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Biomedical subjects

D H Russell

Publications and source records attributed to D H Russell.

At least 127 records · Page 7Linked to original sources
PubMed1984

Urinary polyamine levels are markers of altered T lymphocyte proliferation/loss and rejection in heart transplant patients.

The studies of urinary polyamine excretion in heart transplant patients reported in this article indicate that (1) total urinary polyamine excretion is increased one to three days before a biopsy-proved rejection in conventionally treated patients, (2) the acetylputrescine to N1-acetylspermidine ratio becomes elevated before rejection in cyclosporine-treated patients, and (3) the response to elevated ATG therapy during rejection can be evaluated by monitoring urinary polyamine concentrations. We conclude that daily monitoring of urinary polyamine levels may provide a noninvasive biochemical marker that precedes rejection and which parallels the extent of T lymphocyte suppression during the course of immunosuppressive drug therapy.

Biopsy, Needle↗
PubMed1983

Hypothyroxinemia and hypothermia in rats in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin administration.

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment on body temperature and serum and tissue levels of thyroid hormones, glucose, glucagon, insulin, and somatostatin were investigated. Within 7 days following TCDD administration (45 micrograms/kg), rats exhibited hypothyroidism compared to pair-fed controls and rats fed ad libitum. Body temperature was maintained in the pair-fed and ad libitum-fed controls but was significantly decreased in TCDD-treated rats at 2 days. Within 2 weeks of the administration of 90 micrograms TCDD/kg, body temperature was below 35 degrees C with the lowest mean value of 34.5 degrees C recorded on Day 16. Mean body temperatures for control rats ranged from 36.8 to 37.5 degrees C. One week after TCDD administration (45 micrograms/kg), serum thyroxine (T4) declined to 46% of pair-fed controls. The decreased free-thyroxine index indicated that the measured decrease in thyroxine reflected decreased hormone concentrations as opposed to altered protein binding. Hypoglycemia occurred in TCDD-treated rats subsequent to hypothyroxinemia and hypothermia, but it did not develop in the pair-fed controls. At 1 week after administration of 45 micrograms TCDD/kg, serum and pancreatic insulin levels were reduced to 25 and 76% of ad libitum-fed controls, respectively. Hypophagia was determined to be responsible for the decreased growth rate and hypoinsulinemia but did not account for hypothyroxinemia, hypothermia, and hypoglycemia following the administration of TCDD. No significant alterations were detected in serum glucagon or in pancreatic, hepatic, or serum somatostatin levels. Decreased somatostatin in the gastric antrum coincided with a 29% increase in stomach dry weight. The delayed toxicity of TCDD may result, in part, from these hormonal alterations.

Animals↗
PubMed1983

Analysis of polyamines and acetyl derivatives by a single automated amino acid analyzer technique.

In a single, rapid and precise analysis, monoacetylputrescine, N8-acetylspermidine, N1-acetylspermidine, putrescine, spermidine, and spermine can be separated using a five-buffer system on an automatic amino acid analyzer. This method allows, for the first time, the separation of all the known acetyl derivatives of putrescine and spermidine as well as the parent compounds in urine and tissues with a single automated procedure. The method has been applied to the analysis of biological samples from normal volunteers, cancer patients and a rat liver supernatant. Mass spectral confirmation was obtained for each compound.

Autoanalysis↗
PubMed1983

Ornithine decarboxylase may be a multifunctional protein.

Ornithine decarboxylase may undergo posttranslational modifications which alter its function. Both transamidation of glutamine residues in the enzyme catalyzed by TGase and phosphorylation of serine and threonine residues catalyzed by a polyamine-stimulated protein kinase have been demonstrated. Data are presented which suggest that these modifications result in translocation of the modified protein to the nucleolus where it regulates the activity of RNA polymerase I to transcribe rDNA, the only active nucleolar genes. Transamidation of specific proteins with primary amines catalyzed by intracellular TGase may be an important posttranslational modification, capable of altering genetic transcription. The rapid half-life of ODC (10-15 min) may be related to rapid posttranslational modification with loss of enzymatic activity rather than to protein degradation.

