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Biomedical subjects

D Gillett

Publications and source records attributed to D Gillett.

26 records · Page 2Linked to original sources

Pre-ALL and non-A, non-B hepatitis infection.

We report a case of acute lymphoblastic leukaemia which presented as hypoplastic anaemia following Non-A, Non-B viral hepatitis infection. The role of infection and the mechanisms involved in the evolution of pre-ALL to overt leukaemia remain speculative. However, it is of practical importance to distinguish pre-ALL from aplastic anaemia and the myelodysplastic syndromes during the early pancytopenic phase to avoid inappropriate management.

Anemia, Aplastic↗

Immunochemical study on the contribution of hypolipidaemic-induced cytochrome P-452 to the metabolism of lauric acid and arachidonic acid.

The influence of four hypolipidaemic drugs (clofibrate, WY-14,643, clobuzarit and bezafibrate) on hepatic cytochrome P-450 and fatty acid metabolism in male rat liver microsomes has been investigated. All of the hypolipidaemic drugs tested significantly induced the hydroxylation of lauric acid and, furthermore, this was accompanied by a concomitant 3-fold induction of a specific isoenzyme of cytochrome P-450 (termed cytochrome P-452) as determined by a single radial immunodiffusion technique. In addition, immunochemical quantitation of cytochrome P-452 in control, uninduced rat liver microsomes revealed that this particular isoenzyme constituted 22% of the total carbon monoxide-discernible cytochrome P-450 population. This has led us to the conclusion that cytochrome P-452 is a constitutive cytochrome P-450 isoenzyme and therefore that hypolipidaemic agents function as inducers of constitutive haemoprotein isoenzymes. Cytochrome P-452 plays a significant role in the hydroxylation of lauric acid as evidenced by inhibition of hydroxylase activity in the presence of an anti-P-452 IgG fraction. In addition, this antibody preferentially inhibits the 12-hydroxylation of lauric acid in rat liver microsomes by comparison to the 11-hydroxylase activity. Our studies have also shown that arachidonic acid serves as an excellent substrate for hypolipidaemic-induced cytochrome P-452, resulting in the formation of several metabolites that have been separated by reverse phase HPLC. Furthermore, a specific metabolite (or group of metabolites) of arachidonic acid is induced by clofibrate pretreatment and that the formation of this metabolite(s) is inhibited by an antibody to cytochrome P-452. By comparison, other metabolites of arachidonic acid remain refractory to induction by clofibrate and are not inhibited by the presence of anti-P-452 IgG. In addition, a reconstituted enzyme system containing highly purified cytochrome P-452 actively catalyses the above specific oxidation of arachidonic acid, a reaction that is significantly stimulated by the presence of cytochrome b5. Taken collectively, our data provide compelling evidence that hypolipidaemic agents induce a specific isoenzyme of hepatic microsomal P-450 that readily oxidizes fatty acids and that arachidonic acid may serve as an excellent endogenous substrate for this novel haemoprotein.

Animals↗

Congenital duodenal diaphragm in an adult.

A case of congenital duodenal diaphragm has been presented. The clinical features of protracted vomiting, epigastric pain and discomfort after meals with a gastric splash occurring at any age, the biochemical features of profound hypokalaemia and hypochloraemic alkalosis, and the radiological demonstration of a diaphragm have been shown to be of diagnostic significance. The operation of vagotomy and gastroenterostomy was unsuccessful in this case, and a literature review suggests that duodenotomy with excision of the diaphragm is the preferred method of treatment.

Duodenum↗

Shape and regional volume in immersed lung lobes.

We froze 10 isolated canine lower lobes by immersing them in chlorothene (sp gr 1.4) at -20 degrees C. In six instances the contralateral lower lobe was frozen over dry ice. The lobes were then sliced horizontally, and the volume and weight of each slice were measured so that expansion (specific volume) and the amount of tissue (weight) could be assessed as a function of distance down the lung. Lobes frozen under chlorothene at low [35% total lung capacity (TLC)] and medium [60% TLC] volumes demonstrated a gradient of regional expansion that was about half that predicted on the basis of pleural surface pressure. Lobes frozen under chlorothene at high volumes [80% TLC] did not demonstrate a significant gradient of regional expansion. These results demonstrated tissue interdependence. When lobes frozen under chlorothene were compared with contralateral lobes frozen over dry ice, substantial differences in shape were evident. Chlorothene-frozen lobes had greater vertical height, and a smaller fraction of their weight was present in dependent regions: lobes frozen in chlorothene had half as much tissue over the lower 40% of their vertical height as did lobes frozen over dry ice. We demonstrated two mechanisms by which relative homogeneity of regional expansion was maintained in response to differences in pleural pressure, tissue interdependence and tissue movement from more compressed to less compressed regions.

Air Pressure↗

Volume shifts with partial submersion of isolated lung lobes.

When an isolated lung lobe is partially submerged, volume moves from the submerged part to the unsubmerged part. We partially submerged isolated dog lobes of known weight and volume, and measured airway pressure and, by water displacement, the volume of the submerged part. The lobe was then air-dried and sectioned at the waterline and each part weighed. Multiplying lobar volume by the fractional weight of the submerged part yielded the volume of the submerged part before immersion, and therefore the volume shift to the unsubmerged part due to immersion. Dividing this volume shift by the immersion-induced change in airway pressure gave the compliance (Cr') of the unsubmerged part. Cr' was compared to Cr, the compliance of the unsubmerged part when it was inflated with air. Cr/Cr' was linearly related to the degree of immersion: as immersion increased Cr/Cr' fell; so when lobes were 80% immersed Cr/Cr' was 0.3--0.5, indicating that compressing the lower part of the lung made the upper easier to expand. This behavior could be explained if with immersion lung units moved from the submerged part to the unsubmerged part and this shift increased with the degree of immersion. We demonstrated that when one part of a lobe was compressed lung units moved away from the compressive force and that this movement could occur without similar movement of the pleural surace. Tissue movement probably accounted at least in part for our results.

Animals↗

Automated sequencing of insoluble peptides using detergent. Bacteriophage fl coat protein.

Peptides which are highly nonpolar and insoluble under moderate conditions of pH and ionic strength cannot be subjected to automated sequence analysis. We report a method for solubilization of one such peptide, bacteriophage fl coat protein, by chemical modification in the presence of sodium dodecyl sulfate. Following this treatment the 50-residue peptide was degraded stepwise in an automated sequenator using a single cleavage Quadrol program with high repetitive yield through residue 47. We also report a modified program using detergent incorporated into dimethylallylamine buffer which permitted sequencing with high repetitive yields for at least the first 18 residues of the unmodified and otherwise highly insoluble coat protein. The presence of detergent caused no observable difficulties in detection of residues by gas chromatography, thin layer chromatography, or amino acid analysis.

Amino Acid Sequence↗