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PubMed1989

Lateral diffusion of membrane proteins in protein-rich membranes. A simple hard particle model for concentration dependence of the two-dimensional diffusion coefficient.

A model for the effect of protein concentration on the rate of lateral diffusion of integral membrane proteins is presented, in which the proteins are represented by equivalent hard circular particles on a surface. As the density of particles increases, the probability of finding a vacancy immediately adjacent to a tracer particle into which it may diffuse decreases, resulting in a concomitant reduction of the tracer diffusion coefficient. Using scaled particle theory to calculate the concentration-dependent probabilities, a simple approximate result is obtained in closed form, that is compared with the results of previously published Monte Carlo lattice simulations and experimental observations.

Diffusion↗

PubMed1997

Diffusion coefficients of oxygen and hemoglobin measured by facilitated oxygen diffusion through hemoglobin solutions.

Diffusion coefficients of oxygen (DO2) and hemoglobin (DHb) were obtained from measuring the oxygen flux through thin layers of hemoglobin solutions at 20 degrees C. The liquid layers were supported by a membrane and not soaked in any filter material. Oxygen fluxes were measured from the changes in oxygen partial pressure in the gas phases at both sides of the layer. A mathematical treatment is presented for correct evaluation of the measurements. Measurements were done for bovine and for human hemoglobin. Hemoglobin concentrations (CHb) were between 11 and 42 g/dl, which covers the concentrations in the erythrocyte. Both DO2 and DHb could be fitted to the empirical equation D = D0(1-CHb/C1)10-CHb/C2. The following parameters were obtained: DO = 1.80 x 10(-9) m2/s, C1 = 100 g/dl, C2 = 119 g/dl, for oxygen and D0 = 7.00 x 10(-11) m2/s, C1 = 46 g/dl, C2 = 128 g/dl, for hemoglobin. No difference between the diffusion coefficients of bovine or human hemoglobin was found. The diffusion coefficients of hemoglobin were higher than most values reported in the literature, probably because in this study the mobility of hemoglobin was not hindered by surrounding filter material.

Animals↗

PubMed1991

Effect of varying alveolar oxygen partial pressure on diffusing capacity for nitric oxide and carbon monoxide, membrane diffusing capacity and lung capillary blood volume.

1. To examine the effect of varying oxygen partial pressure (PAO2) on nitric oxide (DLNO) and carbon monoxide (DLCO) diffusing capacity (transfer factor), 10 subjects performed combined DLCO/DLNO measurements with the inspired mixture made up with three different oxygen concentrations (25%, 18% and 15%) to give PAO2 values of 12-20 kPa. 2. A novel method is described for calculating membrane diffusing capacity (DM) and pulmonary capillary volume (Qc) from DLNO and DLCO. 3. The mean DMCO was 52.89 mmol min-1 kPa-1 and Qc was 0.056 litre. Reducing PAO2 from 20 to 12 kPa resulted in an increase in DLCO = -0.124 (O2%) + 11.67 (P less than 0.001) and a fall in DLNO = 0.538 (O2%) + 32.01 (P less than 0.001) and a fall in DLNO/DLCO = 0.107 (O2%) + 2.52 (P less than 0.001). DM (P = 0.59) and Qc (P = 0.64) also tended to fall with falling PAO2. 4. It appears more likely that the minor reduction in DLNO that we have observed with falling PAO2 is due to diffusion rather than reaction limitation.

Blood Volume↗

PubMed2006

Apparent diffusion coefficient maps of pediatric mass lesions with free-breathing diffusion-weighted magnetic resonance: feasibility study.

PURPOSE: To assess the technical feasibility of apparent diffusion coefficient (ADC) mapping based on free-breathing diffusion-weighted magnetic resonance (DW-MR) outside the CNS in children. MATERIAL AND METHODS: Twelve children with mass lesions of varied histopathology were scanned with short-tau inversion recovery (STIR), contrast-enhanced T1-weighted (CE-T1W), and diffusion-weighted (b=0, 500 and 1000 s/mm2) sequences. ADC maps were calculated. Lesion-to-background signal intensity ratios were measured and compared between STIR/CE-T1W/ADC overall (Friedman test) and between viable embryonal tumors and other lesions (Kruskal-Wallis test). RESULTS: ADC maps clearly depicted all lesions. Lesion-to-background signal intensity ratios of STIR (median 3.7), CE-T1W (median 1.4), and ADC (median 1.6) showed no overall difference (chi-square=3.846; P=0.146), and there was no difference between viable embryonal tumors and other lesions within STIR/CE-T1W/ADC (chi-square 1.118/0.669/<0.001; P=0.290/0.414/1.000, respectively). CONCLUSION: ADC mapping is feasible in free-breathing imaging of pediatric mass lesions outside the CNS using standard clinical equipment.

