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At least 1,135 records · Page 63Linked to original sources
PubMed2004

In vitro toxicity of A-431 carcinoma cells with antibodies to epidermal growth factor receptor and epithelial glycoprotein-1 conjugated to radionuclides emitting low-energy electrons.

PURPOSE: The ability of antibodies (Abs) conjugated to radionuclides emitting low-energy electrons to specifically kill nonadherent lymphoma target cells in vitro was demonstrated previously. This study extends this work to adherent carcinoma cells. The fact that these cells are spread out on plastic can potentially make it more difficult to deliver radiation to the nucleus from decays in the cytoplasm or on the cell surface. EXPERIMENTAL DESIGN: The Abs tested were anti-epidermal growth factor receptor and anti-epithelial glycoprotein-1, conjugated to indium-111 or iodine-125, which emit low-energy Auger and conversion electrons. Conjugates of the beta-particle emitter, iodine-131, also were tested, for comparison. Abs were incubated with the cells for 2 days, and then the treated cells were assayed for colony-forming units. The radiation dose delivered to the nucleus was calculated from the cumulative decays per cell. RESULTS: With conjugates of (111)In, very potent killing was obtained with both of the Abs, with 100% kill (approximately 4-5 logs) even at subsaturating Ab concentrations. Lower levels of kill were obtained with (125)I or (131)I conjugates. Conjugates with (131)I, a beta-particle emitter, produced greater nonspecific toxicity. The greater potency of (111)In could be attributed to the higher specific activity that was obtained routinely with this radiolabel, up to 70 mCi/mg. Uptake of radioactivity peaked at approximately 200 cpm per cell. Dosimetry calculations, using subcellular S values, demonstrated that the toxicity observed was consistent with the amount of radiation delivered to the nucleus. CONCLUSIONS: These results are similar to previous results obtained with B lymphoma cells and indicate that this approach is applicable to a wide range of tumor types. Radionuclides emitting low-energy electrons are effective at killing target cells with relatively little nonspecific toxicity, if sufficient activity is delivered to the cell. Most Abs to high-density cell surface antigens would probably be effective.

Carcinoma, Squamous Cell↗
PubMed1999

Deletion of the ryanodine receptor type 3 (RyR3) impairs forms of synaptic plasticity and spatial learning.

Deletion of the ryanodine receptor type 3 (RyR3) results in specific changes in hippocampal synaptic plasticity, without affecting hippocampal morphology, basal synaptic transmission or presynaptic function. Robust long-term potentiation (LTP) induced by repeated, strong tetanization in the CA1 region and in the dentate gyrus was unaltered in hippocampal slices in vitro, whereas weak forms of plasticity generated by either a single weak tetanization or depotentiation of a robust LTP were impaired. These distinct physiological deficits were paralleled by a reduced flexibility in re-learning a new target in the water-maze. In contrast, learning performance in the acquisition phase and during probe trial did not differ between the mutants and their wild-type littermates. In the open-field, RyR3(-/-) mice displayed a normal exploration and habituation, but had an increased speed of locomotion and a mild tendency to circular running. The observed physiological and behavioral effects implicate RyR3-mediated Ca(2+) release in the intracellular processes underlying spatial learning and hippocampal synaptic plasticity.

Animals↗
PubMed1975

Identification of the cell population involved in viral-specific cell-mediated cytotoxicity in man: evidence for T cell specificity.

The nature of the cell population involved in lymphocyte mediated cytotoxicity to baby-hamster-kidney (BHK-21) target cells persistently infected with rubella virus was investigated by a 51Cr-release microassay. After depletion of the T cell population with an antiserum to human0thymus-lymphoid tissue antigen (HTLA), the purified B cell population showed a decrease in E-rosette formation (9.0 +/- 2.2% compared to 69.6 +/- 9.1% before treatment) and an insignificant degree of cytotoxic activity against rubella-infected target cells (specific immune release of 51Cr was 0.9 +/- 2.6% compared to 24.2 +/- 3.8 before treatment). A purified T cell population, prepared by depletion of B cells with an anti-human immunoglobulin serum and complement, was found to show no alteration in E-rosette formation (85.2 +/- 6.2%) or cytotoxicity (30.3 +/- 4.4% SIR) but showed decreased EA- and EAC-rosette formation (2.7 +/- 1.5% and 10.5 +/- 3.2%, respectively, compared to 19.4 +/- 2.9% and 28.0 +/- 4.1% before treatment). A monocyte-depleted population prepared by removal of the plastic adherent mononuclear cells showed no significant alteration of rosette formation or cytotoxicity. These experiments suggest that the predominant lymphoid population responsible for direct cell-mediated cytotoxicity to virus infected target cells in the 51Cr-release microassay appears to be effected by a thymus-dependent lymphocyte population.

