Fractional changes in lung capillary blood volume and oxygen saturation during the cardiac cycle in rabbits.

Changes in local pulmonary capillary blood volume (Vc) and oxygen saturation (S) have been difficult to measure in live animals. By utilizing the differences in absorption of light at two wavelengths (650 and 800 nm), we estimated the fractional change in Vc and S during the course of the cardiac cycle in eight anesthetized, ventilated rabbits at low and high lung volumes. Observations were made of the pattern of diffusely backscattered light, from an approximately 1-cm3 volume of lung illuminated with a point source placed on the pleural surface through a thoracotomy. At low lung volume, the fractional change in Vc was approximately 13%, the change in S was approximately 4.6%, and the mean S was close to 77%. The fluctuations in Vc and S lagged behind peak systemic blood pressure by about one-fifth and three-fifths of a cycle, respectively. At high lung volume, there were no important fluctuations in Vc or S, and the mean S was approximately 82%. These results are consistent with fluctuations in pulmonary capillary pressure and gas exchange over the cardiac cycle, and with decreasing capillary compliance with increasing lung volume.

Mutations in PAX3 associated with Waardenburg syndrome type I.

Waardenburg syndrome (WS) types I, II, and III (McKusick #14882, #19351, and #19350) are related autosomal dominant disorders characterized by sensorineural hearing loss, dystopia canthorum, pigmentary disturbances, and other developmental defects. Disease causing PAX3 mutations have been identified in a few families from each of the three disease subtypes, WS-I, WS-II, and WS-III. In others, although the mutations have not been pinpointed, linkage with the PAX3 locus on chromosome 2q35 has been demonstrated. The PAX3 protein is a transcription factor that contains both a paired-domain and a homeodomain DNA binding motif and appears to play a key role during embryogenesis. In this report, we describe two mutations in the human PAX3 gene that cause WS type I. One mutation is a deletion/frameshift in the paired-domain of PAX3 and results in a protein without functional DNA binding domains. The second mutation is a single-base substitution and results in a premature termination codon in the homeodomain of PAX3. This is the first demonstration of a mutation in the homeodomain DNA binding motif in this protein resulting in WS and one of the few examples of a mutation in a homeodomain of any protein that results in human disease.