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Biomedical subjects

Peter Molnar

Publications and source records attributed to Peter Molnar.

18 recordsLinked to original sources
PubMed2006

Earth science: palaeo-altimetry of Tibet.

The determination of palaeo-elevation has emerged in the past 15 years as an important tool for constraining physical processes that govern the formation of mountain belts. Rowley and Currie report palaeo-elevations for the Lunpola basin within the Tibetan plateau and claim that these elevations are incompatible with 'mantle-thickening models' for mountain formation. We show here that their data do not support this conclusion and, indeed, are consistent with its opposite. The Tibetan plateau could have risen by a kilometre or more as its dense lower lithosphere sank into the underlying mantle.

Comment↗
PubMed2006

A defined system to allow skeletal muscle differentiation and subsequent integration with silicon microstructures.

This work documents the development of an in vitro cell culture model consisting of a novel serum-free medium and a non-biological growth substrate, N-1[3 (trimethoxysilyl) propyl] diethylenetriamine (DETA), to enable functional myotube integration with cantilevers fabricated using MEMS technology. This newly developed, defined in vitro model was used to study the differentiation of fetal rat skeletal muscle and it promoted the formation of myotubes from the dissociated rat fetal muscle cells. The myotubes were characterized by morphological analysis, immunocytochemistry and electrophysiology. Further, it was demonstrated that when the dissociated muscle cells were plated on fabricated microcantilevers, the muscle cells aligned along the major axis of the cantilever and formed robust myotubes. This novel system could not only find applications in skeletal muscle differentiation and biocompatibility studies but also in bioartificial muscle engineering, hybrid actuation system development, biorobotics and for a better understanding of myopathies and neuromuscular disorders.

Animals↗
PubMed2006

Isolation of drug delivery from drug effect: problems of optimizing drug delivery parameters.

A recurring question in the treatment of malignant brain tumors has been whether treatment failure is due to inadequate delivery or ineffective drugs. To isolate these issues, we tested a paradigm in which the "therapeutic" agent was a toxin about which there could be no question of efficacy, provided it was delivered in adequate amounts; we used 10% formalin. We infused 10% formalin into 5- to 8-mm subcutaneous RG-2 and D54-MG gliomas at increasing rates until we achieved 100% tumor cell kill. In RG-2 gliomas, infusions of 10 microl/h x 7 days, and 2, 4, 6, and 8 microl/min x 2 h failed to kill tumors, although growth was delayed, while infusion rates of 12 microl/min x 60 min and 48 microl/min x 15 min produced 100% tumor kill. In D54-MG tumors, infusions of 4, 8, and 24 microl/min produced 100% tumor kill. 14C-Formalin autoradiographs showed a heterogeneous distribution after infusions of 2 microl/min x 2 h, whereas infusions of 48 microl/min x 15 min showed a homogeneous distribution within the tumor, but more than 95% of tissue radioactivity was found in tissue surrounding tumor. Drug delivery remains a major issue in brain tumor treatment: Distribution inhomogeneity, rapid efflux, and consequent treatment failures are likely due to high interstitial fluid pressure. Because the infusion rates being used in the treatment of human brain tumors are low and the tumors are larger, treatment failures can be expected on the basis of inadequate drug delivery alone, regardless of the effectiveness of the drug.

Animals↗
PubMed2006

Viability and electrophysiology of neural cell structures generated by the inkjet printing method.

Complex cellular patterns and structures were created by automated and direct inkjet printing of primary embryonic hippocampal and cortical neurons. Immunostaining analysis and whole-cell patch-clamp recordings showed that embryonic hippocampal and cortical neurons maintained basic cellular properties and functions, including normal, healthy neuronal phenotypes and electrophysiological characteristics, after being printed through thermal inkjet nozzles. In addition, in this study a new method was developed to create 3D cellular structures: sheets of neural cells were layered on each other (layer-by-layer process) by alternate inkjet printing of NT2 cells and fibrin gels. These results and findings, taken together, show that inkjet printing is rapidly evolving into a digital fabrication method to build functional neural structures that may eventually find applications in neural tissue engineering.

Animals↗
PubMed2006

Toxin detection based on action potential shape analysis using a realistic mathematical model of differentiated NG108-15 cells.

