Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “compartmentalization”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources
PubMed2002

High tibial osteotomy with anterior advancement of distal fragment for medial and patellofemoral compartmental osteoarthritis of the knee.

High tibial osteotomy was performed in 73 knees of 50 patients with medial and patellofemoral compartmental osteoarthritis of the knee, which was combined with anterior advancement of the distal fragment. At the operation, parapatellar release of the retinaculum and subperiosteal elevation of contracted medial soft tissue were also adjoined. The average age of the patients at the time of surgery was 64 years. The follow-up period was an average of 58 months. On overall clinical results assessed with the Knee Society score, the average total knee score was improved from preoperative 50 points to postoperative 94, and the preoperative average functional score of 47 points increased to 92 postoperatively. At follow-up, pain from a grinding patella was not found in 68 of 73 knees and pain from grinding and deviating of the patella was relieved in more than 96% of all cases. The mean femorotibial angle was reduced from preoperative 185 degrees to postoperative 167 degrees. On skyline view, the width of the lateral facet joint space was widely opened postoperatively, particularly on the flexion angle of 90 degrees. This operative procedure successfully relieved patellofemoral symptoms of the patients with medial and patellofemoral compartmental osteoarthritis of the knee.

Aged↗
PubMed1999

Spatial Compartmentalization in the Regulation of Glucose Metabolism by Insulin.

Despite intense investigation, major gaps remain in our understanding of the cellular mechanisms that underlie the actions of insulin, as well as the regulation of the enzymes and transport proteins crucial to the orderly control of glucose metabolism. In recent years, the compartmentalization of signaling molecules and metabolic enzymes has been suggested to play an important role in ensuring metabolic balance. We will discuss examples of recent findings, suggesting that spatial compartmentalization and protein translocation might be the keys to understanding the specificity of insulin in the regulation of glucose metabolism.

Journal Article↗
PubMed2006

Beyond switches: ratcheting a particle energetically uphill with a compartmentalized molecular machine.

Here we correlate chemical (covalent), physical (thermodynamic), and statistical (population distribution) descriptions of behavior with the way that two new types of simple molecular machines (the threads of rotaxanes) perform the task of transporting a Brownian substrate (the rotaxane macrocycle) between two distinguishable binding sites. The first machine-substrate ensemble is a [2]rotaxane that operates through a mechanism that intrinsically causes it to change the average position of the macrocycle irreversibly. This contrasts with the behavior of classic stimuli-responsive molecular shuttles that act as reversible molecular switches. The second system is a compartmentalized molecular machine that is able to pump its substrate energetically uphill using the energy provided by a photon by means of an olefin photoisomerization. Resetting this compartmentalized molecular machine does not undo the work it has carried out or the task performed, a significant difference to a simple molecular switch and a characteristic we recognize as "ratcheting" (see Scheme 8). The ratcheting mechanism allows the [2]rotaxane to carry out the transport function envisaged for the historical thought-machines, Smoluchowski's Trapdoor and Maxwell's Pressure Demon, albeit via an unrelated mechanism and using an input of energy. We define and exemplify the terms "ratcheting" and "escapement" in mechanical terms for the molecular level and outline the fundamental phenomenological differences that exist between what constitutes a two-state Brownian switch, a two-state Brownian memory or "flip-flop", and a (two-stroke) Brownian motor. We also suggest that considering the relationship between the parts of a molecular machine and a substrate in terms of "statistical balance" and "linkage" could be useful in the design of more complex systems and in helping to understand the role of individual amino acids and peptide fragments during the directional transport of substrates by biological pumps and motors.

Journal Article↗
PubMed2002

Metabolic compartmentation in cortical synaptosomes: influence of glucose and preferential incorporation of endogenous glutamate into GABA.

Metabolism of glutamine was determined under a variety of conditions to study compartmentation in cortical synaptosomes. The combined intracellular and extracellular amounts of [U-13C] GABA, [U-13C]glutamate and [U-13C]glutamine were the same in synaptosomes incubated with U-13C]glutamine in the presence and absence of glucose. However, the concentration of these amino acids was decreased in the latter group, demonstrating the requirement for glucose to maintain the size of neurotransmitter pools. In hypoglycemic synaptosomes more [U-13C]glutamine was converted to [U-13C]aspartate, and less glutamate was re-synthesized from the tricarboxylic acid (TCA) cycle, suggesting use of the partial TCA cycle from alpha-ketoglutarate to oxaloacetate for energy. Compartmentation was studied in synaptosomes incubated with glucose plus labeled and unlabeled glutamine and glutamate. Incubation with [U-13C]glutamine plus unlabeled glutamate gave rise to [U-13C]GABA but not labeled aspartate; however, incubation with [U-13C]glutamate plus unlabeled glutamine gave rise to [U-13C]aspartate, but not labeled GABA. Thus the endogenous glutamate formed via glutaminase in synaptic terminals is preferentially used for GABA synthesis, and is metabolized differently than glutamate taken up from the extracellular milieu.

