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Platelet splenic transit times in idiopathic thrombocytopenic purpura. Compartmental vs. non-compartmental model.

Platelet splenic transit times following injection of autologous or homologous 111In-labeled platelets were studied in 42 patients with idiopathic thrombocytopenic purpura. The transit times were determined by two methods from the splenic time-activity curves recorded with a gamma camera: closed two-compartmental model and non-compartmental model (deconvolution analysis). By compartmental analysis the mean splenic transit time for platelets was 6.3 +/- 0.3 min (mean +/- S.E.) and by non-compartmental analysis 7.6 +/- 0.4 min for all cases studied. The mean splenic transit time for autologous platelets was significantly (p less than 0.001) shorter (5.1 +/- 0.3 min) in patients with platelet-associated IgG (measured by platelet suspension immunofluorescence test) than in those with no autoantibodies (7.1 +/- 0.4 min), when the compartmental model was employed. There was no significant difference between mean transit times for autologous platelets in antibody positive and negative patients when deconvolution analysis was applied, but the residue of the splenic transfer function was lower for antibody positive than negative patients (7.2 +/- 1.0% vs. 11.7 +/- 1.6%, p less than 0.05). It is concluded that in idiopathic thrombocytopenic purpura the presence of platelet-associated autoantibodies expands the splenic platelet pool and reduces recirculation of platelets.

Adolescent

Compartmentation of intracellular nucleotides in mammalian cells.

The important role of nucleotides in cellular metabolism requires that serious consideration be given to the question of the homogeneity or inhomogeneity of nucleotide pools in cells. The purpose of this review is to summarize the existing evidence for compartmentation of nucleotide pools, discuss the limitations of this evidence, and to discuss the implications of compartmentation for the interpretation of nucleotide concentration measurements. Evidence for nucleotide compartmentation comes from the following types of evidence: compartmentation of RNA precursors; compartmentation of deoxynucleoside triphosphates; mitochondrial compartmentation; the existence of tightly bound nucleotides; pools derived from alternative synthetic routes; compartmentation in cyclic nucleotide metabolism; channeling in the synthesis of pyrimidine nucleotides; and others. The types of evidence adduced for compartmentation will be considered critically and in detail, and alternative explanations considered, as well. Implications of the data and hypotheses on nucleotide compartmentation for the interpretation of nucleotide pool measurements in various types of experiments will be discussed.

Animals

Intracellular compartmentalization of potassium.

The evidence that there is intracellular compartmentalization of potassium is indirect but diverse. Intracellular electrode measurement of potassium activity, 42K radioisotope studies, and more recently 39K nuclear magnetic resonance (NMR) all support such compartmentalization. The use of rubidium to apparently shift potassium between sites with different NMR characteristics (visibility) is strong evidence for such compartmentalization. The evidence that intracellular compartmentalization of potassium is of (patho) physiological significance is also indirect. Postulated roles for regulation of intracellular K+ activity, perhaps by control of compartmentalization, include enzyme activity, protein synthesis, and cell growth. There is also evidence that compartmentalization of potassium may contribute to the maintenance of a stable intracellular environment following potassium loading. The apparent magnetic field dependence of the visibility of K+ by 39K NMR offers the opportunity to explore further the phenomenon of compartmentalization.

Animals

Diagnostic value of computerized exercise testing in men without previous myocardial infarction. A multivariate, compartmental and probabilistic approach.

The value of exercise testing for the diagnosis of coronary artery disease is disputed but very few studies have taken advantage of all recent improvements, namely computer averaging of the ECG signals, multivariate analysis of the data, a compartmental diagnostic approach and probabilistic interpretation of the results. These methods were tested in a group of 387 men who had a computer-assisted multistage maximal exercise test; none had a history of myocardial infarction. In 284 symptomatic patients, the diagnosis was made by arteriography; 103 ostensibly healthy men were also included. The computer-averaged ECG signals (X, Y, Z) recorded at maximal exercise, maximal heart rate, blood pressure and workload, and the onset of angina pectoris during exercise were submitted to a multivariate stepwise discriminant analysis. The pretest likelihood for CAD was calculated from age and history; the post-test likelihood was calculated from Bayes' theorem and the average information content of several diagnostic methods was assessed in categorical and compartmental models. By multivariate analysis, 5 variables collected at maximal exercise were selected, namely the heart-rate, the ST60 segment level, the onset of angina during the test, the workload and the slope of the ST segment in lead X. The average information content of the analysis using 5 variables was 44% in a categorical model versus 55% in a compartmental model (P less than 0.001). For comparison, the information content of the analysis using the ST60 segment level alone was only 16% in the categorical model and 27% in the compartmental model. The clinical value of these diagnostic methods (categorical versus compartmental, univariate versus multivariate) was assessed by a probabilistic classification of the patients. The classification provided by the analysis of the ST60 segment changes was barely better than that one provided by the simple history. The probabilistic use of a multivariate and compartmental analysis of the data led to a significantly better and more accurate classification of the patients (83% of correct classification).

