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.

SourceResearch connectionFrom yearThrough year

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

At least 433 records · Page 24Linked to original sources

PubMed1989

13C nuclear magnetic resonance evidence for gamma-aminobutyric acid formation via pyruvate carboxylase in rat brain: a metabolic basis for compartmentation.

The compartmentation of amino acid metabolism is an active and important area of brain research. 13C labeling and 13C nuclear magnetic resonance (NMR) are powerful tools for studying metabolic pathways, because information about the metabolic histories of metabolites can be determined from the appearance and position of the label in products. We have used 13C labeling and 13C NMR in order to investigate the metabolic history of gamma-aminobutyric acid (GABA) and glutamate in rat brain. [1-13C]Glucose was infused into anesthetized rats and the 13C labeling patterns in GABA and glutamate examined in brain tissue extracts obtained at various times after infusion of the label. Five minutes after infusion, most of the 13C label in glutamate appeared at the C4 position; at later times, label was also present at C2 and C3. This 13C labeling pattern occurs when [1-13C]glucose is metabolized to pyruvate by glycolysis and enters the pool of tricarboxylic acid (TCA) intermediates via pyruvate dehydrogenase. The label exchanges into glutamate from the TCA cycle pool through glutamate transaminases or dehydrogenase. After 30 min of infusion, approximately 10% of the total 13C in brain extracts appeared in GABA, primarily (greater than 80%) at the amino carbon (C4), indicating that the GABA detected is labeled through pyruvate carboxylase. The different labeling patterns observed for glutamate and GABA show that the large detectable glutamate pool does not serve as the precursor to GABA. Our NMR data support previous experiments suggesting compartmentation of metabolism in brain, and further demonstrate that GABA is formed from a pool of TCA cycle intermediates derived from an anaplerotic pathway involving pyruvate carboxylase.

Animals↗

PubMed2006

Abnormal compartmentalization of norepinephrine in mouse dentate gyrus in alpha-synuclein knockout and A30P transgenic mice.

In the dentate gyrus of the mouse hippocampus, presynaptic recruitment of norepinephrine in response to repeated-burst stimulation can be described in terms of an interaction between storage and readily releasable pools. The dynamics of this interaction depends on neuronal activity (bursting), so that the higher the demand for norepinephrine, the faster it is delivered from the storage pool. We also found that alpha-synuclein, a presynaptic protein that plays a crucial role in dopamine compartmentalization in the striatum, is also involved in the compartmentalization of norepinephrine in the dentate gyrus. Experiments in transgenic mice with modified or absent alpha-synuclein revealed that the familial Parkinson's disease-linked alpha-synuclein mutation A30P can cause selective changes in the function of noradrenergic terminals. Addition of mutated human alpha-synuclein abolished the normal norepinephrine mobilization. There were no compensatory mechanisms available in the norepinephrine presynaptic terminals. In contrast, deletion of mouse alpha-synuclein is compensated for by increased vesicle transport from the storage pool. The effects are essentially the same as previously reported for dopaminergic terminals in the striatum, indicating that the important role of alpha-synuclein in neurotransmitter mobilization is not limited to dopaminergic terminals.

Animals↗

PubMed1981

Deep posterior tibial compartmental syndrome after accidental hypothermia in an elderly hypothyroid patient.

Compartmental syndromes are uncommon, but particularly the deep posterior tibial compartmental syndrome, which is usually associated with trauma. It has not previously been recorded as a complication of hypothermic or hypothyroid coma. This case of successful surgical therapy in a 75-year-old woman is reported in the hope that similar occurrences in the future may be recognized in time for curative surgery or at least for palliative surgery which can offer recovery of useful function.