The NG108-15 neuroblastoma/glioma hybrid cell line has been frequently used for toxin detection, pharmaceutical screening and as a whole-cell biosensor. However, detailed analysis of its action potentials during toxin or drug administration has not been accomplished previously using patch clamp electrophysiology. In order to explore the possibility of identifying toxins based on their effect on the shape of intracellularly or extracellularly detected action potentials, we created a computer model of the action potential generation of this cell type. To generate the experimental data to validate the model, voltage dependent sodium, potassium and high-threshold calcium currents, as well as action potentials, were recorded from NG108-15 cells with conventional whole-cell patch-clamp methods. Based on the classic Hodgkin-Huxley formalism and the linear thermodynamic description of the rate constants, ion-channel parameters were estimated using an automatic fitting method. Utilizing the established parameters, action potentials were generated in the model and were optimized to represent the actual recorded action potentials to establish baseline conditions. To demonstrate the applicability of the method for toxin detection and discrimination, the effect of tetrodotoxin (a sodium channel blocker) and tefluthrin (a pyrethroid that is a sodium channel opener) were studied. The two toxins affected the shape of the action potentials differently and their respective effects were identified based on the changes in the fitted parameters. Our results represent one of the first steps to establish a complex model of NG108-15 cells for quantitative toxin detection based on action potential shape analysis of the experimental results.

Action Potentials↗
PubMed2005

Index finger movement imitation by human neonates: motivation, learning, and left-hand preference.

Imitation of a fine motor movement, index finger protrusion, was examined in 39 neonates using an ethologically based objective coding system. Results confirmed that imitation of finger movements exists, and infants demonstrated "learning" as imitation developed through an incomplete imitation stage. Neonatal imitation was more frequently left-handed, an early sign of laterality in motivation to be investigated further. The existence of index finger imitation in human neonates indicates that volitional control of individuated finger movements develops much earlier than previously thought. The differential increase of index finger protrusion movements during the imitation periods suggests that this behavior is not an automatic response triggered by general arousal but instead is a true indicator of purposeful neonatal imitation.

Analysis of Variance↗
PubMed2005

Role of orientation in perception of emotions.

Our study examined whether perception of novel emotions, as with perception of novel objects, elicits a cardiac orientation reaction. Using a habituation-dishabituation paradigm, data from 11 adult subjects showed that orientation to both novel emotions and novel objects elicited a heart-rate deceleration. Results suggest that the orientation reaction may be an integral part of perception of emotion. Perception of emotions, therefore, is a complex, multistep process that includes an early orientation reaction.

Adult↗
PubMed2005

Does increased 18FDG uptake reflect malignant transformation of a low-grade glioma? A diagnostic dilemma.

Benign gliomas of the brain show decreased uptake of 18F fluorodeoxyglucose (FDG) on positron emission tomography (PET). Malignant transformation is usually manifested by an increase of 18FDG uptake. A 45-year-old female has been followed up since 1987 by means of 18FDG-PET for a right hemispheric World Health Organization Grade II oligoastrocytoma. In 1996, increased epileptic activity was accompanied by increased 18FDG uptake within the temporal part of the tumor. After surgery, the epileptic seizures diminished. Histological examination of the resected tumor showed no change in the pathology when compared with the first biopsy. Localized temporal increase of 18FDG uptake was not associated with malignant progression. The decrease of seizure frequency might shed light on a putative connection of hyperglycolysis and epileptic discharges.

Adult↗
PubMed2004

Thinning and flow of Tibetan crust constrained by seismic anisotropy.

Intermediate-period Rayleigh and Love waves propagating across Tibet indicate marked radial anisotropy within the middle-to-lower crust, consistent with a thinning of the middle crust by about 30%. The anisotropy is largest in the western part of the plateau, where moment tensors of earthquakes indicate active crustal thinning. The preferred orientation of mica crystals resulting from the crustal thinning can account for the observed anisotropy. The middle-to-lower crust of Tibet appears to have thinned more than the upper crust, consistent with deformation of a mechanically weak layer that flows as if confined to a channel.

Journal Article↗
PubMed2004

Long-term culture of embryonic rat cardiomyocytes on an organosilane surface in a serum-free medium.

