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PubMed1981

The autonomic nervous system, molder and integrator of function. Review of a concept.

This paper treats a number of topics relative to functions of the autonomic nervous system: its role in the sympathies and emotional inter-reactions essential to society and common endeavor; the history and evolution of our knowledge of the structure, composition and function of this system; the recent concurrent genesis of concepts of the roles this system plays. Among the most recently developed ideas of autonomic system function is that of its integrating role and that of its molding role in determining the color and intensities of behavioral responses. These latter concepts are supported by recent discoveries of the role played in sensory reception, in several disease states, in control of the neuroendocrine and endocrine systems, in modulation of cardiovascular function, in regulation of energy release and use, and, finally, in conditioned behavior. It appears that there is considerable plasticity and possibility of drastically modifying cell of this system which normally would have functioned in a quite different way. Modern methods of anatomical analysis have shown that the central representation of the autonomic outflow is not as simplistically and independently organized as often visualized. Furthermore the same centers which control somatic responses also affect autonomic system activity. There is only one nervous system and the autonomic complex is an integral part thereof, participating in all behavior. It is, however, specially concerned with the emotional component, reactions to real or anticipated emergencies, control of the viscera and maintenance of homeostasis. In addition to integrating the activity of body parts it has a modulatory effect on all functions.

Autonomic Nervous System↗

PubMed2002

Regulation of RPE intercellular junction integrity and function by hepatocyte growth factor.

PURPOSE: To evaluate the effect of hepatocyte growth factor (HGF) on the integrity and function of tight junctions and adherens junctions in the retinal pigment epithelial (RPE) monolayer. METHODS: Fresh bovine eyes were dissected to obtain 2- to 3-mm(2) explants of intact RPE with underlying choroid and sclera. Explants were cultured with or without HGF (20 ng/mL) for various periods (20 minutes to 72 hours). Junction integrity was assessed by transmission and scanning electron microscopy; localization, expression, and phosphorylation of junction proteins; and measurement of transepithelial resistance (TER), diffusion of fluorescent labeling in the plasma membrane, and the migration of RPE cells from the monolayer. RESULTS: Untreated explants consisted of polarized cells with apical microvilli and well-developed tight and adherens junctions. After HGF treatment, the explants showed loss of tight and adherens junctions ultrastructurally, diffusion of fluorescent label from apical to lateral membrane domains, and increased chemotactic migration of RPE cells from the monolayer. Primary cultures of confluent RPE cells showed a progressive decrease in TER. Western blot analysis showed rapid tyrosine phosphorylation of ZO-1, occludin, and beta-catenin within 20 minutes of stimulation. There was a marked loss of ZO-1 protein within 1 hour of HGF treatment. After 6 hours of treatment with HGF, occludin, claudin-1, and beta-catenin were redistributed from the membrane to the cytoplasm. CONCLUSIONS: Treatment of RPE explants with HGF results in rapid disassembly of tight and adherens junctions associated with loss or redistribution of junctional proteins, decreased TER, and increased migration of RPE cells from the monolayer.

Animals↗

PubMed1998

[Integration of functional and morphologic MRI data for preoperative 3D visualization of tumors. Example: cervical carcinoma].

PURPOSE: The goal of this exemplary study was to integrate morphological and functional MRI to establish computer-based, pre-operative therapy planning for tumors, instancing cervical carcinoma. METHODS: For morphological representation T1-weighted, filtered 3D sequences were investigated within a hierarchical segmentation approach. Using a method for image registration, segmented structures were combined and overlaid with functional information of contrast medium-enhanced, dynamic MRI. After assigning colour attributes to the segmented structures, they were presented using a method for direct volume visualisation. RESULTS: Segmentation of organs and vessels as well as tissue differentiation yielded a morphological visualisation of anatomical structures that were overlaid with pharmacokinetic parameters derived from dynamic MRI, subsequently. Thereby, three-dimensional, arbitrary views on the functional data were displayed. CONCLUSIONS: Image analysis and visualisation of the acquired MR data establishes both a morphologic and functional evaluation of suspect lesions and adjacent organs. By integrating morphologic and functional MRI additional information can be gathered that possibly impinge on preoperative planning.

Data Interpretation, Statistical↗

PubMed2001

Multimodal cranial neuronavigation: direct integration of functional magnetic resonance imaging and positron emission tomography data: technical note.

