PubMed Health⌕ Search

Biomedical subjects

G Stevenson

Publications and source records attributed to G Stevenson.

At least 19 recordsLinked to original sources
PubMed2002

Treatment of post-transplant lymphomas with anti-B-cell monoclonal antibodies.

The treatment of post-transplant lymphomas still needs major improvements in order to put the patient in remission and to retain graft function. Chemotherapy is far too toxic in these patients. A more specific treatment such as anti-B-cell monoclonal antibody is very promising. The cytotoxic effect of antibody relies mainly on complement-induced and antibody-dependent cellular cytotoxicity; apoptosis may also induce tumor cell death. B-cell antigens expressed on the cell surface are the targets of antibody attack; some specificities may be chosen because of their level of expression or because of signaling induced within the cell. Anti-B-cell antibodies can be produced by genetic engineering in order to be humanized or to carry bispecific Fabs. The efficacy and safety of anti-B-cell monoclonal antibodies (mAbs) in transplant patients have been proven with different antibodies such as anti-CD21/CD24 mAb, anti-CD38 mAb and anti-CD20 mAb. In a retrospective analysis of different centers in France, rituximab (anti-CD20 mAb, Roche Products) achieved an overall 69% remission rate in 34 organ and bone-marrow transplant patients. But the conditions of use of antibody must be better defined, particularly with regard to the immunosuppressive therapy, the type of tumor and the dose of antibody. We must also improve our understanding of the in vivo mechanisms of action of antibody to develop more efficient antibody constructs.

Antibodies, Monoclonal↗
PubMed2000

The colanic acid gene cluster of Salmonella enterica has a complex history.

The colanic acid gene cluster of Salmonella enterica LT2 was sequenced and compared with that of Escherichia coli K-12. The two clusters are similar with divergence slightly higher than average for genes of the two species. The cluster was divided into four blocks by GC content and seems likely to have transferred from a higher GC content species to the ancestor of E. coli and S. enterica. All 19 genes of K-12 and 13 genes of LT2 appear to have undergone random genetic drift with amelioration of the GC content. However, in the case of S. enterica, we believe that the six genes of the GDP-fucose pathway group were replaced relatively recently by genes closely related to those of the original donor species. Two repetitive elements were observed: a bacterial interspersed mosaic element in the intergenic region between wzx and wcaK in K-12 only and a RSA (repetitive sequence element) sequence between wcaJ and wzx in LT2 only.

Bacterial Proteins↗
PubMed2000

L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid beta-protein precursor gamma-secretase activity.

Progressive cerebral amyloid beta-protein (A beta) deposition is believed to play a central role in the pathogenesis of Alzheimer's disease (AD). Elevated levels of A beta(42) peptide formation have been linked to early-onset familial AD-causing gene mutations in the amyloid beta-protein precursor (A beta PP) and the presenilins. Sequential cleavage of A beta PP by the beta- and gamma-secretases generates the N- and C-termini of the A beta peptide, making both the beta- and gamma-secretase enzymes potential therapeutic targets for AD. The identity of the A beta PP gamma-secretase and the mechanism by which the C-termini of A beta are formed remain uncertain, although it has been suggested that the presenilins themselves are novel intramembrane-cleaving gamma-secretases of the aspartyl protease class [Wolfe, M. S., Xia, W., Ostaszewski, B. L., Diehl, T. S., Kimberly, W. T., and Selkoe, D. J. (1999) Nature 398, 513-517]. In this study we report the identification of L-685,458 as a structurally novel inhibitor of A beta PP gamma-secretase activity, with a similar potency for inhibition of A beta(42) and A beta(40) peptides. This compound contains an hydroxyethylene dipeptide isostere which suggests that it could function as a transition state analogue mimic of an aspartyl protease. The preferred stereochemistry of the hydroxyethylene dipeptide isostere was found to be the opposite to that required for inhibition of the HIV-1 aspartyl protease, a factor which may contribute to the observed specificity of this compound. Specific and potent inhibitors of A beta PP gamma-secretase activity such as L-685,458 will enable important advances toward the identification and elucidation of the mechanism of action of this enigmatic protease.

Amino Acid Sequence↗
PubMed2000

A survey of methohexitone use by anesthetists in the clinical practice of ECT in Edinburgh.

The dosage of methohexitone (methohexital) administered by anesthetic staff was surveyed in a consecutive series of 52 patients referred for electroconvulsive therapy (ECT) in routine clinical practice in Edinburgh. Patients were weighed before the first treatment, and the ratio of administered dose to weight in kilograms calculated. Anesthesia was administered by three consultant staff and six nonconsultant staff. In only one patient (2%) was the administered dose within the range recommended by the Royal College of Psychiatrists (0.75-0.9 mg/kg), and in only four patients (8%) were the doses within the range recommended by the American Psychiatric Association (0.75-1.0 mg/kg). In all other patients the dose exceeded these recommended ranges; the average dose was 1.5 (+/- 0.3) mg/kg. The possible implications of these findings are discussed.