Aged↗

PubMed1999

Right atrial compartmentalization using radiofrequency catheter ablation for management of patients with refractory atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is often refractory to antiarrhythmic drugs, and patients who are intolerant of AF may require the maze operation for cure. As a less invasive alternative, a catheter-based, right atrial compartmentalization procedure was evaluated. METHODS AND RESULTS: Twelve patients with AF refractory to Class I and III antiarrhythmic drugs were studied. Four linear right atrial radiofrequency ablations were performed, from superior to inferior vena cava in the posterior wall and interatrial septum, anteriorly from the superior vena cava to the tricuspid annulus through the appendage, and across the tricuspid valve-inferior vena cava isthmus. The radiofrequency catheter was dragged along each line three to four times, until the atrial electrogram amplitude decreased by 75% and there was bidirectional conduction block in the tricuspid valve-inferior vena cava isthmus. One complication occurred: sinus node dysfunction requiring a pacemaker. Eight patients were discharged from the hospital on no antiarrhythmic drugs, and four were discharged on previously ineffective antiarrhythmic drugs. Total duration of follow-up was 21.3 +/- 11.2 months. Four patients discharged on previously ineffective antiarrhythmic drugs had no recurrence of AF. One patient discharged off antiarrhythmic drugs had no recurrence of AF. Seven patients discharged off antiarrhythmic drugs had recurrent AF by 12.6 +/- 13.0 months (median 6, range 1 to 39); 3 of these 7 responded to previously ineffective antiarrhythmic drugs without further AF and 4 did not. Thus, 8 of 12 patients (67%) had suppression of AF after ablation on previously ineffective medication or no medication. CONCLUSION: Right atrial compartmentalization may alter the substrate for AF, thus improving the efficacy of previously ineffective antiarrhythmic drugs. Because it is relatively safe, it may be a reasonable adjunctive intervention to maintain sinus rhythm in patients with drug-refractory AF.

Adult↗

PubMed2000

Prevention of atrial fibrillation by complete compartmentalization of the left atrium using a catheter technique.

INTRODUCTION: Right atrial compartmentalization has been demonstrated to only reduce the number of atrial fibrillation (AF) episodes; left atrial (LA) fibrillation still occurs. METHODS AND RESULTS: We report successful LA compartmentalization resulting in isolation of all four pulmonary veins in a 51-year-old woman suffering from paroxysmal AF. Deployment of a complete encircling line resulted in dissociation of electrical activation within the isolated area from the remaining LA. Despite attempts at reinduction by pacing maneuvers inside and outside the isolated area, AF was no longer inducible. During 21-week follow-up, the patient remained in stable sinus rhythm with rare atrial extrasystoles. CONCLUSION: If reproducible, this ablation strategy could allow treatment of AF independent of suppression of any triggering event.

Atrial Fibrillation↗

PubMed1984

Coordination between enzyme specificity and intracellular compartmentation in the control of protein-bound oligosaccharide biosynthesis.

This laboratory has developed schemes for the control of biosynthesis of N- and O-glycosyl oligosaccharides based on studies in cell-free systems of glycosyl-transferase substrate specificities. These schemes are based on assumptions that may not be universally correct. For example, we have ignored the possible compartmentation of reactions in different cells or in different organelles within a cell. Recent evidence has indicated that the Golgi apparatus has at least three functionally distinct regions (cis, medial and trans). The addition of galactosyl and sialyl residues to the antennae of complex and hybrid N-glycans probably occurs entirely within the trans-cisternae while the N-acetylglucosaminyl-transferases which initiate these antennae appear to be located in a denser region of the Golgi (cis and/or medial cisternae). We have constructed a modified scheme for the biosynthesis of the antennae of N-glycans. This scheme combines our substrate specificity data (H. Schachter, S. Narasimhan, P. Gleeson and G. Vella, 1983, Can. J. Biochem. Cell Biol., 61, 1049-1066) with compartmentation data. It provides a basis for understanding the control of glycoprotein synthesis in normal tissues and in certain lectin-resistant mutant cell lines.

Animals↗

PubMed2005

Perfusion-diffusion compartmental models describe cerebral helium kinetics at high and low cerebral blood flows in sheep.

