Cytotoxicity of two nitroimidazole radiosensitizers in an in vitro tumor model.
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Cell Division↗
Biomedical subjects
C Koch
Publications and source records attributed to C Koch.
Variability and coding efficiency of noisy neural spike encoders.
Encoding synaptic inputs as a train of action potentials is a fundamental function of nerve cells. Although spike trains recorded in vivo have been shown to be highly variable, it is unclear whether variability in spike timing represents faithful encoding of temporally varying synaptic inputs or noise inherent in the spike encoding mechanism. It has been reported that spike timing variability is more pronounced for constant, unvarying inputs than for inputs with rich temporal structure. This could have significant implications for the nature of neural coding, particularly if precise timing of spikes and temporal synchrony between neurons is used to represent information in the nervous system. To study the potential functional role of spike timing variability, we estimate the fraction of spike timing variability which conveys information about the input for two types of noisy spike encoders--an integrate and fire model with randomly chosen thresholds and a model of a patch of neuronal membrane containing stochastic Na(+) and K(+) channels obeying Hodgkin-Huxley kinetics. The quality of signal encoding is assessed by reconstructing the input stimuli from the output spike trains using optimal linear mean square estimation. A comparison of the estimation performance of noisy neuronal models of spike generation enables us to assess the impact of neuronal noise on the efficacy of neural coding. The results for both models suggest that spike timing variability reduces the ability of spike trains to encode rapid time-varying stimuli. Moreover, contrary to expectations based on earlier studies, we find that the noisy spike encoding models encode slowly varying stimuli more effectively than rapidly varying ones.
Action Potentials↗
Monoclonal antibodies to thioguanine: influence of coupling position on fine specificity.
Thioguanine derivatives with reactive ester groups at positions 6, 7, or 9 of the purine ring were synthesized and coupled to a protein carrier. The purified protein derivative of tuberculin was used as the carrier for immunizing bacillus Calmette-Guerin primed mice. This led to high antibody titers against the homologously coupled hapten, and spleen cells from the immunized mice were used to produce monoclonal antibodies against thioguanine. All monoclonal antibodies were selected for their ability to recognize free thioguanine and were analyzed for their fine specificity by inhibition experiments with a panel of thiopurine derivates. The specificity of the monoclonal antibodies showed a strong dependence on the coupling position of the thioguanine. Within each group of monoclonal antibodies, raised against one of the three different conjugates, there was a high degree of heterogeneity, with antibodies differing in their binding according to the substitution on the thioguanine analogues used in the inhibition experiments. This panel of antibodies may be used for quantitative assays of thiopurines and their metabolites in patients undergoing treatment with thioguanine, 6-mercaptopurine, and azathioprine.
Animals↗
Electrical interactions via the extracellular potential near cell bodies.
Ephaptic interactions between a neuron and axons or dendrites passing by its cell body can be, in principle, more significant than ephaptic interactions among axons in a fiber tract. Extracellular action potentials outside axons are small in amplitude and spatially spread out, while they are larger in amplitude and much more spatially confined near cell bodies. We estimated the extracellular potentials associated with an action potential in a cortical pyramidal cell using standard one-dimensional cable theory and volume conductor theory. Their spatial and temporal pattern reveal much about the location and timing of currents in the cell, especially in combination with a known morphology, and simple experiments could resolve questions about spike initiation. From the extracellular potential we compute the ephaptically induced polarization in a nearby passive cable. The magnitude of this induced voltage can be several mV, does not spread electrotonically, and depends only weakly on the passive properties of the cable. We discuss their possible functional relevance.
Action Potentials↗
Subthreshold voltage noise due to channel fluctuations in active neuronal membranes.
