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PubMed1996

Intestinal and diffuse gastric cancers arise in a different background of Helicobacter pylori gastritis through different gene involvement.

Investigation of extensively sampled nontumor gastric mucosa from 205 early gastric cancers showed Helicobacter pylori colonization in 85% of cases, including 100% of diffuse and 78% (83% in 97 cases with Swiss rolls) of glandular or mixed cancers. Intestinal metaplasia, including its type III variant, was prominent in the mucosa associated with glandular and mixed (but not diffuse) early cancers. Both glandular (usually called "intestinal") and diffuse-type cancers showed admixtures of intestinal and gastric tumor cell phenotypes. Both p53 gene mutations and p53 protein immunostaining were essentially restricted to glandular or mixed cancers and associated dysplastic lesions. Their appearance in the advanced stage of diffuse cancer was partly due to a change of the histologic pattern from glandular to diffuse during progression of some tumors. Loss of laminin, beta I integrin, or zonula adherens junctions was a common finding in both early and advanced diffuse cancer. It is concluded that two main pathways operate in gastric carcinogenesis, both starting from H. pylori gastritis and both leading to phenotypically variable, often mixed gastric/intestinal tumor growth. However, only one of the two pathways involves intestinal metaplasia, its type III variant, p53 gene alteration, and dysplasia to end in glandular cancer. In the other pathway, diffuse cancer apparently arises directly from hyperplastic, sometimes atypical necks of mostly nonmetaplastic gastric glands, through primary involvement of genes affecting cell-cell and cell-matrix junctional proteins.

Age Factors↗

PubMed1999

Diffusely infiltrative endometrial adenocarcinoma: an adenoma malignum pattern of myoinvasion.

The prognostic significance of a diffusely infiltrative intramyometrial growth pattern was evaluated in 110 cases of low-stage (stages I and II) endometrial adenocarcinoma. Fifty cases were associated with diffuse infiltration (DI group), and 50 cases had more conventional granulation tissue type intramyometrial infiltration (GTT group). Ten cases with carcinomatous involvement of deeply situated adenomyosis (ADMY group) were also studied. The diffusely infiltrative "adenoma malignum" growth pattern featured typically round, regular individual glands, clearly within myometrium but with minimal or absent stromal or inflammatory cell response. Myoinvasion of the conventional sort was characterized by irregular, sharply angulated abnormal glands within myometrium without interposed normal glands or endometrial stroma. The abnormal glands were surrounded, at least focally, by edematous stroma with granulation tissue type reaction and/or an inflammatory cell infiltrate. Mean follow-up was 77.8 months (range 3-219 months) for the patients with diffusely infiltrative myoinvasion and deep adenomyosis and 86.9 months (range 1-206 months) for the patients with conventional myoinvasion. Recurrence-free survival for patients with stage I disease and conventional myoinvasion (94%) was similar to that of patients with diffuse adenoma malignum infiltration (98%; p = 0.13). Survival rates for both groups were also similar. Two (4%) of the 50 patients with diffusely infiltrative adenoma malignum pattern of myoinvasion died of endometrial carcinoma 36 and 72 months after hysterectomy, and 2 (4%) of the 50 patients with conventional myoinvasion died 34 and 67 months after hysterectomy (p = 0.41). Survival in these patients correlated with depth of myometrial invasion and stage. There were no recurrences in the patients with deep adenomyosis. These results suggest that although endometrial carcinomas with diffuse myometrial infiltration are fully capable of aggressive clinical behavior, they do not appear to behave any more aggressively than those with conventional myometrial invasion. Prognostic indicators of clinically aggressive disease are similar to those that have been previously identified for endometrial carcinomas with the more conventional pattern of myometrial infiltration. They include cervical involvement, deep myometrial invasion, higher histologic grade, and lymph-vascular space invasion. Endometrial carcinomas with extensive involvement of adenomyosis and adjacent foci of minimal myometrial infiltration appear to have very low malignant potential, but the number of cases with this finding and adequate clinical follow-up is limited. This finding needs to be confirmed in a much larger series of cases.

