Occurrence, biochemical profile of vascular endothelial growth factor (VEGF) isoforms and their functions in endochondral ossification.

Vascular endothelial growth factor (VEGF), initially detected in bovine pituitary follicular cells, is widely localized in hypertrophic zones of chondrocytes in various tissues where focus is on bone growth. Similarly, VEGF found in chondrocytes of articular cartilage of osteo-arthritic/rheumato-arthritic joints reflected need for bone repair. Members of VEGF family of human origin are seven homo-dimeric, heparin-binding glyco-proteins, encoded by different genes located on different chromosomes. They encode seven isoforms: VEGF-A, -B, -C, -D, -E, -F, and PLGF, each catalyzing distinct functions. They are compared with VEGFs derived from bovine origin in biochemical composition and functions. Each isoform and subtype has specific receptors for binding, necessary for expression of specific functions in bone growth or repair. VEGF control is by diffusion of isoforms, hypoxic conditions, and bone (mandibular) positioning. Thus, transformation of cartilage into bone involves proliferation of mesenchymal cells, hypertrophy in chondrocytes, capillary invasion, and calcification by extra cellular matrix (ECM). Inherent limitations of in vitro/in vivo models and chronology of appearance of different isoforms have eluded precise mechanism of VEGF action and regulation. Nonetheless, central role of VEGF in bone growth is quite obvious.

A comparison of purine and pyrimidine pools in Bloom's syndrome and normal cells.

Nucleotide content of normal and Bloom's syndrome fibroblasts and lymphocytes were examined by reversed phase HPLC. The ATP/ADP ratio in primary cultures of normal human fibroblasts was at least three fold higher than in the primary cultures of Bloom's syndrome fibroblasts. After three months in culture the ratios of ATP/ADP of the Bloom's cells approach those of normal fibroblasts. Individual nucleotide measurements showed that initial differences did not reflect excess ADP, but rather very low levels of ATP in Bloom's syndrome fibroblasts. The amount of ATP increased gradually during culture. However, even after three months in culture, significant differences were noted in ATP levels between Bloom's syndrome fibroblasts and normal fibroblasts. Thus a defect in Bloom's syndrome is correlated with a defect in purine biosynthesis or ATP generation.

Chromatographic analyses of isoaccepting tRNAs from avian tumor viruses.

Low-molecular-weight RNA from transforming viruses (Rous sarcoma virus-Rous-associated virus 1, Schmidt-Ruppin strain of Rous sarcoma virus, and sarcoma-B(77)), from nontransforming viruses (Rous-associated virus 1 and sarcoma-NTB(77)), and from chicken liver, chicken embryo fibroblast, and Rous sarcoma virus-Rous-associated virus 1-transformed chicken embryo fibroblast was isolated and purified. To determine if there are modified, qualitatively or quantitatively different isoaccepting species of tRNA in these avian sarcoma viruses as compared with the cell of virus origin, chicken embryo fibroblast or normal chicken liver, methionyl-, arginyl-, and lysyl-tRNA (with high amino acid acceptance activity), and aspartyl- and glutamyl-tRNA from viral-trans-formed cells (with low viral amino acid acceptance activity) were co-chromatographed on reversed phase-5 chromatography columns, and elution profiles were compared. Although in each case the elution profile between a particular viral and host cell tRNA differed quantitatively, there was no qualitative difference in the profiles of corresponding tRNAs from either transforming or nontransforming viruses examined. Minor quantitative differences in the elution profiles might be a reflection of the metabolic state of the cells, since all evidence points to acceptor activity being of host rather than viral origin. Since, with the exception of selective packaging of methionyl-tRNA (IV) species by both transforming and nontransforming viruses, no selectivity was found for isoacceptor species of other tRNAs, it seems that such preferential packaging of methionyl-tRNA (IV) species has no bearing on the event of viral transformation.