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PubMed1987

The compartmental IgM and IgA response within the central nervous system.

The diagnostic value of the locally synthesized IgA and IgM fractions in cerebrospinal fluid is described. The differentiation of the CSF immunoglobulins was performed with the help of a diagram that had been established on empirical grounds. Immunoglobulin G generally dominates the humoral immune response within the central nervous system, but in some diseases a comparatively strong participation of the other immunoglobulins was found: IgA in purulent meningitis and neurotuberculosis, IgM in tick-borne early summer meningoencephalitis. In meningopolyneuritis Bannwarth and mumps meningoencephalitis a broad three class response was found. The diagnostic significance of these findings is independent of the disease stage, since the compartmental immune response lacks the Nossal-Switch from IgM- to IgG- antibodies.

Central Nervous System↗
PubMed1995

Estrogen effects on blood amino acid compartmentation.

The present paper focuses on the study of blood amino acid compartmentation in healthy men (lean and obese) and women, with special emphasis on the estimation of the recently described blood-cell adsorbed amino acid pool. The wide range of changes found in this pool on comparing different physiological situations may be attributable to its proposed characteristic high dynamism on the one hand, but also to the influence of other factors such as hormones. Along these lines, the sex- and obesity-linked variations found here in human blood led to the speculation as to whether these differences could be related to the influence of estrogens. This hypothesis was further tested by chronically treating a group of male rats with estrone and checking their subsequent blood amino acid compartment changes (which yielded a greater difference in the adsorbed pool). From the overall results obtained it may be concluded that the higher production of estrogens in women and obese men affects amino acid availability to the tissues by modulating the blood-cell adsorbed amino acid pool through a mechanism that is, at present, unknown.

Adult↗
PubMed1989

Parameter space boundaries for unidentifiable compartmental models.

Methods for dealing with unidentifiable compartmental models are first reviewed, emphasizing the parameter interval analysis and exhaustive modeling approaches. More general methods are presented for generating the set of all nonnegative parameter solutions that localize the parameters within bounded regions of parameter space and extend previously published parameter bounding strategies. Each point of these regions is an equivalent solution of the parameter identification problem. If a point on the boundary is selected, at least one of the parameters vanishes and an equivalent submodel is obtained. This property shows the close relationship between the exhaustive modeling and parameter interval analysis approaches.

Mathematics↗
PubMed1989

A methodology for compartmental model indistinguishability.

The problem of constructing all minimal compartmental models that are indistinguishable through input-output knowledge alone from some given model is examined. The main tool in this analysis is a set of geometric properties that can be deduced from input-output knowledge and hence must be equally true in any two indistinguishable models. These properties, together with preservation of the form of the model's transfer function(s), provide an effective means for producing a set of candidate models for indistinguishability.

Mathematics↗
PubMed1991

The dynamics of gene amplification described as a multitype compartmental model and as a branching process.

The present work is aimed at developing the mathematical tools by which the dynamics of gene amplification (GA) can be described in detail. Some discrete compartmental models of GA by disproportionate replication and a general model for other putative GA mechanisms are presented and analyzed. The dynamical distribution of gene copy number in the cell population is calculated with the loss of cells taken either as constant or as copy-number-dependent. Our analysis shows that for a one-copy GA process with constant loss of cells, the relative frequency of single-gene-copy cells (sensitive cells) converges to zero, with the rate of convergence depending on the amplification probability. In contrast, for a one-copy GA process with copy-number-dependent loss of cells, the relative frequency of single-copy cells is bounded, implying a bounded compartment of many-gene-copy cells. Using branching processes theory we calculate the dynamical distribution of the single-gene-copy compartment as well as its extinction probability. Our models are used for estimating treatment prognosis as affected by drug resistance due to GA, showing significant differences in prognosis resulting from small changes in drug dose.

Animals↗
PubMed1992

Decomposition-based qualitative experiment design algorithms for a class of compartmental models.

Qualitative experiment design, to determine experimental input/output configurations that provide identifiability for specific parameters of interest, can be extremely difficult if the number of unknown parameters and the number of compartments are relatively large. However, the problem can be considerably simplified if the parameters can be divided into several groups for separate identification and the model can be decomposed into smaller submodels for separate experiment design. Model decomposition-based experiment design algorithms are proposed for a practical class of large-scale compartmental models representative of biosystems characterized by multiple input sources and unidirectional interconnectivity among subsystems. The model parameters are divided into three types, each of which is identified consecutively, in three stages, using simpler submodel experiment designs. Several practical examples are presented. Necessary and sufficient conditions for identifiability using the algorithm are also discussed.

