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Biomedical subjects

K Esser

Publications and source records attributed to K Esser.

At least 37 records · Page 2Linked to original sources
PubMed1991

Immunization of owl monkeys with a recombinant protein containing repeated epitopes of a Plasmodium falciparum glycophorin-binding protein.

A Plasmodium falciparum glycophorin binding protein (GBP-130) has been implicated in protective immunity to malaria. The gene for GBP-130 encodes a protein containing 11 tandemly repetitive 50 amino acid units. We report an immunization trial in Aotus monkeys using a recombinant DNA protein containing three of these 50 amino acid repeats. When administered with aluminum hydroxide, this antigen induced low levels of antibodies that reacted with the recombinant protein by ELISA and with parasite antigens in immunoblot and immunofluorescence assays, but not by immunoprecipitation. When administered with Freund's complete adjuvant, this antigen induced high levels of antibodies that reacted in ELISA, immunoblot, immunofluorescence, and immunoprecipitation assays. Serum from immunized monkeys did not inhibit parasite growth, and protection from intravenous challenge with P. falciparum-infected erythrocytes was not observed in any experimental group. These results suggest that the repetitive region of GBP-130 is not a useful vaccine candidate.

Amino Acid Sequence↗
PubMed1990

Improved transformation frequency and heterologous promoter recognition in Aspergillus niger.

Wild-type strains of Aspergillus niger were transformed with integrative vectors. The number of stable transformants varied from approximately 20-30/micrograms up to 17,000/micrograms using acetamide and hygromycin B selection, respectively. The introduction of deletions of 5' and 3' non-coding regions of the acetamidase gene (amdS+) revealed that these sequences influenced the number of transformants. The molecular characterization of A. niger transformants revealed that several copies of the vectors were tandemly integrated into the nuclear DNA. These oligomers were stably inherited, even after 100 days of growth on non-selective medium. The expression of the vector-encoded genes was confirmed by evidence from the mRNAs and corresponding proteins encoded by the selectable marker genes.

Acetamides↗
PubMed1989

In organello replication and viral affinity of linear, extrachromosomal DNA of the ascomycete Ascobolus immersus.

Linear, extrachromosomal DNA's of the filamentous fungus Ascobolus immersus are localized within the mitochondria. These linear plasmids have no homology to the high molecular weight mtDNA (hmw mtDNA). For analysis of plasmid replication an in organello DNA synthesis system was developed, in which radionucleotides were incorporated into intact mitochondria. Plasmid DNA is labelled preferentially in this system. From replication analysis of a specific plasmid there is evidence of a virus-like protein-primed replication. Sequence analysis of this plasmid reveals that a viral DNA polymerase is encoded. Thus, these genetic elements presumably are viral remnants rather than true plasmids.

Amino Acid Sequence↗
PubMed1989

Multipartite structure of mitochondrial DNA in a fungal longlife mutant.

Rearrangements in the mitochondrial genome of the longlife mutant ex1 of the ascomycete Podospora anserina have led to a heterogeneous population of subgenomic molecules. The restriction maps of individual subcircles were established using overlapping recombinant lambda phages isolated from an ex 1 mtDNA/EMBL3 library. The formation of the subcircles and the resulting multipartite organization of the ex1 mtDNA are discussed.

Ascomycota↗
PubMed1989

Mitochondrial DNA rearrangements are correlated with a delayed amplification of the mobile intron (plDNA) in a long-lived mutant of Podospora anserina.

A new long-lived mutant of Podospora anserina has been isolated and characterized. Its longevity is maternally inherited as revealed by reciprocal crosses. A molecular analysis resulted in the identification of an amplified DNA species (designated pAL2-1) with homology to mitochondrial DNA (mtDNA). The presence of this DNA species is correlated with mtDNA rearrangements and a delayed amplification of the mobile intron (plDNA).

Aging↗
PubMed1989

Sleeping sickness in the Lambwe Valley in 1978.

Even though tsetse control measures were discontinued in the Lambwe Valley in 1974 the prevalence of Rhodesian sleeping sickness remained at low levels. A survey conducted in 1978 verified a low prevalence of disease (0.1%). Thirty-four per cent of the individuals tested were positive for malaria with the highest prevalence (44%) in children aged 0-9 years. Thirteen of 1340 individuals (0.97%) tested and found negative for sleeping sickness in 1978 developed the disease by 1985. Fourteen individuals with moderate titres (2+) in the IFAT but who showed no evidence of disease were traced and found to be alive and well seven years later. Three of these patients still had positive titres but the others had converted to negative. Sera from four patients infected and treated in 1978 were also positive, but only one of five patients treated in 1977 reacted in the test. The CFT as described did not appear useful as a diagnostic test.

