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Biomedical subjects

A Craig

Publications and source records attributed to A Craig.

At least 37 records · Page 2Linked to original sources

A functional analysis of a natural variant of intercellular adhesion molecule-1 (ICAM-1Kilifi).

Intercellular adhesion molecule-1 (ICAM-1) is involved in a range of interactions both within the host and between the host and a number of pathogens. Recently we described a mutation within the coding region of the first N-terminal immunoglobulin-like domain of ICAM-1, present at high frequency within African populations, which increased the risk of cerebral malaria. To understand the mechanism by which such a polymorphism might be maintained despite counter-selection by malaria, we have carried out functional assays using both forms of ICAM-1 as soluble Fc chimeric fusion proteins. ICAM-1Kilifi has reduced avidity for LFA-1 compared with ICAM-1ref and binding to soluble fibrinogen was completely abolished with the Kilifi variant. In Plasmodium falciparum adhesion assays, ITO4-A4u binding to ICAM-1Kilifi was reduced compared with binding to the reference form. These results allow for the possibility of balanced selection between the reference and Kilifi forms of ICAM-1 through modulation of inflammatory responses and indicate the existence of differences within ICAM-1-binding P. falciparum isolates which may be relevant to pathogenesis.

Animals↗

The effectiveness of activating electrical devices using alpha wave synchronisation contingent with eye closure.

Increases in alpha wave amplitude occur with eye closure (EC) and decreases occur when the eyes are opened (EO). The research reports in this paper emphasise effectiveness of people using these alpha wave changes to activate electrical devices. Effectiveness was measured in terms of time taken and errors made when selecting the correct device. Ten non-disabled subjects significantly decreased the time taken and errors made to activate correctly a device using a six-option environmental control system (ECS) in the laboratory. In addition, a severely disabled person was shown to use the ECS successfully to control her television in her home environment. This research demonstrates that alpha wave manipulation contingent with EC and EO can be the basis for a reliable and quick switching system for controlling electrical devices. Applications to disability are discussed.

Adult↗

Can psycotherapy increase the survival time of cancer patients?

OBJECTIVE: The aim of this paper was to review the evidence regarding the possibility of a relationship between psychological intervention and survival time of cancer patients. METHOD: A literature search was conducted using CD ROM databases to identify studies which have evaluated the effects of psychological interventions on the survival time of cancer patients. The identified studies were critically reviewed. RESULTS: Eight studies which used scientifically acceptable methodology to examine this question were identified. Three of these studies found evidence for a relationship between psychological intervention and patients' survival time, while five did not. Methodological issues and potentially confounding factors are discussed. CONCLUSION: To date, a direct relationship between psychological intervention and patient survival time has not been conclusively demonstrated. Large-scale replication studies which are currently under way will provide more conclusive evidence on this question within the next few years.

Depressive Disorder↗

Congenital skull fracture as a presentation of Menkes disease.

We report the rare presentation of Menkes disease with a congenital skull fracture, intracerebral bleeding, and seizures. The diagnosis was made at 3 months of age based on the characteristic features of the syndrome, by which time the child experienced uncontrollable seizures. Following progressive neurodegeneration, death occurred at 3 years of age. The prognosis in Menkes disease is dependent on early copper-histidine therapy. Effective treatment has led to children surviving into adulthood. Diagnosing the syndrome during the neonatal period is difficult. There are no published reports of congenital skull fracture as a presenting sign of Menkes disease. It is concluded that Menkes disease should be considered in any child who presents with congenital skull fracture as early diagnosis and treatment significantly improve the outcome.

Birth Injuries↗

Identification of fish species after cooking by SDS-PAGE and urea IEF: a collaborative study.