Adolescent↗

PubMed1982

Diffusion rates of cell surface antigens of mouse-human heterokaryons. III. Regulation of lateral diffusion rates by calcium ions.

In mouse-human heterokaryons, the lateral diffusion of major histocompatibility (MHC) antigens in the plasma membrane is enhanced by treatment of parent cells with ouabain. Ouabain treatment is ineffective if the medium lacks calcium ion, or if Verapamil, a blocker of calcium channels, is present. The divalent ionophore A23187 also enhances lateral diffusion of MHC antigens, to the same extent as ouabain, A23187 is effective only if calcium is present in the medium. Thus it appears that increased levels of cell calcium release constraints to lateral diffusion of MHC antigens.

Animals↗

PubMed2003

The health assessment questionnaire (HAQ) is strongly predictive of good outcome in early diffuse scleroderma: results from an analysis of two randomized controlled trials in early diffuse scleroderma.

OBJECTIVE: Scoring poorly on the health assessment questionnaire (HAQ) has recently been shown to be a strong predictor of morbidity and mortality in rheumatoid arthritis (RA), while a good HAQ score is predictive of a better outcome. In patients presenting with early diffuse scleroderma prognosis is variable. Our goal was to determine possible baseline predictors of future good outcomes. METHODS: We used the raw data from two randomized controlled trials (RCTs) in early diffuse scleroderma: methotrexate (Pope et al.) and D-penicillamine (Clements et al.). Subjects in the methotrexate trial were divided into the following groups: (1) those with at least 20% improvement in the primary outcome measurements [patient global assessment, physician global assessment, UCLA skin tethering score, modified Rodnan skin score (MRSS), DLCO as % predicted and HAQ disability] at 1 yr vs (2) the others. Baseline factors (including age, gender, skin scores, physician and patient global assessments, HAQ disability and pain scores, DLCO and physical parameters) were analysed to find baseline variables strongly correlated with later improvement. These variables were explored in the D-penicillamine trial to determine if (in a separate trial) they were still predictive of improved outcome at 1 and 2 yr. Adjusted models were used to find baseline predictors of good outcome. The median HAQ-DI was 1.3 (methotrexate) and 1.0 (D-penicillamine). RESULTS: A baseline HAQ disability score of less than the median was predictive of at least a 20% improvement at 1 and 2 yr with odds ratios of 1.77 to 5.05, in four of the five outcome measurements (in both groups); with strongly significant P values for 3 of 5 outcomes (UCLA skin score, MRSS, patient global skin score; P<0.02) from the methotrexate study group. These three outcomes were strongly correlated with improvement (r between 0.25 and 0.35). Although data from the D-penicillamine trial were less convincing, in both trials the less than median HAQ-DI and HAQ pain scores showed a stronger association with improved outcome, more so than age, gender, skin score and baseline global assessment. CONCLUSION: A low baseline HAQ (defined as less than the median HAQ score) is predictive of improved outcome in diffuse scleroderma at 1 and 2 yr.

Dermatologic Agents↗

PubMed2001

Diffusion barriers in ram and boar sperm plasma membranes: directionality of lipid diffusion across the posterior ring.

The plasma membrane of mammalian spermatozoa, like that of other differentiated cells, is compartmentalized into discrete regions or domains that are biochemically and functionally distinct from one another. Physical structures within the membrane, such as the posterior ring at the juncture of the sperm head and tail, have long been thought to act as diffusion barriers to help segregate important molecules required for fertilization within specific domains and to regulate migration of molecules between domains. In this investigation, we used a quantitative photobleaching technique (video-FRAP) to assess the efficacy of the posterior ring as a barrier to exchange of lipids between the postacrosomal and midpiece plasma membranes. A lipid reporter probe (1,1'-diduodecyl-3,3,3', 3'-tetramethylindocarbocyanine; DiIC(12)) was incorporated into the plasma membrane of live ram and boar spermatozoa, and the directionality of its diffusion across the posterior ring was measured by line-profile analysis. Results showed that DiIC(12) was able to traverse the posterior ring from the direction of the postacrosomal plasma membrane and to diffuse onto the midpiece plasma membrane. These results suggest that the posterior ring is not an immutable barrier to lipid exchange in mature spermatozoa and that there are other mechanisms for maintaining in-plane lipid asymmetry, such as differential phase behavior and interaction with the submembranous cytoskeleton.

Acrosome↗

PubMed1995

[Study of diffusion phenomenon using an experimental magnetic resonance system (SIS 200/400) for small animals--reliability and apparent diffusion coefficient of normal animals].

