PubMed Health⌕ Search

Biomedical subjects

L M Corcoran

Publications and source records attributed to L M Corcoran.

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

Virus-transformed pre-B cells show ordered activation but not inactivation of immunoglobulin gene rearrangement and transcription.

Virus-transformed pre-B cells undergo ordered immunoglobulin (Ig) gene rearrangements during culture. We devised a series of highly sensitive polymerase chain reaction assays for Ig gene rearrangement and unrearranged Ig gene segment transcription to study both the possible relationship between these processes in cultured pre-B cells and the role played by heavy (H) chain (mu) protein in regulating gene rearrangement. Our analysis of pre-B cell cultures representing various stages of maturity revealed that transcription of each germline Ig locus precedes or is coincident with its rearrangement. Cell lines containing one functional rearranged H chain allele, however, continue to transcribe and to rearrange the allelic, unrearranged H chain locus. These cell lines appear to initiate but not terminate rearrangement events and therefore provide information about the requirements for activating rearrangement but not about allelic exclusion mechanisms.

Abelson murine leukemia virus↗
PubMed1988

Homologous recombination within subtelomeric repeat sequences generates chromosome size polymorphisms in P. falciparum.

We present restriction maps for chromosomes 1 and 2 of six cloned lines of P. falciparum. These delineate the locations of eight genetic markers, including genes for five antigens. In parasites from diverse areas, chromosome structure is conserved in central regions but is polymorphic both in length and sequence near the telomeres. The telomeres and adjacent sequences comprise a conserved structure at the ends of most P. falciparum chromosomes. However, the subtelomeric zones are polymorphic and coincide with the locations of a repetitive element (rep20). Deletions of rep20 generate clones of P. falciparum that lack rep20 on one or both ends of chromosomes 1 or 2, and larger deletions remove telomere-proximal genes as well. The chromosome length polymorphisms can therefore be largely explained by recombination within these blocks of repeats, a mechanism that is also important in the generation of diversity in genes for repetitive antigens of P. falciparum.

Animals↗
PubMed1988

A second antigenic heat shock protein of Plasmodium falciparum.

We describe here an antigen of Plasmodium falciparum, defined by a cDNA clone designated Ag361. The antigen is a soluble cytoplasmic 70-kD polypeptide present in all isolates analyzed and in all stages of asexual development in the blood. The antigen is a natural immunogen, although it lacks repeating epitopes of many P. falciparum antigens. Ag361 shares extensive sequence homology with the hsp70 proteins of Xenopus laevis, Drosophila melanogaster, Escherichia coli, and man, as well as a previously isolated P. falciparum hsp70 protein. The genome of P. falciparum contains at least five hsp70-like genes, located on at lest four different chromosomes.

Amino Acid Sequence↗
PubMed1988

The B-cell-specific Oct-2 protein contains POU box- and homeo box-type domains.

Transcription of promoters of immunoglobulin genes is controlled by an octanucleotide sequence element. The sequence of a cDNA encoding a B-cell-specific protein, Oct-2, has been determined. This protein specifically recognizes the octanucleotide element and is part of the previously identified NF-A2 family of proteins. The DNA-binding domain of Oct-2 is structurally related to the homeo box consensus and thus contains a potential helix-turn-helix sequence. Oct-2 also possesses a potential 'leucine zipper' domain, where four leucines are each separated by exactly seven residues. Comparisons of Oct-2 with protein Oct-1, which also recognizes the octanucleotide element but is constitutively expressed in all cell types, show high sequence conservation through the 60-residue DNA-binding domain, as well as an adjacent tract of 75 residues. The latter conserved region is also found in regulatory genes expressed in pituitary cells and nematodes and has been termed a POU box. Because two different cDNAs were isolated, it is proposed that the oct-2 gene is expressed as multiple mRNAs that vary in splicing patterns. Most interestingly, the oct-2 cDNA contains a second overlapping open reading frame, 278 residues in length, which might also specify a protein important for B-cell development.

Amino Acid Sequence↗
PubMed1988

GM-CSF produced by recombinant vaccinia virus or in GM-CSF transgenic mice has no effect in vivo on murine cutaneous leishmaniasis.

The hemopoietic growth and differentiation regulators, granulocyte-macrophage colony-stimulating factor (GM-CSF) and the multipotential stimulating factor (multi-CSF) have been shown to have major effects on the effector function of mature macrophages. In this study we have examined the effect of recombinant GM-CSF and multi-CSF expressed transiently from recombinant vaccinia virus, or constitutively in GM-CSF transgenic mice on the development of cutaneous leishmaniasis, caused by Leishmania major in genetically susceptible or resistant mice. We observed no effect on the development of lesions when GM-CSF or multi-CSF were administered before infection, nor on the healing of lesions when they were administered after appearance of lesions. Although only some of the GM-CSF transgenic mice or their normal littermates developed lesions after infection with L. major, there was no difference between the groups in the rate of lesion development or in the size of lesions.