Adult

Network thermodynamic approach compartmental analysis. Na+ transients in frog skin.

We introduce a general network thermodynamic method for compartmental analysis which uses a compartmental model of sodium flows through frog skin as an illustrative example (Huf and Howell, 1974a). We use network thermodynamics (Mikulecky et al., 1977b) to formulate the problem, and a circuit simulation program (ASTEC 2, SPICE2, or PCAP) for computation. In this way, the compartment concentrations and net fluxes between compartments are readily obtained for a set of experimental conditions involving a square-wave pulse of labeled sodium at the outer surface of the skin. Qualitative features of the influx at the outer surface correlate very well with those observed for the short circuit current under another similar set of conditions by Morel and LeBlanc (1975). In related work, the compartmental model is used as a basis for simulation of the short circuit current and sodium flows simultaneously using a two-port network (Mikulecky et al., 1977a, and Mikulecky et al., A network thermodynamic model for short circuit current transients in frog skin. Manuscript in preparation; Gary-Bobo et al., 1978). The network approach lends itself to computation of classic compartmental problems in a simple manner using circuit simulation programs (Chua and Lin, 1975), and it further extends the compartmental models to more complicated situations involving coupled flows and non-linearities such as concentration dependencies, chemical reaction kinetics, etc.

Animals

Relationship of the axonal and dendritic geometry of spiny projection neurons to the compartmental organization of the neostriatum.

Intracellular injection of HRP combined with immunocytochemistry for [Leu]enkephalin was used to demonstrate striatal spiny neuron dendritic and local axonal arborizations in the same section as enkephalin-rich patches (striosomes). Cobalt intensification of the first DAB reaction prior to the immunoperoxidase steps resulted in good contrast between the black reaction product in the intracellularly labeled cells and the brown staining for [Leu]enkephalin. Serial reconstructions of the labeled cells and nearby boundaries between the enkephalin-rich striosomes and enkephalin-poor matrix allowed the relationship between the arborizations of the labeled cells and these boundaries to be established. It was also possible to examine the relationship to compartmental boundaries of a second neuronal class consisting of large, pallidallike neurons whose somatodendritic morphology was outlined by immunoperoxidase-labeled terminals. We found that spiny projection neurons in both compartments have dendritic arbors and local axonal collaterals that are confined by compartmental boundaries. The termination or recurvature of dendrites at such boundaries suggests that the cellular basis of striatal compartmental organization is provided by this class of striatal neuron. On the other hand, large pallidumlike striatal neurons were found to have dendrites that extend across compartmental boundaries. These results support previous reports that striatal spiny projection neurons preserve the compartmental segregation of parallel striatal input-output systems, whereas other classes of striatal neurons may serve to provide limited integration between compartments.

Animals

Compartmentalization of positive and negative self-knowledge: keeping bad apples out of the bunch.

Three studies examined whether categorical organization of knowledge about the self explains variance in self-esteem and depression beyond that which is accounted for by sheer amount of positive or negative content. Compartmentalization is the tendency to organize positive and negative knowledge about the self into separate, uniformly valenced categories (self-aspects). As long as positive self-aspects are activated, access to negative information should be minimized. Compartmentalization was associated with high self-esteem and low depression scores for individuals whose positive self-aspects were important; when negative self-aspects were important, compartmentalization was correlated with low self-esteem and high depression scores. An analysis of self-aspect labels showed that individuals with compartmentalized organization define negative self-aspects in especially narrow terms. A possible relationship between compartmentalized organization and cognitive complexity is discussed.

Achievement

Ontogeny of the subcellular compartmentalization of thyrotropin releasing hormone and luteinizing hormone releasing hormone in the rat hypothalamus.

