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Biomedical subjects

Z Kis

Publications and source records attributed to Z Kis.

At least 19 recordsLinked to original sources

A soluble factor(s) released by MRC-5 cells early and late after human cytomegalovirus infection induces maturation of monocyte-derived dendritic cells.

A human cytomegalovirus (HCMV) strain passaged 10 times on MRC-5 human fibroblast cells failed to express immediate early (IE) antigens in immature dendritic cells (iDCs) after infection. However, both the early and the late HCMV conditioning medium, harvested from MRC-5 cells at 24 h or 7-9 days after infection, respectively, induced a higher ratio of DCs expressing maturation markers (CD40, CD83, CD86 and HLA-DR) on the surface of the cells. HCMV conditioning medium, ultracentrifuged to remove virus particles, exhibited a similarly enhanced expression of DC maturation markers. DCs treated with HCMV conditioning medium harvested late after infection increased the percentages of autologous CD4+ and CD8+ cells of seropositive donors to produce IFN-gamma and stimulated HCMV-specific lymphoproliferative responses. The early HCMC conditioning medium was also able to induce the functional maturation of DCs, as demonstrated by supplementing this medium with a Chlamydia pneumoniae antigen.

B7-2 Antigen↗

Radionuclides in fruit systems: model prediction-experimental data intercomparison study.

This paper presents results from an international exercise undertaken to test model predictions against an independent data set for the transfer of radioactivity to fruit. Six models with various structures and complexity participated in this exercise. Predictions from these models were compared against independent experimental measurements on the transfer of 134Cs and 85Sr via leaf-to-fruit and soil-to-fruit in strawberry plants after an acute release. Foliar contamination was carried out through wet deposition on the plant at two different growing stages, anthesis and ripening, while soil contamination was effected at anthesis only. In the case of foliar contamination, predicted values are within the same order of magnitude as the measured values for both radionuclides, while in the case of soil contamination models tend to under-predict by up to three orders of magnitude for 134Cs, while differences for 85Sr are lower. Performance of models against experimental data is discussed together with the lessons learned from this exercise.

Cesium Radioisotopes↗

Chlamydophila pneumoniae and human cytomegalovirus in atherosclerotic carotid plaques--combined presence and possible interactions.

The aim of our study was to investigate the combination of Chlamydophila pneumoniae and human cytomegalovirus (HCMV) as a pathogenic factor in atherosclerosis. Accordingly, we tested by means of PCR and immunohistochemistry the presence of these pathogens in the same atherosclerotic carotid specimen. The histology of the samples and the patients' antibodies against these pathogens were evaluated. Further, we examined the impact of C. pneumoniae and HCMV infection on the gene expression of the human monocytic cell line U937. Six of the 22 samples contained only C. pneumoniae, 4 contained only HCMV, 7 contained both C. pneumoniae DNA and/or antigens of both pathogens, and 5 samples were negative. No correlation was found between the presence of these microbes and either the cellular structure of the plaques, or the serostatus of the patients. The infection of U937 cells with HCMV and especially C. pneumoniae induced inflammation and atherosclerosis-related genes. Furthermore, the doubly-infected cells produced higher levels of the mRNA of pro-platelet basic protein and fatty acid binding protein 4. In conclusion, C. pneumoniae is often present in combination with HCMV in atherosclerotic carotid lesions. The in vitro coinfection model reveals that the doubly-infected monocytes are potent expressors of proatherosclerotic genes, suggesting that this coinfected population may accelerate the process of atherosclerosis.

Aged↗

Identifying optimal agricultural countermeasure strategies for a hypothetical contamination scenario using the strategy model.

