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P M Brickell

Publications and source records attributed to P M Brickell.

87 records · Page 5Linked to original sources
PubMed1989

Evidence against expression of an endogenous murine leukemia virus causing cellular resistance to lysis by activated macrophages.

In previous studies we observed that resistance of murine SV40-transformed fibroblast cell lines to cytolysis by activated macrophages was frequently associated with cellular expression of the gp70 of an endogenous ecotropic murine leukemia virus (MuLV). The work described here was initiated to test directly for a causative relationship between MuLV expression and resistance to lysis by macrophages. Northern blot analysis revealed that macrophage-resistant cells contain full length retroviral RNA. A panel of mAb which distinguish among host-range classes of MuLV detected only a non-recombinant ecotropic gp70 in these cells. The ecotropic MuLV from two independently derived macrophage resistant cells were isolated by limiting dilution cloning on Mus dunii fibroblasts. These viruses were then used to infect macrophage-sensitive cell lines and the resultant MuLV-positive cells tested for sensitivity to macrophage cytolysis. The MuLV-infected lines remained highly sensitive to macrophage lysis despite their high levels of cell surface gp70 and release of infectious MuLV. Thus, although we cannot rule out the possibility that MuLV or a product thereof is necessary for development of macrophage resistance in transformed cells, expression of MuLV per se is not sufficient to create the resistant phenotype.

Animals↗
PubMed1989

Morphogens in chick limb development.

Retinoic acid is a good candidate for a morphogen in chick limb bud development. The challenge now is to determine how retinoic acid interacts with limb bud cells and how the retinoic acid signal is integrated with other signals to mould and pattern the developing limb.

Animals↗
PubMed1989

Ectodermal inhibition of cartilage differentiation in micromass culture of chick limb bud mesenchyme in relation to gene expression and cell shape.

Ectoderm inhibits the formation of cartilage by chick wing bud mesenchyme in micromass culture. This suggests that the pattern of cartilage formation in the limb bud may result from a restriction of cartilage cell differentiation to the limb bud core as cells leave the progress zone. We have used in situ hybridization to investigate whether ectodermal inhibition in micromass culture occurs at the level of gene transcription. We found that ectoderm completely inhibited the accumulation of cartilage-specific type II collagen transcripts in the mesenchyme cells, whilst the level of type I collagen transcripts was unaffected. Morphometric analysis of electron micrographs revealed that inhibition of chondrogenesis in micromass culture was not preceded by cell flattening. In fact, a rounded cell shape was found not to be a prerequisite for cartilage cell differentiation in micromass.

Animals↗
PubMed1988

Structure and expression of c-fgr protooncogene mRNA in Epstein-Barr virus converted cell lines.

The c-fgr protooncogene is a member of the c-src family of tyrosine kinases. Expression of c-fgr was studied in a series of Epstein-Barr virus (EBV) negative Burkitt's lymphoma cell lines and their EBV-converted derivatives. Two transcripts, of 2.9 kb and 3.5 kb, were present at dramatically elevated levels following EBV-conversion. The structure of the c-fgr transcripts was studied by the isolation and nucleotide sequence analysis of cDNA clones. This indicated that the c-fgr protein encoded by the mature mRNA would contain 529 amino acids and have a molecular weight of approximately 58,000. The N-terminus of the predicted c-fgr protein has low amino acid homology with the N-termini of other members of this family of proteins, suggesting a cell specific function for the N-terminal domain. Analysis of the c-fgr cDNA clones also revealed the presence of alternative functional polyadenylation signals, although the use of these does not account for the size difference between the two major c-fgr transcripts.

Amino Acid Sequence↗
PubMed1988

Kappa/lambda immunoglobulin distribution in Graves' thyroid-stimulating antibodies. Simultaneous analysis of C lambda gene polymorphisms.

From patients with untreated Graves' disease 11 sera showing high cAMP release in the FRTL-5 cell assay were studied for relative proportions of kappa or lambda Ig molecules showing cAMP releasing activity. Immunoabsorption of gamma-globulins was performed using monoclonal murine anti-kappa or anti-lambda antibodies linked to cyanogen bromide-activated sepharose. Specific kappa- or lambda-adsorbed fractions were also eluted from immunoabsorbents using chaotrophic thiocyanate buffers and equilibrated with pH 7.4 low salt buffer by dialysis. Immunoabsorption and elution experiments showed that five Graves' sera contained predominant cAMP-releasing activity within lambda Ig fractions, whereas two Graves' sera showed predominant cAMP-releasing activity in kappa Ig fractions. Four sera showed cAMP release approximately equally divided between kappa and lambda Ig both after immunoabsorption and specific anti-kappa or anti-lambda eluates were studied. C lambda genotypes were examined by Southern blotting and restriction fragment length polymorphism analysis of Eco RI-digested genomic DNA from 158 patients with Graves' disease in parallel with 112 normal controls and 29 patients with autoimmune hypothyroidism. Notable shifts in proportions of 8/8 and 18/18 genotypes were present when Graves' patients were compared with normal controls. Allelic frequencies and ratios of genotype 8 to 18 were significantly different (P less than 0.05) when Graves' patients were compared either to normal controls or to patients with autoimmune hypothyroidism.

