repolarisation time were performed and the heterogeneity of these measurements calculated. Measurements were performed before treatment and after each incremental intravenous dose of dofetilide (3, 10, 30, and 100 micrograms.kg-1), quinidine (1, 3, and 10 mg.kg-1), or saline vehicle. RESULTS: Dofetilide increased repolarisation time via a selective prolongation of activation-repolarisation interval, activation time being unchanged. It reduced the heterogeneity of repolarisation time and activation-repolarisation interval, heterogeneity of activation time being unchanged. Quinidine increased repolarisation time by a non-selective increase of both activation-repolarisation interval and activation time. It increased the heterogeneity of activation times which offset a decrease in heterogeneity of activation-repolarisation intervals to produce no change in heterogeneity of repolarisation times. CONCLUSIONS: Dofetilide, but not quinidine, reduces pacing induced asynchrony of repolarisation in the canine heart and this effect may contribute to its antiarrhythmic activity.

Animals↗
PubMed2005

Quantifying mechanical heterogeneity in canine acute lung injury: impact of mean airway pressure.

BACKGROUND: The heterogeneous pattern of acute lung injury (ALI) predisposes patients to ventilator-associated lung injury. Currently, there is no simple technique that can reliably quantify lung heterogeneity during the dynamic conditions of mechanical ventilation. Such a technique may be of use in optimizing mechanical ventilatory parameters such as rate, tidal volume, or positive end-expiratory pressure. METHODS: To determine the impact of heterogeneity on respiratory mechanics, the authors measured respiratory impedance (Zrs), expressed as respiratory resistance (Rrs) and elastance (Ers), in 11 anesthetized dogs from 0.078 to 8.9 Hz using broadband pressure and flow excitations under baseline conditions and after ALI produced by infusion of 0.08 ml/kg oleic acid into the right atrium. Data were obtained at mean airway pressures (Pao) of 5, 10, 15, and 20 cm H2O. The Zrs spectra were fit by various models of the respiratory system incorporating different distributions of parallel viscoelastic tissue properties. RESULTS: Under baseline conditions, both Rrs and Ers exhibited dependence on oscillation frequency, reflecting viscoelastic behavior. The Ers demonstrated significant dependence on Pao. After ALI, both the level and frequency dependence of Rrs and Ers increased, as well as the apparent heterogeneity of tissue properties. Both Rrs and Ers as well as heterogeneity decreased with increasing Pao, approaching baseline levels at the highest levels of Pao. CONCLUSIONS: These data demonstrate that Zrs can provide specific information regarding the mechanical heterogeneity of injured lungs at different levels of Pao. Moderate increases in Pao seem to be beneficial in ALI by reducing heterogeneity and recruiting lung units. These noninvasive measurements of lung heterogeneity may ultimately allow for the development of better ventilation protocols that optimize regional lung mechanics in patients with ALI.

Airway Resistance↗
PubMed1993

Regional heterogeneity in the proliferative activity of human gliomas as measured by the Ki-67 labeling index.

The effects of regional heterogeneity on the accuracy of histological grading of gliomas are well known, but little has been reported about its implications for other diagnostic modalities. This study investigated the relationships of regional heterogeneity in tumor proliferative activity, measured by Ki-67 labeling indices (LI), and histological grades for 16 regionally sampled glioma resections. There was a strong correlation between histological grades and Ki-67 LI in individual regions (p < 0.001), and both methods demonstrated comparable heterogeneity. Heterogeneity increased with tumor grade, probably as an expression of the increased genetic instability that accompanies tumor progression. Similarly, regions with comparable proliferative activity tended to cluster, paralleling clonal expansion. Thus, both histological grading and Ki-67 LI are subject to heterogeneity-induced sampling errors that limit their diagnostic accuracy, particularly in small biopsies. However, fewer grading errors occurred when using both methods together than when using either method alone, suggesting that the use of multiple techniques may reduce the adverse effects of regional heterogeneity on diagnostic accuracy. Regional heterogeneity appears to be a ubiquitous feature of gliomas: it also has been reported in karyotype, p53 oncogene mutations, and PDGF and EGFR expression. The effects of regional heterogeneity on new methods for studying gliomas need to be considered.