Animals↗
PubMed1983

Etretinate therapy for psoriasis: clinical responses, remission times, epidermal DNA and polyamine responses.

A prospective study was carried out over 12 months involving twenty patients with psoriasis vulgaris who were treated with all-trans-aromatic derivative of vitamin A, etretinate. Etretinate was found to be an effective therapy for this skin disorder. Arthritis accompanying psoriasis vulgaris in four of seven of our patients was greatly improved by retinoid therapy. Side effects were found to be dose-related and included mucocutaneous abnormalities as well as abnormalities of blood lipids and liver function tests. Maintenance therapy appears to be required in nearly all patients, with relapse occurring within approximately 8 weeks. Polyamine biosynthesis has been determined previously to be accelerated in patients with psoriasis vulgaris. Polyamines (putrescine [Pu], spermidine [Sp], and spermine [Sm] were measured in skin samples of six patients with stable plaque-stage psoriasis before treatment and at 4 weeks during treatment. Pu, Sp, Sm levels, as well as the Sp/Sm ratio, fell. Epidermal DNA synthesis is increased in involved and noninvolved psoriatic skin; it was measured before and during treatment (at 4 weeks) in this study and found not to fall significantly during this period of time. Polyamine levels therefore decreased prior to any significant expected decrease in epidermal DNA synthesis measured in both involved and uninvolved skin.

Adult↗
PubMed1983

Microinjection of purified ornithine decarboxylase into Xenopus oocytes selectively stimulates ribosomal RNA synthesis.

This study has utilized stage VI oocytes of Xenopus laevis which have amplified the rDNA gene 1,000-fold to assess whether the microinjection of ornithine decarboxylase (OrnDCase) would stimulate [alpha-32P]guanosine incorporation into 45S and 18S/28S RNA selectively. The injection of purified OrnDCase into individual oocytes resulted in a greater than 2-fold increase in the incorporation of [32P]guanosine into 45S RNA and 18S/28S RNA with no increased incorporation into low molecular weight RNA. Further, an irreversible inhibitor of OrnDCase, alpha-difluoromethylornithine (CHF2-Orn), rapidly inhibited the endogenous activity of OrnDCase when added to the buffered Hepes solution bathing the oocytes and also inhibited the incorporation of [32P]guanosine into rRNA. The inhibitory effect of CHF2-Orn could not be reversed totally by addition of 10 microM putrescine to the oocytes. OrnDCase injected into oocytes in the presence of CHF2-Orn in the media did not stimulate incorporation of [32P]guanosine label into rRNA. However, when CHF2-Orn was removed from the buffered medium at the time of the injection of label and enzyme, a 3-fold increase of 32P incorporation into 18S/28S RNA occurred. Therefore, in an in vivo model in which amplified extrachromosomal rDNA gene copies are present, the microinjection of OrnDCase was capable of specifically stimulating rRNA synthesis. CHF2-Orn, a suicide enzyme inactivator of OrnDCase, was able to inhibit rRNA synthesis and, after washout, there was a more marked stimulation of rRNA synthesis than occurred after only the injection of OrnDCase alone. These data suggest further that OrnDCase is the labile protein that regulates the initiation of RNA synthesis.

Animals↗
PubMed1983

Epidermal polyamine profiles after multiple exposures to ultraviolet radiation.