The 900 x g supernatant fluid prepared from hypothalamic homogenates from male and female rats (ranging in age from -1 to 120 days) was fractionated by means of continuous sucrose density gradient centrifugation. Thyrotropin releasing hormone (TRH) and LH releasing hormone (LHRH) in the gradient fractions were quantified by radioimmunoassay. In adult hypothalamic homogenates, TRH and LHRH were associated with two populations of particles distinguishable by their sedimentation properties. Each peptide was in turn distributed in two subpopulations of parties differing in size but similar in density. The distribution of each peptide within its subpopulations of particles was found to be a function of age. In hypothalami of 22-day-old fetuses, TRH was associated almost entirely with the subpopulation of small particles. However, in the neonates, an age-dependent increase in the fractional amount of the TRH confined to the subpopulation of large particles was observed. By the 7th day of age, the peptide was equally distributed in the two subpopulations. The buoyant density of the 1-day-old neonatal particles and that of the adult small and large particles containing TRH was similar. The ontogeny of the subcellular compartmentalization of LHRH differed appreciably from that of TRH. LHRH was barely detectable in hypothalami of 22-day-old neonates. Nevertheless, at this age, the peptide was confined primarily to the subpopulation of large particles, and a similar compartmentalization was noted in hypothalami of 5- and 7-day-old neonates. However, in hypothalami of 14-day-old males and 21-day-old females, association of LHRH with the subpopulation of small particles was evident. It is concluded that 1) the nature of the hypothalamic subcellular compartmentalization of TRH and LHRH is age dependent, 2) the compartmentalization of each peptide in neonatal hypothalami differs from that in the adults, and 3) the development of the mature profile of subcellular compartmentalization of TRH and LHRH proceeds asynchronously.

Aging

A compartmental model to analyze ruminal digestion.

In contrast to digestion models that include a discrete lag phase, a compartmental digestion model was proposed. It assumed the existence of a lag compartment and a digestion compartment. Substrate present in the digestion compartment was subject to first-order kinetics digestion. Flow of substrate from the lag compartment to the digestion compartment was proposed to be a first-order process and likely was affected by hydration of substrate, bacterial attachment, and colonization. The proposed model was compared with models that assumed the existence of a discrete lag phase. Parameter estimates for these models were obtained either through logarithmic transformation of data or nonlinear regression. Statistically, there was no difference between the compartmental model and the nonlinear model with a discrete lag phase. Differences in parameter estimates between these two models were small. Residual mean squares were higher for the logarithmically transformed models. Differences in parameter estimates between these models and the compartmental model depended on the structure of the experimental data. In a number of cases, the nonlinear parameters of the compartmental model converged to the same value, resulting in a different interpretation of the model. Residual mean squares for predicting rate of disappearance were lowest for the compartmental model.

Animals

Compartmental syndrome. An unified concept.

A compartmental syndrome is defined as a condition in which increased pressure within a space compromises the circulation to the contents of that space. Any cause of increased intracompartmental pressure may result in a compartmental syndrome. The diagnosis should be suspected in any case of pain or neuromuscular deficit in an extremity and may be confirmed by signs of circulatory disturbance of nerve and muscle in association with increased pressure in the compartment. Generous opening of any dressings covering the extremity permits a proper examination and rules out a compartmental syndrome caused by the dressing itself. Immediate decompression is indicated in all cases of compartmental syndrome unless the risk of complications exceeds the possible gains from improvement in circulation. Elevation of an extremity afflicted with a compartmental syndrome is contraindicated. Myoglobinuria and renal failure may complicate severe cases.

Anterior Compartment Syndrome

Role of compartmental resection for soft tissue sarcoma of the limb and limb girdle.

A total of 143 consecutive operations for soft tissue sarcoma of the extremity, performed by one surgeon over a 5-year period, was studied to determine the place of compartmental excision. The surgical aim was to achieve the nearest to radical surgery compatible with preservation of a functional limb. Of the operations, 73 were for previously untreated primary tumour and 70 for local recurrence. Two tumours arose in areas previously irradiated for other malignancies and 35 recurrences had occurred despite prior radiotherapy; of the 106 remaining cases, adjuvant radiotherapy was used for 79. Adjuvant chemotherapy was used only occasionally and was more often regional than systemic. For the majority of tumours, compartmentectomy was inappropriate or inadequate: 49 were extracompartmental in origin and 48 extended beyond their compartment of origin at the time of surgery. The remaining 46 were confined to one compartment; in only 21 of these 46 operations was a radical compartmental excision performed. Compartmental excision was more likely to be performed when the tumour was centrally located within a compartment, was so large that it replaced most of the muscle group, or was high grade or recurrent (particularly when adjuvant radiotherapy had already been used). The general preference was to combine less-than-radical surgery with adjuvant radiotherapy rather than sacrifice entire muscle groups or adjacent, functionally important, structures such as artery or nerve. This reflects the proven efficacy of radiotherapy in controlling microscopic disease. Overall, compartmental excision was considered appropriate in only 15 per cent of operations.

Adolescent

Functional compartmentalization of energy production in neural tissue.