Brain Neoplasms↗
PubMed2002

Chemical and seismological constraints on mantle heterogeneity.

Recent seismological studies that use scattered waves to detect heterogeneities in the mantle reveal the presence of a small, distributed elastic heterogeneity in the lower mantle which does not appear to be thermal in nature. The characteristic size of these heterogeneities appears to be ca. 8 km, suggesting that they represent subducted recycled oceanic crust. With this stimulus, old ideas that the mantle is heterogeneous in structure, rather than stratified, are reinterpreted and a simple, end-member model for the heterogeneity structure is proposed. The volumetrically largest components in the model are recycled oceanic crust, which contains the heat-producing elements, and mantle depleted of these and other incompatible trace elements. About 10% of the mantle's mass is made up of recycled oceanic crust, which is associated with the observed small-scale seismic heterogeneity. The way this heterogeneity is distributed is in convectively stretched and thinned bodies ranging downwards in size from 8 km. With the present techniques to detect small bodies through scattering, only ca. 55% of the mantle's small-scale heterogeneities are detectable seismically.

Computer Simulation↗
PubMed2006

Consequences for host-parasitoid interactions of grazing-dependent habitat heterogeneity.

1. Environmental heterogeneity can produce effects that cascade up to higher trophic levels and affect species interactions. We hypothesized that grazing-dependent habitat heterogeneity and grazing-independent host plant heterogeneity would influence directly and indirectly a host-parasitoid interaction in a woodland habitat. 2. Thistles were planted randomly in 20 birch woodlands, half of which are grazed by cattle. The abundances of two species of seed herbivore and their shared parasitoid were measured, and related to habitat and host-plant heterogeneity. 3. The presence of cattle grazing created a structurally and compositionally distinct plant assemblage from the ungrazed seminatural situation. Grazing did not affect the number or dispersion of the host plant underpinning the host-parasitoid interaction. 4. The density of one insect herbivore, Tephritis conura, and its parasitoid Pteromalus elevatus was significantly increased by the presence of cattle; but another herbivore, Xyphosia miliaria, was unaffected. The percentage of parasitism of T. conura was increased in grazed habitat occurring at twice the rate found in ungrazed habitat. 5. The increase in T. conura abundance was correlated with increased species richness and cover of forbs in grazed sites. This effect of grazing-dependent habitat variation on host insect density cascaded up to parasitoid density and percentage of parasitism. Habitat heterogeneity had a further direct, positive effect on parasitoid density and percentage of parasitism after controlling for host-insect density. 6. Independent of grazing, heterogeneity in host-plant flowering, architecture and stature further affected T. conura and its parasitoid's densities. Parasitoid density was also affected by the dispersion of the host plant. 7. A combination of habitat and host-plant scale environmental heterogeneity influenced a host-parasitoid interaction indirectly and directly, providing a rare example of an anthropogenic disturbance positively affecting a tertiary trophic level. This finding highlights the need to consider not only the importance of bottom-up effects for top-down processes, but also the role of environmental heterogeneity arising from anthropogenic disturbance for trophic interactions such as parasitism.

Animals↗
PubMed2003

Muscle fractal vascular branching pattern and microvascular perfusion heterogeneity in endurance-trained and untrained men.

