Acetylation of spermidine in Chinese hamster ovary cells.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to D H Russell.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The frequency with which the plateau of stable phase occurs after remission-induction chemotherapy, and the kinetic features of this phase, were evaluated in 127 carefully staged patients with multiple myeloma. 56 patients (44%) entered a stable plateau state, this pattern being most common in patients with stages IA, IIA, and IIIA of the disease, and least likely in those with stages IIB or IIIB, especially those with Bence Jones protein only or Bence Jones protein plus a serum M-component. Tritiated thymidine labelling index (LI) of bone-marrow myeloma cells, polyamine measurements, and in-vitro myeloma stem-cell culture findings all indicated that the plateau phase is a cytokinetically quiescent state, compared with the more active induction and relapse phases. The major implications of these findings include the avoidance of aggressive "cycle active" treatment and discontinuation of maintenance treatment in plateau-phase patients.
Explore the source record for details and available documents.
The activation state of cyclic AMP-dependent protein kinase(s)(ATP:protein phosphotransferase, EC 2.7.1.37) is transiently increased 2-fold as a function of G1 progression in mitotically synchronized Chinese hamster ovary cells. The cellular content of type I kinase increases concomitantly with the increase in general protein, whereas the activity of type II kinase increases as a function of time in G1 to a maximum at the G1/S border. In contrast, in the presence of dibutyryl-cyclic AMP, there is a decrease of type II kinase and a several-fold increase of type I kinase. In proliferating cells, the ratio of type I to type II was 0.37, while in the dibutyryl-cyclic AMP growth-arrested cells it was 3.96. The increase in type II kinase during G1 transition and the increase in type I kinase during dibutyryl-cyclic AMP treatment were dependent on protein synthesis. A similar pattern of type I and type II kinase expression during cell cycle progression occurred in Rat-1 fibroblasts and Rat-1 cells transformed by Rous sarcoma virus. The inclusion of dibuityryl-cyclic AMP in the growth media promoted a marked increase in type I holoenzyme, which was inhibited by cycloheximide, and a decrease in type II kinase. Neither AMP nor sodium butyrate had any effect on cellular kinase levels, whereas 8-bromo-cyclic AMP mimicked the action of dibutyryl-cyclic AMP. Estimation of half-lives for the kinase types showed that there was little turnover of either type during normal G1 progression, rapid turnover of both types as cells exited from mitosis, and selective turnover of type II upon addition of dibutyryl-cyclic AMP.
Ornithine decarboxylase, the initial enzyme in the polyamine biosynthetic pathway, is induced in target tissues in response to a variety of trophic agents including polypeptide and amine trophic hormones, cyclic AMP analogs, drugs, and trophic steroid hormones. The induction of ornithine decarboxylase in these systems is regulated at a transcriptional level and is proportional to the extent of stimulation. Because of its rapid half-life (10-20 min), a general maximum of induction is detectable within 4-5 h of stimulation, and its induction pattern can serve as a rapid, specific index of increased RNA and protein synthesis. Implications for its usefulness to pharmacologists, endocrinologists, physiologists, and biochemists are summarized.
A cascade of events leading to hypertrophy has been proposed and implicated in growth regulation in a variety of normal and neoplastic cells and tissues. There is a tightly coupled temporal sequence: (a) cyclic adenosine 3':5'-monophosphate-dependent protein kinase (cAPK) activation; (b) ornithine decarboxylase (ODC) induction; and (c) the accumulation of the organic cation, spermidine, resulting in an increased spermidine/spermine ratio characteristic of both normal and neoplastic growth. The specific activation of type I cAPK has been implicated to ODC induction, and the amounts of type I and type II cAPK alter as a function of growth and transformation. Therefore, we wished to study the alterations in these biochemical parameters as well as that of a putative marker of preneoplastic hepatocytes, gamma-glutamyltranspeptidase, in a rapid multistep hepatocarcinogenesis system. We found a marked and prolonged increase in the cAPK ratio followed by a similar pattern of ODC induction after a single carcinogenic dose of diethylnitrosamine and again in response to partial hepatectomy. Liver foci were detectable within four days of partial hepatectomy in animals that received the entire carcinogen regimen, and the foci contained significant and increasing amounts of gamma-glutamyltranspeptidase activity. The increase in ODC activity was followed closely by an increased spermidine/spermine ratio. Total type I activity in the cytosol decreased most dramatically at the time of foci formation, suggestive of selective activation and turnover. These data suggest that the prolonged activation of cAPK and elevation of ODC may be necessary for hepatocarcinogenesis.
Polyamines react with o-phthalaldehyde forming intensely blue fluorescing condensation products with an activation maximum at 340 nm. Tissue concentrations of polyamines can be detected by cation exchange analysis and putrescine, spermine and spermidine were assayed in specimens of benign hyperplasia of prostate and renal adenocarcinoma and in normal control tissues. Comparison of results on polyamines in normal prostate and kidney tissues revealed significant differences, and changes of polyamines are discussed in relation to hyperplastic and neoplastic growth.