Adult↗
PubMed2005

Neural correlates of reach errors.

Reach errors may be broadly classified into errors arising from unpredictable changes in target location, called target errors, and errors arising from miscalibration of internal models (e.g., when prisms alter visual feedback or a force field alters limb dynamics), called execution errors. Execution errors may be caused by miscalibration of dynamics (e.g., when a force field alters limb dynamics) or by miscalibration of kinematics (e.g., when prisms alter visual feedback). Although all types of errors lead to similar on-line corrections, we found that the motor system showed strong trial-by-trial adaptation in response to random execution errors but not in response to random target errors. We used functional magnetic resonance imaging and a compatible robot to study brain regions involved in processing each kind of error. Both kinematic and dynamic execution errors activated regions along the central and the postcentral sulci and in lobules V, VI, and VIII of the cerebellum, making these areas possible sites of plastic changes in internal models for reaching. Only activity related to kinematic errors extended into parietal area 5. These results are inconsistent with the idea that kinematics and dynamics of reaching are computed in separate neural entities. In contrast, only target errors caused increased activity in the striatum and the posterior superior parietal lobule. The cerebellum and motor cortex were as strongly activated as with execution errors. These findings indicate a neural and behavioral dissociation between errors that lead to switching of behavioral goals and errors that lead to adaptation of internal models of limb dynamics and kinematics.

Adolescent↗
PubMed1999

Seasonal plasticity of neuromuscular junctions in adult male Siberian hamsters (Phodopus sungorus).

Transfer of adult Siberian hamsters, Phodopus sungorus, from long day (16 h light and 8 h dark; 16L:8D) to short day (8L:16D) photoperiods induces an involution of the gonads and a cessation of reproductive behavior 8-10 weeks later. The motoneurons of the spinal nucleus of the bulbocavernosus and their target muscles, the bulbocavernosus and the levator ani, are sexually dimorphic and are necessary for successful reproduction by male mammals. We demonstrate that after transfer of adult male Siberian hamsters to short photoperiods, the bulbocavernosus motoneurons, their target muscles and neuromuscular junctions are all significantly smaller than those of males that remain under long day conditions. Photoperiod also affected the number of active zones within each neuromuscular junction, an apparent remodeling of these synapses. Thus, this neuromuscular system of adult Siberian hamsters demonstrates considerable seasonal plasticity in response to changes in photoperiod.

Animals↗
PubMed1980

Head fixation system for integration of radiodiagnostic and therapeutic procedures.

A head fixation system is described enabling exact transfer of positions between neuroradiological and therapeutic procedures. The key item of the system is a base plate that is rigidly attached to the patient's head, either by a plastic mould or screws onto the calvarium. The base plate may easily and accurately be attached to diagnostic or therapeutic units. Coordinates of target points in the various units are directly related through the exact application of the base plate. Procedures for the exact comparison of spatial information have been worked out. The system has been used for diagnostic procedures such as plain skull radiography, cerebral angiography, CT scanning, position emission tomography, and gamma camera examinations, as well as for therapeutic procedures such as stereotaxic biopsy and radiation treatment.

Head↗
PubMed1989

Modulation of NK activity by thymic hormones: in vitro effects of thymostimulin.

Plastic-adherent depleted or not depleted peripheral mononuclear blood cells (PMBC) from healthy donors showed enhanced lytic activity against 51Cr-labelled K562 target cells when exposed to thymostimulin (TS), 1 microgram ml-1, for 3 h, washed and incubated in TS-free medium before testing for natural killer (NK) cytotoxicity. No modification of NK cell activity was seen when effector cells were treated with placebo (splenic extract). The NK boosting activity of TS was lost when effector cells were treated for 3 h immediately before the performance of the cytotoxic test or when this thymic extract was added directly to the mixture of effector and target cells during the lytic phase of 51Cr release assay.

