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PubMed1981

Physiology of mammalian prevertebral ganglia.

When assessing the physiological role of the prevertebral ganglia, the following should be considered. Ganglion cells in these ganglia receive continuous excitatory synaptic input from peripheral sensory mechanoreceptors and central preganglionic neurons. The latter may result from sensory afferents projecting from the gastrointestinal tract to spinal preganglionic neurons or as a result of endogenous oscillator activity located in the spinal cord (18) or within the ganglion (45). Peripheral and spinal reflex pathways probably do not operate as separate, independent pathways. Rather, they must be considered functionally integrated in the prevertebral ganglia. Because of continuous synaptic input, the prevertebral neuron operates at some level of "neurogenic tone" that provides capabilities for bi-directional responses. An increase in spinal or peripheral synaptic input will be matched by a proportional increase in output firing. The functional effect of spatial summation of peripheral and central input is to prime the prevertebral neuron so that adjustments in its firing frequency can be made without the lag inherent in building up a response in a quiescent system. Not all prevertebral ganglia participate in reflex activity. It may be that reflex activity between prevertebral ganglia and visceral smooth muscle depends upon the nature of the mechanical activity of the muscle. For example, the mechanical activity of smooth muscle of the vas deferens is not characterized by spontaneous, myogenic, regularly occurring contractions. Mechanical activity in this organ occurs in bursts. There is no evidence to suggest that sensory fibers project from the wall of the vas deferens to the hypogastric plexus thereby forming a peripheral reflex arc. Contraction of th smooth muscle of the vas deferens is brought about by bursts of nerve impulses through simple relay connections in the pelvic plexus. Smooth muscles supplied by this ganglion have a direct line to the central nervous system and are secured by a "fail-safe" system. In contrast, the mechanical activity of the gastrointestinal system is characterized by slow spontaneous myogenic activity. Pattern formation of motor activity is achieved by reflex activity within the enteric plexuses. Extrinsic alteration of the nature and pattern of contraction of smooth muscle of the gastrointestinal tract would be best served by prevertebral ganglia that modulate and adjust motor function by continuous integration of convergent weak synaptic input emanating from the peripheral and central nervous systems. When a prevertebral neuron is part of a peripheral reflex loop, its physiological role may be to modulate end organ activity; when it does not participate in a peripheral reflex loop, its role may be to relay CNS input and initiate end organ activity.

Animals↗

PubMed1999

Field theoretical representation of the Hohenberg-Kohn free energy for fluids.

To go beyond Gaussian approximation to the Hohenberg-Kohn free energy playing the key role in the density functional theory (DFT), the density functional integral representation would be relevant, because the field theoretic approach to perturbative calculations becomes available. Then we first derive the associated Hamiltonian of the density functional, explicitly including the logarithmic entropy term, from the grand partition function expressed by configurational integrals. Moreover, two things are done so that the efficiency of the obtained form may be revealed: we demonstrate that this representation facilitates the field theoretic treatment of the perturbative calculation and, further, compare our perturbative formulation with that of the DFT.

Journal Article↗

PubMedDate not supplied

IHE: integrating the healthcare enterprise, towards complete integration of healthcare information systems.

Information systems of a modern hospital govern extremely important functions as patient management, control of work flows, administration etc. However a great variety of recommended standards are used while in most cases no effective coordination and intercommunication is possible. Some years ago to simplify and resolve this problem IHE was created; it is a technical framework which identifies a number of components of the healthcare enterprise (the "actors") whose interactions are defined in terms of "transactions", that should be implemented according to HL7 and DICOM standards. Attempting an in-depth understanding of IHE structure and its principles of function, those transactions that can occur among the various actors, which of these are supported and which require specific actors, are analyzed. IHE is continuously evolving, therefore open to the factual contribution of all health professionals who can point out the main instances that emerge daily from their activity in the field. While its origin was specific for the field of radiology, the true soul and driving force of the project lay on the type of approach used: to get together medical specialists and information technology professionals in order to identify and solve the difficulties which hindered an effective and functional integration of healthcare information systems.

