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Biomedical subjects

M E Munk

Publications and source records attributed to M E Munk.

At least 55 records · Page 3Linked to original sources
PubMed1989

T lymphocytes from healthy individuals with specificity to self-epitopes shared by the mycobacterial and human 65-kilodalton heat shock protein.

The immune response to mycobacterial pathogens comprises a significant percentage of T cells with specificity for a 65-kDa heat shock protein (hsp) which is highly conserved in bacteria and man. PBMC were activated in vitro with killed Mycobacterium tuberculosis and afterward tested for CTL activity on autologous target cells primed with 1) killed M. tuberculosis, 2) intact recombinant 65-kDa hsp of Mycobacterium bovis/M. tuberculosis; or 3) tryptic fragments of the recombinant 65-kDa hsp. Strong CTL activity was observed on targets primed with killed M. tuberculosis or with tryptic fragments of the 65-kDa hsp, but not on those primed with the intact 65-kDa hsp. M. tuberculosis activated T cells from 2/13 donors tested exerted killer activity against unprimed targets. To assess whether T cell responses were directed against self-epitopes shared by the mycobacterial and human 65-kDa hsp, four peptides of at least 10 amino acids length were synthesized corresponding to fully or almost identical regions of these molecules. Peripheral blood T cells from 8/9 individuals tested, after activation with killed M. tuberculosis, expressed strong CTL activity toward autologous targets primed with one or more of these synthetic peptides. By using HLA-DR transfected murine L cells we found that the epitopes were recognized in the context of histocompatible HLA-DR (class II) molecules. We conclude that the demonstration of T cells with specificity to self-epitopes in vitro is not indicative for autoimmune disease. However, if at certain stages of infection such T cells are activated by crossreactive microbial epitopes they could cause autoimmune responses.

Antigens, Bacterial↗
PubMed1989

T cells against a bacterial heat shock protein recognize stressed macrophages.

Heat shock proteins are evolutionarily highly conserved polypeptides that are produced under a variety of stress conditions to preserve cellular functions. A major antigen of tubercle bacilli of 65 kilodaltons is a heat shock protein that has significant sequence similarity and cross-reactivity with antigens of various other microbes. Monoclonal antibodies against this common bacterial heat shock protein were used to identify a molecule of similar size in murine macrophages. Macrophages subjected to various stress stimuli including interferon-gamma activation and viral infection were recognized by class I-restricted CD8 T cells raised against the bacterial heat shock protein. These data suggest that heat shock proteins are processed in stressed host cells and that epitopes shared by heat shock proteins of bacterial and host origin are presented in the context of class I molecules.

Animals↗
PubMed1989

Cell-mediated immunity to mycobacteria: a double-sided sword?

Mycobacteria are intracellular pathogens capable of replicating in resting macrophages. Specific helper T lymphocytes which activate antimycobacterial capacities in infected macrophages represent an important constituent of acquired resistance. In addition, cytolytic T lymphocytes may contribute to resistance. On the other hand, lysis of infected host cells may also comprise autoaggressive consequences. Recent evidence suggest that T cells with specificity for mycobacterial heat shock proteins are involved in the antimycobacterial immune response. Heat shock proteins are evolutionarily highly conserved and cross-reactivity between microbial and mammalian molecules may occur on the B-cell and T-cell level. Thus, T cells directed against shared epitopes of mycobacterial and autologous origin could initiate autoimmune reactions.

Animals↗
PubMed1988

T cell responses of normal individuals towards recombinant protein antigens of Mycobacterium tuberculosis.

Recombinant beta-galactosidase fusion proteins from Mycobacterium tuberculosis were purified by affinity chromatography and used for stimulation of unselected T lymphocytes freshly isolated from healthy individuals. It was found that the 12-kDa, 19-kDa, 65-kDa and 71-kDa recombinant (r) proteins tested stimulated T cells from healthy individuals in an antigen-specific way. These data demonstrate that it is feasible to screen purified r-proteins with unselected T cell populations. The existence of T cells with reactivity to these antigens in healthy individuals suggests T cell activation independent from clinical disease and hence that these proteins are not indicative for active tuberculosis.

Antigens, Bacterial↗
PubMed1988

Listeria monocytogenes reactive T lymphocytes in healthy individuals.

Peripheral blood mononuclear cells of healthy individuals were enriched for T lymphocytes and stimulated with killed organisms of Listeria sp. Different strains of Listeria sp. induced comparable T cell responses independent from their pathogenicity and virulence. Evidence is presented that killed L. monocytogenes organisms lacked mitogenic activity for human B and T lymphocytes. It is concluded that Listeria reactive T lymphocytes are commonly present in healthy individuals and hence may contribute to the rare occurrence of listeriosis in normal adults.

B-Lymphocytes↗
PubMed1988

Automated classification of candidate structures for computer-assisted structure elucidation.

In computer-assisted structure elucidation, a large number of candidate structures for the unknown compound can be generated. A computer program designed to aid in the recognition of significant differences between these structures is described. The goal of the program is to group the candidates into meaningful classes with a minimum of input from the user; each class is distinguished by a substructure its members have in common. A computational approach is developed based on the combinatorial problem of set covering. The program evaluates its results using an information-theoretical criterion. An application of the program to a real-word structure problem is presented.

Chemical Phenomena↗
PubMed1988

Structure generation by reduction: a new strategy for computer-assisted structure elucidation.

A problem common to computer programs for structure elucidation is the efficient and prospective use of the input information to constrain the structure generation process. The input may consist of potentially overlapping substructure requirements and alternative substructure interpretations of spectral data. Other useful information may be structural features that must not be present in the output structures. All of these may interact in a complex manner that is impossible to determine by use of a bond-by-bond structure assembly algorithm. A new method is described called structure reduction. In contrast to structure assembly, this method begins with a set of all bonds and removes inconsistent bonds as structure generation progresses. This results in a more efficient use of the input information and the ability to use potentially overlapping required substructures. Several examples illustrate the application of our computer program COCOA, which uses this method to solve real-world structure elucidation problems.

Chemical Phenomena↗
PubMed1985

Combinatorial problems in computer-assisted structural interpretation of carbon-13 NMR spectra.

Combinatorial problems posed by a method for computer-assisted structural interpretation of 13C NMR spectra based upon fragments consisting of a carbon atom and its alpha neighbors are discussed. The basic problem of generating all structures consistent with a set of inferred fragments that contains mutually exclusive alternatives is divided into two parts: generation of combinations of fragments and exhaustive assembly of each combination into molecules. Algorithmic solutions to both of these problems are presented in detail.

Carbon Isotopes↗
PubMedDate not supplied

Graph automorphism perception algorithms in computer-enhanced structure elucidation.

The concept of graph symmetry is explained in terms of the vertex automorphism group, which is a subgroup of the complete vertex permutation group. The automorphism group can be deduced from the automorphism partition of graph vertices. An algorithm is described which constructs the automorphism group of a graph from the automorphism vertex partitioning. The algorithm is useful especially for graphs which contain more than one vertex-partition set. Several well-known topological symmetry perception algorithms that yield automorphism partitions are compared. The comparison is favorable to the Shelley-Munk algorithm, developed in the framework of the SESAMI system for computer-enhanced structure elucidation.

Algorithms↗