Absorption↗
PubMed1988

In situ hybridization reveals differential spatial distribution of mRNAs for type I and type II collagen in the chick limb bud.

During limb development, type I collagen disappears from the region where cartilage develops and synthesis of type II collagen, which is characteristic of cartilage, begins. In situ hybridization using antisense RNA probes was used to investigate the spatial localization of type I and type II collagen mRNAs. The distribution of the mRNA for type II collagen corresponded well with the pattern of type II collagen synthesis, suggesting control at the level of transcription and mRNA accumulation. In contrast, the pattern of mRNA for type I collagen remained more or less uniform and did not correspond with the synthesis of the protein, suggesting control primarily at the level of translation or of RNA processing.

Animals↗
PubMed1986

Transcriptional induction of cellular gene expression during lytic infection with herpes simplex virus.

Herpes simplex virus Type 2 causes a severe repression of host cell biosynthesis at a number of levels. We show that despite this, non-viral cDNA clones derived from cellular RNA species which accumulate to high levels after infection can be isolated using differential screening techniques. By using nuclear run-off assays, we have shown that this RNA accumulation is mediated by transcriptional induction of the corresponding cellular genes.

Animals↗
PubMed1984

The activation of cellular genes in transformed cells.

We have used differential cDNA cloning techniques to isolate a number of genes that are activated as a result of transformation by the DNA tumour virus Simian virus 40. From the nucleotide sequences of the cDNA clones we have been able to identify some of these genes. One of them derives from the major histocompatibility complex and contains a repetitive element that identifies a large number of RNAs present in pluripotential embryonic cells.

Animals↗
PubMed1983

Transcripts regulated during normal embryonic development and oncogenic transformation share a repetitive element.

We have previously isolated cDNA clones homologous to mRNAs present at elevated levels in transformed mouse fibroblasts. Clones of Set 1 contain a dispersed repetitive element present thousands of times in the mouse genome. This repeat identifies in mouse embryos a large number of transcripts that are quantitatively regulated during development. At maximal expression these RNAs constitute between 1% and 3% of polyadenylated RNA. A pattern of Set 1-related transcripts very similar to that observed in midgestation embryos is found in pluripotential EC and EK cell lines, and the abundance of these RNAs decreases upon differentiation in vitro. However, the F9 line of EC cells, which has a more restricted developmental capacity, exhibits a much simpler pattern of transcripts containing the Set 1 repeat.

Age Factors↗
PubMed1983

Distinct populations of class II molecules identified by monoclonal antibodies.

Binding inhibition and sequential immunoadsorption studies with two rat monoclonal antibodies have been used to demonstrate the existence of distinct populations (isotypes) of HLA-DR like (class II) molecules in human B lymphoma cell lysates. The structures of the molecules isolated by these two reagents have been compared by peptide 'mapping' and appear to be closely similar.

Antibodies, Monoclonal↗
PubMedDate not supplied

Activation of a Qa/Tla class I major histocompatibility antigen gene is a general feature of oncogenesis in the mouse.

A cDNA clone corresponding to a mRNA present at elevated levels in transformed fibroblasts encodes a Qa/Tla class I major histocompatibility complex (MHC) antigen. High levels of this mRNA are found in all tumour cells tested; the transcript can undergo alternative splicing; and a repetitive sequence within the transcription unit has the characteristics of a transposable element. The immunological implications of MHC gene activation in tumour cells are discussed.

Animals↗
PubMedDate not supplied

The class I major histocompatibility antigen gene activated in a line of SV40-transformed mouse cells is H-2Dd, not Qa/Tla.

We have previously described several complementary DNA clones isolated because they correspond to messenger RNAs present at higher levels in the simian virus 40 (SV40)-transformed BALB/c 3T3 cell line SV3T3 Cl38 than in the normal, parental BALB/c 3T3 line. One of these clones, pAG64, hybridizes to RNAs which, while present in BALB/c 3T3 cells, are 10-20-fold more abundant in SV3T3 Cl38 and are found at high levels in a wide variety of transformed cell lines. Nucleotide sequence analysis showed that pAG64 encodes a class I antigen of the major histocompatibility complex. To ascertain the identity of pAG64, we compared its sequence with the available sequences of d haplotype class I antigen genes [K locus, L locus, D locus and the Qa gene defined by genomic clone 27.1] and found that it showed multiple clustered differences from each of these sequences. We therefore concluded that it was not derived from the H-2Kd, H-2Ld or H-2Dd genes and thus must correspond to one of the other class I antigen genes, namely those of the Qa/Tla complex, although it was clearly not the Qa gene defined by the genomic clone 27.1. We now report subsequent findings which indicate that pAG64 in fact corresponds to the H-2Dd gene and not to a Qa/Tla gene.

Animals↗