We have developed a magnetic resonance (MR) spin echo method to obtain diffusion weighted imaging using motion probing gradient (MPG) pulses in orthogonal direction before and after a 180 degree pulse. Phantom models containing water, acetone, cupric sulfate and agar, and normal brains of Wistar rats and puppies were examined. MRI was performed using a SISCO SIS 200/400 MRI/MRS experimental system for small animals (4.7 tesla, 400 mm bore). The apparent diffusion coefficient (ADC) values, given in mm2/sec, were 2.19 +/- 0.02 x 10(-3) in water, 4.51 +/- 0.18 x 10(-3) in acetone, and the ADC of water was independent on longitudinal (T1) or transverse (T2) relaxation time. Time-dependent ADC changes were not demonstrated, however position-dependent ADC changes were significant. It is therefore important to set the sample at the same position for repeated MRI studies and for the evaluation of the time course of experimental studies. Mean ADC values of rat brains were 0.65 x 10(-3) for cortex, 0.69 x 10(-3) for caudate-putamen, 0.69 x 10(-3) (perpendicular to axon) for corpus callosum, 1.11 x 10(-3) (parallel to axon) for optic nerve, and 1.38 x 10(-3) (parallel to axon) for trigeminal nerve. Those of puppies were 1.14-1.42 x 10(-3) for gray matter, 1.17 (parallel to axon) and 0.89 (perpendicular to axon) x 10(-3) for white matter, 1.66 (parallel to axon) and 0.57 (perpendicular to axon) x 10(-3) for internal capsule, and 0.91-0.95 x 10(-3) for thalamus. On the in vivo ADC maps, white matter tracts successfully showed anisotropic diffusion. This technique has promising implications for the evaluation of the time course of cerebral damage and degenerative changes.

Animals↗

PubMedDate not supplied

Diffusion-weighted imaging in the setting of diffuse cortical laminar necrosis and hypoxic-ischemic encephalopathy.

BACKGROUND AND PURPOSE: As is the case for CT scans, MR images may occasionally appear deceptively normal unless proper windowing is used. We sought to illustrate the necessity for proper windowing and for assessing the gray-white matter differentiation on diffusion-weighted (DW) images in the setting of hypoxic-ischemic encephalopathy. METHODS: Six comatose patients (age range, 34-56 years) underwent MR imaging in the early phase (range, 1-5 days) after severe anoxic insult. T2-weighted, turbo fluid-attenuated inversion-recovery, and DW images were obtained in all six patients, with contrast-enhanced T1-weighted images obtained in four and apparent diffusion coefficient (ADC) maps in five of the six patients. RESULTS: At presentation, each of the six patients had symmetric, uniform hyperintensity in the cortex (mean ADC, 0.35 x 10(-3) mm(2)/s) relative to the white matter (mean ADC, 0.91 x 10(-3) mm(2)/s) on DW images. Each also had a poor outcome: brain death in four patients and a permanent vegetative state in two patients. CONCLUSION: The appearance of the MR images in the setting of diffuse cortical laminar necrosis can be deceptive to the unwary radiologist. The key to correct interpretation is proper windowing and the marked gray-white matter differentiation on spin-echo images but best seen on properly windowed DW images in the early subacute phase. This appearance also implies an extremely poor outcome, either a permanent vegetative state or brain death.

Adult↗

PubMed1979

[Measurement of global diffusion capacity for CO, membrane diffusion capacity for CO and capillary blood volume in patients with bronchial emphysema after fominoben HCl. Short- and long-time trials (author's transl)].

The effect of 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)methyl]-aminomethyl)-benzanilide hydrochloride (fominoben HCl, P-B 89 Cl, Noleptan) on the global and membrane diffusion capacities and on the capillary blood volume in patients with emphysematous bronchitis is described. All 3 parameters, independent of the severity of the emphysema and the resulting respiratory insufficiency, are increased. It can thus be concluded that fominoben by improving the ventilation-perfusion ratio leads to an enlargement of the active diffusion surface (capillary surface), from which the increase in the global diffusion capacity results. The site of action of fominoben for its positive effect on respiration is thus established as being in the alveoli.

Adult↗

PubMed2005

Optic nerve diffusion measurement from diffusion-weighted imaging in optic neuritis.