Animals↗
PubMed2002

A compartmental model of hepatic disposition kinetics: 1. Model development and application to linear kinetics.

The conventional convection-dispersion model is widely used to interrelate hepatic availability (F) and clearance (Cl) with the morphology and physiology of the liver and to predict effects such as changes in liver bloodflow on F and Cl. The extension of this model to include nonlinear kinetics and zonal heterogeneity of the liver is not straightforward and requires numerical solution of partial differential equation, which is not available in standard nonlinear regression analysis software. In this paper, we describe an alternative compartmental model representation of hepatic disposition (including elimination). The model allows the use of standard software for data analysis and accurately describes the outflow concentration-time profile for a vascular marker after bolus injection into the liver. In an evaluation of a number of different compartmental models, the most accurate model required eight vascular compartments, two of them with back mixing. In addition, the model includes two adjacent secondary vascular compartments to describe the tail section of the concentration-time profile for a reference marker. The model has the added flexibility of being easy to modify to model various enzyme distributions and nonlinear elimination. Model predictions of F, MTT, CV2, and concentration-time profile as well as parameter estimates for experimental data of an eliminated solute (palmitate) are comparable to those for the extended convection-dispersion model.

Animals↗
PubMed1999

A compartmental analysis of the pharmacokinetics of propofol in sheep.

Conventional compartmental pharmacokinetic analysis may provide inaccurate prediction of drug concentrations after rapid i.v. administration. To examine this, compartment and effect compartment analysis was applied to measured arterial and brain concentrations of propofol in sheep after i.v. administration at a range of doses and dose rates. Although arterial and brain concentrations were reasonably well fitted to compartmental and effect compartment models for individual doses and dose rates, the structure and parameters of all models differed with changes in both dose and rate of administration. There were large discrepancies between predicted and measured arterial and brain concentrations when these models were used to predict drug concentrations across doses and dose rates. These data support the limitations of this type of modeling in the setting of rapid propofol administration.

Anesthetics, Intravenous↗
PubMed1997

Pharmacokinetic analysis of mizolastine in healthy young volunteers after single oral and intravenous doses: noncompartmental approach and compartmental modeling.

This paper presents the analysis of the kinetics of a new antihistamine, mizolastine, in 18 healthy volunteers, from concentrations measured after an intravenous infusion and two different oral administrations: tablet and capsule. Two approaches were used to analyze these data: (i) a noncompartmental approach implemented in PHARM-NCA; (ii) a compartmental modeling approach implemented in a new S-PLUS library, NLS2, which allows the estimation of variance parameters simultaneously with the kinetic parameters. For the compartmental modeling approach, two-compartment open models were used. According to the Akaike criterion, the best model describing the kinetics of mizolastine after oral administration was the zero-order absorption model. The kinetic parameters obtained with PHARM-NCA and NLS2 were similar. The estimated duration of absorption was greater for the tablets than for the capsules (with means equal to 1.13 hr and 0.84 hr respectively). After an intravenous infusion, the mean estimated clearance was 4.9 L/hr, the mean lambda 2-phase apparent volume of distribution was 89.6 L and the mean terminal half-life was 12.9 hr.

Administration, Oral↗
PubMed1991

Compartmental analysis of diprenorphine binding to opiate receptors in the rat in vivo and its comparison with equilibrium data in vitro.

