Basic fibroblast growth factor identified in chronically stimulated cardiomyoplasties.

In the presence of myocardial ischemia, chronic electrical stimulation of a latissimus dorsi (LD) cardiomyoplasty enhances extramyocardial collateral blood flow. We postulated that basic fibroblast growth factor (bFGF) may mediate extramyocardial collateral formation. To test this hypothesis, LDs from goats with cardiomyoplasties were probed for the presence of bFGF by Western blot analysis and immunohistochemistry. Three groups were studied: static LD cardiomyoplasty (group 1); LD cardiomyoplasty stimulated at a 2-Hz frequency for 6 weeks (group 2); and LD cardiomyoplasty electrically stimulated and given human recombinant bFGF (group 3). There was no evidence of bFGF in the left LDs of group 1 by Western blot. Basic fibroblast growth factor-like immunoreactive evidence was found in the left LDs of group 2 goats by both Western blot and immunohistochemistry. In the right LDs of group 2, bFGF-like material was found by immunohistochemistry but not by Western blot, which suggests that the tissue concentrations were low (near the limits of detection). The left LDs of group 3 were positive for bFGF by Western blot and immunohistochemistry. Group 3 right LDs were positive for bFGF by immunohistochemistry. Immunohistochemical findings in group 2 indicate that bFGF is present in goat skeletal muscle. Western blot data from groups 1 and 2 suggest that bFGF may be increased in chronically stimulated cardiomyoplasties. From findings in group 3, we conclude that exogenous bFGF does not downregulate, and may upregulate, endogenous production. These results support the possibility that skeletal muscle bFGF is an important factor in extramyocardial collateral formation.

A single base mutation in the type II procollagen gene (COL2A1) that converts glycine alpha 1-247 to serine in a family with late-onset spondyloepiphyseal dysplasia.

A search for mutations in the gene for type II procollagen (COL2A1) was carried out in a family with late-onset spondyloepiphyseal dysplasia resulting in short sature, restricted mobility and severe pain in joints, deforming arthritis in the hips, and claudication. Analysis of the HindIII and VNTR polymorphisms at the COL2A1 gene in the family raised the possibility that the gene cosegregated with the disease. Screening for mutations in the COL2A1 gene using PCR-denaturing gradient get electrophoresis suggested a sequence variation in exon 19 of one allele of the COL2A1 gene in the proband. Direct sequencing of the PCR products for exon 19 revealed a single base mutation that converted the codon of -GGT- for glycine at alpha 1-247 to -AGT-, a codon for serine. The mutant that converted the present in all affected family members, but absent in nonaffected members and in a group of 50 unrelated healthy individuals. It was also absent in 20 unrelated patients with chondrodysplasia and 30 unrelated patients with early-onset osteoarthritis.