This study evaluated the relative importance of perfusion and diffusion mechanisms in compartmental models of blood:tissue helium exchange in the brain. Helium has different physiochemical properties from previously studied gases, and is a common diluent gas in underwater diving where decompression schedules are based on theoretical models of inert gas kinetics. Helium kinetics across the cerebrum were determined during and after 15 min of helium inhalation, at separate low and high steady states of cerebral blood flow in seven sheep under isoflurane anaesthesia. Helium concentrations in arterial and sagittal sinus venous blood were determined using gas chromatographic analysis, and sagittal sinus blood flow was monitored continuously. Parameters and model selection criteria of various perfusion-limited or perfusion-diffusion compartmental models of the brain were estimated by simultaneous fitting of the models to the sagittal sinus helium concentrations for both blood flow states. Purely perfusion-limited models fitted the data poorly. Models that allowed a diffusion-limited exchange of helium between a perfusion-limited tissue compartment and an unperfused deep compartment provided better overall fit of the data and credible parameter estimates. Fit to the data was also improved by allowing countercurrent diffusion shunt of helium between arterial and venous blood. These results suggest a role of diffusion in blood:tissue helium equilibration in brain.

Animals↗

PubMed1985

Response of the microflora in outdoor experimental streams to pentachlorophenol: compartmental contributions.

Outdoor artificial streams were treated continuously with pentachlorophenol (PCP) for 88 days during the summer of 1983. The contributions of different stream compartments (microbial habitats) to microbial degradation of PCP were determined in a stream treated with 144 micrograms of PCP per liter. The 488-m long stream was composed of mud-bottomed pools alternating with gravel riffles. PCP loss in the stream attributable to microbial degradation after an adaptation period was in the range of 55 to 74%. Contributions to PCP loss were determined for rock surface (epilithic), macrophyte surface (epiphytic), sedimentary, and water column communities by measuring rates of PCP disappearance in stream water, containing ambient concentrations of PCP, in contact with representative compartmental samples. The specific capability, in units of micrograms of PCP per hour per square meter of stream cross-sectional area (macrophytes at maximum plant density, water column at mean depth, upper 10-cm layer of gravel), followed the order rock surface much greater than macrophytes greater than sediment approximately equal to water column. The compartmental contribution to total stream losses in units of grams per hour followed the same order, although the differences were smaller. The rate of PCP disappearance in the water column above sediment cores followed the order oxygen-rich greater than oxygen-poor approximately equal to anaerobic greater than sorption-only conditions. The large difference in specific capability between the rock surface and sediment compartments could be attributed to oxygen deficiency (because of chemical and biological oxygen demand) in the sediments. Free-floating and particle-attached organisms in the water column were important to PCP biodegradation.

Aerobiosis↗

PubMed2006

Compartmentalization of the broad-range phospholipase C activity to the spreading vacuole is critical for Listeria monocytogenes virulence.

Listeria monocytogenes is a bacterial pathogen that multiplies in the cytosol of host cells and spreads directly from cell to cell by using an actin-based mechanism of motility. The broad-range phospholipase C (PC-PLC) of L. monocytogenes contributes to bacterial escape from vacuoles formed upon cell-to-cell spread. PC-PLC is made as an inactive proenzyme whose activation requires cleavage of an N-terminal propeptide. During infection, PC-PLC is activated specifically in acidified vacuoles. To assess the importance of compartmentalizing PC-PLC activity during infection, we created a mutant that makes constitutively active PC-PLC (the plcBDelta pro mutant). Results from intracellular growth and cell-to-cell spread assays showed that the plcBDelta pro mutant was sensitive to gentamicin, suggesting that unregulated PC-PLC activity causes damage to host cell membranes. This was confirmed by the observation of a twofold increase in staining of live infected cells by a non-membrane-permeant DNA fluorescent dye. However, membrane damage was not sufficient to cause cell lysis and was dependent on bacterial cell-to-cell spread, suggesting that damage was localized to bacterium-containing filopodia. Using an in vivo competitive infection assay, we observed that the plcBDelta pro mutant was outcompeted up to 200-fold by the wild-type strain in BALB/c mice. Virulence attenuation was greater when mice were infected orally than when they were infected intravenously, presumably because the plcBDelta pro mutant was initially outcompeted in the intestines, reducing the number of mutant bacteria reaching the liver and spleen. Together, these results emphasize the importance for L. monocytogenes virulence of compartmentalizing the activity of PC-PLC during infection.

