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D Brough

Publications and source records attributed to D Brough.

4 recordsLinked to original sources

Construction of an adenovirus type 7a E1A- vector.

A strategy for constructing replication-defective adenovirus vectors from non-subgroup C viruses has been successfully demonstrated with adenovirus type 7 strain a (Ad7a) as the prototype. An E1A-deleted Ad7a reporter virus expressing the chloramphenicol acetyltransferase (CAT) gene from the cytomegalovirus promoter enhancer was constructed with DNA fragments isolated from Ad7a, an Ad7a recombination reporter plasmid, and the 293 cell line. The Ad7a-CAT virus particle transduces A549 cells as efficiently as Ad5-based vectors. Intravenous infections in a murine model indicate that the Ad7a-CAT virus infects a variety of tissues, with maximal levels of CAT gene expression found in the liver. The duration of Ad7a-CAT transgene expression in the liver was maximally maintained 2 weeks postinfection, with a decline to baseline activity by the week 4 postinfection. Ad7a-CAT represents the first example of a non-subgroup C E1A- adenovirus gene transfer vector.

Adenovirus E1A Proteins↗

Metabolic acidosis is a potent stimulus for cellular inorganic phosphate generation in uraemia.

1. During metabolic acidosis, significant fluxes of inorganic phosphate (Pi) may occur from cellular to extracellular fluid. In this study Pi was measured in erythrocytes of uraemic patients before and after haemodialysis and was related to their plasma pH (acidosis), plasma Pi (hyperphosphataemia) and cellular organic phosphate concentrations. 2. Before dialysis, the ratio of cellular to extracellular Pi concentration correlated inversely with plasma pH, increasing 2.5-fold as pH fell from 7.4 to 7.2. 3. An increase in cellular Pi similar to that seen in the patients was observed within 90 min of adding acid to normal erythrocytes in vitro. 4. The total Pi content of the cell suspension increased 25% on decreasing plasma pH from 7.4 to 7.2, largely as a result of generation of Pi from 2,3-bisphosphoglycerate in the cells. This was accompanied by net efflux of Pi into plasma. 5. In addition, the increase in the steady-state cellular Pi concentration on adding a constant extracellular Pi load was 50% greater at pH 7.2 than at 7.4, implying that alterations in the regulation of the transmembrane Pi gradient also contribute to the rise in cellular Pi observed at low pH. 6. At normal plasma Pi concentration (1 mM), glycolytic flux (lactate production) was inhibited by 20% when pH was lowered from 7.4 to 7.2. However, this inhibition was blocked when cellular Pi was increased by adding Pi to the plasma in vitro. 7. Metabolic acidosis is therefore a potent stimulus for Pi generation in erythrocytes, and this Pi may serve to stimulate glycolysis which is normally inhibited by low pH.

Acidosis↗

BIOLOG - a DNA sequence analysis system in PROLOG.

BIOLOG contains facilities for the analysis of nucleic acid sequences. These facilities are available through queries and commands of the underlying implementation language PROLOG. Familiarity with PROLOG is gained by using the built-in BIOLOG functions. This experience should enable the user to extend the current system and define new facilities.

Amino Acid Sequence↗

A controlled smoking intervention programme in secondary schools.

This paper reports the result of an attempt to modify the cigarette smoking habits and attitudes of third and fourth form secondary school pupils. Baseline data was collected in two schools using an interviewer administered questionnaire. In one school a new intervention programme based on curriculum development was introduced. The other school had routine anti-smoking education only. The smoking habits and attitudes of the pupils were remeasured after seven months. In neither school was there a change in either smoking habits or attitudes. The implications of these results for future health education programmes are discussed.

Adolescent↗