OBJECTIVE: This is the first report of the direct integration of functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) data into cranial neuronavigation. METHODS: In a patient with a left precentral oligodendroglioma (World Health Organization Grade III), the Zeiss MKM system (Carl Zeiss Co., Oberkochen, Germany) was used for navigation based on thin-slice, T1-weighted, contrast-enhanced magnetic resonance imaging (MRI) scans. fMRI and methionine PET data were integrated by landmark matching, with reference to skin fiducials. RESULTS: The inaccuracy of the image fusion between fMRI and T1-weighted MRI data was 1.7 mm, that between PET and T1-weighted MRI data was 4.3 mm, and that for the subsequent registration of the navigation was 1.2 mm. The correct fMRI localization of the precentral gyrus was intraoperatively verified by cortical somatosensory evoked potential (phase-reversal) monitoring. Although the tumor was not clearly defined in the MRI scans, [11C]methionine PET demonstrated a clear tumor border, enabling us to achieve gross total tumor removal without postoperative functional deficits. CONCLUSION: Functional neuronavigation permits observation and preservation of relevant brain areas. Other functional areas (such as short-term memory areas) that can be detected only by fMRI might also warrant future monitoring. The simultaneous integration of fMRI and PET data adds a new dimension to cranial neuronavigation, enabling the observation of tumors in relation to functional cortical areas (in our case, the motor strip).

Brain↗

PubMed1984

Cloning of the integration and attachment regions of bacteriophage P4.

The integration and attachment regions of bacteriophage P4 have been cloned into a multicopy plasmid. This plasmid can integrate into the E. coli chromosome at the same location as the parent phage. Integration increases the stability of the plasmid and allows it to be retained even under conditions in which a non-integrated plasmid would be lost. None of the genes needed for P4 lytic growth is required for integration. The P4 integration and attachment regions have been cloned on separate plasmids. A plasmid that carries the attachment site can integrate into the chromosome only if another plasmid that carries the P4 integration functions is present. A plasmid that carries only this trans-acting integration function cannot integrate. Using deletion mutants of the plasmid, the maximum size of the region needed for integration has been determined to be 1.6 kb, of which no more than 1.2 kb codes for the integrase protein. A nonsense mutant defective in integration has been isolated by using a rapid screening procedure that identifies unstable plasmids.

Base Sequence↗

PubMed2004

Principles and core functions of integrated child health information systems.

Infants undergo a series of preventive and therapeutic health interventions and activities. Typically, each activity includes collection and submission of data to a dedicated information system. Subsequently, health care providers, families, and health programs must query each information system to determine the child's status in a given area. Efforts are underway to integrate information in these separate information systems. This requires specifying the core functions that integrated information systems must perform.

Child↗

PubMed2001

Myocyte transplantation for myocardial repair: a few good cells can mend a broken heart.

Cell transplantation is a potential therapeutic approach for patients with chronic myocardial failure. Experimental transplantation of neonatal and fetal cardiac myocytes showed that the grafted cells can functionally integrate with and augment the function of the recipient heart. Clinical application of this approach will be limited by shortage of donors, chronic rejection, and because it is ethically contentious. By contrast skeletal myoblasts (satellite cells) are abundant and can be grafted successfully into the animal's own heart even after genetic manipulation in vitro. Functional integration of myoblasts, however, is hampered by the lack of intercellular gap junction communication and the difference in excitation-contraction coupling between skeletal and cardiac myocytes. In experimental studies several other cell types have been used to augment cardiac function. In this review we discuss the published results of myocyte transplantation with emphasis on potential sources of cells, the ethics of using donor embryonic and fetal cardiomyocytes, genetic transformation of skeletal myoblasts for myocardial repair, and the functional benefits of cell transplantation to the failing heart.

Animals↗

PubMed1999

Noradrenergically mediated plasticity in a human attentional neuronal network.

