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J Andrews

Publications and source records attributed to J Andrews.

At least 127 records · Page 7Linked to original sources
PubMed1997

Regulation of CCR2 chemokine receptor mRNA stability.

During inflammatory and immunological responses, leukocytes respond to external stimuli by altering the stability of cytokine and cytokine receptor messages. Change in message stability is an effective mechanism for rapidly regulating steady state levels of mRNA. Cytokine messages containing A-U-rich elements located in the 3' untranslated region (ARE) are the best studied examples of this process. AREs have been shown to act as targeting motifs for degradation of cytokine and transcription factor messages. We have recently observed that the interleukin-8 (IL-8) receptor messages, IL-8RA and B (CXCR1 and CXCR2), also undergo changes in stability in response to the inflammatory stimulator lipopolysaccharide (LPS). To determine whether regulation of message stability is a common mechanism for modulation of chemokine receptor mRNA we explored whether the stability of the CC chemokine receptor message for CCR2 (monocyte chemotactic protein-1 receptor) is also regulated by LPS. We found that LPS induces a rapid loss of steady state levels of CCR2 message through message degradation. Furthermore, LPS stimulated the decay of Poly(A) CCR2 mRNA faster than total CCR2 RNA, indicating that deadenylation is the first step in LPS-induced CCR2 RNA degradation. We conclude from these experiments that LPS stimulates the rapid degradation of CCR2 messages through a two-step process, deadenylation followed by degradation of the message body. In contrast to the results obtained for CCR2 mRNA, macrophage inflammatory protein-1alpha messages, which contain an ARE motif, were stabilized by LPS stimulation, indicating that chemokine and chemokine receptor mRNA stability are regulated by different and opposing mechanisms.

Adenine↗
PubMed1997

The use of sonication for the efficient delivery of plasmid DNA into cells.

PURPOSE: Ultrasonic methods have considerable potential for the introduction of macromolecules into cells. In this paper we demonstrate that, under controlled conditions, application of 20 kHz ultrasound to a suspension of yeast cells facilitates the delivery of plasmid DNA into these cells. METHODS: Aliquots of growing yeast cells (Saccharomyces cerevisae, strain AH22) were suspended in buffer and exposed to 20 kHz ultrasound from a laboratory (probe-type) sonicator in the presence of microgram quantities of plasmid DNA. Efficiency of DNA delivery was scored as the number of cells transformed. RESULTS: Cell transformation was optimal at 30 seconds sonication using an output of 2.0 watts and resulted in a 20 fold enhancement over control values. At extended sonication times, fewer cells showed evidence of transformation because of reduced cell viability. The increased DNA uptake and the decreased cell viability were both attributable to acoustic cavitation events during sonication. The extent of acoustic cavitation was measured and it was found that there was an increase in cavitation events with increased sonication time. Cell viability was shown to be directly related to the number of cavitation events. The effects of sonication on plasmid DNA were investigated and indicated that the structural integrity of plasmid DNA was unaffected by the sonication conditions employed. CONCLUSIONS: Under controlled conditions, ultrasound is an effective means of delivering plasmid DNA into cells. The subsequent expression of DNA molecules in cells depends upon a balance between transient cell damage and cell death.

DNA Damage↗
PubMed1997

Family support and conflict: prospective relations to adolescent depression.

The relations between family support, family conflict, and adolescent depressive symptomatology were examined longitudinally in a sample of 231 female and 189 male adolescents and their mothers. Structural equation models revealed that less supportive and more conflictual family environments were associated with greater depressive symptomatology both concurrently and prospectively over a 1-year period. Conversely, adolescent depressive symptomatology did not predict deterioration in family relationships. Depressive symptomatology and, to a greater extent, family characteristics showed high levels of stability over the 1-year period. Counter to our expectations, the relations between family variable and depressive symptomatology were similar for boys and girls. The results suggest that the quality of family interactions is relevant for understanding the development of depressive symptoms in adolescents.

Adolescent↗
PubMed1997

Selection of antigens for use in a virus-vectored immunocontraceptive vaccine: PH-20 as a case study.

The European wild rabbit (Oryctolagus cuniculus) has become the major agricultural and environmental pest species in Australia. Current methods of rabbit control are lethal procedures which are increasingly questioned for their overall efficiency, applicability, specificity, cost and humaneness. New initiatives are required. One such initiative is virus-vectored immunocontraception. In this approach, the lagomorph-specific myxoma virus will be genetically engineered to include genes encoding components of rabbit gametes which can induce an immune response that causes infertility. Central to such a strategy is the ability to identify antigens capable of inducing an immunocontraceptive response. A strategy for identifying such antigens has been described previously. A case study of one sperm antigen, PH-20, is reported here. The issues involved in developing this antigen to the stage where it could be considered as a candidate for insertion into a recombinant myxoma virus with the ultimate goal of testing for immunocontraceptive efficacy are discussed. Techniques for inserting genes into myxoma virus have been described previously. The knowledge gained from research with this particular antigen are broadly applicable to other antigens used for both immunocontraceptive vaccines in general and, specifically, for virus-vectored immunocontraception.

