Biomedical subjects

O Bachar

Publications and source records attributed to O Bachar.

6 recordsLinked to original sources

PubMed2004

Nerve growth factor enhances cholinergic innervation and contractile response to electric field stimulation in a murine in vitro model of chronic asthma.

BACKGROUND: Asthma is a chronic inflammatory disease characterized by airway hyper-responsiveness. Alterations in the neurogenic control are believed to contribute to the pathogenesis. Yet, the long-term interaction between nerves and inflammatory mediators, such as the neurotrophin nerve growth factor (NGF), are not fully understood much due to the absence of appropriate experimental assays. OBJECTIVE: To develop an ex vivo mouse organ culture assay and to investigate the effects of NGF on nerve-mediated airway contractions. METHOD: Mouse tracheal segments were cultured in periods of up to 16 days. Their contractile responses to electric field stimulation (EFS) were investigated. In addition, the effect of 4 days of NGF treatment was analysed using EFS and immunohistochemistry. RESULTS: EFS (0.2-25.6 Hz) induced reproducible and frequency-dependent cholinergic contractions of both fresh and cultured tracheal segments. The main part of the EFS response was blocked by tetrodotoxin or atropine. After 4 days in culture, regional differences appeared, with stronger EFS responses in distal than in proximal segments. More nerve fibres were seen in distal segments than in proximal segments. Treatment with NGF during 4 days of culture increased the innervation of the proximal segments, at the same time as the cholinergic contractile responses to EFS were enhanced dose-dependently. CONCLUSION: Culture of tracheal segments appears to be a suitable assay for the examination of long-term effects induced by inflammatory mediators on neurally mediated airway contractions. NGF treatment enhanced the cholinergic, nerve-dependent contractions and increased the amount of nerve fibres seen in the murine tracheal segments, suggesting a role for NGF in the development of airway hyper-responsiveness.

Animals↗

PubMed1993

A computer vision based technique for 3-D sequence-independent structural comparison of proteins.

A detailed description of an efficient approach to comparison of protein structures is presented. Given the 3-D coordinate data of the structures to be compared, the system automatically identifies every region of structural similarity between the structures without prior knowledge of an initial alignment. The method uses the geometric hashing technique which was originally developed for model-based object recognition problems in the area of computer vision. It exploits a rotationally and translationally invariant representation of rigid objects, resulting in a highly efficient, fully automated tool. The method is independent of the amino acid sequence and, thus, insensitive to insertions, deletions and displacements of equivalent substructures between the molecules being compared. The method described here is general, identifies 'real' 3-D substructures and is not constrained by the order imposed by the primary chain of the amino acids. Typical structure comparison problems are examined and the results of the new method are compared with the published results from previous methods. These results, obtained without using the sequence order of the chains, confirm published structural analogies that use sequence-dependent techniques. Our results also extend previous analogies by detecting geometrically equivalent out-of-sequential-order structural elements which cannot be obtained by current techniques.

Algorithms↗

PubMed1992

An efficient automated computer vision based technique for detection of three dimensional structural motifs in proteins.

As the number of available three dimensional coordinates of proteins increases, it is now recognized that proteins from different families and topologies are constructed from independent motifs. Detection of specific structural motifs within proteins aids in understanding their role and the mechanism of their operation. To aid in identification and use of these motifs it has become necessary to develop efficient methods for systematic scanning of structural databases. To date, methods of structural protein comparison suffer from at least one of the following limitations: (1) are not fully automated (require human intervention), (2) are limited to relatively similar structures, (3) are constrained to linear alignments of the structures, (4) are sensitive to insertions, deletions or gaps in the sequences or (5) are very time consuming. We present a method to overcome the above limitations. The method discovers and ranks every piece of structural similarity between the structures compared, thus allowing the simultaneous detection of real 3-D motifs in different domains, between domains, in active sites, surfaces etc. The method uses the Geometric Hashing Paradigm which is an efficient technique originally developed for Computer Vision. The algorithm exploits the geometrical constraints of rigid objects, it is especially geared towards recognition of partial structures in rigid objects belonging to large data bases and is straightforwardly parallelizable. Computer Vision techniques are for the first time applied to molecular structure comparison, resulting in an efficient, fully automated tool. The method has been tested in a number of cases, including comparisons of the haemoglobins, immunoglobulins, serine proteinases, calcium binding proteins, DNA binding proteins and others. In all examples our results were equivalent to the published results from previous methods and in some cases additional structural information was obtained by our method.

