Interpretation of commonly employed tests of liver function and integrity.
Explore the source record for details and available documents.
Cholestasis↗
SEARCH · PubMed Health
Results for “Integrated functions”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Interneuronal relations within and between cortical areas during conditioning in cats.
Multiunit activity was chronically recorded in auditory, visual and motor cortex during classical conditioning and extinction. A statistical method for cross-correlation analysis of interneuronal relations was used. Plastic changes in cortical integrative function had spatial features and depended upon types of conditioning. Results suggest the spatial features in cortical cell integration in the trained-brain consisting of 3 categories of neuronal system organizations: microset, local and inter-regional. The first two are localized in a cortical projection region, whereas the third occupies cortical regions activated during conditioning. An evaluation of systemic activity in cortical neurons suggests specific organizations of cortical integrative functions in learning.
Animals↗
Olfactory deficits in neuroleptic naive patients with schizophrenia.
Because previous studies have shown deficits in olfactory identification for male patients with schizophrenia, either withdrawn from or receiving neuroleptic medication, the purpose of the current study was to determine if such deficits occurred in male patients who had never received neuroleptics. A sample of male (n = 30) and female (n = 10) patients as well as age appropriate controls (males, n = 28, females, n = 30) was assessed in terms of olfactory acuity and identification ability. No differences were found in olfactory acuity, but an olfactory identification deficit was present in 31% of the male patients with schizophrenia. As the olfactory pathways project through the limbic system and to the orbitofrontal cortex, odour identification may be a measure of the functional integrity of these structures. Therefore, these results suggest that for a sub-sample of male patients, the functional integrity of these structures is compromised.
Adult↗
Melatonin and cortisol serum levels in lung cancer patients at different stages of disease.
BACKGROUND: Numerous interactions exist among the nervous, endocrine, and immune systems, mediated by neurotransmitters, hormones, and cytokines. Melatonin may modulate the integrated functions of a unique neuro-immune-endocrine system. Neoplastic diseases may be linked to progressive loss of integration among these systems. We investigated whether there are differences among healthy elderly people and elderly people suffering from lung cancer at different stages of disease in 24-hour melatonin and cortisol secretory profiles. MATERIAL/METHODS: In seventeen healthy subjects (mean age +/-S.E.: 68.8+/-1.92 years), seventeen patients with stage I and II lung cancer (mean age: 67.2+/-0.80), seventeen patients with stage III and IV lung cancer (mean age: 69.5+/-2.26), melatonin and cortisol serum levels were measured in blood samples collected every four hours for 24 hours. The area under the curve (AUC) and the presence of circadian rhythmicity were evaluated. RESULTS: The circadian rhythm of melatonin was present in all the groups, but serum levels were decreased in the subjects suffering from lung cancer (P<0.05). In these patients, cortisol serum levels were increased (not in a significant way), with a loss of the circadian rhythm of secretion. The melatonin/cortisol ratio was decreased in stage III and IV cancer patients (P<0.05). CONCLUSIONS: The progressive decrease of melatonin secretion and altered cortisol secretion pattern with advancing stage of neoplastic disease may be an expression of a gradual alteration of the integrated function of the neuro-endocrine system in lung cancer patients.
Aged↗
Transmembrane domains participate in functions of integral membrane proteins.
Integral membrane proteins have one or more transmembrane alpha-helical domains and carry out a variety of functions such as enzyme catalysis, transport across membranes, transducing signals as receptors of hormones and growth factors, and energy transfer in ATP synthesis. These transmembrane domains are not mere structural units anchoring the protein to the lipid bilayer but seem to-contribute in the overall activity. Recent findings in support of this are described using some typical examples-LDL receptor, growth factor receptor tyrosine kinase, HMG-CoA reductase, F0-ATPase and adrenergic receptors. The trends in research indicate that these transmembrane domains participate in a variety of ways such as a linker, a transducer or an exchanger in the overall functions of these proteins in transfer of materials, energy and signals.
Animals↗
Site-specific integration of functional transgenes into the human genome by adeno/AAV hybrid vectors.