A collaborative study, to validate the use of SDS-PAGE and urea IEF, for the identification of fish species after cooking has been performed by nine laboratories. By following optimized standard operation procedures, 10 commercially important species (Atlantic salmon, sea trout, rainbow trout, turbot, Alaska pollock, pollack, pink salmon, Arctic char, chum salmon, and New Zealand hake) had to be identified by comparison with 22 reference samples. Some differences in the recoveries of proteins from cooked fish flesh were noted between the urea and the SDS extraction procedures used. Generally, the urea extraction procedure appears to be less efficient than the SDS extraction for protein solubilization. Except for some species belonging to the Salmonidae family (Salmo, Oncorhynchus), both of the analytical techniques tested (urea IEF, SDS-PAGE) enabled identification of the species of the samples to be established. With urea IEF, two laboratories could not differentiate Salmo salar from Salmo trutta. The same difficulties were noted for differentiation between Oncorhynchus gorbuscha and Oncorhynchus keta samples. With SDS-PAGE, three laboratories had some difficulties in identifying the S. trutta samples. However, in the contrast with the previous technique, SDS-PAGE allows the characterization of most of the Oncorhynchus species tested. Only Oncorhynchus mykiss was not clearly recognized by one laboratory. Therefore, SDS-PAGE (Excel gel homogeneous 15%) appears to be better for the identification, after cooking, of fish such as the tuna and salmon species which are characterized by neutral and basic protein bands, and urea IEF (CleanGel) is better for the gadoid species, which are characterized by acid protein bands (parvalbumins). Nevertheless, in contentious cases it is preferable to use both analytical methods.

Animals↗

Posttranslational modifications of p53 in replicative senescence overlapping but distinct from those induced by DNA damage.

Replicative senescence in human fibroblasts is absolutely dependent on the function of the phosphoprotein p53 and correlates with activation of p53-dependent transcription. However, no evidence for posttranslational modification of p53 in senescence has been presented, raising the possibility that changes in transcriptional activity result from upregulation of a coactivator. Using a series of antibodies with phosphorylation-sensitive epitopes, we now show that senescence is associated with major changes at putative regulatory sites in the N and C termini of p53 consistent with increased phosphorylation at serine-15, threonine-18, and serine-376 and decreased phosphorylation at serine-392. Ionizing and UV radiation generated overlapping but distinct profiles of response, with increased serine-15 phosphorylation being the only common change. These results support a direct role for p53 in signaling replicative senescence and are consistent with the generation by telomere erosion of a signal which shares some but not all of the features of DNA double-strand breaks.

Cell Line↗

Manometry based randomised trial of endoscopic sphincterotomy for sphincter of Oddi dysfunction.

BACKGROUND: Endoscopic sphincterotomy for biliary-type pain after cholecystectomy remains controversial despite evidence of efficacy in some patients with a high sphincter of Oddi (SO) basal pressure (SO stenosis). AIM: To evaluate the effects of sphincterotomy in patients randomised on the basis of results from endoscopic biliary manometry. METHODS: Endoscopic biliary manometry was performed in 81 patients with biliary-type pain after cholecystectomy who had a dilated bile duct on retrograde cholangiography, transient increases in liver enzymes after episodes of pain, or positive responses to challenge with morphine/neostigmine. The manometric record was categorised as SO stenosis, SO dyskinesia, or normal, after which the patient was randomised in each category to sphincterotomy or to a sham procedure in a prospective double blind study. Symptoms were assessed at intervals of three months for 24 months by an independent observer, and the effects of sphincterotomy on sphincter function were monitored by repeat manometry after three and 24 months. RESULTS: In the SO stenosis group, symptoms improved in 11 of 13 patients treated by sphincterotomy and in five of 13 subjected to a sham procedure (p = 0.041). When manometric records were categorised as dyskinesia or normal, results from sphincterotomy and sham procedures did not differ. Complications were rare, but included mild pancreatitis in seven patients (14 episodes) and a collection in the right upper quadrant, presumably related to a minor perforation. At three months, the endoscopic incision was extended in 19 patients because of manometric evidence of incomplete division of the sphincter. CONCLUSION: In patients with presumed SO dysfunction, endoscopic sphincterotomy is helpful in those with manometric features of SO stenosis.

Adult↗

Sphincter of Oddi function and dysfunction.

