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PubMed2005

Long-term follow-up of diffuse membranoproliferative glomerulonephritis type I.

In Japan, the school urinary screening system facilitates early detection and treatment of membranoproliferative glomerulonephritis (MPGN) in childhood. The present study investigated the long-term prognosis in 19 children with diffuse MPGN type I who received steroid therapy. Before signs of glomerulonephritis were confirmed, all patients displayed abnormal urinalysis results, predominantly through school urinary screening. Treatment comprised a regimen of alternate-day prednisolone after steroid pulse or cyclophosphamide therapy, and follow-up was continued for 10-24 years. Excluding 1 patient on short-term therapy, 18 patients received long-term alternate-day prednisolone therapy for 4-12 years. Treatment was discontinued when amelioration was confirmed on renal biopsy. As of the last observation, urinary abnormalities and hypocomplementemia had disappeared in 15 patients, while mild proteinuria without hypocomplementemia remained in 4 patients. No patients required hemodialysis. Moreover, no severe adverse effects attributable to treatment were identified other than mild short stature. Early detection and therapy using pulse methylprednisolone followed by alternate-day prednisolone was thus confirmed as safe and useful for treating diffuse MPGN type I.

Adolescent↗
PubMed2004

Chronoamperometry at micropipet electrodes for determination of diffusion coefficients and transferred charges at liquid/liquid interfaces.

Chronoamperometry was carried out at liquid/liquid interfaces supported at the tip of micropipet electrodes for direct determination of the diffusion coefficient of a species in the outer solution. The diffusion coefficient was used for subsequent determination of the transferred charges per species from the diffusion-limited steady-state current. A large tip resistance of the micropipets causes prolonged charging current so that the faradic current can be measured accurately only at a long-time regime (typically t > 5 ms). At the same time, the long-time current response at the interfaces surrounded by a thin glass wall of the pipets is enhanced by diffusion of the species from behind the pipet tip. Therefore, numerical simulations of the long-time chronoamperometric response were carried out using the finite element method for accurate determination of diffusion coefficients. Validity of the simulation results was confirmed by studying simple transfer of tetraethylammonium ion. The technique was applied for transfer/adsorption reactions of the natural polypeptide protamine and also for Ca2+ and Mg2+ transfers facilitated by ionophore ETH 129. With the diffusion coefficient of protamine determined to be (1.2 +/- 0.1) x 10(-6) cm(2)/s, the ionic charge transferred by each protamine molecule was obtained as +20 +/- 1, which is close to the excess positive charge of protamine. Also, the diffusion coefficient of ETH 129 was determined to demonstrate that each ionophore molecule transfers +0.67 and +1 charge per Ca2+ and Mg2+ transfer, respectively, which corresponds to formation of 1:3 and 1:2 complexes with the respective ions.

Calcium↗
PubMed2006

Diffusion changes precede size reduction in neoadjuvant treatment of breast cancer.

Traditionally, tumor response has been assessed via tumor size measurements during the course of a treatment. However, changes in these morphologically based measures occur relatively late in the course of a treatment. Alternative biomarkers are currently being evaluated to enable an earlier assessment of treatment to facilitate early cessation and cost savings. Diffusion-weighted imaging (DWI) has been identified by preclinical studies to be a likely alternative to tumor size measurements. In this study, 10 patients were examined prior to and after the first and second chemotherapy cycle time points. Longest diameter tumor measurements and apparent diffusion coefficients (ADCs) were recorded at each exam. An increase in the mean (normalized) ADC was noted as early as the first cycle time point. However, a reduction in the mean (normalized) longest diameter was only noted at the second cycle time point. Significant alterations from the baseline value were noted for ADC at the first (P=.005) and second cycle time points (P=.004). Longest diameter measurements only achieved a borderline significance at the second time point (P=.057). These results indicate that DWI may provide a suitable biomarker capable of providing an indication of response to treatment prior to tumor size measurements.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Mathematical modelling of lipid transbilayer movement in the human erythrocyte plasma membrane.

