Expression of the IV (reversed and/or heterotaxic) phenotype in SWV mice.

Approximately 50% of iv/iv mice have situs inversus (mirror image reversal of viscera) and 40% have heterotaxia (anomalous arrangement of viscera). The occurrence of heterotaxia is independent of situs. Using the cross-intercross breeding system to put the iv gene on the SWV background, an occasional presumed iv/+ mouse was found that had an IV (situs inversus and/or heterotaxic) phenotype. Testcrosses of these reversed animals indicated an iv/+ genotype. Since iv is linked tightly to Igh-C on chromosome 12, we inferred the genotype with a polymorphism of Igh-C demonstrated using the polymerase chain reaction (PCR). This confirmed them to be iv/+. The expression of the IV phenotype in animals heterozygous for the iv gene may be due to an interaction of iv with an autosomal recessive gene found in SWV. We have not found the IV phenotype in heterozygous iv/+ mice following placement of the iv gene on six other inbred strains. Rarely, we also found that presumed SWV +/+ mice had the IV phenotype. Test matings of these phenodeviants, corroborated by PCR, have confirmed them to be +/+. Although the phenotypes of the affected SWV +/+ and iv/+ mice resembled those found in iv/iv mice, the occurrence of situs inversus and heterotaxia were not independent of each other, and most of the SWV mice with the IV phenotype had heterotaxia with situs solitus. This infrequent dominant expression of the iv gene has so far only been seen when iv is on the SWV background. These findings are consistent with the idea that this phenomenon is due to the interaction of the iv gene with another gene found so far only in the SWV strain.

Examination of subchondral bone architecture in experimental osteoarthritis by microscopic computed axial tomography.

Subchondral bone changes have been proposed as an early event in the pathogenesis of osteoarthritis. In this study, microscopic computed axial tomography was used to evaluate the subchondral bone structure in femoral heads from a guinea pig model of osteoarthritis. Examination of trabecular bone within the femoral head showed a highly significant increase in bone fraction in the experimental animals. This was due to the development of trabeculae that were thicker and closer together. We conclude that trabecular remodeling may be an early event in this model of osteoarthritis.

Acromegalic arthropathy. Characteristics and response to therapy.

Arthropathy was assessed in 19 patients with active acromegaly. Axial or peripheral arthropathy was present in 10 patients, was located most often in large joints or the lumbosacral spine, and was osteoarthritic in nature. The mean duration of acromegaly in patients with arthropathy was 21.6 years, while the mean duration in patients without arthropathy was 7.9 years. A mild-to-moderate improvement in symptoms, estimated functional ability, and crepitus occurred in 8 of 9 patients who were prospectively examined during therapy to lower production of growth hormone. We conclude that this therapy did improve the symptoms of acromegalic arthropathy. Whether objective structural improvements occur remains unclear.

Use of the guinea pig myectomy osteoarthritis model in the examination of cartilage-synovium interactions.

Synovium enhances the release of proteoglycan from articular cartilage in organ culture. Biomechanical stress-induced hip osteoarthritis (OA) was produced in guinea pigs by extra-articular myectomy and tendotomy. Organ culture experiments of control or OA cartilage with control or OA synovium were assayed for proteoglycan release. OA cartilage released more proteoglycan than control cartilage when cultured with either control or OA synovium. No significant difference in the effect of control or OA synovium in stimulating proteoglycan release from OA cartilage was detected, but the difference between control and OA cartilage release was significant.

Cadmium induced limb defects in mice: strain associated differences in sensitivity.

Cadmium (CdSO4) was given ip on day 9 at 12 or 24 mumol/kg to pregnant CD-1 (non-inbred) mice. Fetuses showed malformations of the limbs, face, trunk, and tail. There was a statistically significant relationship between the dose of cadmium and the malformation rate. Cadmium (12 mumol/kg ip on day 9) was then given to mice of six inbred strains three of which (A/J, BALB/cJ, and C57BL6J) carry a gene cdm for resistance to cadmium-induced testicular damage, and three strains (AKR/J, CBA/J, and DBA/2J) which do not. Paradoxically, the three strains resistant to cadmium induced testicular damage were significantly more sensitive to its teratogenic effects than were the other three strains. In all inbred strains most malformations involved the limbs. All forelimb defects found in inbred or non-inbred cadmium treated mice were postaxial and indistinguishable from those produced by acetazolamide in mice. The remarkable similarity of the cadmium- and acetazolamide-induced forelimb malformations may be a reflection of the limited number of ways that a rodent forelimb can react to a teratogenic insult. The hindlimb defects were all preaxial.