Adenocarcinoma, Mucinous↗

PubMed2003

Odor identification deficits in diffuse lewy body disease.

OBJECTIVES: To describe odor identification performance in patients with diffuse Lewy body disease and determine the clinical utility of odor identification tests in distinguishing diffuse Lewy body disease from Alzheimer disease. BACKGROUND: The presence of olfactory deficits, especially odor identification deficits, has been well established in both Alzheimer disease and Parkinson disease. The presence of olfactory deficits in diffuse Lewy body disease is also likely given the overlap of clinical symptoms and neuropathology with Alzheimer disease and Parkinson disease. However, odor identification abilities have not been described previously in diffuse Lewy body disease. METHODS: Nine patients from a clinic sample with diffuse Lewy body disease and nine carefully matched patients with Alzheimer disease were administered an odor identification task as part of their neuropsychologic evaluations. RESULTS: Patients with diffuse Lewy body disease performed significantly worse than patients with Alzheimer disease on the odor identification test. CONCLUSIONS: Odor identification deficits may be more prevalent and severe in people with diffuse Lewy body disease than in people with Alzheimer disease, and olfactory testing may be useful in antemortem differential diagnosis of the two disorders.

Aged↗

PubMed1999

Self-diffusion of grains in a two-dimensional vibrofluidized bed.

The analogy of vibrofluidized granular beds with a thermal gas of hard discs has been tested. Analysis of the mean squared displacement behavior of the grains allowed comparison of the measured diffusion with the predicted value at a particular combination of granular temperature and packing fraction. High speed photography, image analysis, and particle tracking software enabled accurate location of the grains. Appropriate analysis of the three mean squared displacement regimes, ballistic, diffusive, and crossover between the two extremes, allowed both the diffusion coefficient and the granular temperature to be measured at the same packing fraction. Broad agreement between Chapman-Enskog theory relating temperature to self-diffusion and observation was observed up to packing fractions of eta approximately equal to 0.7. At higher packing fractions the grains showed evidence of caging and jump diffusion, with the observed diffusion rapidly diverging from that predicted by theory. Measurement of self-diffusion coefficients and subsequent use of kinetic theory was found to be an accurate method to determine the granular temperature for intermediate packing fractions (eta=0.4-0.6), and would be particularly suitable for those situations where the time resolution of the experimental facility is insufficient to resolve the speed of the grain between collisions.

Journal Article↗

PubMed2000

Power law mass dependence of diffusion: A mode coupling theory analysis

The self-diffusion coefficient of a tagged molecule is known to exhibit a weak mass dependence, especially for solutes with size comparable to or larger than the size of the solvent molecules. Sometimes this mass dependence can be fitted to a power law, with a small exponent, less than 0.1. This weak mass dependence has often been considered as supportive of the hydrodynamic picture (that is, the Stokes-Einstein relation) of diffusion rather than the kinetic theory approach, which predicts a stronger mass dependence, for example, via the Enskog theory. Neither can explain the weak power-law mass dependence. In order to understand this, we have carried out a mode coupling theory (MCT) analysis of diffusion. It is found that a straightforward application of the existing mode coupling theory expressions lead to an inaccurate mass dependence-it predicts an increase of diffusion coefficient with an increase of the mass. We find that this is because of the inadequate description of the initial decay of the collective contributions to the friction. We have proposed a new prescription to accurately describe the short time dynamics of the density and the current term. In addition, we have modified the existing MCT by imposing the full self-consistency between the frequency-dependent friction and the mean square displacement over the whole time and frequency plane. Previously the self-consistency was performed only at the zero frequency level between the zero frequency friction and the diffusion coefficient. With these two generalizations, the mode coupling theory is found to provide a fairly accurate description of the mass dependence. In particular, the theory can correctly reproduce the power-law dependence of solvent-solute diffusion ratio on solute-solvent mass ratio, observed in computer simulations of Bearman and Jolly [Mol. Phys. 44, 665 (1981)]. Another important result is that the current mode is found to play no significant role in determining the diffusion. Thus the hydrodynamic argument of weak mass dependence has little validity for same size solute-solvent systems.

Journal Article↗

PubMed2001

Effect of helicity on the effective diffusivity for incompressible random flows.