The regional binding of the opiate receptor ligand diprenorphine has been examined in rat brain both in vivo and in vitro. The time course of total label in specific brain regions was followed up to 2 h after intravenous bolus injection of [3H]diprenorphine, with or without a pulse chase of unlabelled diprenorphine at 30 min. In addition, total label was measured 30 min after injection of labelled diprenorphine at nontracer concentrations over a range of specific activities. Total data sets for each region were fitted simultaneously to a compartmental model to give estimates of maximal binding capacity (Bmax), the second-order apparent association rate constant, and the first-order dissociation rate constant of the receptor-ligand complex. The model incorporated the use of a reference region with low specific binding (cerebellum). The binding of diprenorphine to rat brain homogenates was measured in vitro under equilibrium conditions at 37 degrees C, pH 7.4, in the presence and absence of naloxone, to give corresponding regional estimates of Bmax and the half-saturation constant Kd. The results showed a close correlation between in vitro and in vivo regional estimates of Bmax over a wide range. There were no significant interregional differences either in Kd in vitro or in the Kd derived from the in vivo analysis, although in vitro and in vivo estimates differed by an order of magnitude. This work was carried out as part of a validation study with a view to the application of the compartmental model to data obtained in vivo in humans using positron emission tomography, when successive studies over a range of specific activities are not feasible.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Spatial compartmentalization and functional impact of conductance in pyramidal neurons.

Dendritic spikes signal synaptic integration at remote apical dendritic sites in neocortical pyramidal neurons in vitro. Do dendritic spikes have a salient signaling role under in vivo conditions, where neocortical pyramidal neurons are bombarded with synaptic input? In the present study, levels of synaptic conductance apparent during active network states in vivo were emulated in vitro. Pronounced enhancement of somatic or apical dendritic conductance was spatially compartmentalized and 'visible' over a dendritic length ( approximately 200 microm) on the order of half the voltage length constant, as predicted by passive cable models. The spatial compartmentalization of conductance allowed independent subthreshold synaptic integration at axo-somatic and apical dendritic sites. Furthermore, spikes generated at distal apical dendritic sites efficiently propagated to the axon to initiate action potentials under high synaptic conductance states. The dendritic arborization and voltage-activated channel complement of rat neocortical pyramidal neurons are therefore optimized to allow distributed processing under realistic conductance states.

Action Potentials↗
PubMed2005

Estimation of iron absorption in humans using compartmental modelling.

OBJECTIVE: To evaluate whether a compartmental model could estimate iron absorption as accurately as the well-validated technique of plasma area under the curve using labelled test meals. DESIGN: The study is a randomised cross-sectional intervention. SETTING: The study was carried out at the Human Nutrition Unit at the Institute of Food Research, Norwich, UK. SUBJECTS: A total of nine female volunteers, aged 33+/-8 y. INTERVENTIONS: Volunteers were given an oral dose (approximately 5 mg) of Fe-57 as iron sulphate in an orange juice test drink and simultaneously infused Fe-58 (approximately 200 microg) as iron citrate over 90 min. Multiple blood samples were taken for the following 6 h. The samples were analysed by mass spectrometry and iron absorption was estimated using a mathematical model based on the appearance of Fe isotopes in plasma and the area under the curve technique. RESULTS: The geometric mean (-1 s.d., +1 s.d.) absorption of the model estimate is 16% (9, 31) and the area under curve estimate is 18% (8, 29). CONCLUSIONS: Results indicate that a compartmental model can be used to estimate labelled iron absorption although it is unlikely that this new method will be used in favour of an existing one. Further studies are now needed with unlabelled iron to assess whether the technique could have application in the assessment of total (haem+nonhaem) iron absorption from food.

Administration, Oral↗
PubMed2005

Compartmentalized cAMP signalling regulates vasopressin-mediated water reabsorption by controlling aquaporin-2.

The cAMP/PKA (protein kinase A) signalling pathway is activated by a plethora of stimuli. To facilitate the specificity of a cellular response, signal transduction complexes are formed and segregated to discrete sites (compartmentalization). cAMP/PKA signalling compartments are maintained by AKAPs (A-kinase anchoring proteins) which bind PKA and other signalling proteins, and by PDEs (phosphodiesterases). The latter hydrolyse cAMP and thus limit its diffusion and terminate PKA activity. An example of a cAMP-dependent process requiring compartmentalization of cAMP/PKA signals is arginine-vasopressin-regulated water reabsorption in renal principal cells. A detailed understanding of the protein interactions within a signal transduction complex offers the possibility to design agents influencing PKA binding to a specific AKAP, the targeting of an AKAP or the interactions of AKAPs with other signalling molecules. The ability to specifically modulate selected branches of a signal transduction pathway would greatly advance basic research, and may lead to new drugs suitable for the treatment of diseases caused by dysregulation of anchored PKA signalling (e.g. renal and cardiovascular diseases).

