Daisy Ayris Lecture--theatre nursing in a competitive environment.
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Economic Competition↗
Biomedical subjects
C Jones
Publications and source records attributed to C Jones.
Molecular recognition of antigenic polysaccharides: a conformational comparison of capsules from Streptococcus pneumoniae serogroup 9.
Aqueous solution conformations of three antigenic bacterial capsular polysaccharides (CPS) from S. pneumoniae serogroup 9 were determined using a combination of NMR data (NOE build-up rates and conformation-dependent chemical shifts), simulated annealing, and molecular dynamics simulations. Each polymer adopts a flexible extended ribbon conformation in solution. Conformations of structural elements shared by each PS are indistinguishable. Differences in conformations are minor and localised at the sites of structural variations; there is no evidence of long-range stabilisation of a secondary structure. It is likely that antigenic specificity of Group 9 PS is dominated by local structural variation rather than by conformational differences.
Bacterial Capsules↗
NMR assignment and conformational analysis of the antigenic capsular polysaccharide from Streptococcus pneumoniae type 9N in aqueous solution.
Complete 1H and 13C NMR assignments, determined by one- and two-dimensional homo- and hetero-nuclear experiments, are reported for the antigenic capsular polysaccharide (CPS) from Streptococcus pneumoniae serotype 9N (S9 in American nomenclature). Distance constraints derived from 1D NOE difference experiments were combined with energy minimisation (simulated annealing) and molecular dynamics (MD) calculations to determine the most favoured conformation of S9 in aqueous solution at 70 degrees C. NOE values simulated for several static conformational models using the NOEMOL program did not correlate well with experimental values, whereas time averaged interproton distances calculated from 500 ps of restrained MD (using the Tropp formalism to account for rapid internal mobility) were in close agreement with experimentally derived distance estimates.
Bacterial Capsules↗
PCR-based immortalization and screening of hierarchical pools of cDNAs.
Starting from sequences of at least 60 bp, PCR-based screening has been developed to recover cDNAs from libraries without the necessity for hybridization or extensive DNA extraction steps. The method maintains the indefinite availability of even scarce cDNA libraries and provides an estimate of the relative abundance of the mRNA species. Isolation of a cDNA clone can be done in less than a week. cDNAs were isolated that were cognate for fragments of expressed sequences and for an exon predicted from genomic sequence.
Animals↗
The effect of hormone replacement therapy on prognostic indices in women with breast cancer.
OBJECTIVE: To examine the effect of hormone replacement therapy (HRT) on breast cancer biology. PATIENTS: Four hundred and sixty Western Australian women with breast cancer who were 40 years or over at the time of their breast cancer surgery. DESIGN AND SETTING: A questionnaire was sent to women seeking information on the use of HRT before breast cancer surgery. To qualify as HRT users, HRT had to have been used continuously for six months or more up to within two weeks of surgery. MAIN OUTCOME MEASURES: Biochemical indices of oestrogen receptor, progesterone receptor, cathepsin D and protein levels, and pathological indices of tumour size, tumour differentiation and lymph node involvement for users and nonusers of HRT. RESULTS: Eighty-seven per cent of questionnaires were recovered and 39 HRT users and 258 non-users were analysed. Twenty-five HRT users used a combination of oestrogen and progestogen and 14 used oestrogen only. Twenty-six had used HRT for more than two years and 13 for two years or less at the time of breast cancer diagnosis. There were no significant differences in the tumour indices between these two groups. The mean level of oestrogen receptors appeared to be lower in oestrogen-only users than in combination HRT users and non-users. The mean cathepsin D level was significantly higher in oestrogen-only users than in non-users. The percentage of all HRT users with involved lymph nodes (23%) was significantly lower than the percentage of non-users (44%). CONCLUSION: Oestrogen-only HRT may have a detrimental effect on tumour biology. The use of a progestogen in combination with oestrogen may offer some protection. On the other hand, HRT users had less lymph node involvement with tumour. This may reflect early detection with increased surveillance in women using HRT.
Adult↗
O-glycosidically linked N-acetylglucosamine-bound oligosaccharides from glycoproteins of Trypanosoma cruzi.