The advection of a passive scalar by a quenched (frozen) incompressible velocity field is studied by extensive high precision numerical simulation and various approximation schemes. We show that second-order self-consistent perturbation theory, in the absence of helicity, perfectly predicts the effective diffusivity of a tracer particle in such a field. In the presence of helicity in the flow, simulations reveal an unexpectedly strong enhancement of the effective diffusivity which is highly nonperturbative and most visible when the bare molecular diffusivity of the particle is small. We develop and analyze a series of approximation schemes which indicate that this enhancement of the diffusivity is due to a second order effect, whereby the helical component of the field, which does not directly renormalize the effective diffusivity, enhances the strength of the nonhelical part of the flow, which in turn renormalizes the molecular diffusivity. We show that this renormalization is most important at a low bare molecular diffusivity, in agreement with numerical simulations.

Journal Article↗

PubMed2001

Diffusion by extrinsic noise in a two-dimensional anisotropic web mapping.

Diffusion by an extrinsic noise is studied in a two-dimensional anisotropic web mapping where the intrinsic web diffusion is negligible, diffusion in one direction is dominant over the other, and the extrinsic noise enters in the dominant dimension only. It is found that the diffusion scaling is governed by the competition between the extrinsic noise and the intrinsic rotation. If the extrinsic noise is weaker than the intrinsic rotation, diffusion scales as lK(1/2) in the dominant direction and as lK(3/2) in the nondominant direction, where l is the extrinsic noise strength and K is the intrinsic perturbation parameter. If the extrinsic noise is stronger, diffusion behaves as l(2)/2 in the dominant direction and as K(2)/4 in the nondominant direction. Diffusion in the nondominant direction can be important if the equilibrium system is translationally invariant in the dominant direction.

Journal Article↗

PubMed2002

Anisotropic self-diffusion in thermotropic liquid crystals studied by 1H and 2H pulse-field-gradient spin-echo NMR.

The molecular self-diffusion coefficients in nematic and smectic-A thermotropic liquid crystals are measured using stimulated-echo-type 2H and 1H pulse-field-gradient spin-echo nuclear magnetic resonance (PGSE NMR) combined with multiple-pulse dipolar decoupling and slice selection. The temperature dependence of the principal components of the diffusion tensor in the nematic phase follows a simple Arrhenius relationship except in the region of nematic-isotropic phase transition where it reflects, merely, the decrease of the molecular orientational order. The average of the principal diffusion coefficients in the isotropic-nematic phase transition region is close to the diffusion coefficient in the isotropic phase. At the nematic-smectic-A phase transition the diffusion coefficients change continuously. The results in nematic phase are best described in terms of the affine transformation model for diffusion in nematics formed by hard ellipsoids. In the smectic-A phase the data are interpreted using a modified model for diffusion in presence of a periodic potential along the director.

Journal Article↗

PubMed2002

Retarding subdiffusion and accelerating superdiffusion governed by distributed-order fractional diffusion equations.

We propose diffusionlike equations with time and space fractional derivatives of the distributed order for the kinetic description of anomalous diffusion and relaxation phenomena, whose diffusion exponent varies with time and which, correspondingly, cannot be viewed as self-affine random processes possessing a unique Hurst exponent. We prove the positivity of the solutions of the proposed equations and establish their relation to the continuous-time random walk theory. We show that the distributed-order time fractional diffusion equation describes the subdiffusion random process that is subordinated to the Wiener process and whose diffusion exponent decreases in time (retarding subdiffusion). This process may lead to superslow diffusion, with the mean square displacement growing logarithmically in time. We also demonstrate that the distributed-order space fractional diffusion equation describes superdiffusion phenomena with the diffusion exponent increasing in time (accelerating superdiffusion).

Journal Article↗

PubMed2003

Infinitely fast diffusion in single-file systems.