Animals↗
PubMed2006

Restricted diffusion of a freely diffusible second messenger: mechanisms underlying compartmentalized cAMP signalling.

It is becoming increasingly evident that the freely diffusible second messenger cAMP can transduce specific responses by localized signalling. The machinery that underpins compartmentalized cAMP signalling is only now becoming appreciated. Adenylate cyclases, the enzymes that synthesize cAMP, are localized at discrete parts of the plasma membrane, and phosphodiesterases, the enzymes that degrade cAMP, can be targeted to selected subcellular compartments. A-kinase-anchoring proteins then serve to anchor PKA (protein kinase A) close to specific targets, resulting in selective activation. The specific activation of such individual subsets of PKA requires that cAMP is made available in discrete compartments. In this presentation, the molecular and structural mechanisms responsible for compartmentalized PKA signalling and restricted diffusion of cAMP will be discussed.

Animals↗
PubMed1995

Compartmental analysis of colonic transit reveals abnormalities in constipated patients with normal transit.

1. The aims of this study were to investigate if compartmental analysis can be used to analyse colonic transit measurements and to search for a relationship between transit time and the parameters deduced from this analysis. In addition, an attempt was made to determine if such analysis could reveal a functional abnormality in patients who complain of constipation but have normal colonic transit. 2. The subjects included 11 healthy controls, 10 patients with chronic diarrhoea and 55 constipated patients. Segmental and total colonic transit time were measured using a previously described method. Compartmental analysis was based on a three-compartment system, with k1, k2 and k3 being the coefficients of diffusion out of the right colon, the left colon and the rectosigmoid area respectively. 3. Patients complaining of constipation who had delayed transit time were the only subjects to have lower values of coefficient k1 than controls. k2 was lower than normal in all patients complaining of constipation, but this decrease was more marked in subjects with delayed colonic transit time than in subjects with normal colonic transit time. All patients complaining of constipation had lower values of k3 than control subjects. 4. This study shows that analysis of colonic transit time is feasible using a simple diffusion law, and that the results are correlated to clinical data. Moreover, this analysis permits detection of abnormalities in two groups of subjects: those who complain of constipation but are labelled as having normal colonic transit time and those who have chronic diarrhoea.

Adult↗
PubMed2003

Analysis of compartmental models of type 4 nuclear renograms with calculation of flow rate parameters and instantaneous drainage rates.

OBJECTIVE: To estimate the dynamic rates of arterial delivery and renal drainage in renograms with the Homsy sign, using optimized computed compartmental modelling. METHODS: Eleven F-15 renograms and one F+15 renogram (using 99mTc-mercaptoacetyltriglycine) with the Homsy sign were studied, with 26 controls. Compartmental models were constructed for each renogram using components (blood, renal, bladder) linked by variables (arterial rate, drainage rate). Each model was optimized using the Marquadt least-squares method to numerical data from the time-activity curves (TACs). The model renal component at sample points along the TAC was minimized and the corresponding drainage rates calculated. RESULTS: The models were optimized, with a mean (range) r2 of 0.811 (0.68-0.88). There were continuous low drainage rates for all type 4 renograms, with no quadrupling of the flow rate, as predicted by the standard model. CONCLUSION: The standard model is unlikely to be correct and the Homsy sign is probably an artefact seen in patients with impeded urinary drainage. Computer modelling of individual renograms is feasible and can provide useful insights into the pathophysiology of renal uptake and drainage.

Computer Simulation↗
PubMed2006

Tight mucosal compartmentation of the murine immune response to antigens of the enteric microbiota.

BACKGROUND & AIMS: The normal host immune response to antigens of the enteric microbiota is poorly defined. In this study, we isolated recombinant microbial antigens from commensal bacteria and used them to probe the normal murine immune response. METHODS: A plasmid DNA expression library was generated from cecal bacteria of C3H/HeJ mice and used to express 20 recombinant intestinal bacterial proteins (rIBs). Antibody responses in serum and secretions were measured by an enzyme-linked immunosorbent assay, and CD4+ T-cell responses were measured by [3H]-thymidine incorporation. Two immunodominant commensal flagellins were also tested. RESULTS: No baseline serum immunoglobulin (Ig)G antibody or splenic CD4+ T-cell systemic response to any rIB or to either flagellin was detected in normal C3H/HeJ mice. However, there were strong systemic responses to all 20 rIBs after parenteral immunization, which were equivalent to the responses to ovalbumin. Substantial levels of intestinal IgA were detected to half the rIBs and to both commensal flagellins. Mucosal immunization with flagellin plus ovalbumin stimulated an intestinal IgA but not a serum IgG response. Antigen-pulsed dendritic cells (DCs) stimulated production of specific IgA in the absence of T-cell help via costimulation by BAFF and/or APRIL, members of the TNF family. CONCLUSIONS: The host immune response to enteric bacteria is tightly compartmentalized to the mucosa in normal mice, with systemic B cells and CD4+ T cells remaining naive rather than tolerant. We postulate that mucosal DCs play a crucial role in this compartmentation.