A model is presented to simulate transverse lipid movement in the human erythrocyte membrane. The model is based on a system of differential equations describing the time-dependence of phospholipid redistribution and the steady state distribution between the inner and outer membrane monolayer. It takes into account several mechanisms of translocation: (i) ATP-dependent transport via the aminophospholipid translocase; (ii) protein-mediated facilitated and (iii) carrier independent transbilayer diffusion. A reasonable modelling of the known lipid asymmetry could only be achieved by introducing mechanism (iii). We have called this pathway the compensatory flux, which is proportional to the gradient of phospholipids between both membrane leaflets. Using realistic model parameters, the model allows the calculation of the transbilayer motion and distribution of endogenous phospholipids of the human erythrocyte membrane for several biologically relevant conditions. Moreover, the model can also be applied to experiments usually performed to assess phospholipid redistribution in biological membranes. Thus, it is possible to simulate transbilayer motion of exogenously added phospholipid analogues in erythrocyte membranes. Those experiments have been carried out here in parallel using spin labeled lipid analogues. The general application of this model to other membrane systems is outlined.

Adenosine Triphosphate↗
PubMed1993

Plasmodesmata: the intercellular organelles of green plants.

Cytokinesis in higher plants results in the incomplete separation of daughter cells, due to the formation of special plasma-membrane-lined cytoplasmic bridges, called plasmodesmata. Within the green algae, these structures coordinate biochemical and physiological processes by facilitating the cell-to-cell diffusion of simple metabolites and ions. Until recently, most plant biologists thought that plasmodesmata perform a similar function in higher plants. However, it is now known that the more structurally advanced plasmodesmata of higher plants can also traffic macromolecules, including proteins and nucleic acids. These findings give new insights into how green plants evolved the ability to orchestrate their developmental and physiological processes in a supracellular rather than a multicellular manner.

Journal Article↗
PubMed2004

Selective inhibition of anandamide cellular uptake versus enzymatic hydrolysis--a difficult issue to handle.

There is considerable debate at present as to whether the uptake of anandamide (AEA) into cells is by a facilitated transport process or by passive diffusion driven by fatty acid amide hydrolase (FAAH). The possibility that both processes occur, but to different extents depending upon the cell type used, has been difficult to investigate pharmacologically since available compounds show little selectivity between inhibition of AEA uptake and inhibition of FAAH. Recently, three compounds, UCM707 [N-(Fur-3-ylmethyl)arachidonamide], OMDM-1 and OMDM-2 [the 1'-(S)- and 1'-(R)-enantiomers of the 1'-4-hydroxybenzoyl analogue of oleoylethanolamide], selective for the uptake process, have been described and we have used these compounds, together with AM404 [(N-(4-hydroxyphenyl) arachidonoyl amide)] and VDM11 [(5Z,8Z,11Z,14Z)-N-(4-Hydroxy-2-methylphenyl)-5,8,11,14-eicosatetraenamide]), with the initial aim of determining which mechanism of uptake predominates in C6 glioma and RBL-2H3 cells. AM404 and VDM11 were both found to decrease the uptake of 2 microM AEA into cells (IC50 values 6-11 microM), but they also inhibited rat brain FAAH (IC50 values 1-6 microM). However, when using a different FAAH assay protocol, VDM11 was a much less potent FAAH inhibitor (IC50>50 microM) regardless of the cell type and animal species used. In contrast, we confirmed that UCM707, OMDM-1 and OMDM-2 were weak inhibitors of FAAH (IC50 values >50 microM) under all conditions used. However, their potency as inhibitors of AEA cellular accumulation appears to be largely dependent on the cell type and assay conditions used. In particular, the potency of UCM707 (IC50 value > or =25 microM) was considerably lower than the submicromolar potency previously reported for U937 cells. It is concluded that the cause/effect relationship between AEA uptake and hydrolysis cannot be investigated uniquely by using supposedly selective inhibitors of each process.

Adsorption↗
PubMed1985

Mechanisms of apparent affinity variation of guarded receptors.

