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PubMed2003

Allelic diversity in the host genetic background may be an important determinant in tumor metastatic dissemination.

Metastasis, the spread and growth of tumors at secondary sites, is an extremely important clinical event, since the majority of cancer mortality is associated with the metastatic tumors rather than the primary tumor. In spite of the importance of metastasis in the clinical setting, the actual process is extremely inefficient. Millions of tumor cells can be shed into the vasculature daily yet few secondary tumors are formed. To successfully colonize a distant site tumor cells must overcome a series of barriers. Failure to complete any single step in the metastatic cascade abrogates the ability to form a secondary lesion. A variety of theories have been proposed to explain the inefficiency of the metastatic process. The most commonly accepted, the progression theory, posits a series of random mutational occurs within a primary tumor to generate a small subpopulation that acquires full metastatic capability. While significant evidence supports this model, recent discoveries demonstrating the ability to predict metastatic propensity from gene expression profiles in bulk tumor tissue are not consistent with only a small subpopulation of cells in the primary tumor acquiring metastatic ability. A second theory of metastatic inefficiency, the transient compartment theory, is more consistent with the microarray data, but does not completely explain observations like metastasis associated loss-of-heterozygosity events. To reconcile the observed results additional variables need to be added to the model of metastatic inefficiency. One possible variable that might explain the discrepancies is genetic background effects. Studies have demonstrated that the genetic background a tumor arises on can have significant affects on the ability of the tumor to metastasize and on gene expression profiles. Thus the observations could be reconciled by combining the theories, with genetic background influencing both metastatic efficiency and predictive gene expression profiles, upon which subsequently occur metastasis-promoting mutational and epigenetic events. If the genetic background is an important determinant of metastatic efficiency it would have significant implications for the clinical prediction and treatment of metastatic disease, as well as for the design of potential prevention strategies.

Animals↗

PubMed1999

Precursors of dangerous substances formed in the loss of control of chemical systems.

Article 2 of Directive 96/82/EC on the control of major accident hazards caused by dangerous substances requires to consider also the hazards due to the dangerous substances "which it is believed may be generated during loss of control of an industrial chemical process", although no generally accepted guidelines are available for the identification of these substances. In the present study, the accidents involving the unwanted formation of dangerous substances as a consequence of the loss of control of chemical systems were investigated. A specifically developed database was used, containing data on more than 400 of these accidents and on the substances involved. The hazardous substances formed in the accidents and the precursors of these substances were identified. The influence of accident characteristics on the substances formed was investigated. In the context of the application of Directive 96/82/EC, an accident severity index and a hazard rating of the precursors of dangerous substances formed in the accidents were proposed. A lumping approach was used in order to develop schemes for the preliminary identification of substances that may be formed in the loss of control of chemical system. The results of accident analysis were used to test the schemes developed.

Accidents, Occupational↗

PubMed1999

Volumetric visualization of head and neck CT data for treatment planning.

PURPOSE: To demonstrate the utility of volume rendering, an alternative visualization technique to surface rendering, in the practice of CT based radiotherapy planning for the head and neck. METHODS AND MATERIALS: Rendo-avs, a volume visualization tool developed at the University of Chicago, was used to volume render head and neck CT scans from two cases. Rendo-avs is a volume rendering tool operating within the graphical user interface environment of AVS (Application Visualization System). Users adjust the opacity of various tissues by defining the opacity transfer function (OTF), a function which preclassifies voxels by opacity prior to rendering. By defining the opacity map (OTF), the user selectively enhances and suppresses structures of various intensity. Additional graphics tools are available within the AVS network, allowing for the manipulation of perspective, field of view, data orientation. Users may draw directly on volume rendered images, create a partial surface, and thereby correlate objects in the 3D scene to points on original axial slices. Information in volume rendered images is mapped into the original CT slices via a Z buffer, which contains the depth information (Z coordinate) for each pixel in the rendered view. Locally developed software was used to project conventionally designed GTV contours onto volume rendered images. RESULTS: The lymph nodes, salivary glands, vessels, and airway are visualized in detail without prior manual segmentation. Volume rendering can be used to explore the finer anatomic structures that appear on consecutive axial slices as "points." Rendo-avs allowed for acceptable interactivity, with a processing time of approximately 5 seconds per 256 x 256 pixel output image. CONCLUSIONS: Volume rendering is a useful alternative to surface rendering, offering high-quality visualization, 3D anatomic delineation, and time savings to the user, due to the elimination of manual segmentation as a preprocessing step. Volume rendered images can be merged with conventional treatment planning images to add anatomic information to the treatment planning process.