Voltage-gated ion channels in neuronal membranes fluctuate randomly between different conformational states due to thermal agitation. Fluctuations between conducting and nonconducting states give rise to noisy membrane currents and subthreshold voltage fluctuations and may contribute to variability in spike timing. Here we study subthreshold voltage fluctuations due to active voltage-gated Na+ and K+ channels as predicted by two commonly used kinetic schemes: the Mainen et al. (1995) (MJHS) kinetic scheme, which has been used to model dendritic channels in cortical neurons, and the classical Hodgkin-Huxley (1952) (HH) kinetic scheme for the squid giant axon. We compute the magnitudes, amplitude distributions, and power spectral densities of the voltage noise in isopotential membrane patches predicted by these kinetic schemes. For both schemes, noise magnitudes increase rapidly with depolarization from rest. Noise is larger for smaller patch areas but is smaller for increased model temperatures. We contrast the results from Monte Carlo simulations of the stochastic nonlinear kinetic schemes with analytical, closed-form expressions derived using passive and quasi-active linear approximations to the kinetic schemes. For all subthreshold voltage ranges, the quasi-active linearized approximation is accurate within 8% and may thus be used in large-scale simulations of realistic neuronal geometries.
Animals↗
Computational vision and regularization theory.
Descriptions of physical properties of visible surfaces, such as their distance and the presence of edges, must be recovered from the primary image data. Computational vision aims to understand how such descriptions can be obtained from inherently ambiguous and noisy data. A recent development in this field sees early vision as a set of ill-posed problems, which can be solved by the use of regularization methods. These lead to algorithms and parallel analog circuits that can solve 'ill-posed problems' and which are suggestive of neural equivalents in the brain.
Humans↗
The effect of two levels of dietary protein on resistance and resilience of dairy goats experimentally infected with Trichostrongylus colubriformis: comparison between high and low producers.
Numerous studies have examined the interactions between protein nutrition and the response to nematode parasitism in sheep, but very few in goats. Compared with other ruminants, goats are less resistant to nematode infection. In addition, in dairy goats, high producing animals have been shown to be less resistant and less resilient to infection compared to low producing ones. The objective of the present study was to examine the consequences of protein supplementation on both resistance and resilience of dairy goats to nematode trickle infection, taking into account the initial level of milk production of the animals. During a 14-week period, 40 milking goats received a high protein (HP) diet supplying 130% of the protein requirements, and 38 goats were fed a intermediate protein (IP) diet (120% of the protein requirements). In addition, half of each group was given a weekly trickle infection with Trichostrongylus colubriformis larvae, the other part of the flock remained non-infected. Faecal egg counts (FEC), eosinophil counts and pathophysiological data (urea, albumin and inorganic phosphate concentrations in the serum) were measured twice a month. Milk production data (milk yield, protein and fat contents) were also recorded every 15 days. The results showed that FECs were lower (p < 0.05) and eosinophil counts higher (p < 0.05) in the animals receiving the HP diet suggesting that resistance was enhanced by protein supplementation. Meanwhile, milk parameters (related to resilience) were not affected by the level of protein in the diet when considering the whole groups. In contrast, in the high producing goats, the milk production and milk composition parameters were improved with the HP diet. To conclude, we have seen that the expression of both resistance and resilience did not appear when the coverage of the protein requirements was insufficient. Because the milk production is dependent on the protein supply, we suggest that there is a competition in the use of the protein between the development of resistance and the milk production.
Animal Nutritional Physiological Phenomena↗
[Efficiency of a postoperative treatment after rotator cuff repair with a continuous passive motion device (CPM)].
AIM: The main objective of this study was to prove that a postoperative combined continuous passive motion (CPM) and physiotherapy treatment protocol (CPM group) can achieve 90 degrees active abduction in the shoulder joint earlier than physiotherapy alone (PT group). The indication was a complete tear of the rotator cuff. METHOD: The study was conducted under in-patient and out-patient conditions. 55 patients were included in this study. The prospective, randomized multicenter study design complies with DIN EN 540. The primary endpoint was the time span until 90 degrees active abduction was achieved by the patients. RESULTS: Patients in the CPM group reached the primary endpoint on average 12 days earlier than the control group. This difference was statistically significant (p = 0.0292). Analyzing the secondary endpoints, e. g., pain and disablement, the results in the CPM group showed again advantages of the combined treatment protocol (CPM + physiotherapy). CONCLUSION: The postoperative treatment of a total tear of the rotator cuff with a combined continuous passive motion and physiotherapy protocol provided a significantly earlier range of motion in the shoulder joint than physiotherapy alone. There was no report of CPM-related adverse effects.
Double-Blind Method↗
Does a liquid supplement improve energy and protein consumption in nursing home residents?