In this report we describe studies on the structures of the O-linked carbohydrate units in cell-surface glycoproteins of epimastigote forms of the G-strain of Trypanosoma cruzi. Mild alkaline reductive degradation of the 38/43 kDa glycoproteins resulted in beta-elimination of glycosylated threonine and/or serine residues, and the liberation of N-acetylglucosaminitol, galactobiosyl-, galactotriosyl-, galactotetraosyl- and galactopentaosyl-N-acetylglucosaminitol. The structures of these oligosaccharide alditols were established by n.m.r. spectroscopy and methylation analysis as: Galf beta 1-4(Galp beta 1-6)GlcNAc-ol; Galp beta 1-3Galp beta 1-6(Galf beta 1-4)GlcNAc-ol; [(Galp beta 1-3)(Galp beta 1-2)Galp beta 1-6](Galf beta 1-4)GlcNAc-ol; [(Galp beta 1-3)(Galp beta 1-2)Galp beta 1-6](Galp beta 1-2Galf beta 1-4)GlcNAc-ol.
Acetylglucosamine↗
The effect of variation of substitution on the solution conformation of heparin: a spectroscopic and molecular modelling study.
The effect of variations in substitution on the conformation of iduronate-containing sequences in heparin and heparan sulphate has been studied using a series of chemically-modified heparins in which substitution with O- and N-sulphate and N-acetyl substituents has been systematically altered. Monosaccharides corresponding to residues in these modified heparins have also been investigated. The conformations of the glycosidic linkages in O- and N-desulphated re-N-acetylated heparin, O-desulphated re-N-sulphated heparin, and 6-O-desulphated re-N-sulphated heparin have been compared with those of N-desulphated re-N-acetylated heparin and of heparin itself, which have been compared with those of N-desulphated re-N-acetylated heparin and of heparin itself, which have previously been reported [B. Mulloy, M.J. Forster, C. Jones, and D.B. Davies, Biochem. J., 293 (1993) 849-858]. The overall conformation of all the polysaccharides is shown to be similar, regardless of substitution pattern. The conformational equilibrium of the pyranose ring of iduronic acid residues in the polysaccharides has been monitored by the use of 13C NMR chemical shift temperature coefficients, and shown to be similar for all the modified heparins with the exception of N-desulphated re-N-acetylated heparin. Circular dichroism spectra of all the polysaccharides are reported, and their variations attributed to differences in the proportions of pyranose ring forms in the iduronate conformational equilibrium.
Carbohydrate Conformation↗
Firearm and motor vehicle injury mortality--variations by state, race, and ethnicity: United States, 1990-91.
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Accidents, Traffic↗
Analysis of transcriptional activation of a cyclic AMP response element by 2,6,10,14-tetramethylpentadecane (pristane) in JB6 mouse epidermal cells.
Pristane is a naturally occurring isoprenoid that is believed to be derived from the phytyl moiety of chlorophyll. Thus, it is not surprising that pristane is present in many common fruits and vegetables. Furthermore, pristane can be detected in the tissues of fish and mammals. In animal models using rodents, pristane can function as a potent tumor promoter. At the molecular level, pristane can induce changes in the plasma membrane, alter the conformation of chromatin, and selectively activate gene expression. Addition of pristane to a mouse epidermal cell line (JB6 P+) allows these cells to grow in an anchorage-independent manner. In contrast, JB6 P-cells are not transformed by pristane. Our study was undertaken to correlate transformation of P+ cells with changes induced by pristane. Transcriptional activation of a cyclic AMP response element (CRE) was induced by pristane in P+ and P-cells. Point mutations in the CRE abolished activation by pristane, thus indicating that an intact CRE was necessary for pristane activation. In P+ cells, pristane repressed phosphodiesterase activity. However, protein kinase A was activated by pristane in P+ and P-cells. Taken together, these results indicated pristane induced novel changes in P+ cells that in turn may facilitate neoplastic transformation.
Activating Transcription Factor 2↗
Parallel costimulatory pathways promote myelin basic protein-stimulated proliferation of encephalitogenic rat T cells.
Activation pathways responsible for myelin basic protein (MBP)-stimulated proliferation of encephalitogenic T cells were studied by derivation of new monoclonal antibodies against rat T cell surface proteins. These monoclonal antibodies were derived by immunization of Balb/c mice with THYB-2 T cell hybrids or with the GP2.E5 line of encephalitogenic T-helper cells. The LRTC1 mAb inhibited MBP-stimulated IL-2 production by THYB-2 hybrids but not by THYB-1 hybrids and did not inhibit the alternative response of MBP-induced growth inhibition by either hybrid subset. Although LRTC1 labeled virtually all rat leukocytes, it selectively inhibited proliferative responses to T cell mitogens but not to B cell mitogens. LRTC1 inhibited MBP-stimulated IL-2 production by GP2.E5 T cells but did not effectively block MBP-stimulated proliferation. Rather, LRTC1 acted in synergy with a second mAb (LRTC2) to effectively inhibit MBP-stimulated proliferation by GP2.E5 T cells. The observation that LRTC1 did not exhibit synergy with a third biologically active mAb (LRTC3) supported the hypothesis that LRTC1 and LRTC2 represented a specific combination of synergistic mAb. In contrast to the inhibitory activity on GP2.E5 T cells, LRTC1 and LRTC2 synergistically stimulated antigen-independent IL-2 production by the THYB-1 hybrid LSS-A1. These results support the hypothesis that GP2.E5 T cells respond to parallel costimulatory pathways that are respectively inhibited by LRTC1 and LRTC2 mAb. Furthermore, these synergistic mAb exhibited inhibitory or stimulatory activities that may be diagnostic of distinct T-helper cell subsets. These novel mAb may thereby facilitate studies of costimulatory pathways and T-helper cell subsets in the pathogenesis of autoimmune disease.
