The early ontogeny of hematopoietic cells studied by grafting cytogenetically labeled tissue anlagen: localization of a prospective stem cell compartment.
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Biomedical subjects
C M Knudson
Publications and source records attributed to C M Knudson.
Effects of colchicine on ultrastructure of the lactating mammary cell: membrane involvement and stress on the Golgi apparatus.
The effects of colchicine on ultrastructure of the lactating mammary cell in the rat and goat were studied by electron microscopy. Changes in tissue of the rat were examined over time (1, 2 and 4 h). The goat gland was evaluated by comparing ultrastructure of tissue at the time of maximum milk flow suppression induced by the drug with that of untreated tissue. Colchicine produced notable changes in the tissue of both species: 1) the secretion of lipid droplets and Golgi vesicle contents (exocytosis) was inhibited and the droplets and vesicles became randomly distributed throughout the cell, 2) the Golgi apparatus was significantly reduced in size, 3) casein and lipid continued to be synthesized as evidenced by greater numbers of secretory vesicles and increased sizes of casein micelles and lipid droplets, 4) secretory vesicles showed a propensity to cluster around lipid droplets, 5) isolated microtubules were found occasionally in the control tissue, ordinarily in the vicinity of the Golgi apparatus, but rarely in the colchicine-treated tissue. These observations indicate that colchicine has two effects leading to suppression of exocytosis in the mammary cell: one involves early interference with capacity of secretory vesicle membranes to fuse and a further effect, related to higher concentrations of colchicine, causes intracellular disorganization and loss of polarity. Microtubules were not seen as directly involved in the mechanisms of exocytosis. The secretion of milk fat globules is coupled to exocytosis and thereby is also inhibited by colchicine.
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The supression of milk fat globule secretion by clochicine: an effect coupled to inhibition of exocytosis.
The effects of colchicine on release of milk lipids from mammary tissue were evaluated by biochemical analysis of milk and morphological study of the tissue following intramammary infusions of the alkaloid into lactating goats. Colchicine produces a reversible drop in milk yield. As the flow of milk resumes, 36--48 h after infusion, the fat content of the milk increases, phospholipid per g of total globule lipid falls, mean size of milk fat globules increases and diameters of fat droplets (presecretory milk fat globules) within lactating cells approximately double. These observations are consistent with the conclusion that colchicine suppresses milk fat globule secretion but that globules continue to grow in size wihtin cells during the suppression period. These findings indicate that secretion of milk fat globules and the skim milk phase are coupled.
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A lethal mutation in mice eliminates the slow calcium current in skeletal muscle cells.
Contraction of a vertebrate skeletal muscle fibre is triggered by electrical depolarization of sarcolemmal infoldings termed transverse-tubules (t-tubules), which in turn causes the release of calcium from an internal store, the sarcoplasmic reticulum (SR). The mechanism that links t-tubular depolarization to SR calcium release remains poorly understood. In principle, this link might be provided by the prominent slow calcium current that has been described in skeletal muscle cells of adult frogs and rats. However, blocking this current does not abolish the depolarization-induced contractile responses of frog muscle, and the function of this slow calcium current is unknown. Here we describe measurements of calcium currents in developing skeletal muscle cells of normal rats and mice, and of mice with muscular dysgenesis, a mutation that causes excitation-contraction (E-C) coupling to fail. We find that a slow calcium current is present in skeletal muscle cells of normal animals but absent from skeletal muscle cells of mutant animals. The effect of the mutation is specific to the slow calcium current of skeletal muscle; a fast calcium current is present in developing skeletal muscle cells of both normal and mutant animals, and slow calcium currents are present in cardiac and sensory neurones of mutant animals. We believe this to be the first report of a mutation affecting calcium currents in a multicellular organism. The effects of the mutation raise important questions about the relationship between the slow calcium current and skeletal muscle E-C coupling.
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Subcellular fractionation of dystrophin to the triads of skeletal muscle.
Duchenne muscular dystrophy (DMD) is a human X-linked biochemical defect resulting in the progressive wasting of skeletal muscle of affected individuals. It is the most common and is considered to be the most devastating of the muscular dystrophies, affecting about 1 in 3,500 live-born males. The gene that, when defective, results in this disorder was recently isolated. Using the cloned complementary DNA sequences corresponding to the DMD gene, antibodies have been produced that react with a protein species of relative molecular mass (Mr) approximately 400,000 (400K) which was absent in two DMD-affected individuals and in mdx mice. This protein species is called dystrophin because of its identification by molecular-genetic analysis of affected individuals. Here we show that dystrophin is associated with the triadic junctions in skeletal muscle, and is therefore probably involved with Ca2+ homoeostasis. We also show that the approximately 450K ryanodine receptor/sarcoplasmic reticulum Ca2+ channel, which has the large size and subcellular distribution characteristics of dystrophin, is an immunologically distinct protein species.
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