Cell Survival↗
PubMed1981

A new assay for cytotoxic lymphocytes, based on a radioautographic readout of 111 In release, suitable for rapid, semi-automated assessment of limit-dilution cultures.

A new assay for cytotoxic T lymphocytes is described, of general application, but particularly suitable for rapid, semi-automated assessment of multiple microculture tests. Target cells are labelled with high efficiency and to high specific activity with the oxine chelate of 111 indium. After a 3-4 h incubation of test cells with 5 X 10(3) labelled target cells in V wells of microtitre trays, samples of the supernatant are spotted on paper (5 microliter) or transferred to soft-plastic U wells (25-50 microliter) and the 111 In release assessed by radio-autography. Overnight exposure of X-ray film with intensifying screens at -70 degrees C gives and image which is an intense dark spot for maximum release, a barely visible darkening with the low spontaneous release, and a definite positive with 10% specific lysis. The degree of film darkening, which can be quantitated by microdensitometry, shows a linear relationship with cytotoxic T lymphocyte dose up to the 40% lysis level. The labelling intensity and sensitivity can be adjusted over a wide range, allowing a single batch of the short half-life isotope to serve for 2 weeks. The 96 assays from a single tray are developed simultaneously on a single small sheet of film. Many trays can be processed together, and handling is rapid if 96-channel automatic pipettors are used. The method allows rapid visual scanning for positive and negative limit dilution cultures in cytotoxic T cell precursor frequency and specificity studies. In addition, in conjunction with an automated densitometer designed to scan microtitre trays, the method provides an efficient alternative to isotope counting in routine cytotoxic assays.

Animals↗
PubMed1983

Basic aspects of development and maturation of the brain: embryological contributions to neuroendocrinology.

The interpretation of studies on the development of neuroendocrine function presupposes a thorough knowledge of the complementary phenomena of morphogenesis and histogenesis of the brain. A short analysis of the morphogenesis of the diencephalic floor is given. The pituitary Anlage can be identified early in the neural plate stage. The hypophysis cerebri appears to be a key structure in the morphogenesis of both the head and the brain. The spatiotemporal pattern of histogenesis within the brain can be analysed by a study of the proliferative activity of the neuroepithelial matrix cell layer; a heterochrony of matrix (ventricular) layer mitotic activity and of mantle (intermediate) layer differentiation can be demonstrated. The process of neuron differentiation shows an articulate sequence of phenomena, among them migration, axon growth, dendrite growth, synapse formation and myelination. Dendritogenesis and the development of synapses in a particular area are strongly influenced by the ingrowth of axon nerve terminals from elsewhere. A number of structures observed in the developing central nervous system are only temporary phenomena that go into regression during subsequent stages; dendrites and synapses especially show a high degree of plasticity. Cell death occurs as a normal concomitant of development. Monoaminergic neuron systems originate early and show a positive histofluorescence shortly afterwards; their target areas are retarded as far as differentiation is concerned. The development of these target regions probably is influenced by the monoaminergic cells. The monoaminergic neurons are not subject to feedback regulation for some time, because of the typical late development of the dendritic receptive apparatus in these cells. Steroid receptors may play a role in the development of intersexual dimorphism of the brain. Probably a modulation of neurotransmitter synthesis is the intermediate between steroid receptor stimulation and a change in synaptogenesis in the target area of the neuron. Neuropeptide systems appear to possess a distribution beyond the limits of the hypophysiotropic area. The early presence of some of the neuropeptides within the embryonic brain suggests a role in histogenesis that is different from the usually presumed neurotransmitter or neuromodulator function of the neuropeptides.

Animals↗
PubMed2005

Plasticity imbalance in mental disorders the neuroscience of psychiatry: implications for diagnosis and research.