Adolescent↗
PubMed1989

In vivo construction of linear vectors based on killer plasmids from Kluyveromyces lactis: selection of a nuclear gene results in attachment of telomeres.

Linear vectors based on plasmids pGKL1 and pGKL2 from Kluyveromyces lactis were obtained by in vivo recombination in Saccharomyces cerevisiae and selected for integration of the nuclear LEU2 gene. The linear hybrid molecules obtained had no proteins attached to their 5' ends, as is found for native pGKL plasmids. However, telomere-specific sequences were added to the ends of pGKL1. In contrast to the cytoplasmically localized pGKL plasmids, the newly obtained linear hybrid vectors probably replicate within the nucleus and provide evidence that the nuclear LEU2 gene cannot be expressed in the cytoplasm.

Base Sequence↗
PubMed1988

Mature liver stages of cloned Plasmodium falciparum share epitopes with proteins from sporozoites and asexual blood stages.

The liver merozoites of malaria parasites are of paramount importance, as they initiate the parasite invasion of red blood cells and start the cycle associated with the clinical features of malaria. Investigating liver merozoite antigen is difficult because of the lack of a rodent model of human malaria. In addition, only a low proportion of cells are obtained in vivo, the parasites from Cebus and Aotus monkeys are immature, and in-vitro experiments with liver cells are often confounded by contamination with the natural mosquito flora copurified with the sporozoites used for seeding the liver cultures. In our study, mature liver schizonts were shown to possess many of the antigenic determinants recognized by MoAbs and sera specific for defined sporozoite and blood-stage antigens. We employed an immunofluorescence procedure based on evaluating parasites in cryosections prepared from infected chimpanzee liver. Sufficient numbers of sectioned parasites were evaluated with each antibody to assure the reproducibility of the results, and the fixation procedure used was sufficiently non-destructive to parasite antigens so that clear differences between reactions of specific antibodies and negative controls were observed. Our evidence for sharing of epitopes by liver merozoites and sporozoites or by liver merozoites and asexual blood-stage parasites raises the possibility that immune responses elicited against sporozoites or asexual stage antigens being considered as vaccine candidates may also act against this important, little-studied stage of the parasite.

Animals↗
PubMed1987

Circulating antibodies to mouse laminin in Chagas disease, American cutaneous leishmaniasis, and normal individuals recognize terminal galactosyl(alpha 1-3)-galactose epitopes.

Sera from patients with American cutaneous leishmaniasis and Chagas disease and from monkeys infected with either Trypanosoma cruzi or Trypanosoma rhodesiense show, in RIAs, strong binding to mouse laminin. A distinct although weaker binding activity is also detected in normal human sera. The antibodies recognize a common carbohydrate epitope present on mouse laminin, which was assigned to a terminal galactosyl(alpha 1-3)-galactose group. Distinct crossreactions were observed with some other basement membrane proteins, rabbit glycosphingolipids, defucosylated human B blood group substance and components produced by some human tumor cells. Only little activity was, however, found on laminin obtained from human placenta. The data indicate that the antibodies arising in infectious diseases are stimulated by similar carbohydrate epitopes present on the surface of parasites. Tissue-specific occurrence of such epitopes may exist and explain the involvement of distinct tissues in autoimmune disorders.

Animals↗
PubMed1986

Plasmids of mitochondrial origin in senescent mycelia of Podospora curvicolla.

Podospora curvicolla displays symptoms of senescence similar but not quite identical to those reported for Podospora anserina. In Podospora curvicolla single hyphae may escape from death leading to a new growth front and consequently to a mode of growth characterized by alternating phases of growth and non-growth. Restriction analyses and hybridization experiments have revealed that the Podospora curvicolla type of senescence is correlated with plasmids originating from amplification of a single distinct region of the mitochondrial DNA containing the 1rRNA gene. In the yeast transformation system sequences of this region may function as autonomously replicating sequences (ARS). Plasmids (pl1, pl2 and pl3) isolated from different, independently aged mycelia are largely homologous to each other but differ in their excision/junction sites and have different sizes: 10.85 kb (p11), 9.01 kb (pl2) and 10.50 kb (pl3). The sequence of the most frequently occurring plasmid in ageing strains of Podospora anserina is absent in Podospora curvicolla either as free plasmid DNA or as an integrated part of the mtDNA. Possibly there is a correlation between the absence of this particular sequence in Podospora curvicolla and the type of senescence displayed in this organism.