One popular strategy to improve the acceptance and efficacy of oral liquid supplements in long-term care is dispensing them during the medication pass, although few studies support its effectiveness. This study evaluated the impact of a supplement medication pass program on energy and nutrient consumption and weight in nursing home residents. Findings indicate that residents maintained their prestudy weight and had a 29% decrease in supplement energy intake, a 19% increase in food energy intake, and a 17% decrease in net energy intake (supplement plus food). Supplement and food protein intake remained stable. Over longer periods, this reduced energy consumption could lead to weight loss, so routine monitoring and periodic evaluations of resident intake (both food and supplement) are recommended to ensure residents are receiving and consuming adequate amounts of daily energy and nutrients.
Aged↗
A method for immunohistochemical detection of osteogenic markers in undecalcified bone sections.
To evaluate the osteogenic potential of novel implant materials, it is important to examine their effect on osteoblastic differentiation. Characterizing the tissue response at the bone-biomaterial interface in vivo at a molecular level would contribute significantly to enhancing our understanding of tissue integration of endosseous implant materials. We describe here a new technique that overcomes difficulties commonly associated with performing immunohistochemistry on undecalcified sawed sections of bone. Sheep mandible specimens were fixed in an ethanol based fixative to maintain adequate antigenicity of the tissue. As a result, it was possible to omit antigen retrieval at high temperature for recovery of antigenicity, and detachment of sections from the slides was avoided. Following dehydration and infiltration, the specimens were embedded in a resin composed of polymethylmethacrylate and polybutylmethacrylate. Polymerization was achieved by adding benzoylperoxide and N,N-dimethyl-toluidine. This resin was selected because it maintained the antigenicity of the tissue, provided adequate properties for cutting 50 microm thick sections, and it facilitated deacrylizing the sawed sections. Acid-resistant acrylic slides were glued to the blocks using an epoxy resin based two-component adhesive to avoid detachment of the slides during the deacrylation procedure. Samples were stained for alkaline phosphatase, type I collagen, osteonectin, osteopontin, osteocalcin and bone sialoprotein. The EnVision + trade mark dextran polymer conjugate two-step visualization system was applied for immunohistochemical detection of these bone matrix proteins. This procedure yielded positive staining for the osteogenic markers in cells and matrix components. The protocol described here facilitates the use of immunohistochemistry on resin embedded sawed sections of bone and provides a convenient and reliable method that can be used routinely for immunohistochemical analysis of hard tissue specimens containing implant materials.
Animals↗
A brief history of time (constants).
That the cerebral cortex processes information at prodigious speeds cannot be doubted. Yet the passive time constant, tau(m), of neurons, often thought of as a measure of the neuron's "response time' to synaptic input, is relatively long. In the 1950s, tau(m) was estimated to be only a few milliseconds for mammalian central neurons; with improvement in recording techniques, its estimated value grew over the years and it now stands near 20-100 msec. However, as we will argue here, the functional meaning of tau(m) is ambiguous. On the basis of a newly introduced definition of local delay, we show that the time window for synaptic integration in passive dendritic trees can be much smaller than the time constant. We argue that the voltage response to very brief synaptic inputs is essentially independent of tau(m). We discuss how tau(m) can change dynamically with the global activity of the network, as well as the difficulties of defining a time constant in structures with voltage-dependent elements. We conclude that the classically defined tau(m) only provides a very rough estimate, typically an overestimate, of the response time of neurons and that alternative measures are required to capture the dependency of the time course of the membrane potential on ligand-gated and/or voltage-dependent membrane conductances.
Animals↗
Safety of aztreonam in patients with cystic fibrosis and allergy to beta-lactam antibiotics.
In an open clinical trial, aztreonam was administered repeatedly to 15 cystic fibrosis patients who were chronically infected with Pseudomonas aeruginosa and had previously had severe hypersensitivity reactions to other beta-lactam antibiotics, including anaphylactic shock, generalized urticaria, and drug-associated fever. After negative results in a skin-prick test and a lack of reaction to an intravenous test dose of aztreonam, the patients were treated with aztreonam (150 mg/[kg.d]) in combination with tobramycin (10-20 mg/[kg.d]) for 14-day periods at 3- to 4-month intervals. To date, a total of 56 course of aztreonam have been administered to these patients (three to six courses per patient), and no type 1 hypersensitivity reactions have occurred. However, as a result of drug-associated fever, the administration of aztreonam had to be discontinued in two of 15 cases. The remaining 13 patients have tolerated treatment well.