Animals↗

PubMed2005

Compartmentalization of hepatitis C virus genotypes between plasma and peripheral blood mononuclear cells.

Differences in hepatitis C virus (HCV) variants of the highly conserved 5' untranslated region (UTR) have been observed between plasma and peripheral blood mononuclear cells (PBMC). The prevalence and the mechanisms of this compartmentalization are unknown. Plasma and PBMC HCV variants were compared by single-strand conformation polymorphism (SSCP) and by cloning or by genotyping with a line probe assay (LiPA) in 116 chronically infected patients, including 44 liver transplant recipients. SSCP patterns differed between compartments in 43/109 analyzable patients (39%). Differences were significantly more frequent in patients with transplants (21/38 [55%] versus 22/71 [31%]; P < 0.01) and in those who acquired HCV through multiple transfusions before 1991 (15/20; 75%) or through drug injection (16/31; 52%) than in those infected through an unknown route (7/29; 24%) or through a single transfusion (5/29; 17%; P < 0.001). Cloning of the 5' UTR, LiPA analysis, and nonstructural region 5B sequencing revealed different genotypes in the two compartments from 10 patients (9%). In nine patients, the genotype detected in PBMC was not detected in plasma and was weak or undetectable in the liver in three cases. This genotypic compartmentalization persisted for years in three patients and after liver transplantation in two. The present study shows that a significant proportion of HCV-infected subjects harbor in their PBMC highly divergent variants which were likely acquired through superinfections.

5' Untranslated Regions↗

PubMed2005

Compartmentalized human immunodeficiency virus type 1 present in cerebrospinal fluid is produced by short-lived cells.

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) during primary infection and persists in this compartment by unknown mechanisms over the course of infection. In this study, we examined viral population dynamics in four asymptomatic subjects commencing antiretroviral therapy to characterize cellular sources of HIV-1 in the CNS. The inability to monitor viruses directly in the brain poses a major challenge in studying HIV-1 dynamics in the CNS. Studies of HIV-1 in cerebrospinal fluid (CSF) provide a useful surrogate for the sampling of virus in the CNS, but they are complicated by the fact that infected cells in local CNS tissues and in the periphery contribute to the population pool of HIV-1 in CSF. We utilized heteroduplex tracking assays to differentiate CSF HIV-1 variants that were shared with peripheral blood plasma from those that were compartmentalized in CSF and therefore presumably derived from local CNS tissues. We then tracked the relative decline of individual viral variants during the initial days of antiretroviral therapy. We found that HIV-1 variants compartmentalized in CSF declined rapidly during therapy, with maximum half-lives of approximately 1 to 3 days. These kinetics emulate the decline in HIV-1 produced from short-lived CD4+ T cells in the periphery, suggesting that a similarly short-lived, HIV-infected cell population exists within the CNS. We propose that short-lived CD4+ T cells trafficking between the CNS and the periphery play an important role in amplifying and maintaining HIV-1 populations in the CNS during the asymptomatic phase of infection.

AIDS Dementia Complex↗

PubMed1987

Glucocorticoid-regulated compartmentalization of cell surface-associated glycoproteins in rat hepatoma cells: evidence for an independent response that requires receptor function and de novo RNA synthesis.

The role of glucocorticoid hormones in the compartmentalization of cell surface-associated mouse mammary tumor virus (MMTV) glycoproteins was examined in M1.54, a cloned line of MMTV-infected rat hepatoma tissue culture cells. The expression of cellular [2-3H]mannose-labeled and cell surface 125I-labeled MMTV glycoproteins was examined throughout a time course of exposure to dexamethasone, a synthetic glucocorticoid. Posttranslational localization of cell surface MMTV glycoproteins required 6 h of exposure to hormone and occurred approximately 4 h after their initial production in an intracellular fraction. This regulated localization to the cell surface correlated with glucocorticoid receptor occupancy and was inhibited by exposure to RU 38486, a powerful antagonist of glucocorticoid-mediated responses. Cell surface immunoprecipitation demonstrated that actinomycin D, an inhibitor of de novo RNA synthesis, prevented regulated expression of cell surface viral glycoproteins, suggesting that newly synthesized cellular components mediate this process. The localization of cell surface MMTV glycoproteins appeared normal in a transcriptional variant (CR1) that produces basal levels of MMTV RNA and glycoprotein precursors in the presence of dexamethasone. Thus, regulated compartmentalization of viral glycoproteins is not an obligate consequence of a critical precursor concentration. Taken together, our results suggest that posttranslational trafficking of cell surface-destined MMTV glycoproteins resulted from an independent glucocorticoid hormone response that required receptor function and de novo RNA synthesis.