In 1895 Freud tried to explain mental disorders using the neurophysiological knowledge of his time. He soon abandoned this attempt realizing it was immature considering the neuroscientific knowledge available to him. For the rest of his career he limited himself to psychological formulations. Along the same lines, lacking etiology for mental disorders, the diagnostic system of psychiatry is exclusively descriptive. The need for a brain related diagnosis of mental disorders is important for developing better treatments and more reliable diagnosis. Today with the development of neuroscience it is time to go back to Freud's initial attempts and explain mental disorders as altered neuronal organizations in the brain. The neural network level is chosen as the relevant description level for mental functions. Plasticity is chosen as a general concept for neuronal dynamics explaining neuropathology of psychiatric disorders. Plasticity is divided according to timescales into "fast plasticity," "slow plasticity" and "stable plasticity". It is proposed that normal mental functions require optimal balance among all the plasticity timescales. Mental disorders arise when such balance is disturbed, thus mental disorders could be reformulated as deficiencies of the different plasticity processes. Changes in coherence synchrony and phase-locking membrane potentials in cortically spread neuronal ensembles are all expressions of fast plasticity. Synaptogenic and neurogenic processes, such as brain derived neurotrophic factor-dependent processes, are defined as slow plasticity. Finally those synaptic and neuronal pathways that consolidated into long lasting circuits are referred to as stable plasticity. With the aid of a neural network model simulating the plasticity imbalance, a mathematical formulation could be realized for mental disorders. Once achieved this mathematical formulation could form a guiding framework for interpreting brain-imaging data collected from psychiatric patients. Such a model is realized using interconnected "modules" each simulating the relevant plasticity dynamics relevant for the model. Diagnosing plasticity imbalance has some advantages over current descriptive psychiatric diagnosis. It is brain-related thus less stigmatising in the sense that mental disorders are brain disorders and not "person" disorders. The diagnostic system is much more flexible allowing for a high degree of variations and combinations in the description of the disorders thus naturally accounting for comorbidities. Most importantly, this diagnostic model is brain-related offering research targets for intervention and a theoretical framework guiding such interventions.

Biomedical Research↗
PubMed2002

Chlorpyrifos targets developing glia: effects on glial fibrillary acidic protein.

The organophosphate pesticide, chlorpyrifos (CPF), is a developmental neurotoxicant. In cell cultures, CPF affects gliotypic cells to a greater extent than neuronotypic cells, suggesting that glial development is a specific target. We administered CPF to developing rats and examined the levels of glial fibrillary acidic protein (GFAP), an astrocytic marker. Prenatal CPF exposure (gestational days 17-20) elicited an increase in GFAP levels in fetal brain, but the effect was seen only at high doses that elicited maternal and fetal systemic toxicity. Early postnatal (PN) CPF treatment (PN1-4) elicited effects only in the cerebellum of male rats; GFAP was suppressed initially (PN5) and showed a rebound elevation (PN10) before returning to normal values by PN30. In contrast, when we administered CPF during the peak of gliogenesis and glial cell differentiation (PN11-14), GFAP was initially decreased across all brain regions and in both sexes; in males, subsequent elevations were seen on PN30, with the largest effect in the striatum; females also showed an increase in striatal GFAP. Our results indicate that CPF disrupts the pattern of glial development in vivo, with the maximum effect corresponding to the peak period of gliogenesis and glial cell differentiation. As glia are responsible for axonal guidance, synaptogenesis and neuronal nutrition, glial targeting suggests that these late-occurring developmental processes are vulnerable to CPF, extending the critical period for susceptibility into stages of synaptic plasticity, myelination, and architectural modeling of the developing brain.

Age Factors↗
PubMed2000

Antigenic diversity of Plasmodium falciparum and antibody-mediated parasite neutralization.

The malaria parasite Plasmodium falciparum, causing the most severe form of the disease in humans, is characterized by a broad antigenic diversity between different strains and isolates of the parasite. The antigenic diversity reflects on the one hand polymorphisms in allelic gene products and, on the other hand, antigenic variation as a result of expression of alternative genes in multigene families. Using selected polymorphic regions in two merozoite surface antigens, a method for genotyping P. falciparum parasites has been developed. This has resulted in new information on the clonal multiplicity and dynamics of parasite populations. Observations from in vivo and in vitro studies have identified many potential parasite-neutralizing immune responses and several of the target antigens are being explored as vaccine candidates. Studies of antibody-mediated neutralization of parasites in P. falciparum in vitro cultures, with or without leukocytes as effector cells, have been instrumental in identifying potential target antigens for protective immunity and for elucidation of the effects of immune pressure on the dynamics of parasite populations and their antigenic plasticity.

Adult↗
PubMed1996

Neuronal abnormalities in microtubule-associated protein 1B mutant mice.