Amino Acid Sequence↗

PubMed1989

Alzheimer's disease antibodies bind specifically to a neurofilament protein in Torpedo cholinergic neurons.

Alzheimer's disease (AD) is characterized by neurofibrillary tangles and neuritic plaques and by the degeneration of central cholinergic neurons. Recent studies indicated the presence of antibodies in the sera and cerebrospinal fluid of AD patients which react with neuronal tissue and which recognize cholinergic neurons. In order to identify the cholinergic antigens against which the AD antibodies are directed, we have recently used the purely cholinergic electromotor neurons of the electric fish Torpedo which are chemically homogenous and cross-react antigenically with mammalian cholinergic neurons. This study revealed that immunoglobulins (IgG) from sera of AD patients bind specifically to an antigen in Torpedo electromotor neurons with an apparent molecular weight of 200 kDa. In the present report we attempt to characterize this antigen. The similarity in size of this protein to that of the heavy neurofilament subunit (NF-H) and the association of neurofilaments with plaques and tangles prompted us to examine the possibility that it is a neurofilament protein. Our findings show that IgG from sera of AD patients bind to the NF-H protein of Torpedo cholinergic neurons. Comparison of the binding of AD and control IgG to Torpedo cholinergic NF-H revealed that AD IgG bind to this neurofilament protein more readily than do control IgG. In contrast, AD and control IgG bind similarly to NF-H obtained from the chemically heterogenous Torpedo spinal cord and rat brain. These findings suggest that AD sera contain a repertoire of anti-NF-H IgG and that a subpopulation of these antibodies whose levels are significantly elevated in AD binds to epitopes highly enriched in Torpedo cholinergic NF-H.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1989

Serum antibodies to cholinergic neurons in Alzheimer's disease.

Alzheimer's disease (AD) is associated with degenerative changes in nuclei of the basal forebrain which provide most of the cholinergic innervation of the cortex and hippocampus. Although the etiology and pathogenesis of AD are not known, several reports indicate the involvement of immunological mechanisms. In the present work we examined the existence of antibodies in sera of AD patients which bind specifically to cholinergic neurons. As antigen we employed the purely cholinergic electromotor neurons of the electric fish Torpedo which are chemically homogeneous and cross react antigenically with human and other mammalian cholinergic neurons. Our findings show that immunoglobulins (IgG) from sera of AD patients bind to the heavy neurofilament subunit (NF-H) of these neurons. Comparison of the binding of AD and control IgG to Torpedo cholinergic NF-H revealed that AD IgG bind to this neurofilament protein more than control IgG. In contrast, AD and control IgG bind similarly to NF-H obtained from the chemically heterogeneous Torpedo spinal cord and from rat brain. These findings suggest that AD sera contain a repertoire of anti NF-H IgG and that a subpopulation of these antibodies, whose levels are significantly elevated in AD, binds to epitopes highly enriched in Torpedo cholinergic NF-H. The diagnostic potential of these AD antibodies is discussed.

Alzheimer Disease↗

PubMed1988

Antibodies to cholinergic neurons in Alzheimer's disease.

Alzheimer's disease (AD) is associated with degenerative changes in nuclei of the basal forebrain which provide most of the cholinergic input to the cortex and hippocampus and with a reduction in presynaptic cholinergic parameters in these areas. Although the etiology and pathogenesis of AD are not known, several reports indicate the involvement of immunological mechanisms. In the present work we examined the existence of antibodies in sera of AD patients that bind specifically to cholinergic neurons. As antigens we employed the purely cholinergic electromotor neurons of the electric fish Torpedo which are chemically homogeneous and cross-react antigenically with human and other mammalian cholinergic neurons. Our findings show that immunoglobulins from sera of AD patients bind to a specific antigen (molecular mass 200 kilodaltons) in the cell bodies and axons of Torpedo electromotor neurons and that the levels of such antibodies are significantly higher in AD patients than in controls. The possible role of these antibodies in the cholinergic dysfunction in AD and their diagnostic potential are discussed.

Aged↗