A spatially implemented model designed to assist the identification of optimal countermeasure strategies for radioactively contaminated regions is described. Collective and individual ingestion doses for people within the affected area are estimated together with collective exported ingestion dose. A range of countermeasures are incorporated within the model, and environmental restrictions have been included as appropriate. The model evaluates the effectiveness of a given combination of countermeasures through a cost function which balances the benefit obtained through the reduction in dose with the cost of implementation. The optimal countermeasure strategy is the combination of individual countermeasures (and when and where they are implemented) which gives the lowest value of the cost function. The model outputs should not be considered as definitive solutions, rather as interactive inputs to the decision making process. As a demonstration the model has been applied to a hypothetical scenario in Cumbria (UK). This scenario considered a published nuclear power plant accident scenario with a total deposition of 1.7x10(14), 1.2x10(13), 2.8x10(10) and 5.3x10(9)Bq for Cs-137, Sr-90, Pu-239/240 and Am-241, respectively. The model predicts that if no remediation measures were implemented the resulting collective dose would be approximately 36 000 person-Sv (predominantly from 137Cs) over a 10-year period post-deposition. The optimal countermeasure strategy is predicted to avert approximately 33 000 person-Sv at a cost of approximately 160 million pounds. The optimal strategy comprises a mixture of ploughing, AFCF (ammonium-ferric hexacyano-ferrate) administration, potassium fertiliser application, clean feeding of livestock and food restrictions. The model recommends specific areas within the contaminated area and time periods where these measures should be implemented.

Agriculture↗

Pentapeptides derived from Abeta 1-42 protect neurons from the modulatory effect of Abeta fibrils--an in vitro and in vivo electrophysiological study.

Short fragments and fragment analogues of beta-amyloid 1-42 peptide (Abeta1-42) display a protective effect against Abeta-mediated neurotoxicity. After consideration of our earlier results with in vitro bioassay of synthetic Abeta-recognition peptides and toxic fibrillar amyloids, five pentapeptides were selected as putative neuroprotective agents: Phe-Arg-His-Asp-Ser amide (Abeta4-8) and Gly-Arg-His-Asp-Ser amide (an analogue of Abeta4-8), Leu-Pro-Tyr-Phe-Asp amide (an analogue of Abeta17-21), Arg-Ile-Ile-Gly-Leu amide (an analogue of Abeta30-34), and Arg-Val-Val-Ile-Ala amide (an analogue of Abeta38-42). In vitro electrophysiological experiments on rat brain slices demonstrated that four of these peptides counteracted with the field excitatory postsynaptic potential-attenuating effect of Abeta1-42; only Arg-Val-Val-Ile-Ala amide proved inactive. In in vivo experiments using extracellular single-unit recordings combined with iontophoresis, all these pentapeptides except Arg-Val-Val-Ile-Ala amide protected neurons from the NMDA response-enhancing effect of Abeta1-42 in the hippocampal CA1 region. These results suggest that Abeta recognition sequences may serve as leads for the design of novel neuroprotective compounds.

Action Potentials↗

Engineering mixed states in a degenerate four-state system.

A method is proposed for preparing any pure and wide class of mixed quantum states in the decoherence-free ground-state subspace of a degenerate multilevel lambda system. The scheme is a combination of optical pumping and a series of coherent excitation processes, and for a given pulse sequence the same final state is obtained regardless of the initial state of the system. The method is robust with respect to the fluctuation of the pulse areas, as in adiabatic methods; however, the field amplitude can be adjusted in a larger range.

Journal Article↗

The interactions between human dendritic cells and microbes; possible clinical applications of dendritic cells.

The dendritic cells comprise several subsets that induce and regulate the immune responses against foreign and self-antigens, and that can therefore function as initiators of protective immunity and inducers of central or peripheral tolerance. The different subpopulations of dendritic cells interact with and also influence other cell populations of the immune system, such as T and B lymphocytes and natural killer cells. The factors that determine the given dendritic cell functions depend on the state of maturation and the local microenvironment. The interactions between dendritic cells and microorganisms are rather complex, but progress in the past few years has shed light on several aspects of these interactions. This review lays emphasis on the interactions between human dendritic cells, important components of the intima of arterial specimens at areas predisposed to atherosclerotic lesions, and Chlamydia pneumoniae and cytomegalovirus, the human pathogens most strongly implicated in the development of atherosclerosis. In addition, several examples of the potential clinical applications of dendritic cells are described.

Arteriosclerosis↗

Kynurenine administered together with probenecid markedly inhibits pentylenetetrazol-induced seizures. An electrophysiological and behavioural study.