BACKGROUND AND PURPOSE: Increases in apparent diffusion coefficient (ADC) from diffusion-weighted (DW) imaging are thought to be due to axonal disruption, and changes have been well documented in multiple sclerosis lesions. DW imaging of the optic nerves, however, presents many challenges. The goal of this study was to measure ADC in patients with optic neuritis by using zonal oblique multisection echoplanar imaging. METHODS: The optic nerves of eighteen patients who had experienced an attack of optic neuritis 1 year previously and 11 control subjects were imaged with the diffusion sequence (usable data were available from 16 patients and 10 control subjects). The orbital optic nerves were segmented by a blinded observer by using a computer-assisted threshold-based contouring technique, and the mean ADC was determined. RESULTS: The mean ADC from diseased optic nerves was 1324 x 10(-6) mm2/s, compared with 990 x 10(-6) mm2/s from healthy contralateral optic nerves (P = .005 versus diseased optic nerves) and 928 x 10(-6) mm2/s from control optic nerves (P = .006 versus diseased optic nerves and P = .40 versus healthy contralateral optic nerves). The diseased optic nerve ADC correlated with both visual (e.g., r(S) = 0.73; P = .001 for logMAR visual acuity) and electrophysiological parameters (e.g., r(S) = -0.57, P = .021 for visual evoked potential central field amplitude [VEP]). CONCLUSION: It has been possible to apply DW imaging in a patient population, and, in the chronic phase following optic neuritis, the correlation of mean ADC with the clinical and electrophysiological parameters suggests that the ADC is giving a surrogate measure of axonal disruption in the chronic, postinflammatory optic nerve lesion.

Adult↗

PubMed2005

Usefulness of the apparent diffusion coefficient in line scan diffusion-weighted imaging for distinguishing between squamous cell carcinomas and malignant lymphomas of the head and neck.

BACKGROUND AND PURPOSE: Squamous cell carcinoma (SCC) and lymphoma are common malignant tumors of the head and neck. The purpose of this study was to determine whether the apparent diffusion coefficient (ADC) in line scan diffusion-weighted imaging (LSDWI) is useful for distinguishing between SCC and lymphoma of the head and neck. METHODS: LSDWI was prospectively performed in 39 patients with SCC and in 14 patients with lymphoma. Images were obtained with a diffusion-weighted factor (b factor) of 5 and 1000 s/mm(2), and ADC maps were generated. ADC values were measured for the two types of tumor. RESULTS: Mean ADC values were 0.96 +/- 0.11 x 10(-3) mm(2)/s for SCC and 0.65 +/- 0.09 x 10(-3) mm(2)/s for lymphoma; the difference was significant (P < .001). All but one of the patients with lymphoma had ADC values lower than the lowest ADC (0.76 x 10(-3) mm(2)/s) in patients with SCC. When an ADC of 0.76 x 10(-3) mm(2)/s was used to distinguish between SCC and lymphoma, accuracy was 98% (52 of 53 lesions). CONCLUSION: ADC values appear to be useful for distinguishing between SCC and lymphoma in the head and neck.

Adolescent↗

PubMed1982

[Cuff pressure changes due to diffusion of nitrous oxide. A contribution to the question of the in vivo-diffusion--area of the cuff].

The mechanisms of nitrous oxide-diffusion through the endotracheal tube-cuff wall are still unknown in detail. In 30 patients we observed the pressure in low and high pressure-cuffs during operations with extracorporeal circulation (ECC). Under the chosen circumstances we found in low pressure-cuffs an increase of the initial pressure of 15.15 mm Hg up to 74,7 mm Hg until the beginning of ECC. During the ECC cuff pressure decreased to 32.25 mm Hg and was dependent on the body-temperature of the patients. After ECC the cuff pressure increased again up to 79.05 mm Hg until the operation was finished. The pressure changes in high pressure-cuffs were similar at different pressure-levels. These results show that in vivo the whole cuff-wall is diffusion-area for nitrous oxide. The main part of gas diffusion occurs through the contact area of the cuff with the tracheal wall.

Anesthesia↗

PubMed1999

Angiotensin-converting enzyme inhibition restores the diffusing capacity for carbon monoxide in patients with chronic heart failure by improving the molecular diffusion across the alveolar capillary membrane.