We have used dynamic Monte Carlo(DMC) methods and analytical techniques to analyze single-file systems for which diffusion is infinitely fast. We have simplified the master equation removing the fast reactions, and we have introduced a DMC algorithm for infinitely fast diffusion. The DMC method for fast diffusion give similar results as the standard DMC with high diffusion rates. We have investigated the influence of characteristic parameters, such as pipe length, adsorption, desorption, and conversion rate constants on the steady-state properties of single-file systems with a reaction, looking at cases when all the sites are reactive and when only some of them are reactive. We find that the effect of fast diffusion on single-file properties of the system is absent even when diffusion is infinitely fast. Diffusion is not important in these systems. Smaller systems are less reactive and the occupancy profiles for infinitely long systems show an exponential behavior.

Journal Article↗

PubMed2004

Diffusion of hard sphere fluids in disordered media: a molecular dynamics simulation study.

Molecular dynamic simulations are reported for the static and dynamic properties of hard sphere fluids in matrices (or media) composed of quenched hard spheres. The effect of fluid and matrix density, matrix structure, and fluid to matrix sphere size ratio on the static and dynamic properties is studied using discontinuous molecular dynamics. The matrix density has a stronger effect on the self-diffusion coefficient than the fluid density, especially at high matrix densities where the geometric constraints due to the quenched spheres are significant. When the ratio of the size of the fluid spheres to that of the matrix spheres is equal to or greater than one, the diffusion increases as the fluid density is increased, at constant total volume fraction. This trend is however reversed if the ratio is smaller than one. Different methods of generating the matrix have a very strong effect on the dynamic properties even though the static correlations are similar. An analysis of the single-chain structure factor of the particle trajectories shows a change in the particle diffusive behavior at different time scales, suggestive of a hopping mechanism, although normal diffusion is recovered at long times. At high matrix densities, there is considerable heterogeneity in the diffusion of the fluid particles. The simulations demonstrate that the correlations in the matrix play a significant role on the diffusion of fluid spheres. For example, the diffusion constant in matrices constructed by different methods can be an order of magnitude different even though the pair correlation functions are almost identical.

Journal Article↗

PubMed2005

Numerical investigation of the spreading-receding cycle in a concentration-dependent lattice gas automaton diffusion model.

This work forms the second part of a numerical study about the dynamics of diffusive fronts in concentration-dependent diffusion processes. We previously demonstrated that one-dimensional spreading of a density front in a concentration-dependent microscopically heterogeneous, macroscopically homogeneous isotropic lattice gas automaton (LGA) substantially deviates from the t(1/2) relation expected from Fick's law over large periods of time. The time exponent was found to be larger than 1/2 , i.e., spreading of the density front is enhanced with respect to standard Fickian diffusion. In this note, we specifically investigate the dynamics of receding by using the same LGA model. We show here that the receding process essentially scales as t(1/2). The LGA simulations of diffusive fronts thus lead to the paradoxical result of Fick's-compatible receding and anomalous superdiffusive spreading for the same microscopic random structure and the same boundary conditions. The results also suggest that hysteresis of the spreading-receding cycle could arise from the contrasted dynamics between spreading and receding. A conceptual model of "offer and demand" which includes both the diffusivity gradient dD(rho)/d(rho) and the conditions applied at boundaries as main parameters is proposed to tentatively account for the dynamics of diffusive fronts in concentration-dependent diffusion processes.

Journal Article↗

PubMed2005

Acceleration of diffusion in randomly switching potential with supersymmetry.

We investigate the overdamped Brownian motion in a supersymmetric periodic potential switched by Markovian dichotomous noise between two configurations. The two configurations differ from each other by a shift of one-half period. The calculation of the effective diffusion coefficient is reduced to the mean first passage time problem. We derive general equations to calculate the effective diffusion coefficient of Brownian particles moving in arbitrary supersymmetric potential. For the sawtooth potential, we obtain the exact expression for the effective diffusion coefficient, which is valid for the arbitrary mean rate of potential switchings and arbitrary intensity of white Gaussian noise. We find the acceleration of diffusion in comparison with the free diffusion case and a finite net diffusion in the absence of thermal noise. Such a potential could be used to enhance the diffusion over its free value by an appropriate choice of parameters.

Journal Article↗

PubMed2005

Direct observation of spatiotemporal dependence of anomalous diffusion in inhomogeneous fluid by sampling-volume-controlled fluorescence correlation spectroscopy.