Noradrenaline is implicated in the modulation of attention and arousal, but the neuroanatomical basis of this effect in humans is unknown. A previous functional neuroimaging study failed to find clear effects of clonidine (alpha2 adrenoceptor agonist) on activity of brain regions implicated in attention. Therefore, we now investigate whether clonidine affects the functional integration of a neuroanatomical attentional network, by modulating connectivity between brain regions rather than activity within discrete regions. Following infusion of either clonidine or placebo, positron emission tomography measurements of brain activity were collected in 13 normal subjects while they were either resting or performing an attentional task. Effective connectivity analysis showed that during rest, clonidine decreased the functional strength of connections both from frontal cortex to thalamus and in pathways to and from visual cortex. Conversely, during the attentional task, functional integration generally increased, with changes being centered on parietal cortex (increased connectivity from locus coeruleus to parietal cortex and from parietal cortex to thalamus and frontal cortex). A drug-induced increase in the modulatory effects of frontal cortex on projections from locus coeruleus to parietal cortex was also observed. Collectively, these results highlight cognitively dissociable effects of clonidine on interactions among functionally integrated brain regions and implicate the noradrenergic system in mediating the functional integration of attentional brain systems. The context-sensitive nature of the changes are consistent with observations that noradrenergic drugs have differential effects on brain processes depending on subjects' underlying arousal levels. More generally, the results illustrate the dynamic plasticity of cognitive brain systems following neurochemical challenge.

Adolescent↗

PubMed2001

The brain and somatic integration: insights into the standard biological rationale for equating "brain death" with death.

The mainstream rationale for equating "brain death" (BD) with death is that the brain confers integrative unity upon the body, transforming it from a mere collection of organs and tissues to an "organism as a whole." In support of this conclusion, the impressive list of the brain's myriad integrative functions is often cited. Upon closer examination, and after operational definition of terms, however, one discovers that most integrative functions of the brain are actually not somatically integrating, and, conversely, most integrative functions of the body are not brain-mediated. With respect to organism-level vitality, the brain's role is more modulatory than constitutive, enhancing the quality and survival potential of a presupposedly living organism. Integrative unity of a complex organism is an inherently nonlocalizable, holistic feature involving the mutual interaction among all the parts, not a top-down coordination imposed by one part upon a passive multiplicity of other parts. Loss of somatic integrative unity is not a physiologically tenable rationale for equating BD with death of the organism as a whole.

Bioethics↗

PubMed2005

Field theory for the global density of states distribution function of disordered conductors.

A field-theoretical representation is suggested for the electron global density of states distribution function P(nu) in extended disordered conductors. This opens a way to study the complete statistics of fluctuations. The approach is based on a functional integration over bilocal functions Psir(1)(r(2)) instead of the integration over local functions in the usual functional representation for moments of physical quantities. The formalism allows one to perform the disorder averaging and to derive an analog of the usual nonlinear sigma model-a slow functional of a supermatrix field Qr(1)(r(2))(r) approximately Psi(rr(1)) composite functionPsi (r(2)r). As an application of the formalism, the long-tail asymptotics of P(nu) is derived.

Journal Article↗

PubMed2005

Cross-modal binding and activated attentional networks during audio-visual speech integration: a functional MRI study.

We evaluated the neural substrates of cross-modal binding and divided attention during audio-visual speech integration using functional magnetic resonance imaging. The subjects (n = 17) were exposed to phonemically concordant or discordant auditory and visual speech stimuli. Three different matching tasks were performed: auditory-auditory (AA), visual-visual (VV) and auditory-visual (AV). Subjects were asked whether the prompted pair were congruent or not. We defined the neural substrates for the within-modal matching tasks by VV-AA and AA-VV. We defined the cross-modal area as the intersection of the loci defined by AV-AA and AV-VV. The auditory task activated the bilateral anterior superior temporal gyrus and superior temporal sulcus, the left planum temporale and left lingual gyrus. The visual task activated the bilateral middle and inferior frontal gyrus, right occipito-temporal junction, intraparietal sulcus and left cerebellum. The bilateral dorsal premotor cortex, posterior parietal cortex (including the bilateral superior parietal lobule and the left intraparietal sulcus) and right cerebellum showed more prominent activation during AV compared with AA and VV. Within these areas, the posterior parietal cortex showed more activation during concordant than discordant stimuli, and hence was related to cross-modal binding. Our results indicate a close relationship between cross-modal attentional control and cross-modal binding during speech reading.

Adult↗

PubMed2005

Hypertonic saline and hemorrhagic shock: hepatocellular function and integrity after six hours of treatment.