Delivery of Health Care, Integrated↗

PubMed1998

Age changes in stem cells of murine small intestinal crypts.

Cell senescence is seen in many types of differentiated cells but age changes in stem cells have not previously been clearly demonstrated. Changes in stem cells may be of great importance for the ageing process, because any decline with age in the numbers and functional integrity of stem cells can lead to progressive deterioration of function and of proliferative homeostasis in tissues. Stem cells of the murine small intestine provide an excellent model system because these cells occupy a well-defined position near the base of the crypts of Lieberkühn. We examined mice aged between 5 and 32 months and found age-related alterations in the histology of the small intestine and in the apoptotic response of stem cells to low-dose irradiation. Apoptosis in the crypts is concentrated around the stem cell position and can be markedly elevated by exposure to radiation or cytotoxic agents, suggesting that "suicide" of damaged stem cells may be an important system for long-term tissue maintenance. Animals aged 5, 15, 18, and 29 months were exposed to either 1 or 8 Gy gamma irradiation. A twofold increase in the level of apoptosis was seen following 1 Gy gamma irradiation in the 29-month-old animals, compared to the young and middle-age groups. After 8 Gy irradiation the level of apoptosis in all age groups was high and the age effect less pronounced. The data suggest that stem cells do undergo some functional alteration with age.

Aging↗

PubMed1989

Interdependence of the left and right ventricles in health and disease.

Since the publication of Bernheim's report it has been clear that the anatomic and functional integrity of each ventricle is an important determinant of the functional characteristics of the other ventricle. How the ventricles interact in health and disease has been of interest to many investigators. This article reviews and considers the structure and function of each ventricle as an independent subunit and as a unified pumping system in the healthy state and in various disease states.

Animals↗

PubMed2005

Factors affecting the plasma membrane function of cooled-stored stallion spermatozoa.

The spermatozoon is a highly specified cell that has the abilities of active motility and fertilization of the ovum. Damage to the sperm plasma membrane results in the irreversible loss of its functions. Because of the high content of unsaturated fatty acids in the plasma membrane, mammalian sperm are sensitive to oxidative stress. While mild peroxidation appears to promote capacitation of the sperm cell, excessive peroxidation will damage the plasma membrane and results in loss of motility and fertility. The functional integrity of the sperm plasma membrane can be determined by functional tests (determination of motility, resistance against hypoosmotic media) or different staining methods. Today, fluorescent dyes that allow the evaluation of membrane-intact cells are preferred. Computer-assisted evaluation or the use of flow cytometry has improved the precision of these methods. The use of cooled-shipped semen has become a routine method in the equine industry and semen stored at 5 degrees C for about 24 h maintains fertility close to that of fresh semen. According to the suitability of their ejaculates for cooled-storage, stallions may be classified as "good coolers" or "poor coolers". Semen processing involves a number of factors that may damage the sperm plasma membrane. This includes addition of semen extender, centrifugation, cooling and storage at a temperature of 4-6 degrees C. Extender media and their ingredients protect the sperm plasma membrane against environmental influences, but unsuitable composition of the extender can also promote membrane damage. Recent advantages in extender composition are based on the substitution of undefined factors such as milk or egg yolk by more defined and stable components.

Animals↗

PubMed2001

Immunosenescence: a review.

Aging involves the morphological and functional integrity of all organs, including the cellular and humoral immunological functions. The main alterations can be listed as follows: (i) Thymic involution resulting in the decreased number of lymphoid precursor T- and B-cells. (ii) Reduced proliferative capacity of T-cells; loss of lymphocyte subgroups as a consequence of the shortening of telomeres. (iii) Qualitative deficiency of B-lymphocytes with a reduced response to exogenous antigens. (iv) Compromised activity of the accessory cells, both directly by depressing the chemotactic and phagocytic responses, and indirectly by increasing the prostaglandin production which inhibit the proliferation of T-cells. (v) Alterations in the production and secretion of various cytokines. (vi) Other factors like the general physiological conditions, the nutritional state, psychological habit and various hormone levels.