The kynurenine pathway converts tryptophan into various compounds, including l-kynurenine, which in turn can be converted to the excitatory amino acid receptor antagonist kynurenic acid, which may therefore serve as a protective agent in such neurological disorders as epileptic seizures. Kynurenic acid, however, has a very limited ability to cross the blood-brain barrier, whereas kynurenine passes the barrier easily. In this study, we tested the hypothesis that kynurenine administered systemically together with probenecid, which inhibits kynurenic acid excretion from the cerebrospinal fluid, results in an increased level of kynurenic acid in the brain that is sufficiently high to provide protection against the development of pentylentetrazol-induced epileptic seizures. CA3 stimulation-evoked population spike activity was recorded from the pyramidal layer of area CA1 of the rat hippocampus, and in another series of behavioural experiments, water maze and open-field studies were carried out to test the presumed protective effect of kynurenine + probenecid pre-treatment against pentylenetetrazol-induced seizures. This study has furnished the first electrophysiological proof that systemic kynurenine (300 mg/kg, i.p.) and probenecid (200 mg/kg, i.p.) administration protects against pentylenetetrazol-induced (60 mg/kg, i.p.) epileptic seizures.

Animals↗

A validation study for the transport of 134Cs to strawberry.

The paper presents results on model validation by field experiment for transport of 134Cs to strawberry. The transfer of 134Cs to herbaceous plants was investigated following a wet deposition after an acute release during 2000. Leaf-to-fruit, soil-to-fruit and direct fruit pathways were examined. The available meteorological and local soil information together with the experimental data were taken into account by the model RUVFRU. The processes are described by first order differential equations. In the case of foliar contamination scenarios measured and calculated results for fruit are in good agreement. However, the results of soil contamination scenarios provide large differences of up to three orders of magnitude between model predictions and experimental values for either fruit or other parts of the plant. The bias could be explained by the underestimation of the interception of the plant at the beginning of the season, in the soil contamination scenario. The model output permits prompt assessment of emergency situations and provides aid making decisions concerning mitigation of the consequences of the accident.

Cesium↗

Hormonal enhancement of neuronal firing is linked to structural remodelling of excitatory and inhibitory synapses.

The ovarian hormone estradiol induces morphological changes in the number of synaptic inputs in specific neuronal populations. However, the functional significance of these changes is still unclear. In this study, the effect of estradiol on the number of anatomically identified synaptic inputs has been assessed in the hypothalamic arcuate nucleus. The number of axo-somatic, axodendritic and spine synapses was evaluated using unbiased stereological methods and a parallel electrophysiological study was performed to assess whether synaptic anatomical remodelling has a functional consequence on the activity of the affected neurons. Estradiol administration to ovariectomized rats induced a decrease in the number of inhibitory synaptic inputs, an increase in the number of excitatory synapses and an enhancement of the frequency of neuronal firing. These results indicate that oestrogen modifications in firing frequency in arcuate neurons are temporally linked to anatomical modifications in the numerical balance of inhibitory and excitatory synaptic inputs.

Animals↗

The modulatory effect of estrogen on the neuronal activity in the barrel cortex of the rat. An electrophysiological study.

In acute experiments, the effects of iontophoretically applied 17 beta-estradiol hemisuccinate on the activity of the primary somatosensory cortical neurons were studied in ovariectomized rats by extracellular single-unit recording. 17 beta-Estradiol increased both the spontaneous and the vibrissa deflection-evoked responses, with an average latency of 24 min. It is suggested that this relatively long latency of the 17 beta-estradiol effect is based not so much on membrane mechanisms as on genomic mechanisms.

Animals↗

Independent and joint effects of antibodies to human heat-shock protein 60 and Chlamydia pneumoniae infection in the development of coronary atherosclerosis.

BACKGROUND: Studies have suggested that the prevalence of antibodies against heat-shock proteins (HSPs), Chlamydia pneumoniae (CPN), and cytomegalovirus (CMV) is associated with coronary artery disease (CAD), but the independent or joint effects of human (h) HSP60 antibodies and these pathogens in patients have not been fully elucidated. METHODS AND RESULTS: A total of 405 subjects (276 patients with CAD and 129 control individuals) were tested for serum antibodies to hHSP60, CPN, and CMV immediate-early-1 (IE1) antigens. Patients were also assessed for serum cholesterol, triglyceride levels, and smoking habit. Significantly elevated levels of antibodies to hHSP60 and CPN but not to CMV-IE1 antigens were documented in CAD patients. Multiple logistic regression analysis and subanalyses of selected subjects showed that these associations were independent of age, sex, smoking, and serum lipid levels. Antibodies to hHSP60 and CPN did not correlate quantitatively; however, the relative risk of disease development was substantially increased in subjects with high antibody levels to both hHSP60 and CPN:, reaching an odds ratio of 82.0 (95% CI 10.6 to 625.0). CONCLUSIONS: High levels of antibodies to hHSP60 and CPN: are independent risk factors for coronary atherosclerosis, but their simultaneous presence substantially increases the risk for disease development.