Previous work in our laboratory has shown that neural trauma results in a disparity between oxidative and glycolytic rates. In non-neural tissue, glycolysis and oxidative phosphorylation have been shown to work independently of one another, a phenomenon known as "energy compartmentalization". We believe that functional compartmentalization of energy production may also occur in the brain with glycolysis providing energy for membrane bound ionic pumps. Spreading depression, induced in rodent brain by topical KCl application, results in K+ shifts. The restoration of K+ gradients is accomplished by energy dependent Na(+)-K+ pumps. If these pumps depend upon glycolysis, blocking glycolysis should prevent reconstitution of normal [K+]e levels. The present series of experiments were designed to suggest that energy compartmentalization may also exist in brain, and that glycolytic energy production is preferentially used by Na(+)-K+ pumps to maintain normal ionic homeostasis by observing the dynamics of spreading depression induced K+ shifts before and after glycolytic blockade. Spreading depression was associated with increased K+ (48.6 +/- 16.6 mM over control) that normalized within 2.9 +/- 0.3 minutes. Following superfusion with a glycolytic blocking agent, spreading depression produced similar increases in [K+]e (40.6 +/- 12.0 mM over control) but time for reconstitution of the normal [K+]e was 400% longer than controls (2.9 +/- 0.3 to 14.9 +/- 2.1 minutes, P less than 0.001). Time required for recovery of EEG was identical pre- and post-blockade. We believe these data suggest that energy compartmentalization may exist in neural tissue and that glycolytic pathways of energy production are functionally tied to membrane Na(+)-K+ pumps.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The effect of tourniquet release on intra-compartmental pressure in the bandaged and unbandaged limb.

Changes in intra-compartmental pressure in bandaged and unbandaged limbs following 90 minutes of tourniquet-induced ischaemia and subsequent tourniquet release are examined in a primate model. Bandaging raises intra-compartmental pressure. Release of the tourniquet is shown to cause a transient increase in intra-compartmental pressure of less than 30 minutes duration. This is followed by a fall in intra-compartmental pressure for up to three hours. Tourniquet release and the ensuing hyperaemia does not appear to put the limb at risk of developing a compartment syndrome.

Animals

Bi-compartmental CSF-serum analysis of NfL and GFAP differentiates central and peripheral pathology in neuroinfectious diseases: A monocentric real-world cohort study.

Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), established biomarkers of neuroaxonal injury and astroglial pathology, are frequently only assessed in blood, which limits conclusions regarding their origin. Bi-compartmental analyses of CSF and serum may help differentiate central or peripheral origin of biomarker elevation. Moreover, studies on NfL and GFAP in distinct neuroinfectious disease (NID) phenotypes, particularly those based on real-world cohorts, are limited. This retrospective monocentric study analyzed CSF and serum from patients with (meningo-)encephalitis/myelitis (TI+; n&#xa0;=&#xa0;48), meningitis (TI-; n&#xa0;=&#xa0;80), (cranial) nerve palsies/polyradiculitis (PND; n&#xa0;=&#xa0;61), and 113 non-neuroinflammatory/non-neurodegenerative controls. A bi-compartmental model using scatter plots and simple linear regression was applied to assess the origin of blood biomarker levels and discriminate between central and peripheral pathology. CSF and serum NfL and GFAP z-scores were significantly higher in TI+ compared with TI- (CSF-GFAP p&#xa0;<&#xa0;0.001/sGFAP p&#xa0;=&#xa0;0.0083; CSF-NfL p&#xa0;=&#xa0;0.003/sNfL p&#xa0;=&#xa0;0.0004). TI+ and PND differed only in GFAP levels, which were higher in TI+ (CSF-GFAP p&#xa0;=&#xa0;0.0049/sGFAP p&#xa0;=&#xa0;0.003). The overall group effect (p&#xa0;&#x2264;&#xa0;0.003) and principal findings remained significant after adjustment for age, sex, QAlb, and time since (symptom) onset to LP. Bi-compartmental analysis revealed simultaneous elevation of CSF and serum NfL in TI+, indicating predominantly central origin, whereas PND demonstrated a shift toward higher sNfL levels suggesting peripheral origin. Higher clinical severity (modified Rankin Scale 3-5) was associated with elevated serum and CSF GFAP and NfL (sGFAP p&#xa0;=&#xa0;0.012/sNfL p&#xa0;=&#xa0;0.002; CSF-GFAP p&#xa0;<&#xa0;0.0001/CSF-NfL p&#xa0;=&#xa0;0.0001), which also predicted unfavorable outcome at discharge (sGFAP p&#xa0;=&#xa0;0.006/sNfL p&#xa0;=&#xa0;0.004; CSF-GFAP p&#xa0;=&#xa0;0.003/CSF-NfL p&#xa0;=&#xa0;0.012). NfL and GFAP were associated with brain/myelon involvement in NID, predominantly reflecting central pathology. Despite strong CSF-serum correlations, bi-compartmental approaches provide additional insight into biomarker origin and disease compartment.