Uncontrolled insertion of gene transfer vectors into the human genome is raising significant safety concerns for their clinical use. The wild-type adeno-associated virus (AAV) can insert its genome at a specific site in human chromosome 19 (AAVS1) through the activity of a specific replicase/integrase protein (Rep) binding both the AAVS1 and the viral inverted terminal repeats (ITRs). AAV-derived vectors, however, do not carry the rep gene and cannot maintain site-specific integration properties. We describe a novel hybrid vector carrying an integration cassette flanked by AAV ITRs and a tightly regulated, drug-inducible Rep expression cassette in the framework of a high-capacity, helper-dependent adenoviral (Ad) vector. Rep-dependent integration of ITR-flanked cassettes of intact size and function was obtained in human primary cells and cell lines in the absence of selection. The majority of integrations were site specific and occurred within a 1000-bp region of the AAVS1. Genome-wide sequencing of integration junctions indicates that nonspecific integrations occurred predominantly in intergenic regions. Site-specific integration was obtained also in vivo, in an AAVS1 transgenic mouse model: upon a single tail vein administration of a nontoxic dose of Ad/AAV vectors, AAVS1-specific integrations were detected and sequenced in DNA obtained from the liver of all animals in which Rep expression was induced by drug treatment. Nonrandom integration of double-stranded DNA can therefore be obtained ex vivo and in vivoby the use of hybrid Ad/AAV vectors, in the absence of toxicity and with efficiency compatible with gene therapy applications.
Adenoviridae↗
The role of cellular development and cell death in neurochemical organization and integrative brain functions--normal and pathological.
In terms of systemic aspects of common molecular mechanisms of development, important part of which is the process of cellular death and integrative activity of nervous system, a complex clinical-experimental study of effects of various neurotrophic and apoptotic factors (proteins S100b, HLDF, brain lectins CSL and R1) on learning and memory and ischemic stroke was performed. Data concerning specific and heterochronic participation of these factors in neurochemical mechanisms of learning and memory in mechanisms of ischemic stroke formation were established. Changes of examined factors and their antibodies as well as the dynamics of changes in sera and cerebrospinal fluid can be considered as prognostic markers of ischemic stroke and efficiency of therapy.
Animals↗
Executive function and memory in relation to olfactory deficits in alcohol-dependent patients.
BACKGROUND: Prior research indicates that chronic alcoholism is accompanied by olfactory deficits. These have been suggested to reflect dysfunctions in olfactory brain regions. The present study investigated the role of neurocognitive functioning in tests (executive function and memory) sensitive to the functional integrity of brain areas that are crucial to olfactory processing in patients with alcohol dependence. METHODS: Performance on olfactory functions (detection threshold, quality discrimination, identification), executive function (Wisconsin Card Sorting Test), and memory (German version of the California Verbal Learning Test) was assessed in 32 alcohol-dependent patients and 30 healthy comparison subjects, comparable in age, gender, and smoking status. RESULTS: Compared with controls, alcohol-dependent patients were impaired in all 3 domains, olfactory functions, executive function, and memory. In patients, olfactory discrimination ability was positively correlated with executive function performance. Regression analyses conducted to clarify the relation between group (patients vs controls), executive function, memory, and olfactory functions indicated that group was the only significant predictor of olfactory detection threshold and identification, and both group and executive function were found to be the significant predictors of olfactory discrimination. CONCLUSIONS: Olfactory deficits in alcohol dependence appear to be associated with prefrontal cognitive dysfunction. Results indicate that olfactory quality discrimination deficits are related to executive function impairment. These findings add to the available research on frontal lobe dysfunction in alcoholism, suggesting that alcohol-related olfactory discrimination deficits may be associated with impairment in the functional integrity of the prefrontal lobe.
Adult↗
Auditory temporal integration and the power function model.
The auditory temporal integration function was studied with the objective of improving both its quantitative description and the specification of its principle independent variable, stimulus duration. In Sec. I, temporal integration data from 20 studies were subjected to uniform analyses using standardized definitions of duration and two models of temporal integration. Analyses revealed that these data were best described by a power function model used in conjunction with a definition of duration, termed assigned duration, that de-emphasized the rise/fall portions of the stimuli. There was a strong effect of stimulus frequency and, in general, the slope of the temporal integration function was less than 10 dB per decade of duration; i.e., a power function exponent less than 1.0. In Sec. II, an experimental study was performed to further evaluate the models and definitions. Detection thresholds were measured in 11 normal-hearing human subjects using a total of 24 single-burst and multiple-burst acoustic stimuli of 3.125 kHz. The issues addressed are: the quantitative description of the temporal integration function; the definition of stimulus duration; the similarity of the integration processes for single-burst and multiple-burst stimuli; and the contribution of rise/fall time to the integration process. A power function in conjunction with the assigned duration definition was again most effective in describing the data. Single- and multiple-burst stimuli both seemed to be integrated by the same central mechanism, with data for each type of stimulus being described by a power function exponent of approximately 0.6 at 3.125 kHz. It was concluded that the contribution of the rise/fall portions of the stimuli can be factored out from the rest of the temporal integration process. In Sec. III, the conclusions that emerged from the review of published work and the present experimental work suggested that auditory temporal integration is best described by a power function in conjunction with the assigned duration definition. The exponent for the power function is typically less than 1.0, and varies with frequency and hearing level. Second, a means of empirically assaying the contribution of the rise-fall portions of the stimuli is presented and evaluated. Finally, properties of a central auditory integrator are hypothesized.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Cerebellar role in fear-conditioning consolidation.