Microtubules play an important role in establishing cellular architecture. Neuronal microtubules are considered to have a role in dendrite and axon formation. Different portions of the developing and adult brain microtubules are associated with different microtubule-associated proteins (MAPs). The roles of each of the different MAPs are not well understood. One of these proteins, MAP1B, is expressed in different portions of the brain and has been postulated to have a role in neuronal plasticity and brain development. To ascertain the role of MAP1B, we generated mice which carry an insertion in the gene by gene-targeting methods. Mice which are homozygous for the modification die during embryogenesis. The heterozygotes exhibit a spectrum of phenotypes including slower growth rates, lack of visual acuity in one or both eyes, and motor system abnormalities. Histochemical analysis of the severely affected mice revealed that their Purkinje cell dendritic processes are abnormal, do not react with MAP1B antibodies, and show reduced staining with MAP1A antibodies. Similar histological and immunochemical changes were observed in the olfactory bulb, hippocampus, and retina, providing a basis for the observed phenotypes.

Animals↗
PubMed2003

Migration of 2-butoxyethyl acetate from polycarbonate infant feeding bottles.

An enforcement campaign was carried out to assess the migration of 2-butoxyethyl acetate (2-BEA) from polycarbonate infant feeding bottles intended for repeated use. Migration was measured by three successive migration tests into two of the European Union official food simulants: distilled water and 3% acetic acid testing at 40 degrees C for 10 days. The Danish Veterinary and Food Administration (DVFA) has assessed that a migration above 0.33 mg for 2-BEA and a group of eight related substances kg(-1) foodstuff from plastics articles used exclusively for infants is unacceptable. Migration of 2-BEA was found from eight of 12 bottles. However, migration above the target value of 0.33 mg kg(-1) was not observed in the third decisive test from any of the 12 different brands of polycarbonate feeding bottles. A migration of between 0.05 and 0.26 mg kg(-1) from seven of 12 bottles was measured to 3% acetic acid in the third test, whereas no migration to distilled water was observed in the third test. The average recovery of 2-BEA after the 10-day exposure at the target value of 0.33 mg kg(-1) was 77% into distilled water and 36% into 3% acetic acid. The limited recovery was understandable as 2-BEA was partly hydrolysed in the aqueous food simulants and 2-butoxyethanol, a hydrolysis product and one of the related substances was identified. Quantification was carried out using gas chromatography after liquid/liquid extraction of the food simulant.

Acetates↗
PubMed2003

Escape of monocyte-derived dendritic cells of HIV-1 infected individuals from natural killer cell-mediated lysis.

OBJECTIVE: To verify whether the in vitro sensitivity of immature dendritic cells (iDC) to lysis by autologous natural killer (NK) cells from HIV-infected individuals might be correlated with HIV disease progression. DESIGN: Both dendritic cells (DC) and interlekin (IL)-2 activated NK cells were obtained from 13 HIV-infected individuals early after seroconversion and not receiving highly active antiretroviral therapy (HAART) and from 14 individuals with chronic HIV infection under HAART. The rate of NK cell-mediated killing of autologous iDC was correlated with classical parameters of HIV evolution. METHODS: Peripheral blood monocytes obtained from the Ficoll-derived leukocyte fraction after adherence to plastic were stimulated with granulocyte-macrophage colony stimulating factor plus IL-4 to induce their differentiation into iDC to be used as target cells in a standard 4-h cytotoxicity assay. A fraction of autologous leukocytes was stimulated with IL-2 to induce activation of NK cells to be used as effector cells. RESULTS: During early HIV infection the extent of ex vivo lysis of monocyte-derived DC by activated autologous NK cells was inversely and directly correlated with the levels of viraemia and with the percentage of circulating CD4 T cells, respectively. In contrast, the capacity of NK cells to kill iDC was lost independently of the levels of plasma viraemia or the concurrence of HAART in chronically infected individuals. Addition of exogenous HIV Tat during the cytotoxicity assay inhibited NK cell-mediated lysis of DC. CONCLUSIONS: NK cell-mediated immune surveillance against infected DC may be effective only during early HIV infection and may not be restored by HAART.

Adolescent↗
PubMed2006

Prism adaptation in the rehabilitation of patients with visuo-spatial cognitive disorders.