Adult↗

Determination and use of the monetary values of the averted person-sievert for use in radiation protection decisions in Hungary.

The monetary value of the averted dose is a key element in the implementation of the optimization principle both in radiation praxis and intervention. The main concept of this principle is to select options so as to maintain exposures at a reasonable level. The feature of this concept is to look for the minimal total cost, i.e., the sum of the costs of protection and health detriment. In its publications, ICRP emphasized the need for developing models which also take into account the "subjective" aspects of health detriment in the optimization process, such as the perception of risk by individuals and the need to put more emphasis on equity in the distribution of individual doses. This paper proposes a modified alpha-value model based on CEPN's model (Centre d'Etude sur L'Evaluation de la Protection dans le Domaine Nucleaire) to put more emphasis on recently published considerations about the smaller effects of the portion of collective dose derived from small doses. The parameters of the monetary value of unit collective dose averted, which is a key element of this type of model, can be estimated by means of approaches like human capital (HC) and willingness to pay (WTP) from the point of view of economic theories. The present study summarizes the results achieved by WTP among the radiation specialists mainly from the Paks Nuclear Power Plant, Hungary. The aim of the effort was to determine the value of a statistical life and the monetary value of a unit person-sievert associated with averted occupational exposure due to ionizing radiation. To apply the WTP method, a questionnaire has been prepared on the basis of the one introduced by CEPN in the late 1990's. The investigations show that the value of US$6,200 person-Sv(-1) seems to be acceptable for the alphabase-value for the occupational situation in Hungary in 1999. WTP assessments should be applied with caution since the economic level of the country, the workplace surveyed, and the computational methods affect the results. In addition, achieving a high level safety culture must rely on international cooperation both from the theoretical and practical viewpoints, and international markets affect the associated costs. Therefore the monetary requirements cannot always be assessed solely on a national basis.

Cost-Benefit Analysis↗

Chlamydia pneumoniae in atherosclerotic middle cerebral artery.

BACKGROUND AND PURPOSE: Atherosclerotic middle cerebral arteries are frequent sites of thrombosis, leading to stroke. Previous studies have suggested a role for Chlamydia pneumoniae in the pathogenesis of atherosclerosis. However, the presence of this pathogen in atherosclerotic middle cerebral arteries has heretofore not been documented. In the present study, we analyzed atheromatous plaques from middle cerebral arteries for the presence of C pneumoniae. METHODS: Atherosclerotic middle cerebral arteries from 15 cadavers who died of natural causes and corresponding nonatherosclerotic arteries from 4 otherwise healthy trauma victims were examined. Assays for C pneumoniae DNA were carried out by nested polymerase chain reaction (nPCR) specific for the C pneumoniae ompA gene. The presence of the bacterium was assessed by transmission electron microscopy. RESULTS: Five of the 15 atherosclerotic arterial samples and none of the control tissues were positive for C pneumoniae by nPCR. Particles similar in morphology and size to C pneumoniae elementary bodies were detected by transmission electron microscopy in 4 of the 5 nPCR-positive atherosclerotic samples. CONCLUSIONS: The demonstration of C pneumoniae in atherosclerotic middle cerebral arteries is consistent with the hypothesis that this bacterium is involved in acute and chronic cerebrovascular diseases.

Adult↗

Chronic infections and atherosclerosis.

The inability of traditional risk factors such as hypercholesterolemia, hypertension, and smoking to explain the incidence of atherosclerosis (AT) in about 50% of the cases prompted a search for additional putative risk factors involved in the development of the disease. Infectious agents have long been suspected to initiate/contribute to the process of AT. It has also been suggested that inflammation, either related to infectious agents or independent from infection, may mediate the atherogenic process [1, 2].

Animals↗

Facial nerve injury-induced disinhibition in the primary motor cortices of both hemispheres.