Potential applications of engineered, functional, cardiac muscle extends from basic research through drug discovery to engineering heart tissue for transplantation. One of the central questions in cardiac tissue engineering is to understand and control the complex interactions between the cardiac muscle cells and their environment. Recent progress in chemistry, material science, and cell biology have made possible the control of the extracellular environment (soluble factors and also cell-substrate signaling) in in vitro systems. In this study we report on the development of a defined system (artificial surface, serum-free medium combination, consistent cell preparation), which promotes the differentiation and long-term survival of rat embryonic cardiomyocytes. Cardiac muscle cells plated on a N-1 (3-(trimethoxysilyl) propyl) diethylenetriamine (DETA) surface in serum-free medium survived for more than 8 weeks in vitro and maintained their contractile and electrophysiological properties. Our methods are also compatible with advanced cell patterning techniques such as microcontact printing and photolithography which now could enable systematic spacial modifications to create growth substrates for the study of the role of contact signaling in cardiac myocyte development and physiology. It also provides a test-bed for the long-term evaluation of soluble compounds such as toxins and drug candidates in a defined system.

Actins↗
PubMed2004

Subcortical [18F]fluorodeoxyglucose uptake in lesional epilepsy in patients with intracranial tumour.

BACKGROUND: We hypothesized that in patients with intracerebral tumours a subcortical metabolical shift may be present when the underlying pathology can, itself, be the epileptogenic focus. We also assumed that by studying the alterations in glucose metabolism beyond the tumour's borders we could identify a modulator area. METHODS: Sixty-seven patients with supratentorial brain tumour associated epilepsy were investigated interictally, in normoglycaemic conditions, by using [18F]fluorodeoxyglucose positron emission tomography (FDG PET). The studies were analysed semiquantitatively by calculating standardized uptake values and asymmetry indices. Normal subjects and patients with non-epileptic brain lesions were used as controls. RESULTS: Compared to normal controls frontal and temporal tumours showed significant changes in thalamic FDG uptake, which reflected hypometabolism of the affected side. It was noted in occipito-medial cortex in temporal tumours and in lentiform nucleus in frontal tumours as well. Comparison to lesional brains only proved that there was significant hypometabolism in lentiform nucleus in temporal tumours. CONCLUSIONS: The quantified values obviously reflect biological changes. The observed subcortical hypometabolism is most likely secondary to underlying pathology. Although seizures in tumorous patients do not originate from subcortical structures their influence on cortical sites of seizure initiation could be explained by defective subcortical regulation of cortical excitability.

Adolescent↗
PubMed2003

Transglutaminase 2-/- mice reveal a phagocytosis-associated crosstalk between macrophages and apoptotic cells.

Tissue transglutaminase (TGase2) is a protein-crosslinking enzyme known to be associated with the in vivo apoptosis program. Here we report that apoptosis could be induced in TGase2-/- mice; however, the clearance of apoptotic cells was defective during the involution of thymus elicited by dexamethasone, anti-CD3 antibody, or gamma-irradiation, and in the liver after induced hyperplasia. The lack of TGase2 prevented the production of active transforming growth factor-beta1 in macrophages exposed to apoptotic cells, which is required for the up-regulation of TGase2 in the thymus in vivo, for accelerating deletion of CD4+CD8+ cells and for efficient phagocytosis of apoptotic bodies. The deficiency is associated with the development of splenomegaly, autoantibodies, and immune complex glomerulonephritis in TGase2-/- mice. These findings have broad implications not only for diseases linked to inflammation and autoimmunity but also for understanding the interrelationship between the apoptosis and phagocytosis process.

Animals↗
PubMed2002

Non-covalent associations of cyclomaltooligosaccharides (cyclodextrins) with carotenoids in water. A study on the alpha- and beta-cyclodextrin/psi,psi-carotene (lycopene) systems by light scattering, ionspray ionization and tandem mass spectrometry.

