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Biomedical subjects

J Maier

Publications and source records attributed to J Maier.

At least 19 recordsLinked to original sources

Quantitative model of electrochemical Ostwald ripening and its application to the time-dependent electrode potential of nanocrystalline metals.

The contact of a metastable nanocrystalline metal ensemble with a metal ion electrolyte leads to an electrochemical Ostwald ripening. The kinetics is modeled on the level of irreversible thermodynamics for the case that the rate is controlled by the electrode/electrolyte transfer resistance. In particular, the kinetic behavior of medium-sized particles and the time dependence of the electromotive force is investigated. Even though it is expressed in electrochemical terms (mixed potential), the modeling is also applicable to chemical Ostwald ripening as long as it is interfacially controlled. Under these conditions, the kinetics exhibits, even though not self-accelerating, strong similarities to selection dynamics, with the competition stemming from the cannibalistic nature of the process.

Journal Article↗

Deoxyribonucleic acid damage and spontaneous mutagenesis in the thyroid gland of rats and mice.

Thyroid tumors are a frequent finding not only in iodine-deficient regions. They are predominantly characterized by somatic genetic changes (e.g. point mutations or rearrangements). Because slow thyroid proliferation is a apparent contradiction to a high frequency of tumor initiation, we characterized mutational events in thyroid. First we studied the frequency of certain base exchanges in somatic TSH receptor (TSHR) mutations and determined the spontaneous mutation rate in thyroid and liver. Then we applied different protocols of the comet assay to quantify genomic DNA damage and conducted immunohistochemistry for 8-oxoguanine as a molecular marker for oxidative stress. Among 184 somatic mutations of the human TSHR found in thyroid tumors, C-->T transitions had a unexpectedly high frequency (>32%). The mutation rate in thyroid is 8-10 times higher than in other organs. The comet assay detected increased levels of oxidized pyrimidine (2- to 3-fold) and purine (2- to 4-fold) in thyroid, compared with liver and lung, and a 1.6-fold increase of oxidized purine, compared with spleen. Immunohistochemistry revealed high levels of 8-oxoguanine in thyroid epithelial cells. We have shown a strikingly high mutation rate in the thyroid. Furthermore, results of the comet assay as well as immunohistochemistry suggest that oxidative DNA modifications are a likely cause of the higher mutation rate. It is possible that free radicals resulting from reactive oxygen species in the thyroid generate mutations more frequently. This is also supported by the spectrum of somatic mutations in the TSHR because more frequent base changes could stem from oxidized base adducts that we detected in the comet assay and with immunohistochemistry.

Animals↗

Generalised Maxwell-Garnett equation: application to electrical and chemical transport.

In this paper we discuss the implementation of different equilibrium concentrations in each of the phases into the Maxwell-Garnett effective medium formula for diffusion in heterogeneous media. We put the derivation given by Kalnin et al., J. Phys. Chem. Solids, 2002, 63, 449, on safer grounds and extend it to non-dilute carrier concentrations. The relation to Maxwell's mixing rule is also elaborated. It is shown that the formula can not only successfully be applied to conductivity problems but also to describe steady state chemical diffusion in heterogeneous media such as polycrystalline samples. The comparison with the brick layer model corroborates these points but also shows that-in the case of heterogeneous media-one has to be cautious in applying steady state results to transient kinetics.

Journal Article↗

On the origin of the lattice constant anomaly in nanocrystalline ceria.

The lattice parameter of nanocrystalline ceria films prepared by sputtering was monitored as a function of annealing temperature. Within the temperature range of 150-420 degrees C, an equilibrium with atmospheric oxygen is established within a few hours, whereas grain growth does not occur. On the basis of the experimental results and analysis of literature data, we present a model that posits the formation of a non-uniform grain structure with stoichiometric interiors and oxygen deficient boundaries. This model, based on defect thermodynamics, correctly describes the dependence of the lattice parameter of nanocrystalline ceria on annealing temperature and grain size and can be extended to other materials as well.