Ornithine decarboxylase (ODC) induction during G1 phase of the cell cycle was compared in Rat-1 fibroblasts and in Rat-1 fibroblasts transformed by the B77 wild-type Rous sarcoma virus (RSV) and by the thermosensitive mutant LA24/RSV. In Rat-1 cells, maximal enzyme activity detectable at mid G1 declined to basal levels by G1-S. The ODC increase was inhibited by actinomycin D and cycloheximide and was dependent on the addition of serum growth factors. Rat-1 (B77 wild-type RSV) cells expressed a greater amount of enzyme activity after serum stimulation, and the maximal level of enzyme activity detectable at mid G1 declined only 50% so that elevated ODC was maintained during G1-S transition. The enzyme increase in the transformed cell line was not dependent on serum growth factors. Fresh medium addition alone induced enzyme activity. Induction in the presence or absence of serum required both RNA and protein synthesis. ODC induction in the transformed cells was less sensitive to repression by exogenous putrescine addition. A 100-fold greater concentration of the diamine was required to produce comparable inhibition in the Rat-1 (B77 wild-type RSV) as compared to the Rat-1 cell. These alterations in the characteristics of ODC expression were found to be a consequence of the transforming function of RSV in the Rat-1 cell line transformed by the thermosensitive viral mutant LA24. In response to serum stimulation at the nonpermissive temperature (39 degrees), Rat-1 (thermosensitive mutant LA24/RSV) cells displayed a discrete G1-phase ODC induction while those cells maintained at the permissive temperature (35 degrees) exhibited a greater and prolonged ODC induction in G1 and S phases. A shift from 39 to 35 degrees in the absence of any medium or serum addition stimulated the induction of ODC expressed in a transformed phenotypic manner. Greater concentrations of exogenous putrescine were required to repress the induction of ODC at 35 than at 39 degrees. Alterations in ODC regulation, therefore, may be inherent to the neoplastic phenotypic change.
Some delinquents who were unreachable and failed to respond to juvenile interventions may at age 17 or 18 become depressed and then be accessible and motivated for treatment and rehabilitation. If their needs and potentials remain unrecognized, they may act out their depression with continued offenses, alcoholism, drug dependence, and social maladaptations. Untreated, such depressions are long-lasting and have far-reaching influences upon family.
Explore the source record for details and available documents.
The amount of total cyclic AMP-dependent protein kinase and of the protein kinase isozymes present in mouse heart changes during development. During embryogenesis, the total cardiac protein kinase activity increases most markedly during the 6 days prior to birth. A maximum kinase level is achieved in the 7 day-old neonate, and then activity progressively declines to an adult level approximating that of the mid-embryo. The type II kinase exhibits a moderate increase during late embryogenesis which declines by the time of birth. The type I isozyme increases throughout embryogenesis and the first neonatal week to a maximum specific activity five-fold higher than the mid-embryogenesis level. The isozyme level then falls to an adult activity similar to the mid-embryonic. These changes in isozyme profile are reflected in a changing type I to type II kinase ratio of 1.1 at 13--14 days embryogenesis, 2.4 at birth, 3.0 in the 7 day-old neonates, and 1 in the adult heart. Thus, the two protein kinase isozymes change in association with the developmental process in an independent fashion.
Children with cystic fibrosis excreted elevated urinary levels of all three polyamines--putrescine, spermidine, and spermine. Heterozygote parents excreted intermediate concentrations of the polyamines, but not levels significantly different from levels in normal controls. Patients with cystic fibrosis who were administered a tracer amount of [14C]spermidine excreted 11--13% of the radiolabel within 72 hr whereas normal controls excreted 60--76% of the radiolabel within 72 hr. Spermine excretion was positively correlated with increased pathology as assessed by the National Institutes of Health (NIH) clinical score, whereas urinary putrescine and spermidine levels were negatively correlated with increased pathology.
After a single injection of diethylnitrosamine (200 mg/kg), there was a rapid increase in the activity ratio of hepatic cyclic adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase (within 1 hr) followed by the induction of ornithine decarboxylase which was detectable by 3 hr. Both the cyclic AMP-dependent protein kinase activity ratio and the activity of ornithine decarboxylase were significantly elevated above controls for 7 days following the administration of diethylnitrosamine. A single noncarcinogenic dose of diethylnitrosamine (25 mg/kg) did not increase the cyclic AMP-dependent protein kinase activity ratio or induce ornithine decarboxylase activity at 24 hr postadministration. However, serial administration of diethylnitrosamine (25 mg/kg) for 4 or 7 days resulted in an increased activity ratio of cyclic AMP-dependent protein kinase and increased ornithine decarboxylase activity. This is the first report of a prolonged increase in both the activity ratio of hepatic cyclic AMP-dependent protein kinase and the activity of ornithine decarboxylase in response to a single carcinogenic dose of diethylnitrosamine.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.