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Biomedical subjects

R Stratford

Publications and source records attributed to R Stratford.

14 recordsLinked to original sources
PubMed2006

Colonoscopy first for iron-deficiency anaemia: a Numbers Needed to Investigate approach.

BACKGROUND: British Society of Gastroenterology guidelines recommend that gastrointestinal investigations should be considered in males and post-menopausal women presenting with iron-deficiency anaemia (IDA). AIM: To compare the diagnostic yields and clinical effectiveness of upper and lower gastrointestinal (GI) investigation in detecting malignancy among patients presenting with IDA. DESIGN: Retrospective review of case notes, endoscopy records and radiology reports. METHODS: We reviewed the results of 3798 investigations in 2600 patients presenting to our hospital with IDA from October 1995 to December 2003. The findings of the 2318 gastroscopies were compared with those of the 896 colonoscopies and the 584 barium enemas. Patients diagnosed with GI malignancy were identified and their outcomes determined. RESULTS: Gastroscopy identified 44 patients with newly-diagnosed upper GI cancer (18 oesophageal, 26 gastric). Thus for patients being gastroscoped for IDA, the Numbers Needed to Investigate (NNI) to detect each cancer was 53. Five-year survival for these 44 patients was 10%, so the NNI to identify each curable upper GI malignancy was 527. Colonoscopy or barium enema identified 111 (7.5%) patients with newly diagnosed colorectal cancer, giving a NNI of 13. Their 5-year survival was 35%, giving a NNI to identify each curable colorectal cancer patient of 38. DISCUSSION: Potentially curable gastrointestinal malignancy was diagnosed over 13 times more commonly using colonoscopy or barium enema vs. gastroscopy. For patients presenting with IDA, our findings favour investigating the lower GI tract first, or performing both gastroscopy and colonoscopy during the same endoscopy list.

Adolescent↗
PubMed2001

A vaccination strategy incorporating DNA priming and mucosal boosting using tetanus toxin fragment C (TetC).

Intramuscular (i.m.) immunisation of BALB/c mice with a DNA vaccine, pcDNA3/tetC, encoding fragment C (TetC) from tetanus toxin, stimulated production of TetC specific IgG2a antibodies in the serum and release of IFN-gamma from TetC stimulated splenocytes. A similar pattern of immune response was detected if pcDNA3/tetC primed mice were boosted i.m. with purified TetC protein or TetC and cholera toxin (included as an adjuvant). In contrast, control mice primed with the empty DNA vector pcDNA3 and boosted i.m. with TetC or TetC and CT, generated a dominant IgG1 specific anti-TetC response in the sera and low or undetectable levels of IFN-gamma from stimulated splenocytes. Thus, i.m. priming with a DNA vaccine modulated the subsequent immune response to the same antigen administered as a protein boost. Similar observations were made when DNA primed mice were boosted using the intranasal mucosal route of immunisation. Interestingly, although mice immunised with pcDNA3/tetC and boosted mucosally with TetC and CT produced anti-TetC IgA in mucosal secretions, the titres were reproducibly lower than those detected in mice immunised with the pcDNA3 vector alone. The immunomodulatory effect of pcDNA3/tetC appeared to be antigen specific as mucosal boosting with an unrelated antigen (pertactin) revealed no significant modulation in terms of the anti-pertactin immune response.

Animals↗
PubMed2001

Early responses to Salmonella typhimurium infection in mice occur at focal lesions in infected organs.

Salmonella typhimurium causes an invasive disease in mice that has similarities to human typhoid, with key roles for cytokines and possibly also inducible nitric oxide synthase (iNOS), in mediating host responses to infection. In this paper we demonstrate that iNOS mRNA, protein and enzyme activity is induced within spleens and livers of infected mice as early as 5 h post-infection. Immunohistochemistry and in situ hybridization indicated that iNOS expression occurs predominantly in macrophages in localized, discrete foci in the infected organs. iNOS activity in spleen and liver was not detectable in uninfected control mice. The presence of mRNA encoding pro-inflammatory cytokines (TNFalpha, IL-1beta and IFNgamma) in infected organs was measured using RT-PCR, all three being present from 2 h post-infection onwards, but not before. These data show that there is a very early host response to S. typhimurium infection in mice, limited to foci within the infected organs.

Animals↗
PubMed2000

Influence of codon usage on the immunogenicity of a DNA vaccine against tetanus.

