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1.  Prevalence of Helicobacter pylori infection and its effect on symptoms and non-steroidal anti-inflammatory drug induced gastrointestinal damage in patients with rheumatoid arthritis. 
Gut  1993;34(12):1677-1680.
Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter (H pylori) are both associated with an increased risk of peptic ulceration and gastropathy. It is not known, however, if there is an interaction between these two agents, and thus whether or not screening for H pylori before NSAID treatment is of value. The aim of this study was to find out if H pylori potentiates the damaging effects of NSAIDs. Fifty two patients with rheumatoid arthritis requiring longterm NSAID treatment were studied. Dyspeptic symptoms were assessed according to a standardised questionnaire. Gastroscopy was performed after a one week washout period during which NSAIDs were discontinued. Gastric and duodenal mucosal damage was graded endoscopically. H pylori was identified by biopsy urease test and by histological tests. Investigations were repeated after one month's treatment with an NSAID. Patients with H pylori infection (n = 26) had a higher dyspeptic symptom score (p < 0.05). One patient with duodenal ulcer (H pylori +ve) and two with endoscopic gastritis (both H pylori +ve) were excluded from further study. Forty two subjects completed the study. After treatment there was a rise in the gastric damage score both in the H pylori +ve (p = 0.06) and the H pylori -ve (p < 0.005) groups. There was no difference in the extent of increase in grade or the final grade at the end of the treatment period between the H pylori +ve and -ve patients. It is concluded that H pylori infection is associated with increased dyspeptic symptoms in patients receiving NSAIDs but that it does not potentiate NSAID gastropathy.
PMCID: PMC1374461  PMID: 8282254
3.  c-Jun is phosphorylated by the DNA-dependent protein kinase in vitro; definition of the minimal kinase recognition motif. 
Nucleic Acids Research  1993;21(5):1289-1295.
The DNA-dependent protein kinase (DNA-PK) phosphorylates a number of transcription factors. Here, we show that the DNA-PK modifies c-Jun in vitro and that serine residue 249 (Ser-249) is required for phosphorylation to occur. This residue corresponds to one of three sites of c-Jun that are phosphorylated in vivo and which negatively regulate c-Jun DNA binding in vitro. However, we find that phosphorylation of c-Jun by the DNA-PK does not interfere with DNA binding, indicating that phosphorylation at other sites is required for this effect. Mutagenesis of the phosphorylated region of c-Jun reveals that the primary amino acid sequence recognised by the DNA-PK consists of the sequence Ser-Gln, and that adjacent acidic residues potentiate kinase activity. Furthermore, when this site is placed within the context of a second protein, it confers DNA-PK directed phosphorylation upon that protein. Our findings will facilitate identification of DNA-PK phosphorylation sites in other transcription factors.
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PMCID: PMC309295  PMID: 8464713
4.  Alteration of clathrin light chain expression by transfection and gene disruption. 
Molecular Biology of the Cell  1993;4(6):647-660.
The light chain subunits of clathrin, LCa and LCb, have been implicated in the regulation of coated vesicle disassembly and other aspects of clathrin cycling within the cell. The potential for functional specialization of each light chain is suggested by tissue-specific variation in the relative amounts of the two light chains and by conservation of differences between LCa and LCb sequences during evolution. To investigate whether there might be exclusive roles for LCa and LCb in clathrin function, the expression of LCa was manipulated in C1R lymphoid cells and PC12 pheochromocytoma cells by transfection with light chain cDNA. These two cell lines differ in their ratios of LCa to LCb, expressing 86 and 25% LCa, respectively. After transfection with exogenous human LCa cDNA, a PC12 cell derivative was produced that completely lost the ability to manufacture LCa. Loss of LCa expression was found to be because of gene disruption and consequent lack of mRNA transcription. In C1R cells, the normally high level of LCa expression was reduced to 25% by overexpression of transfected LCb cDNA under the control of an inducible promoter. The C1R transfectants with reduced levels of LCa and the LCa-negative PC12 transfectant grow normally and show no change in clathrin distribution, clathrin assembly level, or impairment of endocytosis or secretion compared with wild-type cells and cells transfected with vectors lacking light chain cDNA. However, subtle alterations in the hsc70-mediated clathrin uncoating process were observed for vesicles derived from the LCa-negative cells, reflecting the preferential activity of LCa in stimulating the in vitro uncoating reaction.
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PMCID: PMC300971  PMID: 8374173

Results 1-4 (4)