In experimental studies of u.v.-skin-carcinogenesis u.v.-radiation is usually given in discrete amounts over a protracted period of time. Epidermal polyamine profiles were investigated in hairless mice after single and multiple exposures to ultraviolet-B (u.v.B). Hairless mice were irradiated with u.v.B from FS40 sunlamps and sacrificed after 1, 5, 10 or 20 days of daily irradiation with 0.9 kJ/sq m u.v.B at 6, 24 or 48 h after the final irradiation. Epidermis was analyzed for ornithine decarboxylase (ODC) activity, and for its putrescine, spermidine and spermine content. Skin biopsies were examined for histological changes. As previously reported epidermal ODC activity was induced 6 h after one irradiation with u.v.B and reached a maximum activity at approximately 24 h. In contrast after 5, 10 or 20 daily irradiations with u.v.B the epidermal ODC activity was maximal at approximately 6 h after the final irradiation and by 24 h had returned towards control levels. The magnitude of the ODC activity measured 6 h after irradiation increased with the number of irradiations. A similar pattern was seen with epidermal putrescine levels where a marked shift from a peak at approximately 24 h after one irradiation with u.v.B to a peak at approximately 6 h after 20 days of irradiation with u.v.B occurred. Spermidine levels increased as the number of u.v.B exposures was increased and spermine levels tended to decrease. The spermidine/spermine ratio increased most rapidly during the first 5 exposures, and remained elevated through to 20 days of daily irradiation. Chronic irradiation with u.v.B results in rapid induction of ODC activity and putrescine accumulation in the epidermis, events also elevated by chemical or viral transformation.

Animals↗
PubMed1983

Clinical relevance of polyamines.

The polyamines, putrescine, spermidine, and spermine have been established as biochemical markers of normal and pathological growth. In malignancy, the urinary concentrations of spermidine reflect the tumor cell loss and the urinary level of putrescine is related both to the number of tumor cells in cell cycle and to the tumor cell loss factor. A greater than twofold increase in urinary spermidine within 72 hr of chemotherapy predicts a complete or a partial response with a high degree of accuracy. Urinary putrescine may be valuable, not only in assessing the early response to therapy but also in determining whether the chemotherapy promotes a later burst of cell proliferation. Erythrocyte spermidine concentrations also appear to track alterations in tumor kinetics. Alterations in intracellular and extracellular polyamines in other pathologies such as psoriasis, muscular dystrophy, and cystic fibrosis also accurately reflect the disease activity and, in those cases studied, response to therapy. Therefore, the determination of polyamine concentrations in extracellular fluids and in erythrocytes allows for (1) the early assessment of response to multimodality therapy, (2) disease or tumor staging, and (3) assessment of disease activity including long-term monitoring of polyamine concentrations to pinpoint remission and relapse in adjuvant patients. Information obtained by the monitoring of polyamines could result in prolongation of survival time of patients as well as assist in the design of the most effective therapy regimen for the pathology. Since other such specific kinetic markers are not available, polyamines should be clinically utilized to track tumor evolution and tumor response to therapy in those patients at high risk, in which such measurements could be translated into therapeutic efficacy.

Animals↗
PubMed1983

Alteration in cyclic AMP-dependent protein kinases and polyamine biosynthetic enzymes during hypertrophy and hyperplasia of the thyroid in the rat.

After 2 weeks of goitrogen treatment [propylthiouracil (PTU), 0.02% in drinking water], the thyroids of rats increased to 280% of control wet weight, 270% of dry weight, and 250% of control DNA content. Two phases of growth were apparent, an initial hypertrophy phase lasting 3 days (increase in cell size and gland weight with no detectable increase in DNA) and a hyperplastic phase (increase in DNA with histological evidence of cell proliferation) starting at 3-4 days and continuing through 14 days. The cyclic AMP-dependent protein kinase activity ratio (-cyclic AMP/+cyclic AMP) showed a biphasic pattern during the 2-week thyroid growth period, with maxima at day 1 (132% of control) and day 6 (148% of control). Ornithine decarboxylase (EC 4.1.1.17), the initial enzyme in polyamine biosynthesis, showed a similar biphasic pattern with a 6- to 7-fold elevation in activity at 2-3 days and a 4-fold elevation at 6 days. S-Adenosyl-L-methionine decarboxylase (EC 4.1.1.50), the enzyme which catalyzes spermidine synthesis, was elevated 4-fold at 9 days of treatment. The thyroid total supernatant protein kinase activity (+cyclic AMP) increased to 160% of control by 4 days, returning to control by 14 days of PTU treatment. The thyroid had 10% Type I activity and 90% Type II cyclic AMP-dependent protein kinase activity. The specific activity of both Types I and II remained unchanged for the first 2 days of PTU treatment. Both types increased to 150% of control by 4 days. Type I remained elevated throughout the remainder of the 14 days, in contrast to Type II, which decreased conspicuously to control levels by 6 days. A single injection of thyroid-stimulating hormone (TSH, 1.0 unit/100 g of body weight, i.p.) resulted in a 20-fold increase in thyroid ornithine decarboxylase activity by 4 hr. The same dose of TSH produced only a 3-fold induction of ODC in rats hypophysectomized 2 weeks previously. The thyroid specific activity of Types I and II protein kinase was only 55% and 57% of control, respectively, in these unresponsive rats. Thyroids from rats chronically stimulated for 14 days showed an increase in ornithine decarboxylase following TSH administration similar to that of control rats. Changes in the activation as well as specific activity of Types I and II protein kinase during hypertrophy and hyperplasia underlie the complexity of a cyclic AMP-mediated response.