Conductance of alveolar capillary membrane (DM) and capillary blood volume (VC) are the subcomponents of the pulmonary diffusing capacity for carbon monoxide (DLCO). In chronic heart failure, stress failure of the membrane provides a mechanism for reduced DM and subsequent impairment of DLCO. Angiotensin-converting enzyme inhibition improves DLCO in patients with chronic heart failure. This study was aimed at investigating which of the two subcomponents of DLCO is affected by angiotensin-converting enzyme inhibitors. Twenty-seven patients with NYHA class II to III chronic heart failure (group 1) and 13 age- and sex-matched normal subjects underwent pulmonary function testing with determination of DM and VC, while receiving placebo and 48 h and 1 and 2 months after starting enalapril treatment (10 mg twice daily). Nine similar patients (group 2) received isosorbide dinitrate (40 mg thrice daily) for a month then enalapril for another month, and underwent pulmonary function testing at 48 h and 1 month after starting treatments. Effects of angiotensin-converting enzyme inhibition in normal controls were not significant in the short- or mid-term. In group 1 patients, the only change observed at 48 h was a reduction in VC (probably due to a decrease in capillary pulmonary pressure). There was a marked increase in DM to a similar extent at 1 and 2 months, resulting in a significant improvement in DLCO despite a decrease in VC. In group 2 patients, nitrates failed to improve DLCO and DM, whereas enalapril was as effective as in group 1. These observations suggest a modulatory effect of angiotensin-converting enzyme inhibition on the membrane function which emerges gradually and persists over time and is probably dissociated from changes in pulmonary capillary pressure and VC. Chronic heart failure disturbs the alveolar capillary interface and increases gas diffusion resistance; angiotensin-converting enzyme inhibition restores the diffusive properties of the membrane and gas transfer, and protects the lung when the heart is failing.

Analysis of Variance↗

PubMed2004

1H, (19)F, and (31)P PGSE NMR diffusion studies on chiral organic salts: ion pairing and the dependence of a diffusion value on diastereomeric structure.

1H, (19)F and (31)P pulsed field gradient spin-echo (PGSE) diffusion studies on chiral organic salts that contain hexacoordinate phosphate anions, namely tris(tetrachlorobenzenediolato)phosphate(V) (TRISPHAT) and bis(tetrachlorobenzenediolato)mono([1,1']binaphthalenyl-2,2'diolato)-phosphate(V) (BINPHAT), are reported. The first example of the dependence of a diffusion value on diastereomeric structure is presented. Marked solvent and concentration effects on the diffusion constants (D) of these salts are noted and the question of ion pairing is discussed.

Journal Article↗

PubMed1993

Molecular self-diffusion of intracellular metabolites in rat brain in vivo investigated by localized proton NMR diffusion spectroscopy.

Molecular self-diffusion coefficients of water (0.75 +/- 0.05), N-acetylaspartate (0.27 +/- 0.04), creatines (0.27 +/- 0.04), and cholines (0.28 +/- 0.08) x 10(-5) cm2 s-1 were obtained from localized proton NMR spectra of rat brain in vivo using diffusion-weighted stimulated-echo (STEAM) sequences with a diffusion time of (delta--delta/3) = 17 ms.

Animals↗

PubMed1998

Evaluation of cerebrovascular CO2-reactivity and autoregulation in patients with post-traumatic diffuse brain swelling (diffuse injury III).

The present study was undertaken to elucidate the status of autoregulation and CO2-reactivity soon after injury in patients with a post-traumatic diffuse bilateral brain swelling. A prospective study was carried out in 31 consecutively admitted patients with a severe head injury and a Diffuse Brain Injury type III, following the definition stated by the Traumatic Coma Data Bank classification. To evaluate CO2-reactivity, AVDO2 was measured before and after ventilator manipulations. Assuming a constant CMRO2 during the test, changes in 1/AVDO2 reflect changes in CBF. Patients with changes in estimated CBF below or equal to 1% were included in the impaired/abolished CO2-reactivity group. To test autoregulation, hypertension was induced using phenylephrine. Arterial and jugular blood samples were taken to calculate AVDO2 before and after a steady state of MABP was obtained. Cerebrovascular response to CO2 was globally preserved in all but two cases (6.5%). In contrast, autoregulation was globally preserved in 10 (32.3%) and impaired/abolished in 21 cases (67.7%). Our data do not support the premise that increasing cerebral perfusion pressure by inducing arterial hypertension is beneficial in those patients with a diffuse brain swelling in whom autoregulation is impaired or abolished. Clinical implications for treatment are discussed.

Adult↗

PubMed2006

Estimation of diffusive boundary layer thickness in studies involving diffusive gradients in thin films (DGT).

Recent laboratory experiments and field investigations involving diffusive gradients in thin films (DGT) have shown that the thickness (delta) of the diffusive boundary layer (DBL), which can affect the accuracy of the technique, is generally not negligible. Accordingly, the determination of delta has become a matter of considerable practical importance. Though the problem has been addressed in the recent literature, there is room for some improvement. An expression for estimation of delta is presented here, and a practical procedure for determining delta and the concentration of DGT-labile species from sparse experimental data is proposed and illustrated by analyzing data from four experiments with DGT samplers of different diffusive gel thicknesses.

Journal Article↗