Some cerebellar structures are known to be involved in the memorization of several conditioned responses. The role of the interpositus nucleus (IN) and the vermis (VE) in fear-conditioning consolidation was investigated by means of a combined behavioral and neurophysiological technique. The IN and VE were subjected to fully reversible tetrodotoxin (TTX) inactivation during consolidation in adult male Wistar rats that underwent acoustic conditioned stimulus (CS) and context fear training. TTX was injected in different groups of rats at increasing intervals after the acquisition session. Memory was assessed as conditioned freezing duration measured during retention testing, always performed 72 and 96 h after the stereotaxic TTX administration. This schedule ensures that there is no interference with normal cerebellar function during either the acquisition or the retrieval phase so that any amnesic effect may be due only to consolidation disruption. Our results show that IN functional integrity is necessary for acoustic CS fear response memory formation up to the 96-h after-acquisition delay. VE functional integrity was shown to be necessary for memory formation of both context (up to the 96-h after-acquisition delay) and acoustic CS (up to the 192-h after-acquisition delay) fear responses. The present findings help to elucidate the role of the cerebellum in memory consolidation and better define the neural circuits involved in fear memories.
Acoustic Stimulation↗
[Functional changes of neutrophils and monocytes by conditioning and filtration leukapheresis? (author's transl)].
Filtration leukapheresis (FL) is an effective and economic technique to collect large amounts of neutrophils for substitutional treatment of severe, transient neutropenia. An essential factor for effective granulocyte transfusion is functional integrity of the transfused cells. In this study eight hematologically normal donors were subjected to repetitive-cycle-Fl to examine functional changes of the collected neutrophils and monocytes compared to the donor's corresponding blood cells. After conditioning wit dexamethasone, increased neutrophil counts, increased percentage of band forms, decreased activity of leukocyte alcaline phosphatase, and decreased bactericidal activity were demonstrated. These changes indicate increased release of functional immature neutrophils of the nonproliferating bone marrow granulocyte pool. An increased latex-phagocytosis-index was noted during FL, signaling a cell stimulation, possibly by complement activation during Fl. The marked increase of latex-phagocytosis-indices of the eluted neutrophils was possibly induced by the neutrophils direct contact with the nylon fibers of the filter, resulting in mild degranulation, documented by the progressive but slight loss of bactericidal activity during FL. The indices of bactericidal activity were, however, not significantly different as compared to the values in the donor's blood. The repetitive-cycle-FL with minimal duration of contact between blood cells and nylon fibers of the filter, limits the process of degranulation and thereby technically reduces the functional alteration of donor granulocytes. Pretreatment of the donor with dexamethasone resulted only in a minimal change of functional integrity, caused by a transiently increased release of less mature neutrophils to the donor's blood.
Adult↗
Substantia nigra role in fear conditioning consolidation.
The substantia nigra (SN) is known to be involved in the memorization of several conditioned responses. To investigate the role of the SN in fear conditioning consolidation this neural site was subjected to fully reversible tetrodotoxin (TTX) inactivation during consolidation in adult male Wistar rats which had undergone fear training to acoustic CS and context. TTX was stereotaxically administered to different groups of rats at increasing intervals after the acquisition session. Memory was assessed as conditioned freezing duration measured during retention testing, always performed 72 and 96 h after TTX administration. In this way there was no interference with normal SN function during either acquisition or retrieval phases, so that any amnesic effect could be due only to consolidation disruption. The results show that SN functional integrity is necessary for contextual fear response consolidation up to the 24-h after-acquisition delay. On the contrary SN functional integrity was shown not to be necessary for the consolidation of acoustic CS fear responses. The present findings help to elucidate the role of the SN in memory consolidation and better define the neural circuits involved in fear memories.