Animals↗
PubMed1987

Genetic analysis of the human malaria parasite Plasmodium falciparum.

Malaria parasites are haploid for most of their life cycle, with zygote formation and meiosis occurring during the mosquito phase of development. The parasites can be analyzed genetically by transmitting mixtures of cloned parasites through mosquitoes to permit cross-fertilization of gametes to occur. A cross was made between two clones of Plasmodium falciparum differing in enzymes, drug sensitivity, antigens, and chromosome patterns. Parasites showing recombination between the parent clone markers were detected at a high frequency. Novel forms of certain chromosomes, detected by pulsed-field gradient gel electrophoresis, were produced readily, showing that extensive rearrangements occur in the parasite genome after cross-fertilization. Since patients are frequently infected with mixtures of genetically distinct parasites, mosquito transmission is likely to provide the principal mechanisms for generating parasites with novel genotypes.

Adenosine Deaminase↗
PubMed1987

Molecular karyotype of Plasmodium falciparum: conserved linkage groups and expendable histidine-rich protein genes.

We describe fractionation of the Plasmodium falciparum genome into 14 chromosomal DNA molecules by pulsed-field gel electrophoresis. This number agrees with the number of chromosomes observed by electron microscopic visualization of kinetochores. The assignment of 25 markers to 12 of the 14 chromosomes in three cloned parasite lines demonstrates that chromosomal size variation can greatly change the relative migration of genetically equivalent chromosomes. Deletions that include genes for three different histidine-rich proteins, located on chromosomes 2, 8, and 13, contribute to size differences in some clones. Other karyotypic differences result from chromosome segregation and/or recombination during meiosis.

Animals↗
PubMed1986

Structure of the RESA gene of Plasmodium falciparum.

We have determined the nucleotide sequence of the gene encoding the ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum, an antigen that has been shown to confer protective immunity on monkeys. The sequence has enabled us to predict the structure of the RESA gene and the amino acid sequence of its protein product. The gene consists of two exons with a short intron located near the 5' end of the coding region. A hydrophobic amino acid segment predicted for the 3' end of exon 1 is consistent with the possibility that exon 1 encodes trafficking signal sequences. We show that restriction fragment length polymorphisms can be used to define two different alleles of RESA, represented by isolates FC27 and NF7, and compare the FC27 sequence with that of a long cDNA clone from NF7 described previously.

Amino Acid Sequence↗
PubMed1986

Chromosome size polymorphisms in Plasmodium falciparum can involve deletions and are frequent in natural parasite populations.

A comparison of independent cultured isolates of Plasmodium falciparum revealed that while chromosome number was constant, the sizes of analogous chromosomes varied widely. We show here that chromosome size polymorphisms are not generated during differentiation of the asexual blood stages, as the molecular karyotype of a cloned parasite line is constant through this part of the life cycle. Experiments using whole P. falciparum chromosomes as hybridization probes to examine polymorphisms within two independent parasite populations indicate that the polymorphisms observed here are not the consequence of large-scale interchromosomal exchanges, and imply that deletions/duplications represent one mode of generating chromosome length polymorphisms. Although the deletions probably involve repetitive DNA, we show here that structural genes for P. falciparum antigens can also be lost. Furthermore, these dramatic size polymorphisms occur not only in cultured lines of P. falciparum, but with surprising frequency in natural malarial infections.

Animals↗
PubMed1985

Transposition of the immunoglobulin heavy chain enhancer to the myc oncogene in a murine plasmacytoma.

A novel mechanism of oncogene activation by transposition of a tissue-specific cellular enhancer is described. A rearranged c-myc oncogene was cloned from murine plasmacytoma ABPC17 in the expectation that it would reflect the t(6;15) chromosome translocation carried by this tumor. The rearrangement instead reflects an insertion 361 bp 5' to the c-myc gene on chromosome 15. The insert conveys a 2.3 kb segment of the immunoglobulin heavy (H) chain locus from chromosome 12. Since the insertion introduces the lymphoid-specific enhancer from the JH-Smu region and also disrupts a region implicated in normal c-myc control, it may account for the c-myc transcription observed in ABPC17. The structure of the transposed segment and a corresponding deletion in the JH-Smu region suggests that the transposition reflects a complex recombination between chromosomes 15 and 12. Since the t(6;15) breakpoint is not near c-myc, chromosome 15 must have undergone an independent exchange with chromosome 6.

Alleles↗