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L B Rall

Publications and source records attributed to L B Rall.

30 records · Page 2Linked to original sources
PubMed1979

Thionein gene expression in Cd++-variants of the CHO cell: correlation of thionein synthesis rates with translatable mRNA levels during induction, deinduction, and superinduction.

The relationship of thionein synthesis rates to translatable cytoplasmic thionein mRNA levels was investigated for the first time in a cultured cell system. Thionein synthesis was induced in Cdr, a cadmium-resistant variant of CHO, by exposure to 2 microM CdCl2. Following a short (1.5 hr) lag, thionein synthesis increases to a rate that is at least 30 times the uninduced rate 7-8 hr after addition of Cd++. This increase is blocked by the coincident addition of a actinomycin D. Cytoplasmic thionein mRNA levels, measured by translation in a modified wheat germ system, increase rapidly following induction to values approximately 25 times uninduced levels within 6-8 hr. The increase in thionein mRNA precede proportionate increases in thionein synthesis by 0.5-1.0 hr. Continued exposure to Cd++ results in a decreased thionein synthesis rate after 8 hr. By 30 hr, the rate is one-half that seen 6-8 hr after induction. Removal of Cd++ after 8 hr results in a rapid decrease in thionein synthesis (t 1/2 approximately 4 hr). Both decreases are inhibited by the addition of actinomycin. In all instances--induction, deinduction, and actinomycin-mediated "super-induction"--translatable thionein mRNA levels and thionein synthesis rates increase, decrease, or are maintained coordinately. The results suggest that thionein synthesis in Cdr is controlled primarily by the level of translatable cytoplasmic thionein mRNA.

Animals↗
PubMed1979

Multiangle light-scattering analysis of murine teratocarcinoma cells.

Stem cells of the mouse testicular teratocarcinoma are capable of giving rise in vivo and in vitro to a wide variety of cell and tissue types representative of each embryonic germ layer. Multiangle light-scattering measurements in a flow system have been made on these stem cells and on a variety of their differentiated derivatives. This technique is capable of distinguishing the stem cells from parietal yolk sac cells, visceral yolk sac cells, neuronal cells and squamous cells. However, multipotential stem cells cannot be distinguished from stem cells that are restricted in their development to a single pathway.

Animals↗
PubMed1979

Synthesis and accumulation of proinsulin and insulin during development of the embryonic rat pancreas.

Endocrine B cells differentiate normally in embryonic rat pancreatic rudiments cultured in vitro. The specific concentration of immunoreactive insulin based on total protein increases by about 1000-fold during the developmental period, corresponding to days 13--20 of gestation. The rate of (pro)insulin synthesis, measured from the level of radioactive leucine incorporated into insulin, quantitatively accounts for the insulin accumulated during this period. In addition, the relative incorporation of leucine into proinsulin compared to insulin is constant during development and is similar to that found in the B cells of adult islets. Thus, there appears to be no significant change in the rate of conversion of proinsulin to insulin during B cell differentiation.

Animals↗
PubMed1976

The neural crest and the origin of the insulin-producing and other gastrointestinal hormone-producing cells.

It has been proposed that the endocrine cells of the digestive tract derive from the neuroectoderm (neural crest). To test this hypothesis we removed the entire ectoderm, the precursor of the neural crest, of embryonic rats prior to the formation of the neural crest and cultured the mesoendoderm for 11 days. In every case where a pancreas developed, insulin was detected or B cells were observed. Thus, a neural crest origin for these cells is eiliminated.

Amines↗
PubMed1973

Early differentiation of glucagon-producing cells in embryonic pancreas: a possible developmental role for glucagon.

Glucagon and insulin are first detectable at the onset of rat pancreas organogenesis. Initially, the specific activity of glucagon is approximately 100-fold higher than that of insulin. At this early stage, endocrine storage granules, similar to alpha granules, are identifiable in electron micrographs. The granule characteristics, as well as the relative hormone levels, suggest that the early population of differentiated endocrine cells is in fact composed of glucagon-producing (A) cells. This high level of glucagon is present in the embryo much earlier than the metabolic processes thought to be controlled by this hormone. Moreover, glucagon-producing cells may be the first endocrine cells to differentiate. Other known endocrine products accumulate later, during the terminal stages of organogenesis. These observations suggest that glucagon may have a regulatory function in early embryogenesis.

Animals↗
PubMedDate not supplied

Sequence of a cDNA clone encoding human preproinsulin-like growth factor II.

The insulin-like growth factors (IGF) I and II are single-chain serum proteins of 70 and 67 amino acids, respectively, which are synthesized by the liver and possibly other tissues. They are probably required for normal fetal and postnatal growth and development. They also stimulate the growth of cultured cells, possibly by controlling the progression through the G1 phase of the cell cycle. In contrast to IGF-II whose concentration does not vary during postnatal development, the serum levels of IGF-I increase several-fold to adult levels during puberty. The serum concentration of IGF-I is a sensitive monitor of growth hormone levels and is decreased in individuals with growth hormone deficiency and elevated in those with growth hormone-secreting tumours. As a first step in studying the biosynthesis of these proteins and elucidating their role(s) in normal development and in tumorigenesis, we have isolated and sequenced cDNAs prepared from adult human liver mRNA which encode the precursors to IGF-I and -II. We report here the sequence of a cDNA encoding a 180-amino acid protein which is the precursor to IGF-II.