Analysis of Variance↗
Physiological coupling of donor and host cardiomyocytes after cellular transplantation.
Cellular transplantation has emerged as a potential approach to treat diseased hearts. Although cell transplantation can affect global heart function, it is not known if this results directly via functional integration of donor myocytes or indirectly via enhanced revascularization and/or altered postinjury remodeling. To determine the degree to which donor cardiomyocytes are able to functionally integrate with the host myocardium, fetal transgenic cardiomyocytes expressing enhanced green fluorescent protein were transplanted into the hearts of nontransgenic adult mice. Two-photon molecular excitation laser scanning microscopy was then used to simultaneously image cellular calcium transients in donor and host cells within the intact recipient hearts. Calcium transients in the donor cardiomyocytes were synchronous with and had kinetics indistinguishable from those of neighboring host cardiomyocytes. These results strongly suggest that donor cardiomyocytes functionally couple with host cardiomyocytes and support the notion that transplanted cardiomyocytes can form a functional syncytium with the host myocardium.
Animals↗
Experimentally-induced hyperthyroidism is associated with activation of the rat hypothalamic-pituitary-adrenal axis.
OBJECTIVE: Previous studies on the effects of altered thyroid function on the secretion and metabolism of adrenocortical hormones suggest a degree of adrenocortical hyperactivity in hyperthyroidism. We have previously shown that experimentally-induced hyperthyroidism is associated with significant alterations in pituitary-adrenal responsiveness to synthetic ovine corticotropin-releasing hormone (oCRH) that are contingent upon the duration of the altered thyroid function. The purpose of this study was to assess the time-dependent effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis by in vivo stimulation of the hypothalamic CRH neuron and adrenal cortex. METHODS: The functional integrity of the HPA axis was examined in vivo in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given 50 mug of thyroxine every day for 7 or 60 days. Responses to insulin-induced hypoglycemia and IL-1alpha stimulation were used to assess the hypothalamic CRH neuron. Adrenocortical reserve was assessed in response to low-dose adrenocorticotropic hormone (ACTH), following suppression of the HPA axis with dexamethasone. Adrenal and thymus tissue weight, in addition to basal plasma ACTH, corticosterone and thyroid indices were also determined. RESULTS: Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days, cerebrospinal fluid (CSF) corticosterone levels were significantly increased. Basal plasma ACTH levels were similar to controls. Although plasma ACTH responses to hypoglycemic stress and IL-1alpha administration in both short- and long-term hyperthyroidism were normal, corticosterone responses to the ACTH release during the administration of these stimuli were significantly increased. The adrenal reserve was significantly elevated in short-term hyperthyroidsim. Long-term hyperthyroidism, however, was associated with a significant reduction in adrenocortical reserve. A significant increase in adrenal weights and a decrease in thymus weights were observed in both short- and long-term hyperthyroidism. CONCLUSIONS: The available data confirms that hyperthyroidism is associated with hypercorticosteronemia, although the locus that is principally affected still remains unclear. Despite the sustained hyperactivity of the HPA axis, long-term experimentally-induced hyperthyroidism is associated with diminished adrenal functional reserve. The alterations in HPA function in states of disturbed thyroid function were found to be somewhat more pronounced as the duration of thyroid dysfunction increased.
Adrenal Glands↗
On the use of superadditivity as a metric for characterizing multisensory integration in functional neuroimaging studies.
A growing number of brain imaging studies are being undertaken in order to better understand the contributions of multisensory processes to human behavior and perception. Many of these studies are designed on the basis of the physiological findings from single neurons in animal models, which have shown that multisensory neurons have the capacity for integrating their different sensory inputs and give rise to a product that differs significantly from either of the unisensory responses. At certain points these multisensory interactions can be superadditive, resulting in a neural response that exceeds the sum of the unisensory responses. Because of the difficulties inherent in interpreting the results of imaging large neuronal populations, superadditivity has been put forth as a stringent criterion for identifying potential sites of multisensory integration. In the present manuscript we discuss issues related to using the superadditive model in human brain imaging studies, focusing on population responses to multisensory stimuli and the relationship between single neuron measures and functional brain imaging measures. We suggest that the results of brain imaging studies be interpreted with caution in regards to multisensory integration. Future directions for imaging multisensory integration are discussed in light of the ideas presented.