Adolescent↗
PubMed2000

Effects of storage conditions and hemolysis on vitamin E concentrations in porcine serum and liver.

Vitamin E (alpha-tocopherol) is an antioxidant vitamin important in protecting unsaturated fatty acids in lipid membranes from peroxidation. Variation in collection, storage, and shipping conditions of samples can potentially lead to breakdown of vitamin E prior to analysis. Therefore, the purposes of this project were 1) to determine the stability of vitamin E in refrigerated and frozen porcine liver and serum and 2) to evaluate the effects of red blood cell (RBC) hemolysis on porcine serum vitamin E concentrations. Porcine liver and nonhemolyzed serum were collected and stored refrigerated or frozen. Samples were analyzed for vitamin E immediately or on days 2, 3, 7, or 14. In addition, porcine RBCs were added to normal serum at concentrations from 1 x 10(6) to 1 X 10(9) RBC/ml and hemolyzed by freeze-thaw prior to analysis for vitamin E or products of lipid peroxidation.

Animals↗
PubMed1999

Polycyclic aromatic hydrocarbons in fuel-oil contaminated soils, Antarctica.

Where fuel oil spills have occurred on Antarctic soils polycyclic aromatic hydrocarbons (PAH) may accumulate. Surface and subsurface soil samples were collected from fuel spill sites up to 30 years old, and from nearby control sites, and analysed for the 16 PAHs on the USEPA priority pollutants list, as well as for two methyl substituted naphthalenes, 1-methylnaphthalene and 2-methylnaphthalene. PAH levels ranged from 41-8105 ng g-1 of dried soil in the samples from contaminated sites and were below detection limits in control site samples. PAH were detected in surface soils and had migrated to lower depths in the contaminated soil. The predominant PAH detected were naphthalene and its methyl derivatives.

Antarctic Regions↗
PubMed1997

Towards filmless and distance radiology.

To many people radiology is synonymous with films. For 20 years or so, however, it has been possible to capture digitally data traditionally displayed on film, and that was true from the beginning of computed tomography and magnetic resonance imaging too. There is more to picture archiving and communication systems (PACS) than the economies of filmlessness and the ability to modify images. To realise the full potential of PACS requires huge and expensively equipped networks linking the radiology department, hospital wards, outpatient clinics, laboratories, family doctors' clinics, and so on, permitting simultaneous consultations on different sites and almost instant reporting from specialist radiologists at a distance. The data sets that need to be transferred are huge but some of the technical obstacles are now being overcome and the past few years have seen some hospitals move to a filmless state. The more common pattern, though, will be a piecemeal approach. PACS and teleradiology certainly provide a quicker imaging service. How soon a total PACS will save money for a hospital operating budget is less clear.

Humans↗
PubMed1996

Outcome of patients discharged from a coronary care unit with a diagnosis of "chest pain not yet diagnosed".

OBJECTIVE: To determine the outcome and 3-year mortality rate among patients discharged from a coronary care unit (CCU) with a diagnosis of "chest pain not yet diagnosed." DESIGN: Prospective observational cohort study. SETTING: CCU in a university teaching hospital. PATIENTS: All 158 eligible patients discharged from the CCU between August 1986 and December 1988. Of them, 27 refused to participate and 31 did not meet the inclusion criteria because of significant co-morbidity or transportation difficulties. INTERVENTIONS: Evaluation with maximal and thallium exercise stress testing and four major gastrointestinal (GI) investigations: 24-hour intraesophageal pH monitoring, upper GI endoscopy with biopsy, esophageal motility studies and an upper GI barium series. OUTCOME MEASURES: Results of investigations and incidence of recurrent chest pain, CCU readmission, coronary angiography, coronary artery bypass surgery, myocardial infarction and death at 6, 12, 24 and 36 months after the index visit. RESULTS: Of the patients enrolled in the study 79% (79/100) had a normal exercise thallium stress test result, 74% (68/92) had an abnormal result from the 24-hour pH monitoring, 87% (82/94) had abnormal endoscopic results, 90% (84/93) had abnormal manometric results, and 89% (83/93) had signs of reflux with the barium series. At 3 years 50 patients had recurrent chest pain and 3 underwent coronary artery bypass surgery. Three patients died over the 3 years, all of noncardiac causes. CONCLUSION: Many patients discharged from the CCU with a diagnosis of chest pain not yet diagnosed have a high incidence of esophageal disorders and a very low 3-year mortality rate. More research into the early and effective identification and management of patients with such a diagnosis is needed.

Adult↗
PubMed1996

Organization of the Escherichia coli K-12 gene cluster responsible for production of the extracellular polysaccharide colanic acid.