The direct observation of a spatiotemporal behavior of anomalous diffusion in aqueous polymer [hyaluronan (HA)] solution was achieved by fluorescence correlation spectroscopy (FCS) using a modified instrument, enabling continuous change of the confocal volume of a microscope, namely, sampling-volume-controlled (SVC) FCS (SVC-FCS). Since HA chains form a mesh structure with a pore size of about 10-40 nm, the observed diffusion coefficient (Dobs) is markedly dependent on the diffusion distance (L). By SVC-FCS, the curve of the distance dependence of diffusion coefficient was directly obtained as a continuous profile in L = 245-600 nm showing evidence of anomalous diffusion. On plotting Dobs against either of the sampling time (tauobs) or the diffusion distance (L), Dobs turnover was observed near the anomalous diffusion area. The appearance of this turnover is attributed to the nonuniform mesh structure that can be observed only by a fast observation and that should be dynamically averaged by polymer motions with large tauobs. This behavior is similar to that revealed in glass, colloidal systems, and gel solutions using dynamic light scattering, neutron scattering, and other techniques.

Journal Article↗

PubMed1994

A Re-Evaluation of the Role of the Infected Cell in the Control of O2 Diffusion in Legume Nodules.

Two different simulation models were constructed to describe O2 diffusion into the bacteria-infected cells of legume nodules: one based on a central zone of uniform spherical cells and the other on a central zone of packed, uniform cubical cells with air spaces along the edges. The cubical model more closely approximated the geometry and gas diffusion characteristics of infected cells than did the spherical model. The models relied on set values for the innermost O2 concentration in the infected cell (1-20 nM) and predicted values for the free O2 and oxygenated leghemoglobin gradients toward the cell:space interface. The cubical model but not the spherical model predicted saturation of leghemoglobin (Lb) oxygenation at or within a few micrometers of the gas-filled intercellular space and predicted that the space concentration could be as high as 1.3% O2 when the fractional oxygenation of Lb and respiration rate within the infected cell were typical of that which has been measured in vivo. In the model, the higher the space O2 concentration, the greater the saturation of Lb by O2 and the greater the collapse of Lb-facilitated diffusion near the cell:space interface. This was predicted to result in a greater resistance to O2 diffusion from the space to the bacteroids, thereby providing an intrinsic, homeostatic mechanism for controlling the rate of O2 influx into infected cells. Changes in the physiological features of the simulated cubical infected cell, such as the proportion of the cell as cytosol, the surface area of the cell exposed to a space, the maximum rate of cellular respiration, or the concentration of Lb in the cytoplasm, significantly altered the extent to which the infected cell would be able to regulate its diffusive resistance. These results demonstrate the possibility of a Lb-based mechanism for controlling the O2 concentration within the infected cells. If such a mechanism exists in legume nodules, it would give the infected cell an ability to exercise fine control over its internal environment, a process that could complement a physical diffusion barrier that may exist in the inner cortex or elsewhere in the nodule and provide coarse control over O2 diffusion.

Journal Article↗

PubMed2004

Identification of NOL8, a nucleolar protein containing an RNA recognition motif (RRM), which was overexpressed in diffuse-type gastric cancer.

In an attempt to identify novel therapeutic targets for diffuse-type gastric cancer, we had previously compared expression profiles of 20 diffuse-type gastric-cancer tissues with corresponding non-cancerous mucosae by means of a cDNA microarray consisting of 23,040 genes. Among 153 genes whose expression levels were elevated in cancers compared to non-cancerous mucosae, we focused on a gene termed NOL8 that encodes a putative 150-kDa protein with an RNA-recognition motif (RRM) domain in its amino-acid terminal region. Comparison of expression profiles between diffuse-type and intestinal-type gastric cancers showed that NOL8 was specifically up-regulated in diffuse-type cancers. Northern blot analysis revealed that NOL8 was expressed in skeletal muscle, but not expressed or hardly detectable in 22 other tissues examined. Immunocytochemical staining of NOL8 showed specific localization in the nucleolus. Subsequent protein phosphatase analysis coupled with western analysis revealed the presence of the phosphorylated form. Furthermore, transfection of short-interfering RNA (siRNA) specific to NOL8 into three diffuse-type gastric cancer cells, St-4, MKN45 and TMK-1, effectively reduced expression of this gene and induced apoptosis in these cells. These findings provide a new insight into diffuse-type gastric carcinogenesis and may contribute to the development of new therapeutic strategies for diffuse-type gastric cancer.

