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Biomedical subjects

D Jackson

Publications and source records attributed to D Jackson.

At least 163 records · Page 9Linked to original sources

Transforming growth factor-beta induces hemoglobin synthesis in a human erythroleukemia cell line.

We have examined the effects of TGF beta 1 and TGF beta 2 on the HEL human erythroleukemia cell line. It was observed that TGF beta 1 and 2 induced hemoglobin synthesis in these cells without causing a significant negative effect on cell proliferation. The cell surface markers glycophorin A and transferrin receptor that are associated with erythroid differentiation were also increased. This cell line may provide a model system in which to study the regulation of globin gene expression by a physiological growth factor known to act on hemopoietic cells.

Blotting, Northern↗

Direct demonstration of termination signals for RNA polymerase II from the sea urchin H2A histone gene.

Previous studies [1,2] suggested but did not prove that the sea urchin H2A histone gene possesses strong transcriptional termination signals close to, but separate from, the 3' processing signals. In this study we have demonstrated by two independent approaches that these sequences elicit authentic transcriptional termination. First we show by nuclear run off analysis that nascent transcription terminates in the immediate 3' flanking region of the H2A gene, in an A-rich region. Second we show that these termination signals prevent transcriptional read through when placed in the intron of a globin gene. The intronic position of the termination signal rules out any effect on steady state mRNA levels. We have therefore defined DNA sequences which act as a transcription terminator when placed in heterologous RNA polymerase II genes.

Animals↗

Identification of the active-site arginine in rat neutral endopeptidase 24.11 (enkephalinase) as arginine 102 and analysis of a glutamine 102 mutant.

Neutral endopeptidase 24.11 contains an active-site arginine residue involved in binding the free carboxylate of substrate peptides and inhibitors. This arginine reacts rapidly with [14C]phenylglyoxal, and its reaction is selectively blocked by the presence of either the substrate Met5-enkephalin, the competitive inhibitor phenylalanylalanine, or the transition state analog phosphoramidon. The phenylglyoxal-modified peptide was isolated by a procedure involving limited digestion by trypsin, separation of the tryptic peptides by high pressure liquid chromatography (HPLC), further digestion of the modified peptide by pepsin, and a final purification by HPLC. By this procedure arginine 102 was identified as the active-site arginine. Verification of this finding came from the use of site-directed mutagenesis in which this arginine was replaced by glutamine. Both the mutant and wild-type enzyme reacted equally well with an amide containing substrate, glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide. However, reaction of the mutant enzyme with a substrate containing a free COOH-terminal carboxylate, 5-dimethylaminonaphthalene-1-sulfonyl-D-Ala-Gly-(NO2)Phe-Gly, was barely detectable with the mutant enzyme. Similarly the mutant enzyme showed a loss of selectivity in inhibition by D-Ala2-Met5-enkephalin compared to the corresponding amide but exhibited no difference in the maximal velocity for hydrolysis of D-Ala2-Met5-enkephalin and its amide.

Amino Acid Sequence↗

Dopamine released from mesencephalic transplants restores modulation of striatal acetylcholine release after neonatal 6-hydroxydopamine: an in vitro analysis.

After chemical lesions which destroy the nigrostriatal dopamine pathway, transplants rich in dopamine neurons innervate the striatum and, with appropriate stimulation, drive host motor behaviors normally mediated by dopamine. We wished to determine whether dopamine released from the transplant also reinstated dopaminergic inhibition of striatal acetylcholine release. Three-day-old rat pups received bilateral intraventricular injections of 6-hydroxydopamine. Three days later cell suspensions prepared form embryonic ventral mesencephalon were injected unilaterally into the striatum. Tail pinch and amphetamine were able to elicit contralateral turning in many of these animals. Only those animals which rotated greater than or equal to 5 turns/min were included for further analysis. Subsequent assays indicated that 6-hydroxydopamine had depleted striatal dopamine to 4% of control and that the transplant had increased dopamine levels to 11% of control. Superfused striatal slices were stimulated (8 Hz, 1 min) and then exposed to amphetamine (10 microM, 3 min). The slice released dopamine, as measured by HPLC, and acetylcholine, as measured by tritium efflux after preincubation with [3H]choline. Moreover, the release of acetylcholine was inhibited by endogenous dopamine as indicated by the ability of sulpiride (1 microM) to increase tritium efflux. Striatal slices prepared from lesioned animals showed a reduction in dopamine overflow in response to both electrical stimulation (0.6% of control) and amphetamine (1% of control), and a decrease in the ability of sulpiride to increase electrically evoked acetylcholine overflow (12% of control). Transplantation partially restored the dopaminergic response to electrical stimulation (21% of control), and amphetamine (15% of control) and fully restored the sulpiride-induced increase in acetylcholine overflow (98% of control).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Uptake and retention of strontium, iodine and caesium in lowland pasture following continuous or short-term deposition.

