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PubMed1983

Lacrimal scintigraphy. I. Compartmental analysis of data.

Linear compartmental analysis was applied to lacrimal scintigraphy data from asymptomatic and obstructed lacrimal systems. Failure to achieve satisfactory results in most of the asymptomatic systems studied suggests that variable tear flow is a feature of normal lacrimal drainage which precludes linear analysis. However, in cases where the analysis was successful the results were consistent with the occurrence of reflux between the conjunctival and lacrimal sacs, and between the lacrimal sac and nasolacrimal duct. Further support for the existence of reflux between compartments was provided by the analysis of obstructed systems, particularly those with obstruction at the upper end of the nasolacrimal duct. In such cases there was rapid equilibrium of the tracer between the conjunctival and lacrimal sacs, which in the absence of tear flow could be explained by reflux between these 2 compartments.

Computers↗
PubMed2005

Subnuclear compartmentalization of sequence-specific transcription factors and regulation of eukaryotic gene expression.

To date, the majority of the research regarding eukaryotic transcription factors has focused on characterizing their function primarily through in vitro methods. These studies have revealed that transcription factors are essentially modular structures, containing separate regions that participate in such activities as DNA binding, protein-protein interaction, and transcriptional activation or repression. To fully comprehend the behavior of a given transcription factor, however, these domains must be analyzed in the context of the entire protein, and in certain cases the context of a multiprotein complex. Furthermore, it must be appreciated that transcription factors function in the nucleus, where they must contend with a variety of factors, including the nuclear architecture, chromatin domains, chromosome territories, and cell-cycle-associated processes. Recent examinations of transcription factors in the nucleus have clarified the behavior of these proteins in vivo and have increased our understanding of how gene expression is regulated in eukaryotes. Here, we review the current knowledge regarding sequence-specific transcription factor compartmentalization within the nucleus and discuss its impact on the regulation of such processes as activation or repression of gene expression and interaction with coregulatory factors.

Animals↗
PubMed1976

A compartmental model for bilirubin kinetics in isolated perfused rat liver.

Bilirubin kinetics were studied in an isolated, perfused rat liver system using unconjugated (14C) bilirubin (UC(14C)B) and delta-amino (4-14 C) levulinic acid (A(14 C)LA) to derive a suitable compartmental model. Plasma disappearance of UC(14C)B, plasma appearance of conjugated (14c) bilirubin (C(14C)B) and biliary excretion of C(14C)B were followed for 90-120 min following injection of UC(14C)B. Hepatic content of labeled bilirubin 12 min after the injection of UC(14C)B was determined directly in five separate perfusion experiments. UCB was found to reflux back to plasma from liver in two experiments using A(14C)LA. Bilirubin binding to red blood cells (6-8% of the perfusate level) and the components of the perfusion apparatus (4-6% of perfusate level) was estimated by performing a control experiment without the liver. A six compartment model was necessary and adequate to explain the experimental data and current knowledge of bilirubin metabolism: (1) UCB bound to red blood cells and the perfusion apparatus, (2) plasma UCB, (3) liver UCB, (4) liver CB, (5) plasma CB, and (6) bile CB. The proposed model could serve as a reference point for studies of bilirubin kinetics in whole animals for normal and abnormal states.

Aminolevulinic Acid↗
PubMed1987

Compartmental vascular changes in dogs after nephrectomy, DOCA, and saline: effect of nifedipine.

Hypertension (mean arterial pressure, (MAP) 131 +/- 3 mmHg) developed in 18 dogs 4 weeks after left nephrectomy, deoxycorticosterone acetate (DOCA), 5 mg/kg sc twice weekly), and 0.5% NaCl drinking solution. This can be compared with MAP (95 +/- 7 mmHg) of 13 dogs with nephrectomy alone and MAP (86 +/- 4 mmHg) of dogs without nephrectomy. The two-compartment model of the circulation revealed no differences in systemic vascular compliance, compartmental compliance, or flow distribution to the compartments. However, the time constant for venous return for the compartment with the rapid time constant was increased from 0.05 +/- 0.004 min in control animals to 0.07 +/- 0.006 min in the nephrectomy alone group and 0.09 +/- 0.008 min in the hypertensive group (p less than 0.001), as a result of an increase in venous resistance. Arteriolar resistance in this compartment was also increased in the hypertensive animals, as was the mean circulatory filling pressure and overall resistance to venous return. Nifedipine (0.025-0.05 mg/kg) reduced MAP by 15% in the nephrectomy alone group and by 22% in the hypertensive group, with reduction in arteriolar resistance only in the fast time constant compartment. In the slow time constant compartment, arteriolar resistance was increased by more than 100% and flow decreased by more than 50% after nifedipine. Unilateral nephrectomy, DOCA, plus NaCl resulted in hypertension by increasing arteriolar resistance in a vascular compartment with a fast time constant for venous return. Nifedipine countered this effect by inducing arteriolar vasodilation in this compartment. In addition, nifedipine reduced the mean circulatory filling pressure and overall resistance to venous return.