Head↗

PubMed2001

Glial cell abnormalities in major psychiatric disorders: the evidence and implications.

Recent quantitative post-mortem investigations of the cerebral cortex have convincingly demonstrated cortical glial cell loss in subjects with major depression. Evidence is also mounting that glial cell loss may also be a feature of schizophrenia. These findings coincide with a re-evaluation of the importance of glial cells in normal cortical function. In addition to their traditional roles in neuronal migration and inflammatory processes, glia are now accepted to have roles in providing trophic support to neurons, neuronal metabolism, and the formation of synapses and neurotransmission. Consequently, reduced cortical glial cell numbers could be responsible for some of the pathological changes in schizophrenia and depression, including reduced neuronal size, reduced levels of synaptic proteins, and abnormalities of cortical neurotransmission. Additionally, as astrocytes provide the energy requirements of neurons, deficient astrocyte function could account for aspects of the functional magnetic imaging abnormalities found in these disorders. We discuss the possible basis of glial cell loss in these disorders and suggest that elevated levels of glucocorticoids, due to illness-related stress or to hyperactivity of the hypothalamic-pituitary-adrenal may down-regulate glial activity and so predispose to, or exacerbate psychiatric illness through enhanced excitotoxicity. The potential therapeutic impact of agents which up-regulate glial activity or normalise glial cell numbers is also discussed.

Cell Death↗

PubMed2003

The role of oxidant stress and reactive nitrogen species in acetaminophen hepatotoxicity.

Acetaminophen (AAP) overdose can cause severe hepatotoxicity and even liver failure in experimental animals and humans. Despite substantial efforts over the last 30 years, the mechanism of AAP-induced liver cell injury is still not completely understood. It is widely accepted that the injury process is initiated by the metabolism of AAP to a reactive metabolite, which first depletes glutathione and then binds to cellular proteins including a number of mitochondrial proteins. One consequence of this process may be the observed inhibition of mitochondrial respiration, ATP depletion and mitochondrial oxidant stress. In the presence of sufficient vitamin E, reactive oxygen formation does not induce severe lipid peroxidation but the superoxide reacts with nitric oxide to form peroxynitrite, a powerful oxidant and nitrating agent. Peroxynitrite can modify cellular macromolecules and may aggravate mitochondrial dysfunction and ATP depletion leading to cellular oncotic necrosis in hepatocytes and sinusoidal endothelial cells. Thus, we hypothesize that reactive metabolite formation and protein binding initiate the injury process, which may be then propagated and amplified by mitochondrial dysfunction and peroxynitrite formation. This concept also reconciles many of the controversial findings of the past and provides a viable hypothesis for the mechanism of hepatocellular injury after AAP overdose.

Acetaminophen↗

PubMed2003

Epileptic seizures are preceded by a decrease in synchronization.

The exact mechanisms leading to the occurrence of epileptic seizures in humans are still poorly understood. It is widely accepted, however, that the process of seizure generation is closely associated with an abnormal synchronization of neurons. In order to investigate this process, we here measure phase synchronization between different regions of the brain using intracranial EEG recordings. Based on our preliminary finding of a preictal drop in synchronization, we investigate whether this phenomenon can be used as a sensitive and specific criterion to characterize a preseizure state and to distinguish this state from the interictal interval. Applying an automated technique for detecting decreased synchronization to EEG recordings from a group of 18 patients with focal epilepsy comprising a total of 117 h, we observe a characteristic decrease in synchronization prior to 26 out of 32 analyzed seizures at a very high specificity as tested on interictal recordings. The duration of this preictal state is found to range from several minutes up to a few hours. Investigation of the spatial distribution of preictal desynchronization indicates that the process of seizure generation in focal epilepsy is not necessarily confined to the focus itself but may instead involve more distant, even contralateral areas of the brain. Finally, we demonstrate an intrahemispheric asymmetry in the spatial dynamics of preictal desynchronization that is found in the majority of seizures and appears to be an immanent part of the mechanisms underlying the initiation of seizures in humans.

Adult↗

PubMedDate not supplied

Recognizing the phenomenon of readiness: concept analysis and case study.