Two related DNA vaccine vector plasmids, harbouring either wild-type (pcDNA3/ntetC) or synthetic codon optimised (pcDNA3/stetC) DNA encoding fragment C (TetC) of tetanus toxin were constructed. COS-7 cells transformed with pcDNA3/stetC reproducibly expressed higher levels of TetC than similar cells transformed with pcDNA3/ntetC. BALB/c mice immunised intramuscularly with pcDNA3/stetC produced significantly higher levels of anti-TetC antibodies in their serum in the weeks following vaccination compared to mice immunised with pcDNA3/ntetC, even when differences in the CpG content between the two sequences were controlled for using non-expressing DNA.

Animals↗
PubMed1999

Threats to validity in the longitudinal study of psychological effects: the case of short stature.

In all studies of health-related problems and their effects on well-being, research design issues threaten to compromise the validity of findings. This is particularly so in a longitudinal study, essentially stemming from the tension between maintaining participant compliance and retaining investigator objectivity. Such a tension may be exacerbated where measures of dependent variables such as self-esteem are used alongside the collection of physical data which is essential to the study, as in research into the psychological effects of short stature on children and young people. In this paper one particular project, the Wessex Growth Study, is used to illustrate the common threats to validity, both internal and external, of such research, and to consider future improvements in design. The Wessex Growth Study, set up in 1986, was designed to overcome some of the methodological problems found in earlier research with short stature children. It is following the growth and psychological development through their school years of a cohort of short children (below third centile for height when first identified) and case-matched controls (10th-90th centiles) recruited at school entry (ages 5/6). Findings have generally found only small differences between short and average height children. Though these results so far have mainly been presented cross-sectionally, the young people involved are followed up at 6-monthly intervals for height and other data to be collected, and thus to some extent the study also has the advantages and problems of a longitudinal research design. Using Campbell and Stanley's criteria this article makes clear the strain on both internal and external validity in the study, but argues that these problems are to some extent inherent in all longitudinal psychological research, and are outweighed in the present research by the collection of data on short stature which would not otherwise be available. Future data collection within the study will introduce further improvements in design.

Adolescent↗
PubMed1997

Complete RNA1 sequences of two UK isolates of barley mild mosaic virus: a wild-type fungus-transmissible isolate and a non-fungus-transmissible derivative.

The complete RNA1 sequences of two isolates (fungus transmissible and non-fungus transmissible) of barley mild mosaic virus (BaMMV) were obtained. The two isolates' RNA1 sequences had very high sequence identity (99.3%), and of the 15 amino acid differences (out of 2258) between the putative polyproteins, 11 were conservative and unlikely to affect the structure or function of the protein. The remaining amino acid differences were thought unlikely to affect fungus transmission because they occur in the CI- and NIb-coding regions. This strongly suggests that the P73 protein of RNA2 (which has a 364-aa deletion in the non-fungus-transmissible isolate) is involved in fungus transmission of BaMMV.

Amino Acid Sequence↗
PubMed1995

Molecular characterisation of UK isolates of barley yellow mosaic bymovirus.

Several isolates of barley yellow mosaic virus (BaYMV) from different sites in the UK, including some that were virulent on European resistant winter barley cultivars (resistance-breaking strain: BaYMV-2) and some that were not, were examined by RT-PCR, restriction mapping and sequencing of selected parts of the virus genome. Nucleotide and predicted amino acid sequences were determined for the 5'-terminal region, part of the NIa coding region and the coat protein coding region on RNA 1 and an area at the N-terminus of the 70-kDa protein coding region on RNA 2. The sequences differed from those previously reported for a BaYMV isolate from Japan and for two German isolates, one of which was of the BaYMV-2 strain. There were no strain-specific amino acid differences and the few, non-consecutive, nucleotide differences detected were probably not significant and were insufficient to develop a rapid diagnostic test to distinguish BaYMV-2 from other isolates. Restriction mapping of RNA 2 cDNA again showed no consistent strain-related differences. The differences previously reported between the two German isolates are probably not strain-related.

Base Sequence↗
PubMed1994

A trans-spliced leader RNA sequence in plant parasitic nematodes.

A trans-spliced leader gene has been identified in the genomes of the potato cyst nematodes Globodera rostochiensis and G. pallida. The gene contains a 22-nt sequence identical to that of the leader sequence of Caenorhabditis elegans, a consensus splice donor site and a putative Sm antigen binding site. In common with other nematodes the spliced leader gene is present in tandem repeating units together with the 5S ribosomal RNA gene. Variation in the length of the intergenic spacer region has permitted the design of polymerase chain reaction primers which can be used to reveal repeat length variants diagnostic for G. rostochiensis and G. pallida and the Pa1 pathotype of G. pallida.