Carrier Proteins↗

PubMed2006

Allometric studies on growth and development of the human placenta: growth of tissue compartments and diffusive conductances in relation to placental volume and fetal mass.

Correlations between placental size and fetal mass during gestation fail to account for changes in composition that accompany placental growth and maturation. This study uses stereological data on the sizes of different tissue compartments in human placentas from 10 weeks of gestation to term and relates them to placental volume and to fetal mass by means of allometric analysis. In addition, tissue dimensions are used to calculate a physiological transport measure (diffusive conductance) for the villous membrane. Histological sections randomly sampled from placentas and analysed stereologically provided estimates of structural quantities (volumes, exchange surface areas, lengths, numbers of nuclei, diffusion distances). These data were combined with a physicochemical quantity (Krogh's diffusion coefficient) in order to estimate oxygen diffusive conductances for the villous membrane and its two components (trophoblast and stroma). Allometric relationships between these quantities and placental volume or fetal mass were obtained by linear regression analyses after log-transformation. Placental tissues had different growth trajectories: most grew more rapidly than placental volume and all grew more slowly than fetal mass. Diffusion distances were inversely related to placental and fetal size. Differential growth impacted on diffusive conductances, which, again, did not improve commensurately with placental volume but did match exactly growth of the fetus. Findings show that successful integration between supply and demand can be achieved by differential tissue growth. Allometric analysis of results from recent studies on the murine placenta suggest further that diffusive conductances may also be matched to fetal mass during gestation and to fetal mass at term across species.

Biological Transport↗

PubMed2005

Numerical and experimental analysis of an axial flow left ventricular assist device: the influence of the diffuser on overall pump performance.

Thousands of adult cardiac failure patients may benefit from the availability of an effective, long-term ventricular assist device (VAD). We have developed a fully implantable, axial flow VAD (LEV-VAD) with a magnetically levitated impeller as a viable option for these patients. This pump's streamlined and unobstructed blood flow path provides its unique design and facilitates continuous washing of all surfaces contacting blood. One internal fluid contacting region, the diffuser, is extremely important to the pump's ability to produce adequate pressure but is challenging to manufacture, depending on the complex blade geometries. This study examines the influence of the diffuser on the overall LEV-VAD performance. A combination of theoretical analyses, computational fluid (CFD) simulations, and experimental testing was performed for three different diffuser models: six-bladed, three-bladed, and no-blade configuration. The diffuser configurations were computationally and experimentally investigated for flow rates of 2-10 L/min at rotational speeds of 5000-8000 rpm. For these operating conditions, CFD simulations predicted the LEV-VAD to deliver physiologic pressures with hydraulic efficiencies of 15-32%. These numerical performance results generally agreed within 10% of the experimental measurements over the entire range of rotational speeds tested. Maximum scalar stress levels were estimated to be 450 Pa for 6 L/min at 8000 rpm along the blade tip surface of the impeller. Streakline analysis demonstrated maximum fluid residence times of 200 ms with a majority of particles exiting the pump in 80 ms. Axial fluid forces remained well within counter force generation capabilities of the magnetic suspension design. The no-bladed configuration generated an unacceptable hydraulic performance. The six-diffuser-blade model produced a flow rate of 6 L/min against 100 mm Hg for 6000 rpm rotational speed, while the three-diffuser-blade model produced the same flow rate and pressure rise for a rotational speed of 6500 rpm. The three-bladed diffuser configuration was selected over the six-bladed, requiring only an incremental adjustment in revolution per minute to compensate for and ease manufacturing constraints. The acceptable results of the computational simulations and experimental testing encourage final prototype manufacturing for acute and chronic animal studies.

Blood Circulation↗