Animals↗
Differential regulation of platelet-derived growth factor genes in fetal rat lung fibroblasts.
There is increasing evidence to suggest that platelet-derived growth factor (PDGF), or PDGF-like molecules, play a role in fetal lung morphogenesis. The cellular sources of PDGF and its target cells within the fetal lung remain to be defined. In the present study, we investigated the developmental expression of PDGF and its cognate receptor genes in fetal rat lung fibroblasts. Northern analysis revealed that fetal lung fibroblasts express the PDGF A-chain, B-chain, and beta-receptor genes. The cells actively translated these mRNAs into protein as demonstrated by immunocytochemistry and by metabolic labeling with [35S]methionine, followed by immunoprecipitation with specific PDGF-AA and -BB antibodies. Affinity cross-linking with 125I-labeled PDGF-BB demonstrated the presence of PDGF beta-receptors on fetal lung fibroblasts. The development expression of the PDGF genes was examined in fibroblasts derived from the early canalicular (Day 19) to the early saccular stage (Day 21) of lung development (term = 22 days). PDGF A-chain gene expression was at a low but constant level during late gestation. No change in either the transcription rate or stability of the message for this gene was observed with advancing gestation. Despite these mRNA observations, PDGF-AA is the major secreted form in the medium of the fibroblasts. Expression of PDGF B-chain gene was greatest during the early canalicular stage (Day 19) and declined sharply thereafter. The greater expression of PDGF B-chain during the canalicular stage was due to a greater rate of transcription and a greater PDGF B-chain mRNA stability. The PDGF beta-receptor gene was expressed at a lower but constant level in these cells during late gestation. The constant level of PDGF beta-receptor mRNA could be attributed to a balanced increased synthesis of the message coupled to an increased breakdown of the transcript. These data indicate that fetal lung fibroblasts synthesize PDGF-AA, PDGF-BB, and PDGF beta-receptor and that they regulate the developmental expression of these PDGF genes differently.
Animals↗
Mapping of 28 (CA)n microsatellite repeats and 13 Alu markers on human chromosome 11 using a panel of somatic cell hybrids.
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Alleles↗
Chromosomal localization of three human genes coding for A15, L6, and S5.7 (TAPA1): all members of the transmembrane 4 superfamily of proteins.
The A15, L6, and S5.7(TAPA1) proteins are members of the transmembrane 4 superfamily (TM4SF). The A15 is expressed in immature human T cells and in the human brain. The MXS1(CCG-B7) gene which codes for A15 contains triplet nucleotide repeats which have been associated with neuropsychiatric diseases such as Huntington's chorea, fragile X syndrome, and myotonic dystrophy. The L6 antigen is mainly expressed in lung, breast, colon, ovarian carcinomas, and healthy epithelial tissue in humans. The S5.7(TAPA1) antigen is expressed in most human cell lines and is shown to be associated with B-cell surface molecules CD19 and Leu-13. In this study we have used interspecies specific somatic cell hybrids and human-specific cDNA probes to localize the A15 (MXS1), L6 (M3S1), and TAPA1 genes to Xq11, 3q21-25, and 11p15.5, respectively.
Animals↗
Seven loci on human chromosome 4 map onto sheep chromosome 6: a proposal to restore the original nomenclature of this sheep chromosome.