The sphincter of Oddi (SO) is situated at the junction of the bile and pancreatic ducts where they enter the duodenum, and it serves to regulate the flow of bile and pancreatic juices as well as to prevent the reflux of duodenal contents into the pancreatobiliary system. SO dysfunction relates to either the biliary or pancreatic portions of the sphincter. Distinct clinical syndromes relating to either sphincter segment are recognized. The mechanism of dysfunction remains uncertain, but disruption of neural pathways involved in sphincter function seems likely. SO dysfunction is best diagnosed by manometry, which is able to correctly stratify patient groups and determine therapy. Biliary scintigraphy, which is noninvasive, has shown promise as a screening tool for patients with suspected SO dysfunction. Division of the sphincter is an effective treatment for patients with manometrically proven SO stenosis for either the biliary or pancreatic form of the disorder. Other forms of SO dysfunction may benefit from pharmacotherapy.

Common Bile Duct Diseases↗

The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum.

Analysis of Plasmodium falciparum chromosome 3, and comparison with chromosome 2, highlights novel features of chromosome organization and gene structure. The sub-telomeric regions of chromosome 3 show a conserved order of features, including repetitive DNA sequences, members of multigene families involved in pathogenesis and antigenic variation, a number of conserved pseudogenes, and several genes of unknown function. A putative centromere has been identified that has a core region of about 2 kilobases with an extremely high (adenine + thymidine) composition and arrays of tandem repeats. We have predicted 215 protein-coding genes and two transfer RNA genes in the 1,060,106-base-pair chromosome sequence. The predicted protein-coding genes can be divided into three main classes: 52.6% are not spliced, 45.1% have a large exon with short additional 5' or 3' exons, and 2.3% have a multiple exon structure more typical of higher eukaryotes.

Animals↗

p53-Dependent growth arrest and altered p53-immunoreactivity following metabolic labelling with 32P ortho-phosphate in human fibroblasts.

The tumour suppressor gene p53 plays a major role in the cellular response to DNA damage, mediating growth arrest and/or apoptosis. Phosphorylation of the protein occurs at numerous sites in vivo and is likely to be a major mechanism for modulation of its activity as a transcriptional transactivator. Not surprisingly, therefore, p53 has been intensively studied by 32P metabolic labelling. Here we show however, using normal human fibroblasts, that typical labelling conditions induce (i) a p53-dependent inhibition of DNA synthesis and (ii) an increase in the cellular content of p53 protein detectable by the phosphorylation-sensitive antibody DO-1 but not by antibody DO-12. These data demonstrate for the first time that 32P labelling is sufficient to induce a biologically-significant, p53-mediated cellular response and strongly suggest that it perturbs the phosphorylation state of p53 which it is being used to measure. This highlights the need to re-evaluate earlier data by non-radioactive approaches using phospho-specific antibodies.

Antibodies, Monoclonal↗

Development of a sodium dodecyl sulfate-polyacrylamide gel electrophoresis reference method for the analysis and identification of fish species in raw and heat-processed samples: a collaborative study.

A collaborative study was carried out in seven European labs with the aim of achieving a sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) standard operation procedure to identify fish species in raw and cooked samples. Urea and SDS-containing solutions were evaluated as extractants. Several preelectrophoretic operations--such as treatment with RNase/DNase, ultrafiltration and desalting--and up to ten types of gels and three SDS-PAGE systems were considered. The SDS-containing solution allowed a higher protein extractability than urea. Unlike urea extraction, SDS extraction seemed not to be influenced so much by the state of the sample (raw, cooked at 60 degrees C, cooked at 85 degrees C). Desalting, ultrafiltration or treatment with RNase/DNase did not improve the discriminatory power of the protein patterns. Commercial homogeneous 15% ExcelGels, especially when they were silver stained, yielded good results and afforded higher reproducibility, thus allowing a better matching of results among the laboratories participating in this collaborative study. Under the optimized technical conditions described above, all the fish species tested, either raw and cooked, yielded reproducible and discriminant species-specific protein patterns.

Animals↗

A standardized method of identification of raw and heat-processed fish by urea isoelectric focusing: a collaborative study.

