Cellular selection leads to age-dependent and reversible down-regulation of transgenic immunoglobulin light chain genes.

Analysis of immunoglobulin expression in mice transgenic for either a kappa light chain (driven by the kappa enhancer) or lambda light chain (driven by the IgH enhancer) revealed that the transgenic light chains are expressed by the majority of B lymphocytes in the neonatal mice. However, the proportion of B cells that express the transgenes at a detectable level decreases rapidly with age, with a concomitant increase in cells expressing rearrangements of one of the endogenous light chain loci. This appears to be the result of cellular selection. The down-regulation of transgene expression is not due to an irreversible mechanism as incubation of adult splenic lymphocytes with bacterial lipopolysaccharide leads to a rapid increase in the expression of the transgenic light chain on the B cell surface. In mice carrying the lambda transgene (but not in mice carrying the kappa transgene) the change with age in the pattern of transgene expression is accompanied by a shift towards B cells that do not express surface IgD. This shift towards IgM+/IgDlow B cells is also observed in mice transgenic for a chloramphenicol acetyltransferase gene linked to the IgH enhancer. This suggests that the down-regulation of IgD may either be due to the expression of a transgene that impairs B cell development or, alternatively, could be associated with the molecular events responsible for the down-regulation of IgH enhancer activity. The results also draw attention to the contribution of cellular selection in determining the pattern of expression of immunoglobulin transgenes and emphasize the importance of in vivo analysis of neonatal as well as adult transgenic mice.

Infraspinatus muscle contracture associated with trauma in a dog.

Infraspinatus muscle contracture was diagnosed in a 4 1/2-year-old female Doberman Pinscher with lameness characterized by abduction and outward rotation of the right antebrachium and carpus. After infraspinatus tenotomy, the dog recovered. This case differs from previously reported cases of infraspinatus muscle contracture because of an associated history of blunt trauma.

Effects of gastric distention-volvulus on coronary blood flow and myocardial oxygen consumption in the dog.

Gastric distention-volvulus (GDV; at 50 mm of Hg gastric inflation pressure) was experimentally induced in 8 dogs anesthetized using pentobarbital. Hemodynamic indices including heart rate, mean arterial pressure, cardiac output, and coronary blood flow (4 dogs) were measured during a 20-minute period of GDV and for 10 minutes after decompression. Arterial and coronary venous oxygen tensions were also measured for calculation of myocardial oxygen extraction (7 dogs) and myocardial oxygen consumption (4 dogs). Dogs were monitored for 72 hours postoperatively for the occurrence of arrhythmias, then were euthanatized for gross and histologic examination of the heart. Experimental GDV resulted in significant (P less than 0.05) decreases in cardiac output (89%), mean arterial pressure (45%), and coronary blood flow (50%) compared with control values. Myocardial oxygen extraction increased (30%) and overall myocardial oxygen consumption decreased (50%), compared with control values. Evidence of subendocardial necrosis was seen in 6 dogs, 4 of which had developed ventricular arrhythmias 8 to 24 hours postoperatively.