Algorithms↗
PubMed1995

Describing the spread of biological populations using stochastic compartmental models with births.

This paper derives new models for describing the spread of biological populations in space and time from classical birth-death-migration processes. The spatial aspect is incorporated using compartmental analysis and is developed for two spatial areas (or compartments). The exact bivariate distributions for such processes are intractable; hence approximating distributions are constructed by matching cumulants. A basic Markovian model with exponential waiting times between births is investigated first. The individual effects of swarming, multiple births, and Erlang distributed waiting times, all of which enhance the biological realism, are investigated. A full model which includes all of these effects is then studied. The models are illustrated with observed data on the spread of the Africanized honey bee in French Guiana. A full model with swarming, with an average of 2.64 colonies per swarming episode, and with waiting times following an Erlang distribution with shape parameter 5 is found to provide the best description of the observed data. The methodology is very general and should have broad application for other biological population models involving dispersal and growth.

Africa↗
PubMed1994

Indistinguishability for a class of nonlinear compartmental models.

Indistinguishability, as applied to nonlinear compartmental models, is analyzed by means of the local state isomorphism theorem. The method of analysis involves the determination of all local, diffeomorphic transformations connecting the state variables of two models. This is then applied to two two-compartment models, in the first instance with linear eliminations, and then with the addition of eliminations with Michaelis-Menten kinetics. In the nonlinear example, the state transformation turns out to be linear or possibly affine. It is found that the nonlinear analysis could be eased by splitting the state isomorphism equations into those of the initial linear models together with extra equations due to the nonlinearities.

Kinetics↗
PubMed1981

Compartmental body composition of cancer patients by measurement of total body nitrogen, potassium, and water.

Quantitative measurement was made of body composition in patients with several forms of neoplastic disease. Total body nitrogen was determined by means of the prompt gamma neutron activation technique; total body potassium was measured with the use of a whole body counter. The mass and protein content of the muscle compartment and nonmuscle lean tissue were estimated by application of the technique of compartmental analysis. Total body water, determined simultaneously with the use of tritium label, provided a measure of lean body mass. From these data, the body fat can be inferred. The prompt gamma neutron activation and whole body counting techniques represent a considerable advance over the balance and radioisotope techniques used in earlier studies. The new techniques make possible sequential studies over prolonged periods of time with a considerable degree of accuracy. The loss of body weight by patients with solid tumors consisted primarily of the loss of muscle mass and body fat. Even in severe wasting, the patients appear to retain significant amounts of body fat. It is the skeletal muscle which is predominantly lost; the visceral life-supporting system is, to a considerable extent, spared. The nonmuscle tissue including the visceral fraction did not change in this study, and actually appeared to increase in size when comparison was made with the normal contrast population. The loss of total body water was slight in the cancer patients studied.

Adipose Tissue↗
PubMed1982

Evidence for the vivo compartmentation of amino acids between blood cells and plasma in man with liver disease during constant infusion of L (U-14C) tyrosine.

L (U-14C) tyrosine tracer was infused at a constant rate for 8 hrs in a series of five patients with liver disease on two occasions, the first when diet consisted of intravenous glucose, and the second when aminoacids were added. Plateau labelling of both plasma and intracellular blood cell free tyrosine was obtained by 6 hr of each infusion. However, the intracellular specific activities were on average 50% lower (p less than 0.05) when diet was glucose alone, and 54% lower (p less than 0.01) when glucose and aminoacids were given. Change in diet did not significantly affect these differences. The results provide evidence for significant in-vivo compartmentation of aminoacids between plasma and blood cells in man with liver disease, and indicate that whole blood cannot be used in the conventional measurement of whole body protein.

