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Biomedical subjects

A D Watson

Publications and source records attributed to A D Watson.

175 records · Page 10Linked to original sources

Ionic versus nonionic MR imaging contrast media: operational definitions.

An experimental rationale is provided to differentiate between the terms ionic and nonionic for magnetic resonance (MR) imaging contrast media such as gadodiamide and gadopentetate dimeglumine. Four independent types of physical measurements (electric conductivity, osmolality, electrophoresis, and ion exchange) were performed on a range of test compounds, including D-glucose, iohexol, gadopentetate dimeglumine, and gadodiamide. Iohexol, D-glucose, and gadodiamide are shown to be nonionic species at physiologic pH (7.4), not measurably dissociating in solution. A range of gadopentetate salts behave as electrolytes, dissociating into constituent charged ions in aqueous media. Operational definitions for the terms ionic and nonionic are provided, and the terms neutral and net zero charge are compared with nonionic for accuracy. The nomenclature nonionic and ionic is deemed appropriate for differentiating MR imaging contrast media.

Contrast Media↗

Evidence for a role of phospholipid oxidation products in atherogenesis.

There is growing evidence for the accumulation of phospholipid oxidation products (some of which can also be formed enzymatically) in several chronic disease processes including atherosclerosis. There also is considerable evidence that enzymes involved in hydrolysis of these phospholipids (present in both lipoproteins and cells) may be important in regulation of atherogenesis. In vitro studies suggest that these lipids can activate vascular wall cells to states that contribute to the atherosclerotic process. This review focuses on two types of bioactive phospholipids: phosphatidyl cholines in which the sn-2 fatty acid has been modified by oxidation and lysophosphatidic acid in which both the sn-2 and sn-3 positions have been modified. The mechanism by which these phospholipid oxidation products activate cells has revealed the presence of several different receptors and signal transduction pathways.

Animals↗

Preparation and characterization of paramagnetic polychelates and their protein conjugates.

The gadolinium complexes of poly-L-lysine-poly(diethylenetriamine-N,N,N',N",N"-pentaacetic acid) (Gd-PL-DTPA) and poly-L-lysine-poly(1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetr aacetic acid) (Gd-PL-DOTA) and their conjugates with human serum albumin (HSA) have been prepared and characterized. Poly-L-lysine (PL, degree of polymerization approximately 100) was N-acylated with a mixed anhydride of the chelating ligand (DTPA or DOTA). Sixty to ninety chelating groups per molecule of PL could be attached in this way. Following purification of the polychelate by size-exclusion chromatography, the gadolinium complexes were prepared by standard methods and conjugated to HSA with heterobifunctional cross-linking reagents. The molar relaxities of these macromolecular species were 2-3-fold higher than those of the corresponding monomeric metal complexes [( Gd(DTPA)] and [Gd(DOTA)]). The conjugation conditions were optimized to produce conjugates containing 60-90 metal centers per molecule of HSA (ca. one polychelate per protein).

Chelating Agents↗

An immunohistochemical study of histiocytic ulcerative colitis in boxer dogs.

Histiocytic ulcerative colitis (HUC) is an inflammatory bowel disease (IBD) that occurs predominantly in dogs of the boxer breed. The lesions are characterized by mucosal ulceration and mixed inflammatory cell infiltrate that includes the presence of periodic acid-Schiff (PAS)-positive macrophages. However, the phenotype of the inflammatory cells has not been characterized further. In the present study, immunohistochemistry and computer-aided morphometric analysis were used to define populations of leucocyte subsets in the colon of 14 boxer dogs with HUC. Biopsies from six of these dogs included both lesional and non-lesional regions. Colonic tissue from 11 dogs of various breeds without evidence of gastrointestinal disease served as controls. In HUC lesions there were significantly more IgG(+), IgG3(+), IgG4(+)plasma cells, CD3(+)T cells, MHC class II(+)cells, L1(+)cells and PAS(+)cells in the lamina propria than in both control colon and non-lesional colonic regions of affected dogs. In the epithelial compartment, goblet cells were significantly decreased in HUC lesions compared to both control and non-lesional HUC colon, and intensity of enterocyte MHC class II expression was significantly increased. These observations are similar to those documented in human IBD, especially ulcerative colitis, and suggest an important role for the mucosal immune system in the pathogenesis of canine HUC.

Animals↗

Dyserythropoiesis, polymyopathy, and cardiac disease in three related English springer spaniels.

A polysystemic disorder was observed in three related English Springer Spaniel dogs that demonstrated regurgitation from an early age, slowly progressive temporal muscle atrophy with partial trismus, and less pronounced generalized skeletal muscle atrophy. All dogs exhibited moderate dyserythropoietic anemia, polymyopathy with megaesophagus, and varying degrees of cardiomegaly. The prevalence, etiology, underlying pathomechanism, and possible mode of inheritance remain to be elucidated.

Anemia, Dyserythropoietic, Congenital↗

Suspected myelinolysis following rapid correction of hyponatremia in a dog.

A dog developed signs of neurological dysfunction five days after rapid correction of severe electrolyte derangements, including hyponatremia, caused by gastrointestinal parasitism (i.e., trichuriasis). History, laboratory findings, and onset of neurological signs following correction of hyponatremia led to a diagnosis of myelinolysis. Myelinolysis is a noninflammatory, demyelinating brain disease caused by sudden, upward osmotic shifts in central nervous system plasma, often a result of rapid correction of chronic hyponatremia. The pathogenesis is complex, but recovery is possible. Iatrogenic damage due to myelinolysis can be avoided by adherence to therapeutic guidelines for correction of chronic hyponatremia.

Animals↗

Effect of tick-borne fever (Ehrlichia phagocytophila) and trypanosomiasis (Trypanosoma brucei 1066) on the pharmacokinetics of sulfadimidine and its metabolites in goats.

The effect of tick-borne fever (TBF) and trypanosomiasis (TBR) on the plasma disposition of sulfadimidine (SDD) in goats was studied after iv administration of 20 and 200 mg/kg of body weight. In each group of six goats, the plasma disappearance curves showed four animals with rapid and two with slow SDD elimination. It is likely that this difference is determined by oxidative rather than acetylation phenotype. In all goats administered 20 mg/kg, half-life increased with TBF but not with TBR. Vd(beta) decreased with both infections. With 200 mg/kg, Vd did not change, whereas AUC and MRT increased with both infections. Metabolites were examined in TBF experiments: N4-acetyl-SDD (N4Ac), 6-hydroxymethyl-SDD (CH2OH) and its glucuronide, 5-hydroxy-SDD (SOH) and its glucuronide, and 6-carboxy-SDD (COOH) and its glucuronide (COOH-glu). At low dose (20 mg/kg), TBF caused the proportion of dose recovered from urine as unchanged SDD to be halved, whereas N4Ac increased correspondingly (2x). After the high dose (200 mg/kg), elimination was saturated and changes in proportional recovery of SDD in urine were less. However, the N4Ac proportion was still doubled, in contrast to the other metabolites, suggesting that saturation was caused by oxidations rather than by acetylation. Formation of CH2OH was the same in health and disease after the low dose, but glucuronidation dropped from 20% to 4% (rapid) or 7% (slow) of total CH2OH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