Journal Article↗

PubMed2001

Gamma, alpha, delta, and theta oscillations govern cognitive processes.

The increased interest in gamma oscillations, now widely regarded as functionally relevant signals of the brain, underlines the importance of the concept of event-related oscillations for bridging the gap between single neurons and neural assemblies. Taking this concept further, we review experiments showing that oscillatory phenomena such as alpha, theta, and delta responses to events are, just as the gamma band, strongly interwoven with sensory and cognitive functions. This review argues that selectively distributed delta, theta, alpha and gamma oscillatory systems act as resonant communication networks through large populations of neurons. Thus, oscillatory processes might play a major role in functional communication in the brain in relation to memory and integrative functions.

Algorithms↗

PubMed2001

Autoreactivity, dynamic tuning and selectivity.

The immune system adjusts its response to the context in which antigens, including self-antigens, are recognized. Recent observations support a conceptual framework for understanding how this may be achieved at the cellular and cell-population levels. At both levels, 'perturbations' elicit competition between excitation and de-excitation, resulting either in adaptation or in various responses. The responsiveness of individual cells is dynamically tuned, reflecting their recent experience. The tuning of T-cell activation thresholds by self-ligands facilitates positive selection and continuously regulates the level of autoreactivity in the periphery. Autoreactivity appears to be involved in regulation of the immune response, homeostasis, maintaining of the functional integrity of naïve and memory cells, and in other physiological functions.

Adaptation, Physiological↗

PubMed1998

Membrane topology of the human dipeptide transporter, hPEPT1, determined by epitope insertions.

We have used epitope insertion to analyze the transmembrane topology of the human H+-dipeptide symporter hPEPT1. An epitope tag, EYMPME (EE), was inserted into different locations at amino acids 39, 78, 106, 412, and 708 of hPEPT1 by site-directed mutagenesis. The functional integrity of the tagged protein was tested by measuring its dipeptide transport activity in transfected Cos7 cells. Further, cells expressing hPEPT1 or EE-tagged hPEPT1 derivatives were labeled with an anti-EE-monoclonal antibody (anti-EE-mAb) or an antiserum raised against the carboxyl terminus of hPEPT1 (anti-hPEPT1) and examined by immunofluorescence confocal microscopy. EE106-, 412-, and 708-hPEPT1 transported the dipeptide tracer as well as wild-type hPEPT1. Tags at position 106 and 412 were shown to be extracellular because they were accessible to anti-epitope antibody in nonpermeabilized cells. In contrast, the carboxyl-terminal domain and EE708 were shown to be intracellular since they were only accessible to the antibodies in permeabilized cells. These results are consistent with a 12-transmembrane domain (TMD) topological model of PEPT1. Epitope insertions at regions linking the putative TMD1 and TMD2, and TMD2 and TMD3 (EE39- and EE78-hPEPT1), abolished the dipeptide transport into the cells. In transfected Cos7 cells, these tagged proteins remained largely intracellular rather than at the plasma membrane. These results suggest that the integrity of these regions is essential for transporter trafficking and/or function. Thus, the topology of the amino-terminal portion, including putative TMD1 and -2, remains to be clarified.

Amino Acid Sequence↗

PubMedDate not supplied

Matrix metalloproteinase-2 (MMP-2) and MMP-9 in pulmonary pathology.

The lung is affected by a variety of disease processes that can lead to considerable morbidity and mortality. As the lung is the only organ for respiration and gas exchange, the structural and functional integrity of the lung is of primary importance. Various pathological processes affect the extracellular matrix (ECM) of the lung in an adverse manner, causing destruction of tissue integrity followed by tissue remodeling, which together impair normal pulmonary function. Matrix metalloproteinases (MMPs) are neutral proteinases that are involved in the breakdown and remodeling of the ECM under a variety of physiological and pathological conditions. MMP-2 and MMP-9, collectively known as the gelatinases, are particularly important in the pathogenesis of inflammatory, infectious, and neoplastic diseases in many organs including the lung. This review examines the expression of MMP-2 and MMP-9 in disease of the lung and discusses the role these gelatinases may play in disease progression.