Data from the extensive routine environmental monitoring programme around the nuclear reprocessing plant at Sellafield, West Cumbria, are analysed for soil to plant uptake of strontium, iodine and caesium. Relative to the top 10 cm of soil, dry weight concentration ratios derived for lowland pastures for strontium, caesium and iodine are 9, 3 and 2 respectively. Long-term trends indicate a 'spring flush' of activity in vegetation, although this is not statistically significant. Uptake of caesium and iodine is highest generally for mosses and lichen and lowest for grass. The vegetational field loss of these elements over the first 50 days following deposition, is described by: Sr: Reff(t) = 0.7e-0.15t + 0.25e-0.049t + 0.05e-0.011t I: Reff(t) = 0.7e-1.26t + 0.25e-0.17t + 0.05e-0.092t Cs: Reff(t) = 0.6e-0.87t + 0.2e-0.20t + 0.16e-0.065t + 0.04e-0.011t where t is in days. The functions are consistent with the effects of washoff and grazing. Equilibrium plant:soil concentration ratios are established for caesium within about 8 months following short-term deposition. Soil distribution profiles for caesium imply a half-time for transfer through the surface layers of about 6 years.

Cesium Radioisotopes↗

Sex education in Halton secondary schools.

One teacher from each of the secondary schools and four special schools in Halton district completed a questionnaire in a semi-structured interview on sex education in their schools. The results showed that a variety of programmes took place but frequently teachers did not feel adequately prepared to teach this vital but difficult subject. Strengths of the programme included the popularity of parent's evenings to discuss sex education programmes, pastoral syllabuses followed by form tutors, 'student led' sex education programmes and the development of personal and social education courses. Difficulties encountered included a lack of on-going sex education programmes, a lack of sex education in the second year when teenage pregnancies were occurring and a lack of teacher training.

Acquired Immunodeficiency Syndrome↗

Inhibition of striatal acetylcholine release by endogenous serotonin.

We have examined the hypothesis that endogenous serotonin (5-HT) exerts an inhibitory influence on the release of acetylcholine (ACh) in striatum. Striatal slices were prepared from adult rats, preincubated with [3H]choline, superfused, and exposed to electrical field stimulation. The stimulation-induced overflow of tritium into the superfusate was used as a measure of ACh release. We observed that fluoxetine, an inhibitor of 5-HT uptake, reduced ACh overflow in slices prepared from caudal striatum, an area of high 5-HT concentration, but not in slices from rostral striatum, an area of low 5-HT concentration. Moreover, methysergide, a 5-HT antagonist, increased ACh efflux in caudal but not rostral striatum. Finally, direct activation of 5-HT receptors with the 5-HT agonist, quipazine, inhibited stimulation-induced ACh overflow in both rostral and caudal striatum. These results suggest that endogenous 5-HT normally is capable of inhibiting striatal ACh release, and that the extent of the modulation is related to the degree of serotonergic innervation. In addition, 5-HT receptors capable of modulating ACh release are present in 5-HT-poor rostral striatum, as well as in 5-HT-rich caudal striatum.

Acetylcholine↗

Inhibition of striatal acetylcholine release by serotonin and dopamine after the intracerebral administration of 6-hydroxydopamine to neonatal rats.

The intraventricular administration of 6-hydroxydopamine (6-OHDA) depletes the striatum of dopamine (DA). When given to rat pups at an early age, the toxin also increases striatal serotonin (5-HT) content. In the accompanying report we observed that endogenous 5-HT, like DA, exerts an inhibitory influence on the release of acetylcholine (ACh) from striatal slices prepared from control animals and that the extent of this inhibition is related to the degree of serotonergic innervation of the region being examined. To determine whether this hyperinnervation was accompanied by an increase in serotonergic influence on ACh release, striatal slices were prepared from adult rats, preincubated with [3H]choline, superfused, and exposed to electrical field stimulation. The efflux of tritium into the superfusate was used as a measure of ACh release. In confirmation of previous reports, we observed that direct and indirect agonists of DA and 5-HT both reduced ACh overflow from control slices, whereas overflow was increased by antagonists of these amines. Slices prepared from rats given 6-OHDA-induced lesions as adults were responsive to each of these pharmacological manipulations, as well. In contrast, ACh overflow from slices prepared from animals lesioned with 6-OHDA as neonates was not modified by either dopaminergic or serotonergic drugs. These results suggest that the serotonergic hyperinnervation of striatum produced by neonatal 6-OHDA is accompanied by a loss of the inhibitory influence of endogenous 5-HT and DA on striatal ACh release and, thus, provide no evidence for a role for either transmitter in the behavioral sparing associated with such lesions.