The concept of a phenomenon known as readiness will be analyzed. Using the Wilsonian method, the concept is broken down into a practical definition that allows nurses to assess this phenomenon in clinical practice. Nurses in AIDS care work with a patient population whose optimal health is often dependent on the ability to incorporate major lifestyle changes into their daily lives. Nursing interventions that assist patients to incorporate change must be presented to patients at a time when the patient's ability to succeed is optimal. The ability to recognize readiness in patients is essential for nurses providing AIDS care. This article discusses the concept of readiness, which may be necessary before behavior modification can occur. The phenomenon of readiness has application for various changes in behaviors, including adherence to primary prevention strategies.

Decision Making↗

PubMed1988

Grief in multifetal death.

The grief process is examined within the framework of multifetal pregnancy in a variety of demise situations. The case studies examined were obtained from approximately 120 letters and interviews with families predominantly of higher order multiple births, who have experienced either partial or total loss in their pregnancy or afterwards. Objective and subjective factors were addressed. Results indicate the steps of the grief response are worked through in the same order as a singleton demise, but differ in intensity, duration, and frequency, depending on the individual circumstances, type of loss, gestational age, and the parents' backgrounds, expectations and beliefs. A unique feature discovered is that the entire grieving process, from shock through acceptance, appears to be completely experienced twice, with a large percentage of parents experiencing all of the stages three or more times. The general conclusion of the study is that the grieving pattern in multifetal death indeed follows a cycle and pattern of its own and requires special considerations.

Female↗

PubMed2004

Ganglioside/glycosphingolipid turnover: new concepts.

In this review focus is given to the metabolic turnover of gangliosides/glycosphingolipids. The metabolism and accompanying intracellular trafficking of gangliosides/glycosphingolipids is illustrated with particular attention to the following events: (a) the de novo biosynthesis in the endoplasmic reticulum and Golgi apparatus, followed by vesicular sorting to the plasma membrane; (b) the enzyme-assisted chemical modifications occurring at the plasma membrane level; (c) the internalization via endocytosis and recycling to the plasma membrane; (d) the direct glycosylations taking place after sorting from endosomes to the Golgi apparatus; (e) the degradation at the late endosomal/lysosomal level with formation of fragments of sugar (glucose, galactose, hexosamine, sialic acid) and lipid (ceramide, sphingosine, fatty acid) nature; (f) the metabolic recycling of these fragments for biosynthetic purposes (salvage pathways); and (g) further degradation of fragments to waste products. Noteworthy, the correct course of ganglioside/glycosphingolipid metabolism requires the presence of the vimentin intracellular filament net work, likely to assist intracellular transport of sphingoid molecules. ut of the above events those that can be quantitatively evaluated with acceptable reliability are the processes of de novo biosynthesis, metabolic salvage and direct glycosylation. Depending on the cultured cells employed, the percentage of distribution of de novo biosynthesis, salvage pathways, and direct glycosylation, over total metabolism were reported to be: 35% (range: 10-90%) for de novo biosynthesis, 7% (range: 5-10%) for direct glycosylation, and 58% (range: 10-90%) for salvage pathways. The attempts made to calculate the half-life of overall ganglioside turnover provided data of unsure reliability, especially because in many studies salvage pathways were not taken into consideration. The values of half-life range from 2 to 6.5 h to 3 days depending on the cells used. Available evidence for changes of ganglioside/glycosphingolipid turnover, due to extracellular stimuli, is also considered and discussed.

Animals↗

PubMed2006

De-ubiquitinating enzymes: intracellular signalling and disease.

Ubiquitination is now accepted as an important process for regulating intracellular signalling and the realization that many known signalling molecules exhibit E3 ligase activity has led to great strides in our understanding of how these pathways are regulated. However, as most of the de-ubiquitinating enzymes have as yet no identified substrate, little is known about their potential role in the regulation of intracellular signalling. Here, we examine what is known about de-ubiquitinating enzymes and signalling, with particular emphasis on their role in the regulation of immune signalling and the initiation of DNA repair. In addition, we look at the evidence implicating these enzymes in the pathogenesis of diseases such as cancer and neurodegenerative diseases.

Animals↗

PubMed1998

Towards a politics of trust.