PURPOSE OF REVIEW: The traditional focus of neurorehabilitaion has been on the patients' attention on their deficit, such that they should become aware of their problems and gain intentional control of compensatory strategies (descending approach). We review prism adaptation as one of the approaches that emphasize ascending rather than descending strategies to the rehabilitation of visuo-spatial disorders. The clinical outcome of prism adaptation highlights the need for a theoretical reconsideration of some previous stances to neurological rehabilitation. RECENT FINDINGS: Recent years have given rise to a growing body of experimental studies showing that the descending strategy is not always optimal, especially when higher-level cognition is affected by the patients' condition. Ascending approaches have, for example, used visuo-manual adaptation for the rehabilitation of visuo-spatial deficits. A simple task of pointing to visual targets while wearing prismatic goggles can produce remarkable improvements of various aspects of unilateral neglect. SUMMARY: The neural mechanisms underpinning visuo-manual plasticity can be viewed as a powerful rehabilitation tool that produces straightforward effects not only on visual and motor parameters, but on visuo-spatial, attentional and higher cognitive neurological functions. The use of prism adaptation therapy in neglect and other visuo-spatial disorders has just started to reveal its potential, both at a practical and theoretical level.

Adaptation, Physiological↗
PubMed1993

Pathogenesis of infections related to intravascular catheterization.

Over the past few decades, there have been major technological improvements in the manufacture of intravenous solutions and the manufacture and design of catheter materials. However, the risk of infection in patients receiving infusion therapy remains substantial, in part because of host factors (for example, increased use of immunosuppressive therapy, more aggressive surgery and life support, and improved survival at the extremes of life) and in part because of the availability of catheters that can be left in place for very long periods. Microbial components of normal skin flora, particularly coagulase-negative staphylococci, have emerged as the predominant pathogens in catheter-associated infections. Therefore, efforts to prevent skin microorganisms from entering the catheter wound (such as tunnelling of catheters and use of catheter cuffs and local antimicrobial agents) are logical and relatively effective. The specific properties of microorganisms that transform normally harmless commensals such as coagulase-negative staphylococci into formidable pathogens in the presence of a plastic foreign body are being explored. For example, Staphylococcus epidermidis elaborates a polysaccharide adhesin that also functions as a capsule and is a target for opsonic killing. However, the interactions between microorganism and catheter that lead to adherence, persistence, infection, and dissemination appear to be multifactorial.

Animals↗
PubMed2004

Neurogenic pain relief by repetitive transcranial magnetic cortical stimulation depends on the origin and the site of pain.

OBJECTIVE: Drug resistant neurogenic pain can be relieved by repetitive transcranial magnetic stimulation (rTMS) of the motor cortex. This study was designed to assess the influence of pain origin, pain site, and sensory loss on rTMS efficacy. PATIENTS AND METHODS: Sixty right handed patients were included, suffering from intractable pain secondary to one of the following types of lesion: thalamic stroke, brainstem stroke, spinal cord lesion, brachial plexus lesion, or trigeminal nerve lesion. The pain predominated unilaterally in the face, the upper limb, or the lower limb. The thermal sensory thresholds were measured within the painful zone and were found to be highly or moderately elevated. Finally, the pain level was scored on a visual analogue scale before and after a 20 minute session of "real" or "sham" 10 Hz rTMS over the side of the motor cortex corresponding to the hand on the painful side, even if the pain was not experienced in the hand itself. RESULTS: and discussion: The percentage pain reduction was significantly greater following real than sham rTMS (-22.9% v -7.8%, p = 0.0002), confirming that motor cortex rTMS was able to induce antalgic effects. These effects were significantly influenced by the origin and the site of pain. For pain origin, results were worse in patients with brainstem stroke, whatever the site of pain. This was consistent with a descending modulation within the brainstem, triggered by the motor corticothalamic output. For pain site, better results were obtained for facial pain, although stimulation was targeted on the hand cortical area. Thus, in contrast to implanted stimulation, the target for rTMS procedure in pain control may not be the area corresponding to the painful zone but an adjacent one. Across representation plasticity of cortical areas resulting from deafferentation could explain this discrepancy. Finally, the degree of sensory loss did not interfere with pain origin or pain site regarding rTMS effects. CONCLUSION: Motor cortex rTMS was found to result in a significant but transient relief of chronic pain, influenced by pain origin and pain site. These parameters should be taken into account in any further study of rTMS application in chronic pain control.

Adult↗