Humans

The organization and development of compartmentalized innervation in rat extensor digitorum longus muscle.

1. We have examined the innervation of the rat extensor digitorum longus (EDL) muscle by the two extramuscular branches formed from the bifurcation of its muscle nerve. Observations of muscle contractions, recordings of end-plate potentials, and glycogen depletion of young adult muscles show that each branch innervates a separate region or 'compartment' in the muscle. The branch entering the muscle nearer the knee (the K branch) innervates fibres in the anteromedial half of the muscle whereas the branch entering closer to the foot (the F branch) innervates fibres located posterolaterally. Individual EDL motoneurones project either into the K or the F branch and therefore innervate fibres located in one compartment. The boundary between the compartments is usually sharply delineated. No obvious anatomical feature exists within the muscle which would explain the division of the muscle into two distinct regions. 2. The presence of a segmentotopic projection from the spinal cord to the muscle was investigated to evaluate its possible contribution to the compartmental pattern. The most posterior neurones of the EDL motor pool were found to project more frequently to the posterolateral F compartment; similarly, the most anterior neurones most frequently project to the anteromedial K compartment. However, each compartment is innervated by both anteriorly and posteriorly located motoneurones. The segmentotopic projection is too weak to explain the presence of neuromuscular compartments. 3. The post-natal period of synapse elimination appears to play at best a minor role in setting up the compartmentalized innervation. Glycogen depletion and intracellular recording in 1-2-day-old muscles show that each nerve branch innervates fibres in the same region of the muscle as in the adult. Most of the fibres in each compartment are polyneuronally innervated by axons in their own particular nerve branch, although fibres located near the boundary between the two compartments are innervated by axons from both nerve branches. This convergent innervation from the two branches disappears in concert with the elimination of polyneuronal innervation throughout the muscle. A random elimination of these convergent inputs appears adequate to explain the final compartmental pattern. 4. Our findings suggest that the compartmental pattern is primarily the consequence of te segregation of EDL motoneurones into two nerve branches which are directed into separate regions of the muscle.

Animals

Compartmental distribution of ventral striatal neurons projecting to the mesencephalon in the rat.

The ventral striatum is characterized by an intricate neurochemical compartmentation that is reflected in the distribution of most of its afferent fiber systems. In the present study, the compartmental relationships of ventral striatal neurons projecting to the mesencephalon were studied by combining tract tracing with the immunohistochemical localization of leu-enkephalin. Injections of the retrograde tracer cholera toxin subunit B were placed at various sites in the ventral mesencephalon. The anterograde tracer Phaseolus vulgaris leucoagglutinin was injected in single compartments in the rostrolateral part of the nucleus accumbens. The projections from the ventral striatum to the dopaminergic cell groups in the ventral mesencephalon and those to the substantia nigra pars reticulata originate from distinct subpopulations of ventral striatal neurons that respect neurochemically defined compartmental boundaries. In the "shell" of the nucleus accumbens, neurons that project to the dopaminergic cell groups are located outside areas of high cell density and weak enkephalin immunoreactivity (ENK-IR). Rostrolaterally in the "core" of the nucleus accumbens, neurons inside large areas of strong ENK-IR surrounding the anterior commissure project to the dorsomedial part of the substantia nigra pars reticulata, whereas neurons outside these areas innervate the ventral tegmental area and/or the medial part of the substantia nigra pars compacta. By contrast, more caudally in the dorsal part of the nucleus accumbens and in the ventral part of the caudate-putamen, the relationships are reversed: neurons in- or outside small patches of strong ENK-IR project respectively to the pars compacta or the pars reticulata of the substantia nigra. Since the thalamic and cortical afferents of the ventral striatum are compartmentally ordered as well, the present results imply that through the ventral striatal compartments information from disparate combinations of cortical and thalamic sources may be conveyed to distinct mesencephalic targets. The component of the ventral striatomesencephalic system reaching the dopaminergic cell groups A10, A9, and A8 may modulate the dopaminergic input to virtually the entire striatum. The other component can, by way of the pars reticulata of the substantia nigra, participate in nigrothalamic and nigrotectal output pathways of the basal ganglia.

Animals