A urea-isoelectric focusing (urea-IEF) method of identifying fish species in processed fishery products was investigated as an interlaboratory collaborative study. The technique was optimized with respect to (i) protein extraction conditions, composition of the extraction solution (urea and SDS solutions), determination of protein concentrations of the fish extracts (five tested methods); (ii) nature of gel (with carrier ampholytes and Immobilines), conditions of rehydration of commercial dry gels, urea concentration; (iii) staining conditions, Coomassie blue and silver staining. The results of various experiments were compared to select the most appropriate methodology, with respect to the discrimination power of differentiating species with the minimal influence of heat processing, reproducibility, speed, and ease of application. The method recommended meets the requirements of food control and customs laboratories.

Fish Products↗

Clinical aspects of sphincter of Oddi function and dysfunction.

The sphincter of Oddi (SO) functions to regulate the flow of bile and pancreatic juices as well as to prevent the reflux of duodenal contents into the pancreatobiliary system. When dysfunction of the sphincter occurs, symptoms develop relating to either the biliary or pancreatic portions of the sphincter. The mechanism of this dysfunction remains speculative. SO manometry remains the "gold standard" to correctly diagnose the disorder and stratify therapy. Division of the sphincter is effective for SO stenosis, but there is no proven therapy for SO dyskinesia.

Bile↗

A comparison of transnasal and transoral endoscopy with small-diameter endoscopes in unsedated patients.

BACKGROUND: The aim of this study was to compare use and tolerance of transnasal and transoral diagnostic endoscopy with small-diameter endoscopes in unsedated patients. METHODS: Patients being seen for diagnostic endoscopy were randomly assigned to have an unsedated transnasal or transoral procedure. Two prototype narrow-diameter endoscopes (a 5.3 mm fiberoptic endoscope and a 5.9 mm videoendoscope) were used. RESULTS: Of 170 patients (64 women and 106 men) enrolled, 86 underwent transoral and 84 underwent transnasal endoscopy. The procedure was successfully completed using the transoral route in 85 of 86 patients and using the transnasal route in 74 of 84 patients (p = 0.004). Sixteen patients experienced mild epistaxis after transnasal endoscopy. The larger videoendoscope, when compared with the fiberoptic endoscope, accounted for a significantly higher proportion of failures (8 of 41 vs. 2 of 43, p = 0.046) and cases of epistaxis (12 of 33 vs. 4 of 41, p = 0.007). The time taken for transoral endoscopy was shorter than the transnasal route (oral mean 13.7 +/- 0.5 minutes, nasal mean 15.2 +/- 0.6 minutes, p = 0.054). There was no difference between the 2 groups with respect to tolerance of the procedure. From the endoscopist's perspective, the only statistically significant difference between the 2 groups was that endoscope insertion was easier by the oral route (p = 0.007). CONCLUSIONS: Unsedated transnasal endoscopy with the videoendoscope was less successful compared with the transnasal fiberoptic instrument or when compared with either instrument passed transorally. Use of the larger diameter videoendoscope also resulted in significantly more epistaxis in the transnasal endoscopy group. Endoscopists find transoral introduction of the endoscope easier; this may reflect their relative unfamiliarity with the nasal route. Once intubation has been successfully achieved for either route, patient tolerance is the same.

Adult↗

Cytoadherence, pathogenesis and the infected red cell surface in Plasmodium falciparum.

The particular virulence of Plasmodium falciparum compared with the other malaria species which naturally infect humans is thought to be due to the way in which the parasite modifies the surface of the infected red cell. Approximately 16 hours into the asexual cycle, parasite encoded proteins appear on the red cell surface which mediate adherence to a variety of host tissues. Binding of infected red cells to vascular endothelium, a process which occurs in all infections, is thought to be an important factor in the pathogenesis of severe disease where concentration of organisms in particular organs such as the brain occurs. Binding to uninfected red cells to form erythrocyte rosettes, a property of some isolates, is linked to disease severity. Here we summarise the data on the molecular basis of these interactions on both the host and parasite surfaces and review the evidence for the involvement of particular receptors in specific disease syndromes. Finally we discuss the relevance of these data to the development of new treatments for malaria.

Animals↗