Journal Article↗

CoCoDat: a database system for organizing and selecting quantitative data on single neurons and neuronal microcircuitry.

We present a novel database system for organizing and selecting quantitative experimental data on single neurons and neuronal microcircuitry that has proven useful for reference-keeping, experimental planning and computational modelling. Building on our previous experience with large neuroscientific databases, the system takes into account the diversity and method-dependence of single cell and microcircuitry data and provides tools for entering and retrieving published data without a priori interpretation or summarizing. Data representation is based on the framework suggested by biophysical theory and enables flexible combinations of data on membrane conductances, ionic and synaptic currents, morphology, connectivity and firing patterns. Innovative tools have been implemented for data retrieval with optional relaxation of search criteria along the conceptual dimensions of brain region, cortical layer, cell type and subcellular compartment. The relaxation procedures help to overcome the traditional trade-off between exact, non-interpreted data representation in the original nomenclature and convenient data retrieval. We demonstrate the use of these tools for the construction, tuning and validation of a multicompartmental model of a layer V pyramidal cell from the rat barrel cortex. CoCoDat is freely available at . Its application is scalable from offline use by individual researchers via local laboratory networks to a federation of distributed web sites in platform-independent XML format using Axiope tools.

Action Potentials↗

Nanoionics: ion transport and electrochemical storage in confined systems.

The past two decades have shown that the exploration of properties on the nanoscale can lead to substantially new insights regarding fundamental issues, but also to novel technological perspectives. Simultaneously it became so fashionable to decorate activities with the prefix 'nano' that it has become devalued through overuse. Regardless of fashion and prejudice, this article shows that the crystallizing field of 'nanoionics' bears the conceptual and technological potential that justifies comparison with the well-acknowledged area of nanoelectronics. Demonstrating this potential implies both emphasizing the indispensability of electrochemical devices that rely on ion transport and complement the world of electronics, and working out the drastic impact of interfaces and size effects on mass transfer, transport and storage. The benefits for technology are expected to lie essentially in the field of room-temperature devices, and in particular in artificial self-sustaining structures to which both nanoelectronics and nanoionics might contribute synergistically.

Biosensing Techniques↗

Reading with the ears.

We studied the cortical networks of Morse code reading with functional magnetic resonance imaging (fMRI). Four expert radio telegraphists performed two closely matched reading experiments, one in binaurally presented high speed Morse code and one in print. Performance was equal for both conditions. Reading single nouns in Morse code resulted in predominantly left-sided activation of the frontal and temporal perisylvian language areas, prefrontal cortex, and premotor cortex. In a within-subject comparison between reading Morse code and reading print, the activation pattern in the left temporoparietal association cortex was similar for both forms of reading, suggesting that reading Morse code shares part of its cortical networks with reading print.

Acoustic Stimulation↗

Structures of BaF2-CaF2 heterolayers and their influences on ionic conductivity.

Recently, artificial ion conductors have been prepared by growing epitaxial heterolayers consisting of BaF2-CaF2 using molecular beam epitaxy. The ionic conductivity of these heterolayers shows a strong dependence on the layer thickness [N. Sata, S. Eberman, K. Eberl, and J. Maier, Nature 408, 996 (2000)]. In this paper three such heterolayers with different spacings (sample A: 80 nm, sample B: 10 nm, sample C: 1 nm) are investigated by conventional transmission electron microscopy and high-resolution transmission electron microscopy. The spacings are chosen such that they fall into the three conductivity regimes observed in N. Sata et al. (l > 50 nm; 8 < l < 50 nm; l < 8 nm). In accordance with conductivity studies, the samples with spacings of 10 nm or greater (A,B) are epitaxial and continuous, whereas in the case of extremely small spacing (C) the continuity of the layers is destroyed by formation of a column-like structure. Analytical electron microscopy reveals that, instead of forming multilayers, Ca and Ba separate in different columns in sample C. The structure properties of sample A (large l) are quite ideal: Planar interfaces with regular arrays of misfit dislocations with their Burgers vectors on the interface are observed. In the case of sample B (medium l) the lattice misfit is accommodated, in addition, by wavy interfaces associated with dislocations characterized by a Burgers vector that makes a large angle to the interfaces. The (111) lattice spacing very close to the interfaces is markedly changed due to this novel relaxation mechanism in the multilayer. The influences of the crystallographic defects on the ionic conductivity are also discussed.