Animals↗

PubMed1998

Quantifying changes in retinal circulation: the generation of parametric images from fluorescein angiograms.

Fluorescein angiography is an established technique for examining the functional integrity of the retinal circulation. The ability to quantify this function offers the possibility of early detection of changes due to retinopathy. We have developed a technique to generate functional, parametric images of the retinal circulation. A given angiogram is first registered to align consecutive frames. At each point in the retina, a graph of fluorescein intensity versus time is then constructed and fitted with a gamma variate curve. Parameters are extracted from these curves and formed into parametric images showing the variation in fluorescein passage across the entire area of the angiogram. Parameters examined to date include time to maximum intensity, time of arrival and rise time. The technique has been demonstrated using photographic and scanning laser ophthalmoscopic angiograms of both normal subjects and patients with a variety of retinopathies. The time to maximum images of the normal subjects reveals a similar fillings pattern in each case, whilst the pathologies present in the abnormal angiograms are clearly identified. The generation of functional time to maximum images enables the health of the retinal circulation to be quantified with respect to the rate at which the vasculature fills with fluorescein. This offers a potential tool for detecting the onset of retinopathy and monitoring its progression.

Fluorescein Angiography↗

PubMed2000

Integration of foveal orientation signals: distinct local and long-range spatial domains.

Human observers can discriminate the orientation of a stimulus configuration composed of a pair of collinear visual patterns much better than that of a single component pattern alone. Previous investigations of this type of orientation signal integration and of other similar visual integrative functions have shown that, for closely spaced elements, there is integration only for stimuli with the same contrast polarity (i.e., both lighter or both darker than the background) but, at greater separations, integration is independent of contrast polarity. Is this effect specific to differences in contrast polarity, which is known to be an important parameter in the organization of the visual system, or might there be a cluster of other stimulus dimensions that show similar effects, indicating a more widespread distinction between the processes limiting integration at local and long-range spatial scales? Here, we report a similar distance dependence for orientation signal integration across stimulus differences in binocular disparity, direction of motion, and direction of figure-ground assignment. We also demonstrate that the selectivity found at short separations cannot be explained only by "end-cuts," the small borders created at the junction of abutting contrasting patterns. These findings imply the existence of two distinct spatial domains for the integration of foveal orientation information: a local zone in which integration is highly selective for a number of salient stimulus parameters and a long-range domain in which integration is relatively unselective and only requires that patterns be roughly collinear.

Contrast Sensitivity↗

PubMed1977

Absence of the eighth component of complement in association with systemic lupus erythematosus-like disease.

A 56-yr-old black woman with absence of the eighth component of complement and a disease compatible with systemic lupus erythematosus is described. Her disease is characterized by the presence of photosensitive "malar" rash, alopecia, polyarthritis, and nephrotic syndrome. Hemolytic and immunochemical assays of the serum complement components were normal, except for C8 which was undetectable. Hemolytic activity could be restored to normal by the addition of functionally pure C8. In vitro tests to investigate the functional integrity of the classical and alternative pathways indicated that the functions mediated by activation of C3 and C5 were intact whereas heatlabile bactericidal activity was totally absent. Addition of C8 restored this function to normal levels. One of two brothers of the proband was shown to have serum C8 levels approaching 50% of normal indicating the hereditary nature of the defect. HLA typing studies showed that the normal brother had identical haplotypes to the proband while the proposed heterozygous brother only shared one haplotype with the patient, suggesting that the gene controlling the C8 defect was not closely linked to the major histocompatibility complex. If the association of a connective tissue disease and absence of a terminal component of complement is not coincidental, these results suggest that C8 deficiency may be associated with a subtle defect in the defense mechanisms to viral infection leading to viral persistance and perhaps to diseases such as systemic lupus erythematosus where chronic viral infections have been implicated.