Animals↗

PubMed2026

Longitudinal characterization of mixed-genotype SARS-CoV-2 infections in a military cohort reveals compartmentalized viral populations.

UNLABELLED: Mixed-genotype severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are a concern due to the potential generation of novel recombinants that give rise to new variants. To better understand intra-host viral dynamics, we analyzed specimens from 24 participants from the U.S. Military Health System's Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential COVID-19 cohort with suspected mixed-genotype SARS-CoV-2 infections. From an initial 24 suspected cases, we confirmed 17 as genuine coinfections and graded them by evidence: 7 were "strong"; 4 were "moderate"; 6 were "weak"; and 7 were deemed unlikely to be true mixed-genotype infections. Access to swabs from multiple body sites across the course of infection allowed us to observe compartmentalization and shifts in variant dominance that would have been missed by a single-timepoint analysis, as well as one recombinant Omicron BA.1/BA.2 genome. By using an evidence-based bioinformatic framework to assess sequencing data from well-characterized clinical cases, we distinguished genuine coinfections from bioinformatic artifacts. Our findings emphasize the importance of both extensive specimen collection and careful bioinformatic approaches in ascertaining dual genotype infections. IMPORTANCE: Novel recombinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) arise from coinfections with different lineages, but mixed infections are not screened for despite risk to public health, and most surveillance relies on single swabs. We analyzed a longitudinal data set with specimens from multiple body sites, providing an opportunity to assess intra-host dynamics. To distinguish true coinfection from bioinformatic artifacts with confidence, we applied a framework that grades evidence for mixed genotypes by incorporating lineage and clade with manually validated variant calls. This allowed investigation beyond abundance levels of mixed genotypes within a single specimen, including observations of compartmentalization and a recombinant virus. This work enables further study of evolutionary, immunological, and clinical implications of mixed SARS-CoV-2 genotypes. Detecting dual-genotype infections and discriminating between true dual-genotype infection vs potential bioinformatics-based artifacts support public health and military readiness. These efforts provide evidence to bolster decision-making in molecular epidemiological studies to track transmission and for the choice of effective countermeasures.

SARS-CoV-2↗

PubMed1994

Model-based compartmental analyses in nutrition research.

Kinetic tracer studies have been used extensively in understanding digestion, absorption, and whole-body metabolism of nutrients. Optimal interpretation of changes in tracer levels over time and movement across body pools often requires sophisticated data analysis. The use of model-based compartmental analysis (MCA) can yield more detailed quantitative and predictive information concerning system dynamics, compared with direct stochastic approaches. With MCA, tracer and tracee data from both experimental and literature values are fit to a model that best approximates the system on the basis of experimental data at hand. The number of compartments of the model is determined by the shape of the curve fit to the tracee and tracer data and by literature information. On this basis, MCA can yield information about compartment numbers and sizes, fractional and net turnover, as well as catabolic and synthetic rates. PC-based MCA programs are now available. Whereas earlier editions required use of a programming language, the most recent versions being developed are completely menu driven. Model-based compartmental analyses thus represent important biotechnological advances permitting maximal interpretation of kinetic data in nutrition research.

Animal Nutritional Physiological Phenomena↗

PubMed2001

Compartmentation of G protein-coupled signaling pathways in cardiac myocytes.