Journal Article↗

Acid-base centers and acid-base scales in ionic solids.

For the case of ionic crystals it is shown to be most straightforward and consistent to define acidity/basicity by the (electro-)chemical potential of the respective ion, in a similar fashion to the way that the Fermi level (i.e.. electrochemical potential of the electron) characterizes the redox state. The isomorphy is explicitly expressed by using the energy-level diagrams introduced for electrons in semiconductor physics. Without having to make further assumptions it is possible 1) to compare acidity/basicity between different solids, 2) to link internal and surface acidity/basicity, and 3) to establish acidity/basicity scales for ionic solids. The point defects are revealed to be the natural acidic and basic elementary centers, and associates between them to be the internal acids/bases exchanging these elementary centers. Even though acidity/basicity is an overall property of the solid, the number of point defects (if dilute) directly represents these properties in the same way as H+ or OH- accomplish this for aqueous solutions.

Journal Article↗

Genomic organization of the X-linked inhibitor of apoptosis and identification of a novel testis-specific transcript.

Here we report the genomic organization and mapping of the X-linked inhibitor of apoptosis gene (BIRC4, also known as XIAP and hILP) and the identification of a closely related transcript. BIRC4 is located on Xq25 and is composed of seven exons. The intron/exon structure is highly conserved between the mouse homologue and its human counterpart. Four bands cross-react with a BIRC4 coding region probe on a genomic Southern blot. One of these cross-reactive bands encodes an intronless gene that expresses a 2.2-kb transcript solely in the testis. This testis-specific transcript contains a putative open reading frame (ORF) that is homologous to the carboxy-terminal end of BIRC4; overexpression of this ORF shows protective effects against BAX-induced apoptosis.

Animals↗

Role of nitric oxide synthase in the light-induced development of sporangiophores in Phycomyces blakesleeanus.

Blue light controls the development of sporangiophores in the zygomycete Phycomyces blakesleeanus Burgeff. Light represses the production of microsporangiophores and enhances the development of macrosporangiophores. Inhibition of the biosynthesis of tetrahydrobiopterin, a cofactor of NO synthase, inhibits this photomorphogenesis. Light induces production of citrulline from arginine in the mycelium and in sporangiophores. The citrulline-forming activity is dependent on NADPH, independent of calcium, and inhibited by NO synthase inhibitors. It is reduced in tetrahydrobiopterin-depleted mycelium. Light induces emission of NO from the developing fungus in the same order of magnitude as citrulline formation from arginine. The NO donor sodium nitroprusside can replace the light effect on sporangiophore development, and inhibitors of NO synthase repress it. We suggest that a fungal NO synthase is involved in sporangiophore development and propose its participation in light signaling.

Biopterins↗

Interferon-independent, human immunodeficiency virus type 1 gp120-mediated induction of CXCL10/IP-10 gene expression by astrocytes in vivo and in vitro.