Animals↗
PubMed1996

COMPARTMENTATION OF PROTEINS IN THE ENDOMEMBRANE SYSTEM OF PLANT CELLS.

This review focuses on four interrelated processes in the plant endomembrane system: compartmentation of proteins in subdomains of the endoplasmic reticulum, mechanisms that determine whether storage proteins are retained within the ER lumen or transported out, the origin and function of biochemically distinct vacuoles or prevacuolar organelles, and the cellular processes by which proteins are sorted to vacuolar compartments. We postulate that ER-localized protein bodies are formed by a series of orderly events of protein synthesis, protein concentration, and protein assembly in subdomains of the ER. Protein concentration, which facilitates protein-to-protein interactions and subsequent protein assembly, may be achieved by the interactions with chaperones and by the localization of storage protein mRNAs. We also describe recent developments on the coexistence of two biochemically distinguishable vacuolar compartments, the possible direct role of the ER in vacuole biogenesis, and proposed mechanisms for transport of proteins from the ER or Golgi apparatus to the vacuole.

Journal Article↗
PubMed2006

Nuclear and mitochondrial compartmentation of oxidative stress and redox signaling.

New methods to measure thiol oxidation show that redox compartmentation functions as a mechanism for specificity in redox signaling and oxidative stress. Redox Western analysis and redox-sensitive green fluorescent proteins provide means to quantify thiol/disulfide redox changes in specific subcellular compartments. Analyses using these techniques show that the relative redox states from most reducing to most oxidizing are mitochondria > nuclei > cytoplasm > endoplasmic reticulum > extracellular space. Mitochondrial thiols are an important target of oxidant-induced apoptosis and necrosis and are especially vulnerable to oxidation because of the relatively alkaline pH. Maintenance of a relatively reduced nuclear redox state is critical for transcription factor binding in transcriptional activation in response to oxidative stress. The new methods are applicable to a broad range of experimental systems and their use will provide improved understanding of the pharmacologic and toxicologic actions of drugs and toxicants.

Animals↗
PubMed1975

Compartmental evaluation of osteoarthritis of the knee. A comparative study of available diagnostic modalities.

The distribution and severity of osteoarthritis were investigated in 56 knees by history and physical examination, assessment of knee function, radiography with and without weight-bearing, double-contrast arthrography, and 99mTc-polyphosphate bone imaging. Compartmental involvement (medial, lateral, patellofemoral) was graded independently by 2 or 3 observers for each modality and was correlated with that observed during arthroscopy or direct surgical inspection. The more involved compartments were graded abnormal by all methods. In the less involved compartments, the gamma camera image was most sensitive to pathology, followed by arthrography. The choice of surgical technique and the prognosis depend upon accurate preoperative knowledge of the extent of disease.

Adult↗
PubMed1999

Regional blood flow, capillary permeability, and compartmental volumes: measurement with dynamic CT--initial experience.

Sequential computed tomographic scanning was performed in patients with neck tumors after contrast material administration. For data analysis, a pharmacokinetic two-compartment model was employed that takes into account both capillary blood supply and bidirectional diffusion of the contrast agent across the capillary wall. This approach offers the possibility to quantitatively characterize tissue microcirculation with regional blood flow, capillary permeability, and relative compartmental volumes.

Blood Volume↗
PubMed2005

Three-dimensional compartmentalization of myosin heavy chain and myosin light chain isoforms in dog thyroarytenoid muscle.