This paper draws upon sociological theory to demonstrate that the manufacture and deployment of trust is an integral part of the function of complex systems such as health care. The discussion begins by identifying the error within the nursing literature which arises from a rather technical conceptualization of trust. This tends to limit the dimensions to trust which is established, and fails to recognize that trust may be subject to competition and conflict. The paper continues by drawing upon the work of two theorists, Niklas Luhmann and Susan P. Shapiro, to demonstrate how trust functions within systems such as health care and the mechanisms through which it is controlled. The title of this paper, 'Towards a politics of trust', identifies that this is merely the first stage in the analysis. Further stages are necessary which analyse the ways in which power is exercised in the conflict for control within discrete elements of the system.

Health Care Reform↗

PubMed2003

Training needs of midwifery assistants.

BACKGROUND: Increasingly in the United Kingdom (UK) assistants are being introduced as part of the midwifery workforce. However, there appears to be little standardization in the qualifications and training provided. AIM: The aim of this study was to investigate what an educational programme for midwifery assistants should contain. RESEARCH METHODS: A total of 100 qualified midwives and 58 midwifery students were asked to complete a mailed questionnaire and subsequently 20 of these respondents were interviewed. RESULTS: Respondents identified three levels of competencies that midwifery assistants should possess. They also acknowledged that midwives required specific training in how best to supervise assistants. Respondents maintained that each assistant should have a clinically-based midwifery mentor and that rotation around different clinical areas should be included as part of a training programme. Furthermore, it was stressed that because midwives initiate, teach and supervise assistants, they should have a key role in planning training programmes and in the teaching and assessment processes. Nonetheless, it was accepted that such a role could divert the midwife from valuable contact time with the mother and baby, the opposite of what the introduction of assistants was intended to do. CONCLUSIONS: Before working in clinical areas midwifery assistants need practice-based training that focuses on skills development. Communications and interpersonal skills should be included in the training as should placement experience in a variety of clinical settings. Midwives have a role in providing this training, and in mentoring and supervising midwifery assistants, but it is accepted that this could add to their workloads. Developments of this kind need to be evaluated, especially in terms of the impact on direct care by midwives.

Attitude of Health Personnel↗

PubMed2003

Extra-adrenal production of corticosteroids.

1. The major corticosteroids aldosterone and cortisol (corticosterone in rodents) are secreted from the adrenal cortex under the regulation of the renin-angiotensin system and the hypothalamic-pituitary-adrenal axis. 2. In addition to their accepted roles in such processes as blood pressure regulation, glycogenesis, hepatic glyconeogenesis and immunosuppression, the corticosteroids have been implicated in the development of cardiac fibrosis, modulation of hippocampal neuron excitability, memory formation and neurodegeneration. 3. The advent of sensitive molecular biological techniques has produced a wealth of evidence to support the existence of extra-adrenal corticosteroidogenic systems. Most attention has been paid to the cardiovascular system and the central nervous system, where the full array of enzymes required for the de novo synthesis of corticosteroids from cholesterol has been identified. 4. Although the evidence for local corticosteroid production is strong, the quantities of steroid would be small compared with adrenal production. Therefore, it is still a matter of debate as to whether extra-adrenal corticosteroids are of any physiological significance. This will depend on factors such as local concentration, proximity to target cells and, possibly, to tissue-specific control mechanisms.

Adrenal Cortex Hormones↗

PubMed2002

Resistance to propagation of amygdaloid kindling seizures in rats with genetic absence epilepsy.

PURPOSE: The existence of absence epilepsy and temporal partial seizure pattern in the same patient is an uncommon state. In the present study, we aimed to evaluate whether the process of kindling as a model of complex partial seizures with secondary generalization is altered in rats with genetic absence epilepsy. METHODS: Six- to 12-month-old nonepileptic control Wistar rats and genetic absence epileptic rats from Strasbourg (GAERS) were used in the experiments. One week before the experiments, bilateral stimulation and recording electrodes were implanted stereotaxically into the basolateral amygdala and cortex, respectively. Animals were stimulated at their afterdischarge threshold current twice daily for the process of kindling and accepted as fully kindled after the occurrence of five grade 5 seizures. Bilateral EEGs from amygdala and cortex were recorded continuously during 20 min before and 40 min after each stimulus. RESULTS: All control Wistar rats were fully kindled after stimulus 12 to 15. Although the maximal number of stimulations had been applied, GAERS remained at stage 2, and no motor seizures were observed. The afterdischarge duration in bilateral amygdala and the cortex after the kindling stimulus was shorter in GAERS when compared with control rats. CONCLUSIONS: Occurrence of only grade 2 seizures and no observation of grade 3-5 seizures in GAERS with the maximal number of stimulations would suggest that the generalized absence seizures may be the reason of the resistance in the secondary generalization of limbic seizures during amygdala kindling.