Amino Acids↗
PubMed1993

Kinetic evidence for compartmentalization of myo-inositol in hepatocytes.

myo-Inositol uptake and conversion to phosphatidylinositol (PI) was studied in isolated rat hepatocytes. Uptake of myo-[2-3H]-inositol into the trichloroacetic acid (TCA)-soluble fraction showed no evidence of saturation, while incorporation into lipid had an apparent Km of 0.28 mmol/L for external myo-inositol. With 50 mumol/L myo-[2-3H]-inositol, approximately half of the radiolabel was found in lipid at 30 minutes. Glucose and galactose were weak inhibitors, while phlorizin at 1 mmol/L reduced uptake by 50%. Metabolic inhibitors reduced incorporation of myo-[2-3H]-inositol into lipid, but had no effect on uptake. Hepatocytes maintained myo-inositol levels of 0.4 mmol/L for 60 minutes when incubated with 50 mumol/L myo-inositol, but levels increased when incubated with 1 mmol/L myo-inositol. Efflux of label was studied in hepatocytes prelabeled for 20 minutes with myo-[2-3H]-inositol. Loss of label was initially rapid, but had slowed by 20 minutes, with much of the label remaining in the cells. Phlorizin inhibited the loss of myo-[2-3H]-inositol, while increasing myo-inositol concentration in the medium enhanced efflux. The effects of these agents on the rate of efflux was found in lipid rather than in the TCA-soluble myo-inositol fraction. These findings suggest that myo-inositol is compartmentalized within hepatocytes, with a bulk metabolically inert pool and a smaller active pool that equilibrates with extracellular myo-inositol via an energy-independent carrier-mediated mechanism, and is preferentially available for efflux or for synthesis of phosphoinositides.

Animals↗
PubMed1977

Iron metabolism and placental transfer of iron in the term rhesus monkey (Macaca mulatta): a compartmental analysis.

The kinetics of iron and the transplacental iron transport in the near-term rhesus monkey were investigated by means of injection of 59Fe(III) bound to rhesus monkey transferrin into the maternal or into the fetal circulation. The experimentally obtained 59Fe(III) bound to rhesus monkey transferrin into the maternal or into the fetal circulation. The experimentally obtained 59Fe dissappearance and appearance curves were analyzed. The analyses were based on a 5-compartmental system. Alternative models were considered but found to be inadequate. Very high maternal as well as fetal iron turnover were calculated. The daily reflux of iron in the mother and in the fetus amounted to 75% of the amount of iron cleared from the plasma compartment daily. The calculated iron transport from mother to fetus was about 1.0 mumol/day/100 g fetus. The reverse transplacental iron transport was negligible. A small placental iron pool of exchangeable iron had to be assumed. There were no clear difference in the distribution of 59Fe over the fetal organs when the tracer dose was injected into the maternal or into the fetal circulation. Only one of the experiments showed a preferential labeling of the fetal liver when the label was given to the mother, a preference which would be expected on the basis of the hypothesis of Fletcher and Suter (1969).

Animals↗
PubMed1990

Effects of acute and chronic administration of cocaine on striatal uptake, compartmentalization and release of [3H]dopamine.

The effects of acute and repetitive administration of cocaine were studied on several parameters associated with the uptake and release of [3H]dopamine ([3H]DA) in the striatum. It was found that repetitive administration of cocaine followed 7 days later by acute challenge with cocaine, produced an increase in the Vmax with no change in the affinity of the uptake carrier for either dopamine (DA) or cocaine. The intracellular compartmentalization of [3H]DA in synaptosomes was not altered by either acute or repeated treatment with cocaine. However, chronic administration of cocaine abolished the stimulatory effect that 1 microM amphetamine normally has on the efflux of [3H]DA from the fast pool in untreated synaptosomes. The K(+)-stimulated release of [3H]DA from slices of striatum was not affected by acute or chronically administered cocaine; however, chronically administered cocaine, plus acute challenge with cocaine potentiated the effect of amphetamine on the K(+)-induced release of [3H]DA. This was accompanied by a reduction of the effect of amphetamine on the spontaneous release of DA. In addition, chronically administered cocaine plus acute challenge with cocaine increased K(+)-stimulated release of [14C]acetylcholine [( 14C]ACh). These data suggest that repetitive administration of cocaine, in a regimen that elicits behavioral sensitization, alters the substrates through which amphetamine exerts its effects on the subcellular distribution and release of [3H]DA, and further, that challenge with cocaine of sensitized rats produces a compensatory increase in the uptake of [3H]DA that is correlated with increased depolarization-induced release of [14C]ACh.

Acetylcholine↗
PubMed1990

The action of notexin from tiger snake venom (Notechis scutatus scutatus) on acetylcholine release and compartmentation in synaptosomes from electric organ of Torpedo marmorata.