The thyroarytenoid muscle, a vocal fold adductor, has important roles in airway protection (e.g., prevention of aspiration) and phonation. Isoform expression of myosin heavy chain (MHC), a major determinant of muscle-shortening velocity, has been reported to be heterogeneous in this muscle in several mammals, differing markedly between the medial and lateral divisions. The objective was to determine the isoform expression patterns of both MHC and myosin light chain (MLC), with the latter having a modulatory role in determining shortening velocity, to further test whether the expression of both myosin subunits differs in multiple specific sites within the divisions of the dog thyroarytenoid muscle, potentially revealing even greater compartmentalization in this muscle. Our results indicate the existence of large gradients in the relative levels of individual MHC isoforms in the craniocaudal axis along the medial layer (i.e., airflow axis), where levels of MHC-I and MHC-IIA are low at both ends of the axis and high in the middle and MHC-IIB has a reciprocal distribution. The lateral layer is more uniform, with high levels of MHC-IIB throughout. The level of MHC-IID is relatively constant along the axis in both layers. Large differences exist in the distribution of MHC isoforms among single fibers isolated from sites along the craniocaudal axis, especially in the lateral layer. Systematic regional variations are apparent in the MLC isoform composition of single fibers as well, including some MLC isoform combinations that are not observed in dog limb muscles. Variations of MHC and MLC isoform expression in the dog thyroarytenoid muscle are greater than previously recognized and suggest an even broader range of contractile properties within this multifunctional muscle.

Animals↗
PubMed1986

Eicosonoid metabolism and beta-adrenergic mechanisms in coronary arterial smooth muscle: potential compartmentation of cAMP.

Beta-Adrenergic relaxation in bovine coronary arteries is enhanced by inhibition of eicosonoid metabolism and inhibited by its stimulation. We investigated the interaction between eicosonoid metabolism and beta-adrenergic mechanisms by studying the effect of perturbations of eicosonoid metabolism on vascular adenosine 3',5'-monophosphate (cAMP) content and the cAMP-dependent relaxation of isometric force and activation of glycogen phosphorylase. KCl (35 mM) elicited a contraction, activated phosphorylase, and slightly decreased cAMP content. Isoproterenol (10(-7) M) relaxed the KCl contraction, further increased phosphorylase activity, and increased cAMP. Neither indomethacin (5 X 10(-6) M) nor arachidonic acid (3 X 10(-5) M) affected the KCl contraction, but arachidonic acid increased both cAMP and phosphorylase activity and indomethacin decreased cAMP. Indomethacin potentiated the relaxation induced by isoproterenol but inhibited the activation of phosphorylase and had no effect on the isoproterenol-induced increase in cAMP. Arachidonic acid, on the other hand, inhibited the isoproterenol-induced relaxation but potentiated both the increases of phosphorylase activity and cAMP. Thus neither relaxation nor phosphorylase activity was related in a straightforward manner to the total cAMP content. A direct relation between cAMP, relaxation, and phosphorylase can be reconciled with the antiparallel effects of alterations of eicosonoid metabolism observed in this study by a proposed model in which the effects of cAMP are assumed to be functionally compartmentalized.

Animals↗
PubMed1989

Inositol lipid turnover and compartmentation in canine trachealis smooth muscle.

We established conditions for the study of metabolism and compartmentation of inositol phospholipids in canine trachealis muscle. Unstimulated muscle was incubated with myo-[3H]inositol for 30 min at 37 degrees C which resulted in labeling of the tissue free myo-inositol pool, whereas only a small amount of radioactivity was incorporated into inositol phospholipids or inositol phosphates. After addition of 5.5 microM carbachol, phosphatidylinositol (PI), phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP2), specific radioactivities increased exponentially, reaching apparent constant values in 180-240 min. Initial rates of increases in PI, PIP, and PIP2 specific radioactivities were 39, 32, and 66 times that measured in unstimulated muscle. Metabolic flux rates (nmol.100 nmol total lipid Pi-1.min-1) during development of force averaged 0.42 +/- 0.09 and during force maintenance averaged 0.14 +/- 0.01. Fractions of total PI, PIP, and PIP2 pools that were linked to muscarinic cholinergic activation were estimated to be 0.97, 0.85, and 0.65, respectively. Initial rates of increase in specific radioactivities and specific radioactivities during carbachol activation were similar in PI, PIP, and PIP2 fast active compartments, suggesting metabolic flux from PI to PIP to PIP2 was in near chemical equilibrium. Turnover times for PI, PIP, and PIP2 fast active compartments were estimated to be 21, 1.6, and 4.0 min, respectively.

Animals↗
PubMed2003

Regulation of vasopressin secretion by ETA and ETB receptors in compartmentalized rat hypothalamo-neurohypophysial explants.