Less heterogeneous skeletal muscle perfusion has recently been reported in endurance-trained compared to untrained men at macrovascular level. The causes of this difference in perfusion heterogeneity are unknown as is whether the same difference is observed in microvasculature. We hypothesised that the difference could be caused by changes in muscle vascular branching pattern. Perfusion was measured in resting and exercising muscle in 14 endurance-trained and seven untrained men using [(15)O]water and positron emission tomography. Fractal dimension (D) of perfusion distribution was calculated as a measure of fractal characteristics of muscle vascular branching pattern. Perfusion heterogeneity in microvascular units (1 mm(3) samples) was estimated using the measured heterogeneity in voxels of positron emission tomography (PET) images (relative dispersion, RD = S.D./mean) and corresponding D values. D was similar between the groups (exercising muscle 1.11 +/- 0.07 and 1.14 +/- 0.06, resting muscle 1.12 +/- 0.06 and 1.14 +/- 0.03, trained and untrained, respectively). Trained men had lower perfusion (151 +/- 44 vs. 218 +/- 87 ml min(-1) kg(-1), P < 0.05) and macrovascular perfusion heterogeneity (relative dispersion 21 +/- 5 vs. 25 +/- 5 %, P < 0.05) in exercising muscle than untrained men. Furthermore, estimated perfusion heterogeneity in microvascular units in exercising muscle was also lower in trained men (33 +/- 7 vs.48 +/- 19 %, P < 0.05). These results show that fractal vascular branching pattern is similar in endurance-trained and untrained men but perfusion is less heterogeneous at both the macro- and the microvascular level in endurance-trained men. Thus, changes in fractal branching pattern do not explain the differences in perfusion heterogeneity between endurance-trained and untrained men.

Adult↗
PubMedDate not supplied

How heterogeneous bronchoconstriction affects ventilation distribution in human lungs: a morphometric model.

Convective dependent flow heterogeneities associated with airways proximal to the acini are the dominant cause of abnormal ventilation distribution during induced bronchoconstriction (Verbanck, S., D. Schuermans, A. Van Muylem, M. Paira, M. Noppen, and W. Vincken. Ventilation distribution during histamine provocation. J. Appl. Physiol. 83:1907-1916, 1997). We applied a morphometric model of the human lung to predict flow distributions among the acini during heterogeneous bronchoconstriction and relate these distributions to impairments in the mechanical properties of the lung. The model has an asymmetrical branching airway system. Heterogeneous constriction was invoked by defining an airway constriction distribution with a mean (mu) and coefficient of variation (CV) and either a Gaussian or log normal distribution. The lung resistance (RL) and elastance (EL) were most sensitive to severely heterogeneous constriction that produced a few highly constricted or closed airways dispersed randomly throughout the periphery. Ventilation distribution in the healthy lung was effectively homogeneous over the frequency range of 0.1-5.0 Hz. With homogeneous or mildly heterogeneous constriction (CV< or =20%) ventilation remained fairly homogeneous at low frequencies (< or =0.1 Hz) but rapidly became heterogeneous as frequency increased. Conversely, a low mean but severely heterogeneous constriction that produced random airway closure produced abnormal ventilation distribution in most acini at all frequencies, and some acini received up to 25 times the normal ventilation. This suggests that certain forms of heterogeneity can lead to shear induced lung injury even at common mechanical ventilation rates.

Animals↗
PubMed1998

Analytical approach to heterogeneity correction factor calculation for brachytherapy.

In brachytherapy treatment planning, the effects of tissue and applicator heterogeneities are commonly neglected due to lack of accurate, general, and fast three-dimensional (3D) dose-computational algorithms. A novel approach, based on analytical calculation of scattered photon fluxes inside and around a disk-shaped heterogeneity, has been developed for use in the three-dimensional scatter-subtraction algorithm. Specifically, our model predicts the central-ray dose distribution for a collimated photon isotropic source or brachytherapy "minibeam" in the presence of a slab of heterogeneous material. The model accounts for the lateral dimensions, location, composition, density, and thickness of the heterogeneity using precalculated scatter-to-primary ratios (SPRs) for the corresponding homogeneous problem. The model is applicable to the entire brachytherapy energy range (25 to 662 keV) and to a broad range of materials having atomic numbers of 13 to 82, densities of 2.7 g.cm-3 (Al) to 21.45 g.cm-3 (Pt) and thicknesses up to 1 mean free path. For this range of heterogeneous materials, the heterogeneity correction factors (HCFs) vary from 0.09 to 0.75. The model underestimates HCF when multiple scattering prevails and overestimates HCF when absorption dominates. However, the analytic model agrees with Monte Carlo photon transport (MCPT) benchmark calculations within 1.8% to 10% for 125I, 169Yb, 192Ir, and 137Cs for a wide variety of materials, with the exception of Ag. For 125I shielded by Ag, where the mean discrepancy can exceed 25%, the error is due to K-edge characteristic x rays originating within the heterogeneity. The proposed approach provides reductions in CPU time required of 5 x 10(4)-10(5) and 100 in comparison with direct MCPT simulation and 1D numerical integration, respectively. The limitations of model applicability, as determined by the physical properties of heterogeneity material and accuracy required, are also discussed.