At rest, in the presence of calcium, notexin induced a rapid and concentration-dependent leakage of acetylcholine from nerve endings. In the presence of 20 nM notexin (5 min), synaptosomes were well-preserved structurally and they responded to addition of A23187 ionophore by a normal calcium-dependent acetylcholine release. When stimulated by high-K+ depolarization, evoked acetylcholine release was increased when notexin was present. These findings demonstrate that notexin (up to 100 nM) does not inhibit the acetylcholine release process itself. Further studies on intracellular acetylcholine compartmentation showed that, in the presence of calcium, nm concentrations of notexin were able to mobilize vesicular acetylcholine, the amount of which strongly decreased and fed the cytoplasmic compartment leading to an important redistribution of the neurotransmitter. Other metabolic studies under notexin confirmed the inhibition of the synaptosomal membrane choline transport, but failed to elicit changes in the choline acetyltransferase activity. In order to distinguish between the phospholipase A2 activity of notexin and its neurotoxic effects, we compared effects of notexin to those obtained with a non-neurotoxic pancreatic phospholipase A2. The latter exhibits similar effects but at a higher range of concentration than notexin.

Acetylcholine↗
PubMed1990

Nuclear compartmentation of glycoprotein B of human cytomegalovirus.

Maturation of glycoprotein B (gB) of human cytomegalovirus (HCMV) includes a series of sequential glycosylation steps followed by proteolytic cleavage of the precursor protein. Inhibitors of glycosylation and glycoprotein processing, including tunicamycin, monensin, and bromoconduritol, were used to define further the processing pathway of HCMV gB. The results of these studies indicated that cotranslational glycosylation and intracellular transport are essential for subsequent cleavage of the precursor; early trimming in the endoplasmic reticulum is not a prerequisite but facilitates this processing event. Analysis of purified nuclei with gB-specific monoclonal antibody suggested that the mannose-rich gB-precursor intermediate(s) is (are) compartmentalized in the nuclear fraction. Immunoelectron microscopy revealed that HCMV gB was localized in the outer as well as in the inner nuclear membranes of HCMV-infected fibroblasts.

Acetylglucosaminidase↗
PubMed1989

A compartmental model of platelet aggregation in vitro: the kinetics of single platelets.

A compartmental model of platelet aggregation which accurately describes both reversible and irreversible aggregation in vitro is presented. This model is substantiated by correlative analyses of agonist-induced aggregation as monitored by both routine aggregometry and resistive counting of single platelets. Previously unresolved differences in the reported reaction order of the aggregation process are explained. The model suggests that aggregation includes, in addition to the association and dissociation of platelets, the stabilization of aggregates. We find reversible aggregation requires that single platelets associate more rapidly than aggregates stabilize. For irreversible aggregation, our results suggest the presence of subpopulations of single platelets which associate at different rates. As an unexpected consequence of this study, quantitative relationships between photometric and resistive methods of monitoring platelet aggregation are elucidated.

Adenosine Diphosphate↗
PubMed1987

Involvement of the esterase active site of egasyn in compartmentalization of beta-glucuronidase within the endoplasmic reticulum.

Organophosphorous compounds, which are potent inhibitors of egasyn-esterase activity, caused a rapid dissociation of the high molecular weight egasyn-microsomal beta-glucuronidase complex when administered in vivo or when added in vitro to microsomal suspensions. The dissociation was relatively specific to phosphodiester inhibitors of the esterase active site. Also, the egasyn-esterase active site was inaccessible to substrates and to inhibitors when egasyn was complexed to beta-glucuronidase. Dissociation of the egasyn-microsomal beta-glucuronidase complex in vivo by organophosphorous compounds was followed by massive and rapid secretion of microsomal beta-glucuronidase, but not egasyn, into plasma. These experiments implicate the egasyn-esterase active site in attachment of microsomal beta-glucuronidase to egasyn by a novel mechanism that, in turn, compartmentalizes beta-glucuronidase within the endoplasmic reticulum.

Animals↗
PubMed1988

Compartmentalization of MHC class II gene expression in transgenic mice.

A set of transgenic mouse lines carrying Ek alpha genes with promoter region deletions was created in an attempt to compartmentalize MHC class II gene expression. Fine immunohistological analyses established that one transgenic line is essentially devoid of E complex in the thymic cortex, another displays almost no E in the thymic medulla or on peripheral macrophages, and two lines display no E on greater than 98% of B cells. We have assayed these mice for immune function: E-dependent tolerance, antigen presentation, T cell priming, and antibody response. Certain of the findings are difficult to reconcile with currently popular hypotheses, e.g., tolerance induction to E molecules in the virtual absence of E complex in the thymic medulla and efficient antibody responses to E-restricted antigens when almost all B cells are E-.

Animals↗