The CXC chemokine gamma interferon (IFN-gamma)-inducible protein CXCL10/IP-10 is markedly elevated in cerebrospinal fluid and brain of individuals infected with human immunodeficiency virus type 1 (HIV-1) and is implicated in the pathogenesis of HIV-associated dementia (HAD). To explore the possible role of CXCL10/IP-10 in HAD, we examined the expression of this and other chemokines in the central nervous system (CNS) of transgenic mice with astrocyte-targeted expression of HIV gp120 under the control of the glial fibrillary acidic protein (GFAP) promoter, a murine model for HIV-1 encephalopathy. Compared with wild-type controls, CNS expression of the CC chemokine gene CCL2/MCP-1 and the CXC chemokine genes CXCL10/IP-10 and CXCL9/Mig was induced in the GFAP-HIV gp120 mice. CXCL10/IP-10 RNA expression was increased most and overlapped the expression of the transgene-encoded HIV gp120 gene. Astrocytes and to a lesser extent microglia were identified as the major cellular sites for CXCL10/IP-10 gene expression. There was no detectable expression of any class of IFN or their responsive genes. In astrocyte cultures, soluble recombinant HIV gp120 protein was capable of directly inducing CXCL10/IP-10 gene expression a process that was independent of STAT1. These findings highlight a novel IFN- and STAT1-independent mechanism for the regulation of CXCL10/IP-10 expression and directly link expression of HIV gp120 to the induction of CXCL10/IP-10 that is found in HIV infection of the CNS. Finally, one function of IP-10 expression may be the recruitment of leukocytes to the CNS, since the brain of GFAP-HIV gp120 mice had increased numbers of CD3(+) T cells that were found in close proximity to sites of CXCL10/IP-10 RNA expression.

Animals↗

Grids and high kilo-volt-peak-setting in bedside chest radiographic examinations.

Bedside chest radiographic examinations in intensive care units with grids are impaired by artefacts caused by angulation of the grid (grid cut-off). Two different grids--a grid with a high strip density of 70 lines per cm and the "InSight portable imaging system"--were examined in an intensive care unit with respect to their susceptibility to angulation, image quality and handling of the grid. Five radiologists compared 50 radiographs of each grid considering ten image quality criteria. Using the "InSight portable imaging system" major artefacts were undetectable even at an angulation of 10%; no adjustment of the grid was required, which reduced the amount of time needed to take the radiograph by 26%. The increase in dosage demanded by the employment of the grids at low kilovolt peak setting could be partially compensated by the use of high kilovolt peak setting. The image quality of the "InSight portable imaging system" together with a high kilovolt peak setting is satisfactory, and due to its simplified handling, the portable imaging system has proved to be suitable for bedside chest radiography in intensive care.

Artifacts↗

Giardia lamblia: incorporation of free and conjugated fatty acids into glycerol-based phospholipids.

Giardia lamblia trophozoites are flagellated protozoa that inhabit the human small intestine, where they are exposed to various dietary lipids and fatty acids. It is believed that G. lamblia, which colonizes a lipid-rich environment of the human small intestine, is unable to synthesize phospholipids, long-chain fatty acids, and sterols de novo. Therefore, it is possible that this protozoan has developed a special process for acquiring lipids from its host. We have previously shown that G. lamblia can take up saturated fatty acids and incorporate them into phosphatidylglycerol (PG) and other glycerol-based phospholipids (Stevens et al., Experimental Parasitology, 86, 133-143, 1997). In the present study, an attempt has been made to investigate the underlying mechanisms of transesterification and interesterification reactions of giardial phospholipids by free and conjugated fatty acids. Results show that exogenously supplied, unsaturated, fatty acids were taken up by Giardia and incorporated into various phosphoglycerides, including PG. To test whether this intestinal pathogen can utilize conjugated fatty acids, live trophozoites were exposed to either [3]H;cbphosphatidylcholine (PC), where the fatty acid was 3H-labeled at its sn2 position, or to [14C]lyso-PC (fatty acid was 14C-labeled at the sn1 position) for 90 min, followed by phospholipid analysis using thin-layer chromatography. The results suggest that conjugated fatty acids, like free fatty acids, were incorporated into PG. It was also observed that aristolochic acid, an inhibitor of Ca2+-ionophore-stimulated phospholipase A2, decreased the transfer of fatty acids from [3H]PC to PG, indicating that giardial phospholipases were involved in these esterification reactions. Additional experiments, which include culturing trophozoites in serum-supplemented and serum-deprived medium, along with numerous biochemical analyses suggest that (i) PG is a major transesterified and interesterified product, (ii) it is likely that giardial phospholipases are involved in esterification reactions, (iii) in G. lamblia, PG is localized in perinuclear membranes, as well as intracellularly, but not in the plasma membrane, and (iv) various synthetic analogs of PG inhibit the growth of the parasite in vitro. These studies suggest that PG is an important phospholipid of Giardia and a potential target for lipid-based chemotherapy against giardiasis.