Adenosylmethionine Decarboxylase↗
PubMed1982

Effects of insulin-glucagon interactions on glycogenolysis and protein kinase activity in rat hepatocytes.

The effects of insulin and glucagon on cAMP accumulation, protein kinase activation, and glycogenolysis were investigated in isolated rat hepatocytes. Glucagon (0.01 nM to 10 micro M) increased the activation state of protein kinase and the rate of glucose accumulation. Addition of 1.0 nM insulin to cells preincubated with 0.1 nM glucagon attenuated the rate of glucose accumulation, but did not alter the protein kinase activity ratio. Addition of 0.1 nM glucagon to cells preincubated with 1.0 nM insulin caused a rapid activation of protein kinase; however, glycogenolysis was not immediately affected. These effects were enhanced with pharmacological concentrations of glucagon and insulin. These data indicate that the degree of protein kinase activation does not always correlate temporally or quantitatively with rates of glycogenolysis in liver cells exposed to insulin and glucagon.

Animals↗
PubMed1982

Inhibition of ornithine decarboxylase activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the activity of rat liver ornithine decarboxylase (ODC) were investigated. Sixteen hours after partial hepatectomy, rats that had been pretreated with TCDD for 1 week exhibited a 3- to 4-fold increase in ODC activity, while vehicle controls exhibited to 8- to 10-fold increase. This inhibition of ODC induction by TCDD was time dependent since TCDD administration at the time of partial hepatectomy did not produce inhibitory effects on the subsequent ODC induction. ODC induction after either aminophylline or dexamethasone administration, agents which act via cAMP-mediated and direct nuclear events, respectively, also was inhibited by pretreatment with TCDD. It was concluded that TCDD pretreatment decreased the ability of the liver to respond to hormonal stimulation as reflected in the attenuation of ODC induction. RNA polymerase I activity, which positively correlates with ODC activity in growth and development, decreased concomitantly with decreased induction of ODC. In unstimulated liver RNA polymerase I activity, as well as protein, DNA, and RNA levels, remained unchanged 1 week after TCDD. However, TCDD administration resulted in decreased liver concentrations of putrescine and spermidine, but not spermine. This suggests that TCDD pretreatment results in a time-dependent decrease in hormone responsivity.

Animals↗
PubMed1982

Posttranslationally modified ornithine decarboxylase may regulate RNA polymerase I activity.

Purified ornithine decarboxylase (EC 4.1.1.17, ODC) transamidated with four putrescine moieties on four glutamine residues through the action of transglutaminase (EC 2.3.2.13, TGase) purified from guinea pig liver, when added to isolated rat liver nuclei, stoichiometrically increased the activity of RNA polymerase I (EC 2.7.7.6). The increase was relative to the pmoles of purified conjugated ODC added to the reaction and could be reinitiated after the reaction had plateaued by the further addition of ODC-putrescine conjugate. The kinetics of the reaction suggest that the ODC-putrescine conjugate was not reused but degraded after each initiation. Otherwise, the rapid plateau would not be observed. The repeated addition of 278 pmoles of purified ODC-putrescine conjugate to rat liver nuclear preparations containing 200 micrograms total protein consistently stimulated the incorporation of 600-700 pmoles UMP/mg protein. We suggest that ODC transamidated by its product putrescine may be the posttranslationally modified 65,000 Mr protein which has been reported by several laboratories to serve as a labile subunit of RNA polymerase I.