Adolescent↗
Retrospective clinical study of hypersensitivity reactions to aztreonam and six other beta-lactam antibiotics in cystic fibrosis patients receiving multiple treatment courses.
A total of 2,793 courses of treatment with seven beta-lactam antibiotics were administered to 121 cystic fibrosis patients chronically infected with Pseudomonas aeruginosa, and the patients were evaluated with respect to clinical hypersensitivity reactions. Seventy-five patients (62%) experienced 125 reactions, for an overall frequency (based on the number of courses) of 4.5%. Immediate reactions occurred in 34 patients (28.1%) during 53 courses (1.9%). The highest rate of reactions involved piperacillin (50.9% of patients), and the lowest rate involved imipenem and aztreonam (4.0% and 6.5% of patients, respectively); intermediate reaction rates were noted for carbenicillin (23.6% of patients), azlocillin (20.8%), cefsulodin (17.1%), and ceftazidime (13.0%). Cross-reactivity did not appear to be a major problem. Reactions to aztreonam seemed to be restricted to a small group of patients with a high propensity for beta-lactam hypersensitivity.
Anti-Bacterial Agents↗
Genetic analysis of cystic fibrosis in Denmark. Implications for genetic counselling, carrier diagnosis and prenatal diagnosis.
Cystic fibrosis is the most common, severe, inherited disease in the Caucasian population. As a consequence, the demand for genetic counselling of patients with cystic fibrosis and their families is large. In Denmark the incidence of cystic fibrosis is 1:4700, which is quite low compared to other European countries. We have investigated 268 Danish cystic fibrosis patients with respect to DNA markers (haplotypes) and the most common mutation delta F508. The delta F508 mutation is found on 88% of all cystic fibrosis chromosomes, the highest frequency reported so far. This had had an important impact on genetic counselling, prenatal diagnosis and eventually population screening. In the Danish population 78% of all couples at risk will be informative for delta F508 and will be identifiable by simple screening methods.
Cystic Fibrosis↗
Soil surface structure effect on isoproturon and diflufenican loss in runoff.
Because soil surface structure has a considerable influence on infiltration rate, the sealing process is postulated to have a significant effect on herbicide loss through runoff. We evaluated the effect of degraded soil surface structures on herbicide loss in runoff, and used the experimental data to test the uniform mixing zone concept and two-site sorption kinetics for modeling herbicide transfer to runoff. The experiments were done with simulated rainfall on 10-m2 plots in the field and 0.25-m2 plots in the laboratory after a surface application of 1.5 kg ha(-1) of isoproturon [3-(4-isopropylphenyl)-1,1-dimethylurea] and 0.187 kg ha(-1) of diflufenican [2',4'-difluoro-2-(alpha,alpha,alpha-trifluoro-m-tolyloxy) nicotinanilide]. Isoproturon (IPU) and diflufenican (DFF) concentrations were very high in the first runoff (up to 60 mg L(-1) for IPU and 2 mg L(-1) for DFF) when simulated rainfall was applied 24 h after the treatment. The concentrations decreased very rapidly with total rainfall depth. Degradation of the structural state of the soil surface increased the ratio of pesticide loss to application rate from 0.3 to 10% for IPU and from 0.7 to 7.8% for DFF for a runoff depth of less than 1 mm. The structural state of the soil surface influences the rapidity at which runoff begins after the onset of rain, and the runoff coefficient at steady state. Furthermore, the development of a surface seal seems to limit the depth of soil-runoff interaction and thus influences the dynamics of herbicide mobilization. Concentrations of IPU in the runoff were satisfactorily described with a model incorporating a uniform mixing zone and two-site sorption-desorption.
Forecasting↗
[First results of combined implants of endocrine organs in anterior eye chamber of guinea pigs].
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Animals↗
The coronary sinus is the superior route for cardioplegia delivery in hearts with multivessel coronary artery lesions.
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Animals↗