Colanic acid (CA) is an extracellular polysaccharide produced by most Escherichia coli strains as well as by other species of the family Enterobacteriaceae. We have determined the sequence of a 23-kb segment of the E. coli K-12 chromosome which includes the cluster of genes necessary for production of CA. The CA cluster comprises 19 genes. Two other sequenced genes (orf1.3 and galF), which are situated between the CA cluster and the O-antigen cluster, were shown to be unnecessary for CA production. The CA cluster includes genes for synthesis of GDP-L-fucose, one of the precursors of CA, and the gene for one of the enzymes in this pathway (GDP-D-mannose 4,6-dehydratase) was identified by biochemical assay. Six of the inferred proteins show sequence similarity to glycosyl transferases, and two others have sequence similarity to acetyl transferases. Another gene (wzx) is predicted to encode a protein with multiple transmembrane segments and may function in export of the CA repeat unit from the cytoplasm into the periplasm in a process analogous to O-unit export. The first three genes of the cluster are predicted to encode an outer membrane lipoprotein, a phosphatase, and an inner membrane protein with an ATP-binding domain. Since homologs of these genes are found in other extracellular polysaccharide gene clusters, they may have a common function, such as export of polysaccharide from the cell.

Acetyltransferases↗
PubMed1995

A plasmid-borne O-antigen chain length determinant and its relationship to other chain length determinants.

We identify a function-controlling O antigen chain length for a plasmid-borne gene, cldpHS-2, harboured by Flexneri strains of Escherichia coli known to cause reactive arthritis. The predicted amino acid sequence of the gene product is very similar to those of other cld genes and that of fepE, thought to be part of the enterobactin iron uptake system of E. coli. The predicted proteins are compared with rfb-associated chain length determinants as a family of related genes.

Amino Acid Sequence↗
PubMed1994

Identification of L-tryptophan derivatives with potent and selective antagonist activity at the NK1 receptor.

As part of a program of screening the Merck sample collection, N-ethyl-L-tryptophan benzyl ester was identified as a weak antagonist at the substance P (NK1) receptor. Structure-activity studies showed that the indole ring system could be replaced by 3,4-dichlorophenyl, alpha- or beta-naphthyl, or benzthiophene with retention or only small loss of affinity. It was found that acylation of the tryptophan nitrogen gave compounds with higher affinity than N-ethyl or other basic amines. Optimization of substitution on the benzyl ester led to the identification of the 3,5-bis-(trifluoromethyl)benzyl ester of N-acetyl-L-tryptophan 26 as a potent and selective substance P receptor antagonist. Compound 26 blocked substance P induced dermal extravasation in vivo and was the most potent compound from this structurally novel class of antagonists which further adds to the diversity of small molecules that bind to the (NK1) receptor.

Acylation↗
PubMed1994

Pneumatic reduction of intussusception using carbon dioxide.

Pneumatic reduction using air has recently become popular for the initial non-surgical management of intussusception. Since carbon dioxide (CO2) is rapidly absorbed from body surfaces, it should theoretically result in less cramping and distension following reduction. We reviewed our recent experience with the pneumatic reduction of intussusception using CO2 in 26 children. In 22 of these the intussusception was reduced (85%). There was one performation with CO2; the patient did not suffer any postoperative complications. Five additional children who had been treated unsuccessfully with barium had intussusception subsequently reduced with CO2. Following CO2 reduction, most children were fed within hours, and there were no instances of significant abdominal distension or cramping. We conclude that pneumatic reduction of intussusception using CO2 is safe and effective, and has the theoretical advantage of more rapid absorption from the gastrointestinal tract than air.

Carbon Dioxide↗
PubMed1994

Structure of the O antigen of Escherichia coli K-12 and the sequence of its rfb gene cluster.

Escherichia coli K-12 has long been known not to produce an O antigen. We recently identified two independent mutations in different lineages of K-12 which had led to loss of O antigen synthesis (D. Liu and P. R. Reeves, Microbiology 140:49-57, 1994) and constructed a strain with all rfb (O antigen) genes intact which synthesized a variant of O antigen O16, giving cross-reaction with anti-O17 antibody. We determined the structure of this O antigen to be -->2)-beta-D-Galf-(1-->6)-alpha-D-Glcp- (1-->3)-alpha-L-Rhap-(1-->3)-alpha-D-GlcpNAc-(1-->, with an O-acetyl group on C-2 of the rhamnose and a side chain alpha-D-Glcp on C-6 of GlcNAc. O antigen synthesis is rfe dependent, and D-GlcpNAc is the first sugar of the biological repeat unit. We sequenced the rfb (O antigen) gene cluster and found 11 open reading frames. Four rhamnose pathway genes are identified by similarity to those of other strains, the rhamnose transferase gene is identified by assay of its product, and the identities of other genes are predicted with various degrees of confidence. We interpret earlier observations on interaction between the rfb region of Escherichia coli K-12 and those of E. coli O4 and E. coli Flexneri. All K-12 rfb genes were of low G+C content for E. coli. The rhamnose pathway genes were similar in sequence to those of (Shigella) Dysenteriae 1 and Flexneri, but the other genes showed distant or no similarity. We suggest that the K-12 gene cluster is a member of a family of rfb gene clusters, including those of Dysenteriae 1 and Flexneri, which evolved outside E. coli and was acquired by lateral gene transfer.

Acetylation↗