Amygdala↗

PubMed2002

Four applications of reinforced polyethylene fiber material in orthodontic practice.

Four different orthodontic applications of a polyethylene fiber material are shown and discussed in case reports. Ribbond (Ribbond Inc, Seattle, Wash), a bondable, reinforced polyethylene fiber material, was successfully used in a fixed orthodontic retainer, a space maintainer, a temporary postorthodontic fixation device to attach a pontic to abutment teeth during periodontal therapy, and a posttraumatic stabilization splint. This clinical practice was based on earlier studies showing that the polyethylene fiber material adapted easily to dental contours and could be manipulated during the bonding process. It also has acceptable strength because of good integration of fibers with composite resin; this leads to good clinical longevity. Because thinner composite resins can be used, the volume of the splint can be minimized. There is no need for significant tooth structure removal, so the technique is reversible and conservative. It also satisfies patients' esthetic expectations. These cases show that Ribbond is a promising splint material for use in orthodontic practice.

Adolescent↗

PubMed2001

Septo-optic dysplasia with olfactory tract and bulb hypoplasia.

Optic nerve hypoplasia can be associated with other central nervous system malformations. When associated with absence of the septum pellucidum or thinning of the corpus callosum, it is termed septo-optic dysplasia. Considered to be a first trimester event, the embryologic timing and etiology of this syndrome still is not clearly defined. This report represents the first documented case of septo-optic dysplasia with associated hypoplasia of the olfactory tract. Optic nerve hypoplasia is attributed to an abnormal developmental process during gestation. Generally accepted to be due to a first trimester insult, the timing of this abnormality has been debated given its association with other central nervous system abnormalities. These central nervous system abnormalities often include cerebral hemispheric and hypothalmic-pituitary axis abnormalities. Specifically, the presence of optic nerve hypoplasia with absence of the septum pellucidum and thinning of the corpus callosum has been termed septo-optic dysplasia or de Morsier's syndrome. Septo-optic dysplasia in association with olfactory tract and bulb hypoplasia has not been reported previously.

Abnormalities, Multiple↗

PubMed1989

Spatial and orientation specific integration in the tilt illusion.

Lateral inhibition across a population of cells in visual cortex which are tuned to local orientation has been proposed and widely accepted as a basic process in the analysis of contour in the visual field. The tilt illusion is usually explained in terms of this inhibition. Experiments are reported which cast new light on the analysis of visual orientation. It is shown that tilt illusions may be obtained with very thin inducing annuli which are spatially remote from the test figure. In experiments in which remote crossed-grating plaids were used, an illusion which was pattern (global) rather than component (local) selective was seen. It is difficult to account for these observations in terms of local inhibitory mechanisms. Rather, the results support the existence of a secondary mechanism which is involved in basic orientation analytic processes. The relevance of these observations to models of visual contour analysis is discussed.

Attention↗

PubMed1998

Interaction between like-charged colloidal spheres in electrolyte solutions.

How colloidal particles interact with each other is one of the key issues that determines our ability to interpret experimental results for phase transitions in colloidal dispersions and our ability to apply colloid science to various industrial processes. The long-accepted theories for answering this question have been challenged by results from recent experiments. Herein we show from Monte-Carlo simulations that there is a short-range attractive force between identical macroions in electrolyte solutions containing divalent counterions. Complementing some recent and related results by others, we present strong evidence of attraction between a pair of spherical macroions in the presence of added salt ions for the conditions where the interacting macroion pair is not affected by any other macroions that may be in the solution. This attractive force follows from the internal-energy contribution of counterion mediation. Contrary to conventional expectations, for charged macroions in an electrolyte solution, the entropic force is repulsive at most solution conditions because of localization of small ions in the vicinity of macroions. Both Derjaguin-Landau-Verwey-Overbeek theory and Sogami-Ise theory fail to describe the attractive interactions found in our simulations; the former predicts only repulsive interaction and the latter predicts a long-range attraction that is too weak and occurs at macroion separations that are too large. Our simulations provide fundamental "data" toward an improved theory for the potential of mean force as required for optimum design of new materials including those containing nanoparticles.

Journal Article↗