The synovial fluid or group II secretory phospholipase A 2 (sPLA 2 ) has been implicated as an important agent involved in a number of inflammatory processes. In an attempt to determine the role of sPLA 2 in inflammation, we set out to generate sPLA 2 -deficient mice. During this investigation, we observed that in a number of inbred mouse strains, the sPLA 2 gene was already disrupted by a frameshift mutation in exon 3. This mutation, a T insertion at position 166 from the ATG of the cDNA, terminates out of frame in exon 4, resulting in the disruption of the calcium binding domain in exon 3 and loss of both activity domains coded by exons 4 and 5. The mouse strains C57BL/6, 129/Sv, and B10.RIII were found to be homozygous for the defective sPLA 2 gene, whereas outbred CD-1:SW mice had variable genotype at this locus. BALB/c, C3H/HE, DBA/1, DBA/2, NZB/B1N, and MRL lpr/lpr mice had a normal sPLA 2 genotype. The sPLA 2 mRNA was expressed at very high levels in the BALB/c mouse small intestine, whereas in the small intestine of the sPLA 2 mutant mouse strains, sPLA 2 mRNA was undetectable. In addition, PLA 2 activity in acid extracts of the small intestine were approximately 40 times higher in BALB/c than in the mutant mice. Transcription of the mutant sPLA 2 gene resulted in multiple transcripts due to exon skipping. None of the resulting mutant mRNAs encoded an active product. The identification of this mutation should not only help define the physiological role of sPLA 2 but also has important implications in mouse inflammatory models developed by targeted mutagenesis.

No abstract

We found that there was a close association between geometry and mechanical properties regardless of the imaging modality (MRI or pQCT) used.

The elimination from plasma of the peptide hormones vasopressin (VP) and atrial natriuretic peptide (ANP) as well as the time course of release and elimination of these hormones after a physiological stimulus were studied in anesthetized rabbits. As an inverse relationship was found to exist between carotid sinus pressure and plasma IR-ANP, a decrease in carotid sinus pressure to 60 mm Hg was used to stimulate ANP as well as VP release. The elimination of VP after iv injection involved a rapid initial phase and a slow late component, with corresponding half-life (t1/2) values of 0.9 and 5.4 min, respectively. After reduction of carotid sinus pressure to 60 mm Hg, plasma VP increased significantly within 1 min and reached a maximum at 10 min. When carotid sinus pressure was increased to 160 mm Hg to inhibit VP release, the t1/2 of VP was 1.3 min. The t1/2 of immunoreactive (IR) ANP after iv infusion was 1.2 min. Plasma IR-ANP was significantly increased 2 min after carotid sinus pressure was decreased, and a maximum was observed at 10 min. The t1/2 of IR-ANP after elevation of carotid sinus pressure to 160 mm Hg was 3.2 min. These studies indicate that both VP and IR-ANP are rapidly eliminated in the anesthetized rabbit.

The effect of streptozocin-induced diabetes (STZ-D) on right atrial structure was investigated in male Wistar rats. STZ (55 mg/kg) or saline (1 ml/kg) was administered by intravenous injection 12 wk before the experimental studies. Tissue was sampled from four regions of the atrium, processed, and embedded in plastic. Quantitative stereological analysis indicated that in STZ-D rats, there was a significant diminution in size of the musculi pectinati (muscular ridges), which form a network making up the wall of the atrium. In addition, within the muscular ridges, there was a significant reduction in the relative proportion of cardiocytes within the cardiac tissue. The rest of the cardiac tissue consisted of interstitial regions, connective tissue, and blood vessels, which correspondingly increased. This suggests there was some form of cardiomyopathy. When atrial granularity was determined relative to cardiocyte volume density, a significant decrease (54%) was found in tissue from STZ-D rats. The blood pressure of conscious STZ-D rats was significantly lower than control rats, whereas right atrial pressure was not different. The level of resting plasma immunoreactive atrial natriuretic factor (ANF) in conscious STZ-D rats (98 +/- 5 pg/ml) was significantly higher than in control rats (52 +/- 7 pg/ml). The decreased atrial granularity could be related to the higher resting plasma ANF levels, suggesting a more rapid turnover or increased synthesis bypassing storage in the granular form.