Unilateral facial nerve transection induces plastic reorganization of the somatotopic order in the primary motor cortex area (MI). This process is biphasic and starts with a transient disinhibition of connections between cortical areas in both hemispheres. Little is known about the underlying mechanisms. Here, cortical excitability has been studied by paired pulse electrical stimulation, applied either within the MI or peripherally to the trigeminal nerve, while the responses were recorded bilaterally in the MI. The ratios between the amplitudes of the second and first evoked potentials (EPs or fEPSPs) were taken as measures of the inhibitory capacity in the MI ipsilateral or contralateral to the nerve injury. A skin wound or unilateral facial nerve exposure immediately caused a transient facilitation, which was followed by a reset to some level of inhibition in the MI on both sides. After facial nerve transection, the first relatively mild reduction of inhibition started shortly (within 10 min) after denervation. This was followed by a second step, involving a stronger decrease in inhibition, 40-45 min later. Previous publications have proved that sensory nerve injury (deafferentation) induces disinhibition in corresponding areas of the sensory cortex. It is now demonstrated that sham operation and, to an even greater extent, unilateral transection of the purely motoric facial nerve (deefferentation), each induce extended disinhibition in the MIs on both sides.

Animals↗

Estrogen effects on arcuate neurons in rat. An in situ electrophysiological study.

In acute experiments, the effects of i.p. 17beta-estradiol on the activity of arcuate neurons were studied in ovariectomized rats. 17Beta-estradiol (100 microg/100g, i.p.) increased the spontaneous activity of the observed arcuate neurons with a latency of 20-25 min. In some neurons spontaneous activity could be influenced by stimulation of the olfactory and somatosensory systems. Activation of the trigeminal system significantly increased the spontaneous activity of the studied units, while stimulation of the accessory olfactory bulb decreased it, both with and without 17beta-estradiol treatment. It is suggested that the 20-25 min latency of the 17beta-estradiol effect is based not so much on membrane as on genomic mechanisms. This suggestion is supported by immunocytochemical studies: 17beta-estradiol treatment significantly decreased the number of GABA-positive axo-somatic synapses in the arcuate nucleus.

Animals↗

Comparative study of the neuronal plasticity along the neuraxis of the vibrissal sensory system of adult rat following unilateral infraorbital nerve damage and subsequent regeneration.

The aim of the present study was to examine the physiological consequences of a unilateral infraorbital nerve lesion and its regeneration at different levels of the somatosensory neuraxis. In animals whose right infraorbital nerve had been crushed, a large unresponsive area was found in the main brainstem trigeminal nucleus (Pr5). Responses evoked by ipsilateral vibrissal deflection in the middle of Pr5 reappeared only on days 22-35 after the nerve had been transected, whereas recovery from the nerve crush took only 7-9 days. However, no sign of short-term neuronal plasticity was observed in Pr5 after peripheral nerve injury. An enlargement of the receptive fields in two-thirds of the units and a lengthening in the delay of the evoked responses were observed as long-term plastic changes in Pr5 neurons after peripheral-nerve regeneration. In the ventral posteromedial nucleus of the thalamus (VPM) of partly denervated animals, however, only minutes or hours after the nerve crush, certain units were found to respond in some cases not only to the vibrissae, but also to mechanical stimulation of the face over the eye (two units), the nose (one unit), and the midline (one unit). Apart from the experiments involving incomplete denervation, the vibrissal representation areas of the VPM were unresponsive to stimulation of both the vibrissae and other parts of the face until nerve regeneration had occurred. In the somatosensory cortex, an infraorbital nerve crush immediately resulted in a large cortical area being unresponsive to vibrissal deflection. It was noteworthy, however, that shortly after the nerve crush, this large unresponsive whisker representation cortical area was invaded from the rostromedial direction by responses evoked by stimulation of the forepaw digits. In spite of the reappearance of vibrissa-evoked responses 7-10 days after the nerve crush, an expanded digital representation could still be observed 3 weeks after the nerve crush, resulting in an overlapping area of digital and vibrissal representations. The withdrawal of the expanded representation of forepaw digits was completed by 60 days after the nerve crush. The results obtained in Pr5, the VPM, and the cortex strongly suggest that the higher the station in the neuraxis, the greater the degree of plasticity after infraorbital nerve injury.

Animals↗