The endothelins (ET) have been implicated in vasopressin (AVP) release in vivo and in vitro. The effects of ET in this system are complex, and the net AVP secretory response likely depends on a unique combination of ET isoform, ET receptor subtype, and neural locus. The purpose of these studies was to examine the role of ET receptor subtypes at hypothalamic vs. neurohypophysial sites on somatodendritic and neurohypophysial AVP secretion. Experiments were done in cultured explants of the hypothalamo-neurohypophysial system of Long Evans rats. Either the whole explant (standard) or only the hypothalamus or posterior pituitary (compartmentalized) was exposed to log dose increases (0.01-10 nM) of the agonists ET-1 (ET(A) selective), ET-3 (nonselective), or IRL-1620 (ET(B) selective) with or without selective ET(A) (BQ-123, 2-200 nM) or ET(B) (IRL-1038, 6-600 nM) receptor antagonism. In standard explants, ET-1 and ET-3 dose-dependently increased, whereas IRL-1620 decreased net AVP release. Hypothalamic ET(B) receptor activation increased both somatodendritic and neurohypophysial AVP release. At least one intervening synapse was involved, as tetrodotoxin blocked the response. Activation of ET(A) receptors at the hypothalamic level inhibited, whereas ET(A) receptor activation at the posterior pituitary stimulated, neurohypophysial AVP secretion. Antagonism of hypothalamic ET(A) receptors potentiated the stimulatory effect of ET-1 and ET-3 on neurohypophysial secretion, an effect not observed with ET(B) receptor-induced somatodendritic release of AVP. Thus the response of whole explants reflects the net result of both stimulatory and inhibitory inputs. The integration of these excitatory and inhibitory inputs endows the vasopressinergic system with greater plasticity in its response to physiological and pathophysiological states.

Animals↗
PubMed1985

Use of residence time moments in compartmental analysis.

Residence time moments, particularly mean residence times, can be very useful in the modeling and kinetic analysis of physiological systems. They are defined and illustrated, and their practical utility is then explored by comparing the model formulation based on these moments with three alternative formulations: component half-lives, compartmental model rate coefficients, and multiexponential model coefficients and exponents. The residence time moment formulation is shown to have several advantages: a smaller number of parameters are usually needed to describe a biological system; they have a clear physical interpretation; their statistical "power" to detect certain treatment differences is greater; and they are computationally simpler in many situations.

Animals↗
PubMed1991

Kinetics of copper metabolism in rats: a compartmental model.

Model-based compartmental analysis was used to describe data on the whole body kinetics of copper metabolism in rats. Data were collected on recovery of radio-copper in plasma, liver, skin, skeletal muscle, bile, and feces for 3 days after the injection of 10 micrograms iv of copper labeled with 64Cu. Data on copper masses and on 64Cu kinetics were analyzed by the stimulation, analysis, and modeling computer programs. Observed data were fit to a 16-component "working hypothesis" model; fractional transfer coefficients were estimated, and steady-state compartment masses and copper transfer rates were calculated. The model postulates a rapid turnover of plasma nonceruloplasmin (NCp) copper (8.5 h-1), which exchanged a large amount of copper with extrahepatic tissues (16 micrograms/h) as well as liver (13 micrograms/h). In comparison, ceruloplasmin (Cp) transferred relatively little copper to tissues (less than 1 microgram/h). NCp copper is postulated to be the precursor for biliary copper. Regarding the intracellular metabolism of copper in hepatic and extrahepatic tissues, the data were compatible with a faster turning-over compartment that exchanged copper with NCp and a slower turning-over compartment with input from Cp. In the liver, the slower turning-over compartment was the copper present in peak II (mol mass 30,000-40,000 Da); this received much of its input from the faster turning-over compartment (peak III), which was hypothesized to represent, in large part, copper in metallothionein.

Animals↗
PubMed1994

A compartmental model of zinc metabolism in adult men used to study effects of three levels of dietary copper.