Complement C8↗

PubMed1979

ATPase activity of sulfhydryl-modified cardiac myosin from normal and isoproterenol-treated rats.

The possible role of sulfhydryl groups in the adaptation of cardiac myosin to work overload has been examined. The functional integrity of sulfhydryl groups was evaluated by measurement of Ca2+- and K+-(EDTA)-ATPase activities of myosins following sulfhydryl modification. No activation of Ca2+-ATPase of normal rat cardiac myosin was observed after pMB or NEM pretreatment. The decrease in Ca2+-ATPase of myosin from hypertrophied hearts was eliminated following sulfhydryl modification: moreover, slight stimulation of Ca2+-ATPase was observed. An increase in KCl concentration did not stimulate the Ca2+-ATPase of NEM-modified myosins obtained from either control or hypertrophied hearts. The sulfhydryl content of rat cardiac myosin expressed as moles of SH per 10(5) g of myosin was 6.99 +/- 0.30 and in IPR-induced hypertrophy did not change it significantly. In the authors' opinion an alteration in the integrity of the sulfhydryl groups may be responsible for the functional partition (decreased Ca2+-ATpase with unchanged K+-[EDTA]-ATPase activity) of myosin from hypertrophied hearts.

Adenosine Triphosphatases↗

PubMed1993

Effects of cycloheximide and tunicamycin on lysosomal cystine transport in rat FRTL-5 cells.

Rat thyroid FRTL-5 cells were employed to study the synthesis and degradation of a functional integral lysosomal membrane protein, the lysosomal cystine transporter. This carrier exhibited countertransport and closely resembled the cystine transport system of human leucocytes, fibroblasts, and lymphoblasts shown to be defective in the lysosomal storage disease, nephropathic cystinosis. Using cycloheximide to prevent new protein synthesis, the half-life of the FRTL-5 cell lysosomal cystine carrier was determined to approximate 21 h. Carrier function was not influenced by the N-glycosylation inhibitor tunicamycin, nor by the oligosaccharide processing inhibitors castanospermine and deoxymannojirimycin. The data suggest that the lysosomal cystine carrier is a protein without strict functional requirements for N-linked oligosaccharides, and that rat FRTL-5 cells can be employed in future investigations into the structure and function of other integral lysosomal membrane proteins as well.

Animals↗

PubMed1976

A psychometric study of chronic cerebellar stimulation in man.

Groups of patients with intractable epilepsy or spasticity of varying etiologies underwent psychological testing before and during chronic cerebellar cortex stimulation, a neurosurgical technique designed for the relief of these symptoms. The battery of psychological tests permitted a standardized assessment of intellectual, memory, and perceptual functions. Other behavioral dimensions were assessed through structured interviews. No apparent declines in higher integrative functions followed shorter or longer term cerebellar stimulation. In contrast, stimulated patients tended to show increments in tests of recent memory and verbal output beyond that of unoperated comparison groups. Subjective reports of increased "alertness" and reduced depression and anxiety were also frequently given. Psychological and neural factors may both contribute to the observed behavioral alterations. It was concluded that the cerebellum participates in behavioral functions by modifying cortical and subcortical mechanisms relevant to integrative behavior and emotions. Specific hypotheses were presented.

Adolescent↗

PubMed2002

Towards an integrative theory of cognition.

A framework is outlined for connecting brain imaging activity with the underlying biophysical properties of neural networks, and their mechanisms of action and organizing principles. The main thrust of the framework is a dynamic theory of semantics based on functional integration of biophysical neural networks. It asserts that higher-brain function arises from both synaptic and extrasynaptic integration in the neuropil where information on environmental changes are represented dynamically through a discourse of semantics. Consequently, integrative neural modeling is shown to be an important methodology for analyzing the response activities of functional imaging studies in elucidating the relationship between brain and structure, function and behavior.

Biophysical Phenomena↗