The sickening of medical research: multiple diagnoses and two remedies.
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Biomedical subjects
Publications and source records attributed to R Smith.
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A circadian context has been used to develop information about the proliferative and functional behavior of the cell populations that function to model the long bones of growing rats. We asked: Are the proliferating cells in the growth cartilages and diaphyseal bone of young adult growing rats distributed within single or multiple populations? Can cytomorphometry (TEM-C) be used to determine ultrastructural correlates to the well-defined circadian rhythm of matrix formation displayed by functionally synchronous populations of metaphyseal osteoblasts? Can TEM-C reveal changes in osteoclast ultrastructure that could index a biological rhythm for osteoclastic bone mineralysis/resorption? Kinetic results derived from multiple radiothymidine labeling (DNA synthesis) support the single population model for chondrocytes and diaphyseal osteoprogenitor cells. TEM-C studies at the midpoints of the daily light and dark spans show that osteoblast RER-membrane development and cysternal volumes are maximal at the recorded daytime peak of net collagen synthesis. The extent of metaphyseal osteoclast surface ruffling (mineralysis) is also twofold greater during the day than the night--an observation supporting the concept that bone formation and resorption activities are coupled.
Mouse embryonal carcinoma cell lines that differ in their patterns of expression of the potential oncogene int-2 have been exploited in a structural analysis of the multiple RNA transcripts characteristic of this gene. Ribonuclease protection experiments indicate that four major classes of int-2 RNA initiate at heterogeneous cap sites within two distinct promoter regions, P1 and P2, spanning approximately 50 and 150 bp respectively. The more downstream promoter P2 is located in a region of the DNA that constitutes an intron in RNA transcripts that initiate at the upstream promoter P1. Otherwise, all four RNA structures share the same splice donor and acceptor sites that define the boundaries of the second and third exons. Further complexity arises through usage of two distinct polyadenylation signals, both variants of the normal consensus, that are separated by 1100 bp. Despite these structural variations, the results suggest that all four major classes of RNA encode the same protein product which shows significant homology to the family of heparin-binding proteins typified by basic fibroblast growth factor (FGF).