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Biomedical subjects

J C Neil

Publications and source records attributed to J C Neil.

At least 91 records · Page 5Linked to original sources

Detection of antibodies to extractable nuclear antigens using calf thymus and rabbit thymus. A comparative study of 1000 consecutive anti-nuclear antibody positive patients.

A comparison between calf thymus extract and rabbit thymus extract to determine their suitability for clinical laboratories in detecting antibodies to extractable nuclear antigens (ENA) was undertaken. Calf thymus extract (CTE) detected 90% more ENA positive patients and 155% more lines than rabbit thymus extract (RTE). In contrast to RTE, CTE resolved Sm and RNP into two distinct lines, had superior stability at -80 degrees C and produced greater clarity of definition of precipitin lines.

Animals↗

Receptor-mediated leukaemogenesis: hypothesis revisited.

The discovery of the first example of retroviral transduction of an immunological effector molecule has led us to reconsider the possible importance of cell surface receptors of the immune system in leukaemia development. Antigen receptors on lymphoid cells not only bind external ligands but are crucial in the control of cellular proliferation. The concept of autocrine stimulation in oncogenesis is already well established and we see no reason to exclude the possibility of analogous mechanism operating through antigen receptors. At present, we are investigating the oncogenic function of the retrovirus (FeLV-T17) carrying a T-cell receptor gene (v-tcr). In addressing the general concept of oncogenesis by ligand/receptor interactions in the immune system we face the problem of the diversity and, for T-cell antigen receptors, the complex nature of receptor-ligand interaction. Nevertheless, the implications of the model encourage us to continue to search for new experimental tools and approaches to the question.

Animals↗

Altered structure and expression of c-myc in feline T-cell tumours.

The c-myc gene is rearranged in a subset of feline T-cell lymphosarcomas. Detailed mapping of c-myc rearrangements showed that some result from feline leukaemia virus (FeLV) proviral integration within or upstream of c-myc, but one case involves a complex 3' alteration and amplification which is apparently not directly virus-induced. S1 nuclease mapping of RNA from normal cells using c-myc probes revealed two presumptive 5' ends, each corresponding to a promoter-like sequence (P1 and P2), and a major 3' discontinuity which mapped to the 3'-most of two possible polyadenylation signals. Analysis of RNA from a series of tumours revealed different modes of c-myc expression. All tumours produced P1 and P2 transcripts with apparently normal structure except for one case where an insertion in intron 1 displaced exon 1 sequences. The abundance ratio of P1/P2 transcripts varied considerably and was high in tumours which carry a rearrangement adjacent to c-myc, but some other T-cell tumours with no apparent myc alteration displayed an equally high ratio. However, a consistent feature was the lack of detectable RNA from normal c-myc alleles in tumours which express a rearranged c-myc allele or a transduced FeLV v-myc gene. We suggest that this may prove to be a useful indicator of the presence of an oncogenically active myc gene, whether this is a rearranged c-myc or transduced v-myc sequence.

Alleles↗

Conservation of the c-myc coding sequence in transduced feline v-myc genes.

We have cloned the normal feline c-myc locus and determined the nucleotide sequence of all three exons. The feline c-myc gene shows close homology to other mammalian c-myc genes, particularly human c-myc. The feline and human sequences are colinear within the open reading frame for the putative c-myc product but show insertions and deletions relative to each other outside this domain. We have also analyzed a cloned FeLV provirus, CT4, which contains the host-derived myc gene. In this provirus the v-myc sequences are located at the 3' end of the pol gene, replacing pol and env sequences. Nucleotide sequence analysis of CT4 shows an open reading frame for a v-myc gene product which may be expressed without fusion to any viral protein sequences. This contrasts with another FeLV v-myc (LC), in which myc and gag sequences were found to be fused. Unlike previously identified avian v-myc genes, the feline v-myc genes contain exon 1-derived sequences, but these have been truncated or internally deleted. The FeLV CT4 v-myc sequence shows very few coding changes relative to c-myc and the FeLV LC v-myc coding sequence is unchanged relative to c-myc apart from fusion to gag. These results are discussed in relation to the mechanism of transduction and activation of myc by FeLV.

Amino Acid Sequence↗

Nucleotide sequences of a feline leukemia virus subgroup A envelope gene and long terminal repeat and evidence for the recombinational origin of subgroup B viruses.

Molecular clones of the subgroup A feline leukemia virus FeLV-A/Glasgow-1 have been obtained. Nucleotide sequence analysis of the 3' end of the proviral genome and comparison with the published sequence of FeLV-B/Gardner-Arnstein showed that the most extensive differences are located within the 5' domain of the env gene. Within this domain, several divergent regions of env are separated by more conserved segments. The 3' end of env is highly conserved, with only a single amino acid coding difference in p15env. The proviral long terminal repeats are also highly conserved, differing by only eight base substitutions and one base insertion. Specific probes constructed from the FeLV-A or FeLV-B env genes were used to compare the env genes of various exogenous FeLV isolates and the endogenous FeLV-related proviruses of normal cat DNA. An FeLV-A-derived env probe showed no hybridization to normal cat DNA but detected all FeLV-A and FeLV-C isolates tested. In contrast, an FeLV-B env probe detected independent FeLV-B isolates and a family of endogenous FeLV-related proviruses. Our observations provide strong evidence to support the hypothesis that FeLV-B viruses have arisen by recombination between FeLV-A and endogenous proviral elements in cat DNA.

Antigens, Viral↗

Immune complexes in ovarian cancer: association between IgM class complexes and antinuclear autoantibodies in ascitic fluid.

Samples of ascitic fluid from patients with ovarian cancer were analyzed for autoantibodies to nuclear and cytoplasmic antigens and for immune complexes (ICs) detectable by the Clq deviation and polyethylene glycol (PEG) precipitation (either IgG or IgM class) assays. The predominant autoantibody was antinuclear (ANA); this was detected in 29 of 58 samples (59% showing the homogeneous and 41% the speckled pattern). The antibody was not reactive to saline extractable nuclear antigens. A strong association between this autoantibody and the PEG-precipitated IgM class ICs was shown, suggesting the possible participation of this autoantibody in IgM class ICs formation. The lack of association between C1q-reactive and IgG class ICs and the autoantibodies indicates that the IgG class ICs may be more related to the tumor.

Adult↗