Algorithms↗
PubMed1984

Heterogeneity of Rhizobium lipopolysaccharides.

The lipopolysaccharides ( LPSs ) from strains of Rhizobium leguminosarum, Rhizobium trifolii, and Rhizobium phaseoli were isolated and partially characterized by mild acid hydrolysis and by polyacrylamide gel electrophoresis. Mild acid hydrolysis results in a precipitate which can be removed by centrifugation or extraction with chloroform. The supernatant contains polysaccharides which, in general, are separated into two fractions ( LPS1 and LPS2 ) by Sephadex G-50 gel filtration chromatography. The higher-molecular-weight LPS1 fractions among the various Rhizobium strains are highly variable in composition and reflect the variability reported in the intact LPSs (R. W. Carlson and R. Lee, Plant Physiol. 71:223-228, 1983; Carlson et al., Plant Physiol. 62:912-917, 1978; Zevenhuizen et al., Arch. Microbiol. 125:1-8, 1980). The LPS1 fraction of R. leguminosarum 128C53 has a higher molecular weight than all other LPS1 fractions examined. All LPS2 fractions examined are oligosaccharides with a molecular weight of ca. 600. The major sugar component of all LPS2 oligosaccharides is uronic acid. The LPS2 compositions are similar for strains of R. leguminosarum and R. trifolii, but the LPS2 from R. phaseoli was different in that it contained glucose, a sugar not found in the other LPS2 fractions or found only in trace amounts. Polyacrylamide gel electrophoretic analysis shows that each LPS contains two banding regions, a higher-molecular-weight heterogeneous region often containing many bands and a lower-molecular-weight band. The lower-molecular-weight bands of all LPSs have the same electrophoretic mobility, which is greater than that of lysozyme. The banding pattern of the heterogeneous regions varies among the different Rhizobium strains. In the case of R. leguminosarum 128C53 LPS, the heterogeneous region of a higher molecular weight than is this region from all other Rhizobium strains examined and consists of many bands separated from one another by a small and apparently constant molecular weight interval. When the heterogeneous region of R. Leguminosarum 128C53 LPS was cut from the gel and analyzed, its composition was found to be that of the intact LPS, whereas the lower-molecular-weight band contains only sugars found in the LPS2 oligosaccharide. In the case of R. leguminosarum 128C63 and R. trifolii 0403 LPSs, the heterogeneous regions are similar and consist of several band s separated by a large-molecular-weight interval with a the major band of these heterogeneous regions having the lowest molecular weight with an electrophoretic mobility near that of beta-lactoglobulin. The heterogeneous region from R. phaseoli 127K14 consists of several bands with electrophoretic mobilities near that of beta-lactoglobulin, whereas this region from R. trifolii 162S7 shows a continuous staining region, indicating a great deal of heterogeneity. The results described in this paper are discussed with regard to the reported properties of Escherichia coli and Salmonella LPSs.

Carbohydrates↗
PubMed2006

Influence of culture heterogeneity in cell surface charge on adhesion and biofilm formation by Enterococcus faecalis.