Studies of interactions between blocking agents such as antiarrhythmic drugs and gated ion channels have suggested apparent variations in binding site affinity. In this report, we develop a model by which these properties of ion channels can be explained simply on the fact that blocking agent access to the channel receptor is regulated by the channel gating apparatus. We view ion channel blockade as a two stage process: diffusion of drug to a region near the channel binding site and coupling of drug to the binding site resulting in a non-conducting, drug complexed channel. We define a guarded receptor as a receptor where binding site access is regulated by some process such as gated control of the ligand diffusion path. Relationships for equilibrium properties of guarded receptors differ from those of traditional unguarded receptors. With periodic activation of channel gates, as in cardiac muscle, a true equilibrium may never be reached due to transient receptor access. Lack of equilibrium can complicate analysis. For gated ion channels we derive equilibrium block properties under conditions of no stimulation. We show that a fixed affinity guarded receptor appears as an apparent variable affinity receptor in gated channels. These results are consistent with observations of apparent variations in receptor affinity derived from studies of local anesthetics in cardiac muscle. Furthermore, by separating drug diffusion and receptor binding, this description may facilitate quantitative characterization of local anesthetics and antiarrhythmia drugs in excitable membranes.

Animals↗
PubMed2004

Spontaneous separation of bi-stable biochemical systems into spatial domains of opposite phases.

Bi-stable chemical systems are the basic building blocks for intracellular memory and cell fate decision circuits. These circuits are built from molecules, which are present at low copy numbers and are slowly diffusing in complex intracellular geometries. The stochastic reaction-diffusion kinetics of a double-negative feedback system and a MAPK phosphorylation-dephosphorylation system is analysed with Monte-Carlo simulations of the reaction-diffusion master equation. The results show the geometry of intracellular reaction compartments to be important both for the duration and the locality of biochemical memory. Rules for when the systems lose global hysteresis by spontaneous separation into spatial domains in opposite phases are formulated in terms of geometrical constraints, diffusion rates and attractor escape times. The analysis is facilitated by a new efficient algorithm for exact sampling of the Markov process corresponding to the reaction-diffusion master equation.

Adaptation, Physiological↗
PubMed1972

Ethylene: A Natural Regulator of Sex Expression of Cucumis melo L.

Sex expression in cucumber (Cucumis sativus L.) and muskmelon (C. melo L.) was correlated with endogenous ethylene production. Plants of gynoecious (all female) sex types of the two species produced more ethylene than monoecius (male-female) plants. C. melo plants of a gynoecious sex type that normally produce only pistillate (female) flowers, when grown with hypobaric ventilation to facilitate removal of endogenous gases by diffusion, produced perfect (hermaphroditic) flowers. When either the plant was returned to atmospheric pressure or when the reduced-pressure ventilating stream was supplemented with ethylene, the same plants produced pistillate flowers. Enrichment of the atmosphere at either normal or reduced pressure with CO(2), a competitive inhibitor of ethylene action, also resulted in development of perfect flowers. Foliar application of a benzothiadiazole, a postulated inhibitor of ethylene action, resulted in formation of perfect flowers on gynoecious plants of C. melo and of staminate (male) flowers on gynoecious C. sativus. Based on these findings, it is proposed that ethylene is an endogenous regulator of sex expression in C. sativus and C. melo.

Journal Article↗
PubMed1992

A chemical approach to designing Turing patterns in reaction-diffusion systems.

A systematic approach is suggested to design chemical systems capable of displaying stationary, symmetry-breaking reaction diffusion patterns (Turing structures). The technique utilizes the fact that reversible complexation of an activator species to form an unreactive, immobile complex reduces the effective diffusion constant of the activator, thereby facilitating the development of Turing patterns. The chlorine dioxide/iodine/malonic acid reaction is examined as an example, and it is suggested that a similar phenomenon may occur in some biological pattern formation processes.

Journal Article↗
PubMed2004

Brain edema in neurooncology: radiological assessment and management.