Animals↗
Induction of the paroxysmal nocturnal hemoglobinuria phenotype in normal human erythrocytes: effects of 2-aminoethylisothiouronium bromide on membrane proteins that regulate complement.
To investigate the mechanism by which treatment of normal human erythrocytes with the sulfhydryl reagent 2-aminoethylisothiouronium bromide (AET) induces susceptibility to complement mediated lysis, the effects of AET on the structural and functional integrity of decay accelerating factor (DAF), membrane inhibitor of reactive lysis (MIRL), and complement receptor type 1 (CR1) were examined. Following treatment with AET, erythrocyte MIRL and CR1 were no longer recognized in situ by antibodies, and antibody binding to DAF was diminished by approximately 50%. These studies indicated that the structural integrity of the three complement regulatory proteins was either partially (DAF) or completely (MIRL and CR1) disrupted by AET. Subsequent experiments showed that functional inactivation paralleled the structural disruption. Treatment of normal erythrocytes with AET induced susceptibility to cobra venom factor-initiated hemolysis, indicating that the functional activity of MIRL had been destroyed. The capacity of erythrocyte CR1 to serve as a cofactor for factor I-mediated cleavage of iC3b to C3c and C3dg was lost following treatment with AET. C3 convertase activity increase markedly following treatment of erythrocytes with AET, but convertase activity on AET cells was approximately 50% less than that observed when DAF function on normal cells was completely inhibited by antibody. Susceptibility of AET cells to acidified serum lysis was shown to be due primarily to inactivation of MIRL. Unexpectedly, in acidified serum the activity of the amplification C3 convertase of the APC was found to be controlled by MIRL as well as by DAF. These studies show that AET induces susceptibility to complement-mediated lysis by disrupting the structural and functional integrity of membrane constituents that regulate the activity of both the C3 convertases and the membrane attack complex of complement.
Antibodies↗
Resistin-like molecule beta regulates innate colonic function: barrier integrity and inflammation susceptibility.
BACKGROUND: Resistin-like molecule (RELM) beta is a cysteine-rich cytokine expressed in the gastrointestinal tract and implicated in insulin resistance and gastrointestinal nematode immunity; however, its function primarily remains an enigma. OBJECTIVE: We sought to elucidate the function of RELM-beta in the gastrointestinal tract. METHODS: We generated RELM-beta gene-targeted mice and examined colonic epithelial barrier function, gene expression profiles, and susceptibility to acute colonic inflammation. RESULTS: We show that RELM-beta is constitutively expressed in the colon by goblet cells and enterocytes and has a role in homeostasis, as assessed by alterations in colon mRNA transcripts and epithelial barrier function in the absence of RELM-beta. Using acute colonic inflammatory models, we demonstrate that RELM-beta has a central role in the regulation of susceptibility to colonic inflammation. Mechanistic studies identify that RELM-beta regulates expression of type III regenerating gene (REG) (REG3beta and gamma), molecules known to influence nuclear factor kappaB signaling. CONCLUSIONS: These data define a critical role for RELM-beta in the maintenance of colonic barrier function and gastrointestinal innate immunity. CLINICAL IMPLICATIONS: These findings identify RELM-beta as an important molecule in homeostatic gastrointestinal function and colonic inflammation, and as such, these results have implications for a variety of human inflammatory gastrointestinal conditions, including allergic gastroenteropathies.
Animals↗
Alpha oscillations in brain functioning: an integrative theory.
The old concept stating that EEG alpha (10-Hz) activity reflects passive or idling states of the brain is giving way to modern views of 10-Hz oscillations in relation to diverse brain functions comprising sensory, motor, and memory processes: (1) Spontaneous alpha activity is not pure noise as shown by methods of chaos analysis. (2) Evoked alpha oscillations patterns (precisely time-locked to a stimulus; duration approx. 200-300 ms) depend on the modality of stimulation and the recording site. (3) Induced alpha oscillations are initiated by, but not closely time-locked to a stimulus. (4) 10-Hz oscillations are recorded in nervous systems of different complexities, from the human brain to isolated ganglia of invertebrates. The neural origins of 10-Hz oscillations are demonstrated by recordings at the cellular level. (5) Rather than trying to locate a unique alpha generator, it is preferable to assume that a 'diffuse and distributed alpha system' exists. A particular support for this hypothesis is given by stimulus-dependent hippocampal alpha responses in the cat brain. (6) The major physiological meaning of 10-Hz oscillations may be comparable to the putative universal role of gamma responses in brain signaling.
Alpha Rhythm↗