Animals↗

Anti-tumor immunity induced by murine melanoma cells transduced with the Mycobacterium tuberculosis gene encoding the 38-kDa antigen.

The Mycobacterium tuberculosis Ag38 gene, which encodes a highly immunogenic protein, was cloned into a retroviral vector in-frame with the leader and the transmembrane portion of the nerve growth factor receptor, and transduced into murine melanoma cell line B16-B78. Significant protection was observed in mice immunized with the transduced melanoma cells and subcutaneously challenged with parental melanoma cells since only 20% of mice developed tumors. Necroscopy of mice immunized with the transduced melanoma cells revealed dramatic inhibition of experimental metastases induced by intravenous (i.v.) inoculation of parental melanoma cells. Moreover, vaccination with transduced cells significantly prolonged survival of mice challenged i.v. with parental melanoma cells. These data indicate that the presence of the mycobacterial 38-kDa protein greatly enhances immunological recognition of structures expressed by the parental melanoma cells. Comparison of Th1 and Th2 responses in mice immunized with parental melanoma cells versus mice receiving the transduced cells revealed a clear predominance of Th1 responses when the Ag38 protein was endogenously expressed. This transduction approach may represent a promising immunotherapeutic strategy for the treatment of cancer patients.

Animals↗

Rebound increase of plasminogen activator inhibitor type I after cessation of thrombolytic treatment for acute myocardial infarction is independent of type of plasminogen activator used.

Plasma concentrations of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1), and D-dimer were investigated in 50 patients treated intravenously for acute myocardial infarction with either streptokinase (n = 23), urokinase (n = 17), or recombinant t-PA (rt-PA, n = 10). The fibrinolytic variables were measured by enzyme immunoassay on admission; 1, 2, 4, 6, 8, 12, and 24 h later; and then daily until day 7 after admission. In each subgroup of patients treated with different thrombolytic agents, PAI-1 increased significantly (P < 0.01) approximately 3 h after cessation of thrombolytic therapy. PAI-1 peak concentrations did not differ significantly (P = 0.82) among these three subgroups. t-PA and D-dimer did not differ significantly (P > 0.14) among subgroups except for higher t-PA in the rt-PA group attributable to detection of the therapeutically administered exogenous rt-PA by the t-PA assay. Our findings demonstrate a marked PAI-1 increase after thrombolytic therapy for acute myocardial infarction, which seems to be a common, drug-independent antifibrinolytic rebound phenomenon in response to thrombolytic treatment.

Adult↗

Markers of activated coagulation for early diagnosis of acute myocardial infarction.

Intracoronary thrombosis plays a key role in the pathogenesis of acute myocardial infarction (AMI), and the formation of an occlusive thrombus usually precedes the development of myocardial damage. Therefore we evaluated and compared the early sensitivities of thrombin-antithrombin III complex (TAT), D-dimer, myoglobin, creatine kinase (CK) MB mass concentration, and cardiac troponin T (cTnT) on admission to a coronary care unit (CCU) before heparin or thrombolytic therapy was started. We investigated 31 consecutive patients admitted to CCU for evolving AMI within 6 hours from the onset of infarct-related symptoms; the median delay from chest pain onset to CCU admission was 135 minutes. Of all biochemical markers tested TAT had the highest early sensitivity on admission to the CCU, and TAT was significantly more sensitive than cTnT, CKMB mass, myoglobin, and D-dimer. However, TAT increases give no information about the location of clot formation in the body, and the diagnosis of AMI must be subsequently verified by an increase in more cardiac specific proteins, such as troponins or CKMB.

Acute Disease↗