Vasogenic brain edema is a common diagnostic and management problem in brain tumor patients. Molecular mechanisms play a role in the pathophysiology, including abnormalities of tumor endothelium, vascular endothelial growth factor and leukotriene synthase. Edema diagnosis is facilitated by the development of neuroradiological imaging techniques, with diffusion-weighted imaging (DW-MRI) differentiating tumor grades or abscesses and tumors, and diffusion tensor imaging representing an advanced technique to potentially differentiate malignant glioma from metastasis or facilitate preoperative planning. Edema is a prognostic factor for meningioma and metastases but not for glioma. Therapy includes, amongst others, tumor-directed measures such as debulking surgery, radio- and chemotherapy. However, local therapeutic approaches might also induce or exacerbate edema formation. Peritumoral edema can usually be managed with corticosteroids. However, patients on corticosteroids are at greater risk of metabolic changes, Pneumocystis carinii pneumonia, and thromboembolism. More recently, inhibitors of cyclooxygenase-2 as well as boswellic acids have been explored as antiedema agents in patients with brain tumors.

Brain Edema↗
PubMedDate not supplied

Endothelial modulation of ouabain-induced contraction and sodium pump activity in aortas of normotensive Wistar-Kyoto and spontaneously hypertensive rats.

The influence of vascular endothelium on ouabain-induced contractions and sodium pump activity in aortic segments of Wistar-Kyoto (WKY) and spontaneously hypertensive rat (SHR) was analyzed. De-endothelialization increased and reduced ouabain-induced contractions in WKY and SHR segments, respectively. The effects of de-endothelialization were not reproduced by pretreatment of the segments with NG-nitro-L-arginine methyl ester, indomethacin, or 5, 8, 11, 14-eicosatetraenoic acid, acetyl salicylic acid, dazoxiben, phosphoramidon, BQ-123, or superoxide dismutase. Bioassay experiments suggest that ouabain releases a diffusible factor from endothelial cells that inhibits or facilitates digitalis-induced contractions in WKY and SHR segments, respectively. In a potassium-free solution, potassium-induced relaxation in segments of both strains was abolished by ouabain in de-endothelialized aortas and reduced in intact ones. Ouabain-sensitive 86Rb+ uptake was significantly reduced by de-endothelialization both in WKY and in SHR. These results suggest that the vascular endothelium of WKY and SHR aortas releases a diffusible factor that stimulates the sodium pump and/or protects it from ouabain blockade. Ouabain also releases a diffusible endothelium-derived factor in SHR aortas that facilitates ouabain-induced contractions.

Animals↗
PubMed1987

Parathyroid imaging.

Advances in diagnostic imaging methods during the last decade have facilitated the identification of focal or diffuse parathyroid abnormalities. Major advances have included improvements in computed tomography and high-resolution ultrasonography, and the introduction of thallium-201-technetium-99m parathyroid subtraction scintigraphy. The more invasive methods of venous sampling and selective angiography have also been refined, but they have not been used as extensively because of the need for highly skilled personnel. The role of these diagnostic tools before surgery in the routine evaluation of patients with suspected primary hyperparathyroidism is unclear because a skilled surgeon should be able to achieve cures in 90% of these patients during exploratory surgery. However, most physicians would agree that, in those patients whose abnormalities go undetected during exploratory surgery of the neck, diagnostic imaging methods should be used before additional surgery is planned. Further prospective studies are needed to determine if routine localization before surgery is cost effective.

Angiography↗
PubMed1992

Scanning electron microscopic (SEM) examination of structures which supply subcapsular and midcortical region postglomerular microcirculation in sheep kidney.

Sheep kidneys were injected with polyester crystic (Dewilux 511-0196) and three dimensional forms of the structure forming the postglomerular microcirculation were examined by scanning electron microscope. During the examination of the afferent and efferent arterioles, a glomerulus with double efferent arterioles were examined and microdiverticular structures were observed in the terminal end of peritubular capillary plexus. It is concluded that these structures widen the surface area of the capillaries as a result of which diffusion across the capillary bed is facilitated.

Animals↗
PubMed1991

Ultrastructural observations on the transformations of osmotically stressed and electrically pulsed red cell carriers at stages during their formation.