Seven new loci, casein alpha-S1 (CSN1S1), casein alpha-S2 (CSN1S2), casein beta (CSN2), the Hardy-Zuckerman 4 feline sarcoma viral (v-kit) oncogene homolog (KIT), albumin (ALB), phosphodiesterase cyclic GMP (rod receptor) beta polypeptide (PDEB), and complement component 1 (IF), were assigned to sheep Chromosome (Chr) 6 by Southern hybridization to a panel of chromosomally characterized sheep x hamster cell hybrids. By isotopic in situ hybridization, CSN2 was regionally localized to sheep Chr (OOV) 6q22-q31, anchoring this syntenic group of markers on to OOV6 and confirming its homology at a molecular and cytological level with cattle Chr 6. The assignment of these loci, from PDEB (located on human Chr 4p16.3) to IF (on HSA4q24-q25), and the observation that interleukin 2 (IL2, on HSA4q26-q27) and tryptophan 2,3-dioxygenase (TDO2, on HSA4q31) are not located on OOV6, is further evidence of the close evolutionary relationship of sheep and cattle and the conserved synteny in these species of this extensive region of human Chr 4. On the basis of this conserved synteny, and the similar G- and Q-banding patterns of this chromosome in cattle and sheep, we propose that this sheep chromosome be numbered as 6, not 4 as recommended by ISCNDA (1990).
Animals↗
Structural analysis of novel rhamnose-branched oligosaccharides from the glycophosphosphingolipids of Leptomonas samueli.
Mild alkaline hydrolysis of the glycophosphosphingolipids of the protozoan Leptomonas samueli liberated several phosphoinositol-containing oligosaccharides (PI-oligosaccharides), which were purified by high performance anion exchange chromatography. The oligosaccharides in the resulting four fractions were characterized by methylation analysis, fast atom bombardment mass spectrometry and two-dimensional nuclear magnetic resonance spectroscopy. The oligosaccharides contain the core structure Man alpha (1-4)GlcN alpha (1-6)-myo-inositol-1-OPO3, and are substituted with 2 mol of 2-aminoethylphosphonate per mol of oligosaccharide. The nonreducing ends of the oligosaccharides were terminated by rhamnose branched neutral and acidic xylose-containing penta-, hexa-, hepta- and octasaccharides, of which the three most abundant were shown to have the structures: [formula: see text] More tentative structures are also proposed for three minor oligosaccharides.
Animals↗
Physical and genetic mapping of human chromosome 3 loci containing microsatellite repeats.
One hundred and six microsatellite repeat-containing loci, including 59 CA-containing repeats from the CEPH/Genethon collection, were regionally assigned on human chromosome 3 using a somatic cell hybrid mapping panel, diving the chromosome into 14 intervals. The others were dinucleotide and tetranucleotide repeat-containing loci newly developed for human chromosome 3, of which 26 were also localized by means of genetic linkage analysis against selected CEPH microsatellites. The regional assignment of these two marker sets in a common mapping panel facilitates their integration. Incorporation of these highly polymorphic loci into the developing physical and genetic maps should provide useful information for studies of various diseases involving chromosome 3.
Base Sequence↗
Mutation and expression of the XPA gene in revertants and hybrids of a xeroderma pigmentosum cell line.
A series of ultraviolet (UV)-resistant cell lines have been generated from a UV-sensitive XP group A cell line homozygous for a stop codon (TGA) in the chromosome 9 XPA gene. Three lines generated by chemical mutagenesis acquired the ability to excise (6-4) photoproducts but not cyclobutane dimers from the whole genome; two lines generated by a fusion procedure with hamster cells acquired the ability to excise both (6-4) photoproducts and cyclobutane dimers from the whole genome. A central region of the hamster XPA gene was cloned and sequenced. With the use of species-specific primers in the polymerase chain reaction, we found that the hybrid cell lines do not contain a hamster XPA gene. Sequence analysis showed that all of the UV-resistant cell lines contain reversions of the human stop codon, resulting in missense mutations (glycine or leucine for arginine) or wild-type sequences. The concentration of XPA protein in revertant cell lines was about one-half that in normal cells, which would be expected from heterozygous cells; there was no evidence that the mutant proteins were less stable than the wild-type proteins. These results are consistent with the idea that the XPA protein initiates repair by binding to damaged sites with various affinities, depending on the photoproduct and the transcriptional state of the region. A concentration of XPA protein near 50% is needed before repair can proceed into nontranscribed regions of the genome. The revertant cell lines represent a class of missense mutations in the XPA gene that may have altered specificity and that can be used to understand some of the regulatory differences in repair of photoproducts in various regions of the genome.
Amino Acid Sequence↗
Characterization of chimpanzee-hamster hybrids by chromosome painting.
A panel of chimpanzee-human somatic cell hybrids was characterized by dual Alu-PCR of the chimpanzee DNA in the hybrid and subsequent hybridization of the labeled PCR products to human and chimpanzee chromosomes. In addition to the identification of the intact chimpanzee chromosomes retained in each hybrid, chromosome fragments were identified that will be useful in regional mapping. This technique also revealed the presence of centric inversions.
Animals↗