The effect of dietary copper level on zinc metabolism in five healthy adult men was studied using compartmental modeling. The subjects were fed one level of dietary zinc (11.2 +/- 1.6 mg/day) and three levels of dietary copper (1.68, 0.785, and 7.52 mg/day). The stable isotope tracers 70Zn and 67Zn were administered intravenously (3 times) and orally (4 times), respectively. Plasma, urinary, and fecal 67Zn and 70Zn levels were measured. An existing model of zinc metabolism was used as a basis for our model. Model rate constants were modified to simulate multiple oral and intravenous doses of stable isotope tracers given during the 90-day study. Most rate constant changes occurred in the absorption and excretion pathways. The model predicted that movement of zinc through the gastrointestinal tract increased when the highest level of copper was fed and the urinary zinc excretion rate tended to increase. The fractional rate constant representing absorption of zinc decreased slightly when the highest level of copper was fed. Total body zinc was predicted to be approximately 2,000 mg, with 95% in tissues other than the liver, red blood cells, or plasma and approximately 2.25% in the blood (with 95% of that in the red blood cells), which follows expected zinc masses within the body and those predicted by previous models.

Adult↗
PubMed1995

A compartmental model of 3-methylhistidine metabolism in humans.

Urinary 3-methylhistidine (3MH) excretion has been proposed as a noninvasive in vivo marker of muscle protein breakdown, but such analysis requires quantitative collection of urine and yields few details about the metabolism of 3MH. In this study, we propose that data from a single bolus dose of tracer and serial blood samples over 72 h can be described by a kinetic model that defines 3MH metabolism in humans. Plasma concentration of the tracer was described by a linear time-invariant three-compartment model. The model defines masses and fluxes of 3MH within the subjects and, in particular, the intracellular de novo production of 3MH. The de novo production of 3MH as calculated by the model was not different from that calculated via the traditional collection of urinary 3MH (3.09 vs 2.57 mumol.kg-1.day-1, respectively; P > 0.30). These data indicate that 3MH production can be measured by a compartmental model that can be used to measure muscle proteolysis without quantitative urine collections.

Adult↗
PubMed1996

Compartmentalization of protein traffic in insulin-sensitive cells.

Insulin-sensitive cells, adipocytes and myocytes, translocate a number of intracellular proteins to the cell surface in response to insulin. Among these proteins are glucose transporters 1 and 4 (GLUT-1 and GLUT-4, respectively), receptors for insulin-like growth factor II (IGF-II)/mannose 6-phosphate (Man-6-P) and transferrin, the aminopeptidase gp 160, caveolin, and a few others. In the case of insulin-activated glucose transport, this translocation has been proven to be the major, if not the only regulatory mechanism of this process. It seems likely that the cell surface recruitment of the IGF-II/Man-6-P and transferrin receptors also serves the nutritional needs of cells, whereas the physiological role of the aminopeptidase gp160 remains uncertain. Analysis of the compartmentalization and trafficking pathways of translocatable proteins in fat cells identified more than one population of recycling vesicles, although all have identical sedimentation coefficients and buoyant densities in vitro. GLUT-4-containing vesicles include essentially all the intracellular GLUT-4, gp160, and the acutely recycling populations of receptors for IGF-II/Man-6-P and transferrin. Besides these proteins, which can be considered as vesicle "cargo", GLUT-4-containing vesicles have other components, like secretory carrier-associated membrane proteins (SCAMP), Rab(s), and vesicle-associated membrane protein (VAMP)/cellubrevin, which are ubiquitous to secretory vesicles and granules from different tissues. GLUT-1 and caveolin are excluded from GLUT-4-containing vesicles and form different vesicular populations of unknown polypeptide composition. In skeletal muscle, two independent populations of GLUT-4-containing vesicles are found, insulin sensitive and exercise sensitive, which explains the additive effect of insulin and exercise on glucose uptake. Both vesicular populations are similar to each other and to analogous vesicles in fat cells.

Adipocytes↗
PubMed1997

Glucose kinetics in interstitial fluid can be predicted by compartmental modeling.

The purposes of this study were to define in sheep a compartmental model for glucose kinetics in the basal condition and to test the hypothesis that interstitial fluid obtained by sampling thoracic duct lymph (TDL) represents one or more peripheral compartments of the glucose model. A bolus of [6,6-(2)H]glucose was injected in nine animals, followed by frequent sampling of blood and TDL. Linear kinetic modeling has been applied to plasma data, indicating that a three-compartment model adequately describes glucose kinetics. Both catenary and mammillary models were identified, and their predictions for the tracer behavior in nonaccessible pools were evaluated. In all experiments, regardless of the model structure, predictions in the compartment most rapidly exchanging with blood (pool 2) well matched the measured tracer-to-tracee ratio in TDL. Furthermore, modeling analysis showed that 90-95% of the tracer in TDL comes from this pool. This supported the physiological identification of a peripheral pool of glucose kinetics as extracellular fluid represented by TDL measurements.

Animals↗