Although annealed red blood cell (RBC) carriers, when made by different methods, encapsulate similar quantities of methotrexate (MTX) molecules, the mechanisms by which the carrier cells are formed and by which molecules are taken up may be very different as evidenced by electron microscopy (EM) of the cells at various stages during their formation. Scanning electron microscopy (SEM) revealed that dialysis- and preswell-prepared carriers, both procedures which involve exposure to hypotonic buffer, initially transform from discocytes to echinocytes, but later exhibit morphologically heterogeneous cell types. In contrast, electroporated carriers, formed under isotonic conditions, uniformly show an initial discocyte-spheroechinocyte transformation. Transmission electron microscopy (TEM) of osmotically stressed RBC carriers demonstrates that uptake of molecules can be facilitated both by endocytosis and passive diffusion, whereas electrically pulsed carriers encapsulate material only by passive diffusion. Such experiments provide evidence that methods can be refined potentially for producing and isolating carriers that would have more predictable properties in vivo.

Drug Carriers↗
PubMed1993

[How to edit a scientific article and where to publish it?].

The editorial aspect of scientific writing cannot be dissociated from the scientific message it carries. Precision, clearness and conciseness are qualities which express the level of rigour reached in the scientific work presented. By gaining knowledge of the universally accepted rules for medical writing, and abiding by them, authors can expect optimal diffusion of the scientific content and facilitate reader comprehension. This paper outlines the precise rules common to all scientific articles and gives details on the elements on which a biomedical journal bases its decision on whether or not to publish the results of the author's work.

Humans↗
PubMed2002

Temperature response of mesophyll conductance. Implications for the determination of Rubisco enzyme kinetics and for limitations to photosynthesis in vivo.

CO(2) transfer conductance from the intercellular airspaces of the leaf into the chloroplast, defined as mesophyll conductance (g(m)), is finite. Therefore, it will limit photosynthesis when CO(2) is not saturating, as in C3 leaves in the present atmosphere. Little is known about the processes that determine the magnitude of g(m). The process dominating g(m) is uncertain, though carbonic anhydrase, aquaporins, and the diffusivity of CO(2) in water have all been suggested. The response of g(m) to temperature (10 degrees C-40 degrees C) in mature leaves of tobacco (Nicotiana tabacum L. cv W38) was determined using measurements of leaf carbon dioxide and water vapor exchange, coupled with modulated chlorophyll fluorescence. These measurements revealed a temperature coefficient (Q(10)) of approximately 2.2 for g(m), suggesting control by a protein-facilitated process because the Q(10) for diffusion of CO(2) in water is about 1.25. Further, g(m) values are maximal at 35 degrees C to 37.5 degrees C, again suggesting a protein-facilitated process, but with a lower energy of deactivation than Rubisco. Using the temperature response of g(m) to calculate CO(2) at Rubisco, the kinetic parameters of Rubisco were calculated in vivo from 10 degrees C to 40 degrees C. Using these parameters, we determined the limitation imposed on photosynthesis by g(m). Despite an exponential rise with temperature, g(m) does not keep pace with increased capacity for CO(2) uptake at the site of Rubisco. The fraction of the total limitations to CO(2) uptake within the leaf attributable to g(m) rose from 0.10 at 10 degrees C to 0.22 at 40 degrees C. This shows that transfer of CO(2) from the intercellular air space to Rubisco is a very substantial limitation on photosynthesis, especially at high temperature.

Algorithms↗
PubMed2006

Sorption kinetics of toluene in humic acid: a computational approach.

Molecular dynamics, a computational technique aiming to describe the time-dependent movement of molecules, has been applied to study the sorption kinetics of volatile organic contaminants in soil organic matter. The molecular dynamics simulation results obtain reasonably accurate estimates of diffusion rates and activation energy of the penetration of a volatile organic compound molecule into a model humic substance. The sorption rate of toluene to humic acid decreases with the density of the humic acid matrix and increases with temperature. All the present results indicate that the sorption of toluene into humic acid is mainly diffusion controlled. Finally, the present studies have shown that molecular dynamics of volatile organic compounds in humic substances yields meaningful results, which help in the understanding of diffusion at the molecular level and which facilitate the problem-solving capability for removing the contaminants from the soils.

Adsorption↗