There is a large body of functional data that supports the existence of subcellular compartmentation of the components of cyclic AMP action in the heart. Data from isolated perfused hearts and from purified ventricular myocytes imply a fixed and hormone-specific spatial relationship amongst components of cyclic AMP synthesis, response, and degradation. Available data demonstrate that within a cardiac myocyte, not all cyclic AMP gains access to all cyclic AMP-dependent protein kinase (PKA), that not all PKA interacts with all possible cellular substrates of PKA, and that only a subset of the myocyte's phosphodiesterases (PDEs) may degrade cyclic AMP after a given synthetic stimulus. Molecular mechanisms contributing to compartmentation are being discovered: localization of receptors, G proteins, and adenylyl cyclases in caveolar versus noncaveolar regions of the sarcolemma; localization of PKA by A-kinase anchoring proteins; localization of PKA substrates, PDE isoforms, and phosphoprotein phosphatases in discrete subcellular regions; and differential regulation of multiple isoforms of adenylyl cyclase, phosphoprotein phosphatase, and PDE in distinct subcellular compartments.

Animals↗

PubMed2004

Dynamic contrast-enhanced CT of intracranial meningioma: comparison of distributed and compartmental tracer kinetic models--initial results.

Dynamic contrast material-enhanced computed tomographic images of intracranial meningioma were analyzed by using both distributed-parameter and conventional compartmental tracer kinetic models. The distributed-parameter models were found to yield consistently better fitting of data sets than were conventional compartmental models. Although linear correlations were found between the kinetic parameters of the two models, some of these parameters (such as perfusion and mean transit time) did not correspond quantitatively. For all models, the kinetic parameters associated with the extravasation of tracer were found to be distinctly higher in meningiomas than in normal white- and gray-matter tissues.

Contrast Media↗

PubMed2002

pH dependence and compartmentalization of zinc transported across plasma membrane of rat cortical neurons.

In this study, Zn(2+) transport in rat cortical neurons was characterized by successfully combining radioactive tracer experiments with spectrofluorometry and fluorescence microscopy. Cortical neurons showed a time-dependent and saturable transport of (65)Zn(2+) with an apparent affinity of 15-20 microM. (65)Zn(2+) transport was pH dependent and was decreased by extracellular acidification and increased by intracellular acidification. Compartmentalization of newly transported Zn(2+) was assessed with the Zn(2+)-selective fluorescent dye zinquin. Resting cortical neurons showed uniform punctate labeling that was found in cell processes and the soma, suggesting extrasynaptic compartmentalization of Zn(2+). Depletion of intracellular Zn(2+) with the membrane-permeant chelator N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN) resulted in the complete loss of punctate zinquin labeling. After Zn(2+) depletion, punctate zinquin labeling was rapidly restored when cells were placed in 30 microM Zn(2+), pH 7.4. However, rapid restoration of punctate zinquin labeling was not observed when cells were placed in 30 microM Zn(2+), pH 6.0. These data were confirmed in parallel (65)Zn(2+) transport experiments.

Animals↗

PubMed1989

A compartmental model to quantitate in vivo glucose transport in the human forearm.

Glucose transport is a critical step in the control of glucose disposal that, until presently, has not been quantitated in vivo in humans. We have employed the perfused forearm and euglycemic insulin-clamp techniques in combination with a dual-tracer injection to measure basal and insulin-mediated glucose transport in six normal subjects. L-[3H]glucose, which is not transported, was used to trace extracellular glucose kinetics; 3-O-[14C]-methyl-D-glucose, transportable but not metabolizable, was used to monitor glucose movement across the cell membrane. After bolus intra-arterial injection of the two tracers, plasma samples were obtained every 15-30 s for 10 min from a deep forearm vein to determine the washout curves. A linear compartmental model was developed that accounts for blood flow heterogeneity. It consists of three parallel, two-compartment chains merging into the sampling compartment to which cellular compartments are appended. A priori identifiability analysis was performed. The uniquely identifiable parameterization includes the transport rate constants of glucose into and out of the cell. The model was identified using nonlinear least-squares parameter estimation. Transport parameters are estimated with very good precision, and their reproducibility is satisfactory. The model also allows the estimation of the mean arteriovenous transit times of both the extracellular and the transported tracer. The compartmental model provides a novel approach to investigate glucose transport in vivo in humans.

3-O-Methylglucose↗