Animals↗
PubMed1975

[An approximation for improving the accuracy of compartmental analysis after intravenous 133Xe].

Perfusion of transplanted kidneys is studied in our clinic by intravenous injection of 133Xe with subsequent graphic compartmental analysis of time-activity curves. Where there is poor perfusion of the renal cortex, it is not possible to obtain a half-value time for the first compartment--which is the significant measure for specific blood flow -- since few points are available for the tail end of the curve. A correction is described which produces an approximation to a bolus, based on the time-activity curve of the expired air. If this is applied to the proximal part of the time-activity curve, with respect to background activity, compartmental analysis can be performed with a higher degree of accuracy in the calculation of renal perfusion.

Air↗
PubMed2002

Left atrial radiofrequency compartmentalization for chronic atrial fibrillation during heart surgery.

BACKGROUND: The excellent results of the Maze III operation have demonstrated that a surgical cure of atrial fibrillation (AF) is possible. A simplified Maze procedure with radiofrequency (RF)ablation of the atrial tissue added to open heart surgery may help to cure chronic AF with low risk. METHODS: From May 1998 to March 2001, an RF left atrial compartmentalization concomitant to a cardiac surgical intervention was performed on 40 of 1,258 patients (3.2 %). Thirty-seven patients had mitral valve disease, two had aortic valve disease and one had coronary artery disease. All patients presented with chronic refractory AF for a mean time of 40.4 months ranging from 4 months to 18 years. RESULTS: Mitral valve replacement (MVR) was performed in 19 patients, mitral valve repair in 12, combined aortic and mitral valve procedures were performed in 6, aortic valve replacement(AVR) in 2 and CABG in 1 patient. Cardiopulmonary bypass time for the complete procedure was 138 +/- 32 minutes with an ablation time of 19 +/- 5 minutes. No complication related to RF application was noted. Sinus rhythm was present in 68% after 12.5 +/- 8.5 months. CONCLUSIONS: RF left atrial compartmentalization combined with cardiac surgical interventions proved to be easy and safe to perform. The long-term results still have to be confirmed with further regular patient follow-up examinations.

Aged↗
PubMed2005

Selection of ribozymes that catalyse multiple-turnover Diels-Alder cycloadditions by using in vitro compartmentalization.

In vitro compartmentalization (IVC) has previously been used to evolve protein enzymes. Here, we demonstrate how IVC can be applied to select RNA enzymes (ribozymes) for a property that has previously been unselectable: true intermolecular catalysis. Libraries containing 10(11) ribozyme genes are compartmentalized in the aqueous droplets of a water-in-oil emulsion, such that most droplets contain no more than one gene, and transcribed in situ. By coencapsulating the gene, RNA, and the substrates/products of the catalyzed reaction, ribozymes can be selected for all enzymatic properties: substrate recognition, product formation, rate acceleration, and turnover. Here we exploit the complementarity of IVC with systematic evolution of ligands by exponential enrichment (SELEX), which allows selection of larger libraries (>/=10(15)) and for very small rate accelerations (k(cat)/k(uncat)) but only selects for intramolecular single-turnover reactions. We selected approximately 10(14) random RNAs for Diels-Alderase activity with five rounds of SELEX, then six to nine rounds with IVC. All selected ribozymes catalyzed the Diels-Alder reaction in a truly bimolecular fashion and with multiple turnover. Nearly all ribozymes selected by using eleven rounds of SELEX alone contain a common catalytic motif. Selecting with SELEX then IVC gave ribozymes with significant sequence variations in this catalytic motif and ribozymes with completely novel motifs. Interestingly, the catalytic properties of all of the selected ribozymes were quite similar. The ribozymes are strongly product inhibited, consistent with the Diels-Alder transition state closely resembling the product. More efficient Diels-Alderases may need to catalyze a second reaction that transforms the product and prevents product inhibition.

Alkenes↗