Animals↗
PubMed1982

Transglutaminase may mediate certain physiological effects of endogenous amines and of amine-containing therapeutical agents.

Transglutaminase mediation of the effects of certain primary amines and alcohols may be important in receptor coupling to physiological responses. Many of the therapeutic and toxic side effects of drugs also may be related to their covalent linkage of glutamine residues of key regulatory proteins through the catalytic action of transglutaminase. This paper suggests that important therapeutic agents such as digoxin, tetracycline, adriamycin, and actinomycin D may have some effects related to transglutaminase action.

Amines↗
PubMed1982

Single-step high-performance liquid chromatographic method for the analysis of acetylated polyamines.

A high-performance liquid chromatography method for the determination of urinary acetyl derivatives of the polyamines putrescine, cadaverine and spermidine is described. This procedure utilizes an ion-exchange column for the separation of acetyl derivatives and the compounds are quantitated by fluorescence after reaction with o-phthalaldehyde. The steps necessary for sample preparation are minimized, and the assay is both sensitive and reproducible. This chromatographic procedure was used for the determination of the urinary acetylated polyamines of seven normal volunteers and three cancer patients.

Chromatography, High Pressure Liquid↗
PubMed1982

Intracellular distribution of transglutaminase activity during rat liver regeneration.

Transglutaminase and ornithine decarboxylase activities have been assayed at intervals after partial hepatectomy in regenerating liver cells fractionated to obtain nuclear, cytoplasmic-particulate, and cytoplasmic-soluble fractions. Ornithine decarboxylase activity, localized entirely in the cytoplasmic fractions, undergoes a dramatic induction during the first 4 h after partial hepatectomy and remains elevated. This induction is very sensitive to inhibition by cycloheximide and actinomycin D, as previously reported. Transglutaminase activity is localized in both the cytoplasm and the nucleus with the highest specific activity in the nucleus. Nuclear transglutaminase activity approximately doubles in the first 2 h of liver regeneration, apparently as a result of a translocation of enzyme from the cytoplasm to the nucleus. Inhibitor studies indicate that the translocation is not dependent upon protein or RNA synthesis. In the first 2 h, actinomycin D slightly activates transglutaminase activity in the cytoplasmic-particulate and nuclear fractions. Only at 4 h after the onset of regeneration do actinomycin D and cycloheximide show some inhibition of transglutaminase activity indicating de novo synthesis at this time. A broad increase of transglutaminase activity occurs from hours 12-16 to hour 32 after partial hepatectomy in the nuclear and cytoplasmic-particulate fraction. These data suggest the existence of a function for transglutaminase in the nucleus of rat liver cells.

Acyltransferases↗
PubMed1982

A model of delayed aortic coarctation employing arterial and venous catheters for chronic blood sampling in conscious dogs.

We have developed a reproducible model of cardiac hypertrophy in conscious, unrestrained dogs after recovery from surgical trauma. The model has many potential applications due to the availability of non-stressful blood sampling from four arterial and/or venous vascular locations. Samples of blood for biochemical or pharmacological measurements were obtained from the carotid and femoral arteries as well as the pulmonary artery and inferior vena cava. Left ventricular hypertrophy up to 128% of the non-operated control animals was produced at 96 h post-intraluminal aortic coarctation. Inflation of a balloon in the descending aorta increased outflow resistance and resulted in hypertrophy. Hemodynamic parameters of cardiac function were obtained via a Swan-Ganz cardiac output catheter located permanently in the pulmonary artery. Complications observed in the dog model were minimal and mortality did not occur during the experimental period. This animal model employing multiple implanted catheters for blood sampling plus the ability to impose aortic coarctation in the unrestrained animal provides a flexible model system for biochemical and pharmacological research.

Animals↗