Ascomycota↗
PubMed1985

The onset of senescence is affected by DNA rearrangements of a discontinuous mitochondrial gene in Podospora anserina.

Mapping and transcription studies have revealed that in Podospora anserina the causative agent of senescence, a mitochondrial plasmid (plDNA), is identical with intron 1 of the discontinuous gene for cytochrome-c-oxidase subunit 1 (COI), which is 2 kpb from the discontinuous gene for cytochrome b (Cytb). A mitochondrial mutant (ex1) devoid of the COI, but not of the Cytb gene provides longevity. A molecular model for the onset of senescence is presented.

Amino Acid Sequence↗
PubMed1984

Topologic mapping of protective and nonprotective epitopes on the variant surface glycoprotein of the WRATat 1 clone of Trypanosoma brucei rhodesiense.

Monoclonal antibodies were used in competitive antibody binding assays to define and map epitopes on the variant surface glycoprotein of the WRATat 1 clone of T. b. rhodesiense. By using a panel of 30 WRATat 1-specific monoclonal antibodies, 16 epitopes were defined that fall into four clusters, having 1, 1, 3, and 11 distinct epitopes respectively. All epitopes were easily classified as being 1) exposed uniformly on the surface of the trypanosome, 2) exposed only in the region of the flagellar pocket, or 3) "buried", based on the ability or inability of the monoclonal antibodies to bind living trypanosomes in a fluid phase immunofluorescence assay. Monoclonal antibodies that bind exposed surface epitopes are protective, whereas only three of seven that bind exclusively to flagellar pocket epitopes are protective. None of the nine monoclonal antibodies that recognize buried epitopes are protective. Also, antibody-mediated immunity to WRATat 1 trypanosomes is not associated with any particular subclass of antibody. The IgM, IgG1, IgG2a, IgG2b, IgG3, and IgA subclasses each contain examples of protective monoclonal antibodies.

Animals↗
PubMed1982

Replication and expression of a bacterial--mitochondrial hybrid plasmid in the fungus Podospora anserina.

Hybrid plasmids consisting of the bacterial plasmid pBR322 and plasmid-like DNA (pl DNA) sequences from the fungus Podospora anserina are not only able to replicate in Escherichia coli but also in the fungus. This was proved by both biophysical and biological evidence involving buoyant density profiles, DNA.DNA hybridization, and restriction analysis--all confirming that pl DNA behaves as a true plasmid. During its amplification in P. anserina, the hybrid plasmid does not lose its prokaryotic coding capacity as shown after retransfer and subsequent cloning in E. coli. P. anserina is able to express both the eukaryotic and the prokaryotic genetic information of the hybrid plasmid because the occurrence of senescence and the production of beta-lactamase could be shown in experiments involving specific hybrid plasmids. In the same systems, it was possible to demonstrate that a hybrid plasmid containing, instead of pl DNA, a pl DNA homologous region of native mtDNA also could function as a true plasmid. This hybrid plasmid contained about 25% of the genetic information pl DNA, which corresponds to about 6% of the genetic information of mtDNA. Thus, the data show that hybrid plasmids may be used to shuttle genetic information between P. anserina and E. coli. hence, through the use of a mtDNA replicon, as evidenced by the pl DNA of P. anserina, another pathway in genetic engineering is established.

DNA Replication↗
PubMed1980

Characterization and cloning of plasmid like DNA of the ascomycete Podospora anserina.

The previously reported existence of plasmid-like (pl) DNA in senescent mycelia of Podospora anserina was confirmed using new methodology. Detailed anaysis of bulk DNA has further shown a possible relationship between pl DNA and mt DNA. According to biophysical and electron microscopic experiments the pl DNA was found to consist of oligomeres having a basic unit with a contour length of 0.75 micrometer corresponding to 2.4 kb. To overcome the handicap that pl DNA is only produced in rather small amounts in the aging mycelia, this DNA was cloned in E. coli after insertion into a bacterial plasmid vector, pBR 322. It was possible to isolate a stable hybrid plasmid consisting of the vector and only one integrated monomere of pl DNA. The composition of this hybrid plasmid was confirmed by restriction endonuclease analysis and heteroduplex formation. A restriction map of the pl DNA is presented and its insertion site onto pBR 322 indicated.

Ascomycota↗