Animals↗
PubMed1993

Cloning and sequence analysis of the coat protein gene of barley mild mosaic virus.

The sequence of the 3' 1462nts of RNA-1 of a UK isolate of the fungal-transmitted virus barley mild mosaic (BaMMV) has been determined. An open reading frame encoding the coat protein gene was identified within this region using amino acid sequence information obtained by cyanogen bromide cleavage of virus particles. The amino acid sequence of the full-length coat protein was deduced from the nucleotide sequence. Amino acid sequence comparisons revealed highest homology to the coat protein of barley yellow mosaic virus. In addition, a significant, but limited, number of the amino acid residues that are conserved between aphid-transmitted potyviruses were also conserved between BaMMV and potyviruses.

Amino Acid Sequence↗
PubMed1993

Salicylic acid-inducible binding of a tobacco nuclear protein to a 10 bp sequence which is highly conserved amongst stress-inducible genes.

A 10 bp sequence motif (TCATCTTCTT) which is repeated several times in the 5' non-transcribed region of a barley beta-1,3-glucanase gene is also present in the non-translated regions of over 30 different plant genes which are known to be induced by one or more forms of stress. Gel retardation assays and South-western blotting experiments provide evidence that the motif is the binding site for a tobacco nuclear protein with an apparent molecular weight of 40 kDa. Binding activity is increased when nuclear extracts from salicylic acid-treated plants are analysed compared with extracts from control plants, indicating that the protein itself is either induced or modified under conditions of stress. These observations suggest roles for the 10 bp motif and its binding protein as cis- and trans-acting regulators of gene expression during response to stress.

Base Sequence↗
PubMed1989

Segregation of cauliflower mosaic virus symptom genetic determinants.

We have created a series of hybrid cauliflower mosaic virus (CaMV) genomes between a severe virus strain (Cabb BJI) and a mild strain (Bari 1) to map the virus genetic loci responsible for specific systemic symptom characters produced in infected turnip plants. Recombinants were generated in vivo by recombinational rescue and in vitro by restriction enzyme fragment exchange. On infection, hybrids induced either parental (wild-type) symptoms or segregated parental characters. Some of the engineered hybrid genomes produced novel symptomatic effects not observed in either of the parental strains whilst others reverted to express parental symptom characters following passaging. Determinants defining differences between the two CaMV strains in respect of four specific symptom characters were delimited to separate genome regions. A locus involved in determining the rate of spread of systemic vein clearing symptoms mapped to a region containing part of gene VII and gene I (nts 109-780). This phenomenon is consistent with the putative involvement of the CaMV gene I product in mediating virus movement within infected plants. Determinants influencing the degree of leaf chlorosis were located in a separate genome domain encompassing part of gene VI together with the large intergenic region and part of gene VII (nts 6103-90). Determinants controlling timing of initial systemic symptom appearance were mapped to a region between nts 2150 and 4438 containing part of gene III, gene IV, and part of gene V. Plant stunting was influenced by loci in at least two separate regions, one containing parts of gene I and II, and a second within the reverse transcriptase gene (V). We conclude that symptoms produced by CaMV infection can be subdivided into individual characters, the genetic determinants of which segregate to different virus genetic loci and are not restricted to a single gene product.

Brassica↗
PubMed1989

Peripheral vision and simple catching: the screen paradigm revisited.

The importance of effector visual feedback has previously been indicated using an opaque screen to prevent sight of the catching hand for the final 150-200 ms of a flight path of 850 ms in total. Attention was drawn to the finding that the ability to position the arm correctly in the line of flight of the ball deteriorated as a consequence of the number of trials without visual feedback. However, the use of only 20 test trials allows a possibility that the proprioceptive system may be able to re-establish predominant control under conditions of prolonged visual decrement. In order to verify this notion, the number of experimental trials was quadrupled for 24 subjects of mixed sex in a replication of the initial paradigm. The results provided preliminary support for the view that the positioning of the catching arm is more seriously affected by visual occlusion than the timing of the grasp phase. However, increments in accuracy of limb orientation were evidenced in all screen conditions, as the number of trials increased. The grasp component of one-handed catching appeared to remain unaffected by the increase in experimental trials. The relative influence of skill level on catching errors was next addressed by comparing the performance of the six best and worst catchers in the group. The results did not support previous research which found a relation between skill level and error type. The number of position, but not grasp, errors decreased as a function of task practice for both subgroups. Future investigations should, perhaps, focus on the developmental nature of movement control in one-handed catching to obtain a clearer picture of this relation.

Adult↗