Water-soluble complexes of the dietary carotenoid psi,psi-carotene (lycopene 1) with cyclomaltohexaose (alpha-cyclodextrin, alphaCD) and cyclomaltoheptaose (beta-cyclodextrin, betaCD) have been prepared and characterized via multiangle light scattering (MALS), ionspray/electrospray ionization (IS/ESI) mass spectrometry (MS) and tandem MS. MALS experiments point out that large aggregates of particles, on the nanometer-size scale, are present in water, with meaningful differences in the shape of the alphaCD/1 aggregates with respect to betaCD/1 analogues. The true 1:1 alphaCD/1 inclusion complex has been observed by IS/ESIMS and confirmed by tandem MS. The structure of CD/1 aggregations in water is proposed which are consistent with the combined MALS and MS experimental results.

Carotenoids↗
PubMed2002

The binding of Xanthophylls to the bulk light-harvesting complex of photosystem II of higher plants. A specific requirement for carotenoids with a 3-hydroxy-beta-end group.

The pigment composition of the light-harvesting complexes (LHCs) of higher plants is highly conserved. The bulk complex (LHCIIb) binds three xanthophyll molecules in combination with chlorophyll (Chl) a and b. The structural requirements for binding xanthophylls to LHCIIb have been examined using an in vitro reconstitution procedure. Reassembly of the monomeric recombinant LHCIIb was performed using a wide range of native and nonnative xanthophylls, and a specific requirement for the presence of a hydroxy group at C-3 on a single beta-end group was identified. The presence of additional substituents (e.g. at C-4) did not interfere with xanthophyll binding, but they could not, on their own, support reassembly. cis isomers of zeaxanthin, violaxanthin, and lutein were not bound, whereas all-trans-neoxanthin and different chiral forms of lutein and zeaxanthin were incorporated into the complex. The C-3 and C-3' diols lactucaxanthin (a carotenoid native to many plant LHCs) and eschscholtzxanthin (a retro-carotenoid) both behaved very differently from lutein and zeaxanthin in that they would not support complex reassembly when used alone. Lactucaxanthin could, however, be bound when lutein was also present, and it showed a high affinity for xanthophyll binding site N1. In the presence of lutein, lactucaxanthin was readily bound to at least one lutein-binding site, suggesting that the ability to bind to the complex and initiate protein folding may be dependent on different structural features of the carotenoid molecule. The importance of carotenoid end group structure and ring-to-chain conformation around the C-6-C-7 torsion angle of the carotenoid molecule in binding and complex reassembly is discussed.

Isomerism↗
PubMedDate not supplied

Adult rat spinal cord culture on an organosilane surface in a novel serum-free medium.

In this study, we have documented by morphological analysis, immunocytochemistry, and electrophysiology, the development of a culture system that promotes the growth and long-term survival of dissociated adult rat spinal cord neurons. This system comprises a patternable, nonbiological, cell growth-promoting organosilane substrate coated on a glass surface and an empirically derived novel serum-free medium, supplemented with specific growth factors (acidic fibroblast growth factor, heparin sulfate, neurotrophin-3, brain-derived neurotrophic factor, glial-derived neurotrophic factor, cardiotrophin-1, and vitronectin). Neurons were characterized by immunoreactivity for neurofilament 150, neuron-specific enolase, Islet-1 antibodies, electrophysiology, and the cultures were maintained for 4-6 wk. This culture system could be a useful tool for the study of adult mammalian spinal neurons in a functional in vitro system.

Animals↗
PubMedDate not supplied

Electrophysiological and morphological characterization of rat embryonic motoneurons in a defined system.

In an attempt to integrate biological components with silicon-based devices and systems, artificial silane surfaces have been successfully used to grow motoneurons in a defined environment. In this study we characterized the morphology and electrophysiology of purified rat embryonic (E14) motoneurons grown on a self-assembled monolayer (SAM) of N-1[3-(trimethoxysilyl)propyl]diethylenetriamine (DETA) versus that on ornithine/laminin surfaces in serum-free media. On DETA motoneurons were flat and grew more processes, whereas on ornithine/laminin they tended to aggregate. The membrane time constant, a characteristic associated with electrotonic compactness, was significantly longer for motoneurons grown on DETA. Other electrophysiological parameters were similar for the motoneurons on the different surfaces. This is the first study where purified ventral horn motoneurons were cultured in a completely defined (nonbiological surface, serum-free) environment.

Action Potentials↗