PURPOSE: The comparison after 6 h of hemorrhagic shock (HS) treatment with NaCl 7.5% (Hypertonic Saline Solution-SSH) or Ringer Lactate (RL) on liver function and integrity. METHODS: Male Wistar rats were submitted to HS (Mean Arterial Pressure-MAP= 45 mmHg) during 60 min and then treated with NaCl 7.5% (SSH, 10% of blood loss, n=8) or Ringer Lactate (RL, 400% of blood loss, n=8). After 6 h rats were anesthetized, hepatic function was assessed by bile flow measurement and liver integrity evaluated by determination of alanine aminotransferase (ALT) and bilirubin activities. RESULTS: There was no difference in MAP between the groups during the whole experiments. Biliary flow showed a significant recovery after SSH treatment (p<0.05), and significant decrease of ALT (p<0.001) and bilirubin levels (p<0.001) in comparison to RL. CONCLUSION: Resuscitation of HS with NaCl 7.5% promoted better recovery of liver function and lesser hepatocellular damage after 6 h of treatment compared to RL. The improvement is very likely related to increased microvascular perfusion provided by small volume resuscitation.

Alanine Transaminase↗

PubMed1983

Motor disabilities and effects of thyrotropin-releasing hormone on ataxia of spinocerebellar degeneration.

Fine aiming task was studied quantitatively in 20 patients with spinocerebellar degeneration (SCD) and 8 normal control subjects, utilizing a manual control system with random-step input signal. The transfer function of the system was an integral function and ability to perform a 'differentiating action' compensating for this integral function was analyzed. This 'differentiating action' was defective in all patients with SCD and was normal in all control subjects. A display of the dynamic characteristics of subjects on the plane defined by principal component analysis of the parameters showed definite delineation of the characteristics of patients from those of the controls. The intramuscular injection of thyrotropin-releasing hormone (TRH) resulted in an increase in amplitude of manipulation, a shortening of reaction time and consequently an improvement in motor disabilities in 65% of 20 patients with SCD.

Adolescent↗

PubMed2002

Parameters and techniques to determine intestinal health of poultry as constituted by immunity, integrity, and functionality.

The intestinal microflora lives in intimate contact with its surrounding intestinal wall and the bacteria can exert beneficial or deleterious effects on the host, depending on whether they are classified as probiotics or as pathogens. The interaction is determined on one hand by characteristics of the microorganisms, and on the other hand by characteristics of the intestinal wall. Together they determine the health status of the intestine. This review describes parameters and techniques (with advantages and disadvantages) available for poultry to identify the characteristics of the intestinal health, as constituted by three components: immunity, integrity, and functionality. To investigate intestinal immunity, in situ detection of various cell populations of the immune system with specific monoclonal antibodies using immunocytochemical staining is a reliable, semi-quantitative method. In vitro assays to measure functional aspects of T lymphocytes, B lymphocytes, plasma cells, natural killer cells, macrophages, and phagocytes are applicable to intestinal wall tissue. For investigation of intestinal integrity, in situ detection of villous height and crypt depth and their ratio, and villus arrangement is still an easy, routine histological method. In addition, expression levels of specific molecules, such as E-cadherin, different growth factors, and trefoil factor, seem promising parameters. To investigate functionality of the intestine, the permeability can be measured as the rate of transport of tracer molecules across the epithelial surface. Furthermore, determination of the level of mucus secretion and its composition are a valuable tool. These parameters for immunity, integrity and functionality, or a combination thereof, are indispensable to investigate the influence of intestinal microorganisms on intestinal health.

Animals↗

PubMed2005

Modulation of aconitase, metallothionein, and oxidative stress in zinc-deficient rat intestine during zinc and iron repletion.

Potential interactions between zinc and iron during absorption and its functional consequences on intestinal oxidative damage and antioxidant status were studied using the zinc-deficient rat as a model. Zinc depletion produced mild-moderate iron deficiency in addition to zinc deficiency, which could be corrected by repletion with iron and zinc. The localization and intensity of both iron and zinc in the intestinal mucosa showed a pronounced decrease in the presence of the other metal, indicating negative interactions. Zinc-deficient intestine exposed to iron alone exhibited elevated peroxidative damage and compromised functional integrity, despite increased expression of ferritin. Inclusion of zinc significantly reduced the damage and improved the functional integrity, accompanied by decreased expression of ferritin. Decreased expression of ferritin in the presence of zinc was consistent with reduced aconitase activity, suggesting its modulation by zinc. Further, inclusion of iron along with zinc was associated with induction of ferritin and metallothionein in tune with the amount of iron and zinc localized in the intestinal mucosa, respectively. These results suggest that zinc and iron interact negatively with cytosolic aconitase, but prove beneficial in reducing the oxidative stress, apart from improving functional integrity and iron/zinc status.