Animals↗
PubMed1997

Activity of a new glycopeptide antibiotic (LY333328) against enterococci and other resistant gram-positive organisms.

A new semi-synthetic glycopeptide, LY333328, was tested for in-vitro activity against 197 strains of enterococci including strains resistant to other glycopeptides. Activity was also assessed against species with intrinsic resistance to glycopeptides. For strains of enterococci tested the LY333328 MIC90s were < or = 0.5 mg/L. Enterococcus faecalis was less susceptible to LY333328 than other enterococci with a maximum MIC of 2.0 mg/L. Glycopeptide-resistant strains of enterococci were not more resistant to LY333328 than glycopeptide-susceptible strains but intrinsically resistant species had MICs between 4 and 8 mg/L.

Ampicillin↗
PubMed1996

Heterogenous point mutations in the BRCA1 breast cancer susceptibility gene occur in high frequency at the site of homonucleotide tracts, short repeats and methylatable CpG/CpNpG motifs.

Heterogeneous mutations in the BRCA1 tumour suppressor gene are responsible for a large percentage of inherited breast cancers as well as breast/ovarian cancers in families with a high incidence of both cancer types. Over a hundred BRCA1 mutations have been reported, but little is known of the mechanism(s) responsible for BRCA1 mutagenesis. To determine the significance of specific nucleotide sequences at mutational sites within the BRCA1 gene, we assessed how frequently independent BRCA1 mutations occur at the site of short direct repeats, single nucleotide repeats (homonucleotides) and at CpG and CpNpG motifs. We found that homonucleotide and short direct repeats are commonly associated with small deletions and insertions. Substitution mutations are frequently associated with homonucleotide repeats and with methylatable CpG dinucleotides and CpNpG trinucleotides. Our methylation and sequencing experiments show that CpG and certain CpNpG motifs are methylated, supporting the hypothesis that DNA methylation specificity at these sites may be an important contributor to BRCA1 mutagenesis. We suggest that BRCA1 mutations are acquired by replication errors and are retained by cells through an intricate balancing of replication and repair mechanisms. Such mutations may provide a proliferative advantage for a cell, leading to the tumour phenotype.

BRCA1 Protein↗
PubMed1996

Congenital absence of permanent second molars.

During the last eight years, Canterbury Archaeological Trust has excavated over 1,600 articulated human skeletons from sites under threat of redevelopment in Kent. The recovered material, ranging in date from prehistoric to Victorian, provides a unique corpus for the study of disease and abnormalities in earlier societies.

Anodontia↗
PubMed1996

Animal donors.

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Animal Rights↗
PubMed1996

Counting beds.

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Bed Occupancy↗
PubMed1996

Investigation of chronic hepatitis C infection in individuals with haemophilia: assessment of invasive and non-invasive methods.

Hepatitis C virus (HCV) infection is the major cause of chronic liver disease in individuals with haemophilia. A wide spectrum of disease severity is found in this group, ranging from mild hepatitis to cirrhosis. We have studied a cohort of 87 anti-HCV positive haemophiliacs who have been infected with HCV for 10-25 years and assessed the relative value of invasive and non-invasive methods of evaluating liver disease. The severity of liver disease was assessed using ultrasound scan (n = 77), upper GI endoscopy (n = 50), laparoscopic liver inspection (n = 33) and liver biopsy (n = 22). Invasive investigations were performed without any significant bleeding complications. Evidence of severe liver disease was found in approximately 25% of patients. There was agreement between the severity of liver histology and the information derived from the laparoscopic liver inspection, endoscopy and ultrasound in 86%. Co-infection with HIV was significantly associated with more severe liver disease (P = 0.006). This study provides further evidence that liver disease is emerging as a major complication in haemophiliacs and severe liver disease is more common in those co-infected with HIV. We have shown the potential value of laparoscopic liver inspection, in combination with endoscopy and ultrasound, in staging the extent of liver disease, and suggest that most patients may be managed without resorting to liver biopsy.

Adolescent↗
PubMed1996

The stoned locus of Drosophila melanogaster produces a dicistronic transcript and encodes two distinct polypeptides.

The stoned gene of Drosophila melanogaster is required for normal neuronal function in both adult and larva. We have identified DNA sequences that lie within a genetic region that is known to include the stoned gene and that also reveal restriction site variations in two stoned lethal mutants. This genomic region contains a single transcription unit coding for an approximately 8.4-kb transcript. The transcript is preferentially expressed in the head of adult flies. The isolation and sequencing of cDNA and genomic clones reveals that stoned appears to encode a dicistronic mRNA, although the possible existence of other forms of mRNA cannot be excluded. Antibody cross-reactivity shows that two proteins are translated from the stoned locus in vivo. Both open reading frames (ORFs) encode novel proteins. The protein encoded by the first ORF contains four tandemly repeated motifs, and one domain of the protein encoded by the second ORF shows similarity to a family of proteins (AP50s) associated with clathrin assembly protein complexes.

Amino Acid Sequence↗