Amino Acid Sequence↗
PubMedDate not supplied

Localization of insulin-like growth factor genes to human chromosomes 11 and 12.

The insulin-like growth factors IGF-I and IGF-II are required for growth and development. Both are single-chain proteins (of 70 and 67 amino acids respectively) derived from precursors by proteolytic processing. IGF-I may be particularly important in promoting normal stature and IGF-II may be a fetal growth hormone. The IGF proteins are probably synthesized by many normal tissues and by some tumours. The secretion of growth factors by tumours and tumour-derived cell lines suggests that they may act as autocrine regulators of cell proliferation. Because of the possible role of these proteins in growth disorders and cancer, and their sequence homology with insulin, we have determined their chromosomal localization. Using somatic cell hybrids and cloned cDNA probes for these proteins, we have assigned the genes for IGF-I and IGF-II to human chromosomes 12 and 11, respectively. We present evidence that the IGF-II gene is located on the short arm of chromosome 11 with a ras proto-oncogene and the insulin structural gene, and also suggest the existence of a fragment length polymorphism using the IGF-I probe.

Animals↗
PubMedDate not supplied

Mouse prepro-epidermal growth factor synthesis by the kidney and other tissues.

Epidermal growth factor (EGF), a protein comprising 53 amino acids, is derived from a precursor of 1,217 amino acids that includes at least seven EGF-like sequences. EGF has diverse biological activities: it is a potent mitogen for many tissue culture cells, inhibits gastric acid secretion from the intestinal mucosa and promotes healing of the corneal epithelium. EGF given to fetal animals accelerates several developmental processes including palate formation, incisor eruption, eyelid opening and lung maturation. However, the physiological roles of EGF in vivo are unknown. The presence of high-affinity receptors in many fetal and adult tissues suggests that EGF is involved in normal cellular functions. Immunocytochemical studies have revealed the presence of EGF in mouse and human submaxillary glands, rat brain and human intestine. The low levels of EGF in extracts from many tissues may reflect sequestration rather than synthesis of the polypeptide. We show here that several mouse tissues contain preproEGF mRNA and that it is synthesized mainly in the distal tubules of the kidney. PreproEGF does not seem to be processed to EGF or other peptides in this tissue.

Animals↗
PubMedDate not supplied

Insulin-like growth factor-II gene expression in Wilms' tumour and embryonic tissues.

Wilms' tumour (nephroblastoma) is an embryonal neoplasm occurring in hereditary and spontaneous forms. Both types show rearrangements of the short arm of chromosome 11. The germ line of children with the rare inherited triad of aniridia, genito-urinary abnormality and mental retardation carry a chromosome 11 that has a deletion in its short arm (band 11p13) and these children are at increased risk of developing Wilms' tumour. Neonates with the Beckwith-Wiedemann syndrome, in which there may be duplication of the 11p13-11p15 region, are similarly predisposed. In the spontaneous form of the tumour a deletion of the 11p14 band in tumour cells, but not in normal cells, has been reported, and the development of homozygosity for recessive mutations in the 11p region is implicated in the aetiology of Wilms' tumour. In view of these chromosomal rearrangements and because Wilms' tumour is histologically indistinguishable from the early stages of kidney development, we have now examined the expression of genes localized to 11p in Wilms' tumour and human embryonic tissue. In 12 sporadic tumours examined, the expression of the gene coding for insulin-like growth factor-II (IGF-II), localized to the 11p15 region, was markedly increased relative to adult tissues, but was comparable to the level of expression in several fetal tissues including kidney, liver, adrenals and striated muscle. This may reflect the stage of tumour differentiation, but could also contribute to the malignant process, as IGF-II is an embryonal mitogen.

Female↗
PubMedDate not supplied

Autoregulation of tubulin synthesis in enucleated cells.

The effects on tubulin messenger RNA levels and tubulin protein synthesis of treating cells with microtubule-depolymerizing drugs or directly microinjecting cells with tubulin have suggested that non-polymerized tubulin depresses its own synthesis. The precise level of this control is unclear. It has been shown that enucleated cells, termed cytoplasts, retain many properties of the original cell, including maintenance of cell shape, pinocytic activity and locomotion as well as biosynthetic activities such as protein synthesis and replication of cytoplasmic viruses. Furthermore, cytoplasts retain most of the components of the cytoskeleton including the centrioles. If cytoplasmic activities alone are responsible for regulating tubulin biosynthesis, cytoplasts should contain the necessary components. To distinguish between regulation which would occur in the nucleus, that is, alterations in mRNA synthesis or modifications of the mRNA, from alterations in mRNA stability and/or translatability which would take place in the cytoplasm, we examined the autoregulation of tubulin synthesis in enucleated cells. Here, we report that enucleated mouse fibroblasts retain the ability to turn off tubulin protein synthesis in response to microtubule depolymerization, the reduction in tubulin synthesis being accompanied by a corresponding decrease in tubulin mRNA levels. Thus, transcription, processing and transport of tubulin mRNA from the nucleus are not likely to be the loci of regulation. Instead, tubulin must reduce, either directly or indirectly, the translatability of its own mRNA.

Animals↗