Aconitate Hydratase↗

PubMed1996

Use of a specific zona pellucida (ZP) protein 3 antiserum as a clinical marker for human ZP integrity and function.

OBJECTIVE: To evaluate binding characteristics of a specific zona pellucida (ZP) protein 3 (ZP3) antiserum to human oocytes in order to determine its usefulness as a clinical marker for human ZP integrity and function and its correlation with IVF outcome. DESIGN: Prospectively designed, blinded, internally controlled study. SETTING: Tertiary care academic center. PATIENTS: Patients undergoing IVF therapy who had either total failed fertilization or partial fertilization were studied. INTERVENTIONS: Metaphase II oocytes showing absence of pronuclear formation were salt stored 48 hours after insemination and bisected into matching hemizonae using micromanipulation. One hemizona was incubated with AS ZP3-6 (an antiserum generated against a synthetic ZP3 peptide derived from an amino acid sequence that is highly conserved in the structure of ZP3), whereas the matching hemizona was incubated with AS ZP3-7, an antiserum detecting exclusively mouse ZP3 (internal, negative control). Antibody binding was visualized using the peroxidase-antiperoxidase method and diaminobenzidine as color reagent. RESULTS: A total of 104 unfertilized oocytes were evaluated. Analysis of variance showed a significant interaction between gamete factor groups (sperm and oocyte) and antiserum factor. Patients with oocyte factor had significantly lower mean staining scores for the AS ZP3-6-treated hemizonae than patients with sperm factor. CONCLUSIONS: These results demonstrate that anomalies of human ZP3 can be identified with AS ZP3-6 and that these ZP abnormalities correlate with fertilization failure during IVF treatment. Thus, this newly developed biomarker may be of clinical significance in the identification of oocyte defects that are associated with fertilization disorders and may help in the decision-making process in the IVF-assisted fertilization setting.

Adult↗

PubMed2005

Flow cytometry applications in the evaluation of sperm quality: semen analysis, sperm function and DNA integrity.

Flow cytometry (FCM) has been extensively used to study mammalian sperm in the areas of reproductive toxicology (to monitor effects from environmental, occupational and therapeutic exposures), veterinary science (to preselect the gender of offspring by sorting X- and Y-chromosome-bearing sperm) and clinical andrology (to assess individual fertility potential). Using FCM, a variety of sperm features can now be rapidly measured on a cell-by-cell basis such as sperm count, viability, acrosomal integrity, mitochondrial function and DNA integrity; the last one is involved in postfertilization failure and embryo toxicity. It is foreseen that only a multiplex approach, which includes FCM assays together with the new genomics/proteomics methods, could increase the predictive power of fertility status and help identify susceptible subpopulations of men at risk for infertility, spontaneous abortions and birth defects.

Animals↗

PubMed2003

Classical nucleation theory revisited.

A field-theoretic derivation of the correction to classical nucleation theory due to translational invariance of a nucleating droplet is proposed. The correction is derived from a functional integral representation of the classical partition function, where the two-body interaction potential is decomposed into a short-range repulsive part and a long-range attractive part. The functional integral is evaluated in the mean-field approximation, and the spatially nonuniform density solution of the Euler-Lagrange equation is approximated by a physically motivated hyperbolic tangent profile. Leading-order effects of the nonlocal attractive interaction are highlighted through a density-gradient expansion. The capillarity approximation to the droplet free energy of formation is obtained by performing a density resummation of the uniform state, low-density expansion of the Helmholtz free energy density, and by retaining the leading-order density-gradient term. The resulting translational-invariance correction modifies the droplet free energy by an additive mixing-entropy term. The additional contribution, which contains a logarithmic correction to the surface-energy term, defines a scaling volume that depends on the range of the coarse-grained attractive potential.

Journal Article↗