Acetylcholine↗

Ionization and phase behavior of fatty acids in water: application of the Gibbs phase rule.

The phase behavior of several medium-chain (10- and 12-carbon) and long-chain (18-carbon) fatty acids in water was examined as a function of the ionization state of the carboxyl group. Equilibrium titration curves were generated above and below fatty acid and acid-soap chain melting temperatures and critical micelle concentrations, and the phases formed were characterized by X-ray diffraction, 13C NMR spectroscopy, and phase-contrast and polarized light microscopy. The resulting titration curves were divided into five regions: (i) at pH values less than 7, a two-phase region containing oil or fatty acid crystals and an aqueous phase; (ii) at pH approximately 7, a three-phase region containing oil, lamellar, and aqueous (or fatty acid crystals, 1:1 acid-soap crystals, and aqueous) phases; (iii) between pH 7 and 9, a two-phase region containing a lamellar fatty acid/soap (or crystalline 1:1 acid-soap) phase in an aqueous phase; (iv) at pH approximately 9, a three-phase region containing lamellar fatty acid-soap (or crystalline 1:1 acid-soap), micellar, and aqueous phases; and (v) at pH values greater than 9, a two-phase region containing micellar and aqueous phases. Interpretation of the results using the Gibbs phase rule indicated that, for oleic acid/potassium oleate, the composition of the lamellar fatty acid/soap phase varied from approximately 1:1 to 1:3 un-ionized to ionized fatty acid species. In addition, constant pH regions observed in titration curves were a result of thermodynamic invariance (zero degrees of freedom) rather than buffering capacity. The results provide insights into the physical states of fatty acids in biological systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Fatty Acids, Nonesterified↗

Effects of simulated intraoperative electrophysiological testing on function of the canine left ventricle.

With the increasing application of arrhythmia surgery, intraoperative electrophysiological study is done frequently, although its potential to cause acute depression of cardiac function remains unresolved. This study examines the acute effects of simulated electrophysiological testing on left ventricular function. Seven dogs were anesthetized with sodium pentobarbital and instrumented for measurement of heart rate, mean aortic pressure, cardiac output (CO), and systemic vascular resistance (SVR). Systolic pressure-dimension work loops were analyzed over varying preloads. Contractility was assessed from the end-systolic pressure-dimension relationship (Ees) and from preload recruitable stroke work (PRSW). After the collection of control data, electrophysiological testing was simulated by pacing at 200 beats per minute for 30 seconds, fibrillating for 15 seconds, and finally defibrillating with a 10-J countershock. Data were recorded after 3 and 6 simulations of ventricular fibrillation (VF3, VF6). Mean heart rate and mean aortic pressure did not vary significantly during the course of the experiment. CO decreased from a control value of 2.7 +/- 0.2 L/min (+/- the standard error of the mean) to 2.0 +/- 0.1 (p less than 0.05) after VF3 and remained significantly depressed after VF6. SVR increased from a control value of 3,231 +/- 211 dyne sec cm-5 to 3,976 +/- 305 dyne sec cm-5 after VF3 (p = not significant) and increased further to 4,774 +/- 442 dyne sec cm-5 after VF6 (p less than 0.05). Neither Ees nor PRSW varied significantly even after 6 EP simulations, thereby indicating that contractility was unchanged during the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

SRI Gallup describes selection process.

This is the third article in a series on Franciscan Health System's geriatric marketing initiative. Last month FHS's director of marketing and planning, described the process of putting out a request for proposal to market research vendors. In this article, an SRI Gallup senior vice president tells how his firm landed the project and how clients can avoid selection pitfalls.

Competitive Bidding↗

Developing a market research survey.

This is the fourth in a series on a systemwide geriatric-care marketing initiative. Other articles outlined gaining voluntary involvement of internal marketing segments and detailed putting out a request for proposal to market research vendors. This article explores the development of a market research survey that meets the needs of the system's membership.

Aged↗