Biofilm formation is an increasing problem in medicine, due to the intrinsic resistance of microorganisms in the biofilm mode of growth against the host immune system and antimicrobial therapy. Adhesion is an important step in biofilm formation, influenced, among other factors, by the surface hydrophobicities and charges of both the substratum and the adhering microorganisms. Enterococcus faecalis strains generally display subpopulations with different surface charges, expressed as bimodal zeta potential distributions. Two-thirds of E. faecalis strains isolated from clogged biliary stents displayed such heterogeneity of surface charges in culture. In this study, the influence of this culture heterogeneity on initial adhesion and subsequent biofilm formation was investigated. Heterogeneous strains were retained in higher numbers on polystyrene than homogeneous strains. Also, biofilm formation was much more pronounced for heterogeneous strains than for homogeneous strains. In a population enriched to display only one subpopulation, fewer bacteria were retained than in its original heterogeneous culture. Also, the enriched subpopulation formed less biofilm than its original heterogeneous culture. The presence of ox bile during adhesion resulted in fewer retained bacteria, although heterogeneous strains were still retained in significantly higher numbers than were homogeneous strains, and, in general, the presence of ox bile reduced biofilm formation. The initial adhesion and biofilm formation were independent of the presence of the gene encoding the enterococcal surface protein (esp) or the expression of gelatinase (GelE). It is concluded that heterogeneity in cell surface charge represents an advantage for bacteria in the colonization of surfaces.

Bacterial Adhesion↗
PubMed2000

Correlation between ventilation and perfusion determines VA/Q heterogeneity in endotoxemia.

Endotoxin increases ventilation-to-perfusion ratio (VA/Q) heterogeneity in the lung, but the precise changes in alveolar ventilation (VA) and perfusion that lead to VA/Q heterogeneity are unknown. The purpose of this study was to determine how endotoxin affects the distributions of ventilation and perfusion and the impact of these changes on VA/Q heterogeneity. Seven anesthetized, mechanically ventilated juvenile pigs were given E. coli endotoxin intravenously, and regional ventilation and perfusion were measured simultaneously by using aerosolized and injected fluorescent microspheres. Endotoxemia significantly decreased the correlation between regional ventilation and perfusion, increased perfusion heterogeneity, and redistributed perfusion between lung regions. In contrast, ventilation heterogeneity did not change, and redistribution of ventilation was modest. The decrease in correlation between regional ventilation and perfusion was responsible for significantly more VA/Q heterogeneity than were changes in ventilation or perfusion heterogeneity. We conclude that VA/Q heterogeneity increases during endotoxemia primarily as a result of the decrease in correlation between regional ventilation and perfusion, which is in turn determined primarily by changes in perfusion.

Animals↗
PubMed2004

DNA-ploidy in advanced gastric carcinoma is less heterogeneous than in early gastric cancer.

This analysis of DNA-ploidy heterogeneity in advanced gastric carcinomas is consistent with the hypothesis of the emergence of a single aneuploid cell clone as a crucial mechanism in the progression from early gastric carcinoma to advanced gastric cancer. The prognostic value of DNA-ploidy in gastric cancers has been a matter of controversy. Tumour DNA-ploidy heterogeneity, the presence within the same tumour of multiple stemlines differing in DNA content, has been described in various tumours including gastric cancers. The occurrence of such heterogeneity has been accepted as an explanation for the divergent DNA-ploidy results in this type of tumours. A previous study of early gastric cancers suggested that in pure diploid superficial carcinomas, genetic instability might lead to a cell clone which has undergone a ploidy shift and is more aggressive. If so, this would initially result in DNA-ploidy heterogeneity. Proliferative dominance of the aneuploid clone could eventually evolve to a homogeneous aneuploid tumour. In order to test this hypothesis, we studied DNA-aneuploidy and DNA-ploidy heterogeneity in advanced gastric carcinomas. We performed DNA cytophotometry on multiple samples collected from 16 advanced gastric carcinomas and found 15 DNA-aneuploid tumours (94%) and one diploid tumour. Multiple DNA-stemlines were found in 4 cases (26%). Analysis of proliferative activity performed on the same samples revealed higher proliferation rate in DNA-ploidy homogeneous tumours than in aneuploid heterogeneous tumours. Heterogeneous tumours did not overexpress p53. These results confirm that DNA-aneuploidy is frequent in advanced gastric cancer and demonstrate that a majority of these aneuploid tumours are not DNA-ploidy heterogeneous. Furthermore, the higher proliferative activity in homogeneous-aneuploid carcinomas and their more frequent overexpression of p53 support the hypothesis that in gastric cancer tumour progression implies the development of a dominant and more aggressive (higher proliferative activity, p53 overexpression) aneuploid cell clone.

Aged↗