Developing a creative in-service education program.
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Games, Experimental↗
Biomedical subjects
D Jackson
Publications and source records attributed to D Jackson.
Expression patterns of myb genes from Antirrhinum flowers.
Six genes that contain sequence encoding the DNA binding domain of the Myb oncoproteins have been isolated from a cDNA library prepared from Antirrhinum majus (snapdragon) flowers using oligonucleotide probes directed against part of this domain. The derived amino acid sequences of these genes reveal acidic domains in their carboxy termini, suggesting that they might act as transcriptional activators. Analysis of their expression patterns with respect to organ specificity, floral differentiation, and response to light suggests that these genes are not involved in controlling anthocyanin biosynthesis, unlike the characterized myb-related genes C1 and Pl from maize. One of the genes is expressed mainly in the nectary and the transmitting tract of the style, two major secretory tissues of the flower, suggesting that the function of this gene is related to active carbohydrate secretion. We conclude that plants contain a number of myb-related transcriptional activators involved in a diversity of gene regulation.
Amino Acid Sequence↗
The Chiang Mai lactation project: study design and implementation.
The Chiang Mai lactation project is a longitudinal field study of human lactation carried out among northern Thai women living in the Sanpatong area of Chiang Mai Province. Its aim was to measure the volume and composition of breast milk transferred from mothers to their infants in the first year postpartum, and to relate it to predictors of milk production, and to the growth of the child. Breast milk and supplementary food intake, and nursing patterns, were recorded over two consecutive 24-hour periods six times during the first year. Samples of breast milk and of supplementary foods were analysed for energy and protein. Supplementary foods were also analysed for bacterial contamination. The growth of the child was measured, and health assessed using a combination of health diaries and examination by a physician. Recruitment to the study was excellent. After recruitment, two subjects left the study area, but otherwise only two dropped out, so complete sets of data covering these variables are available for 58 of the 62 recruited subjects.
Body Weight↗
Basic medical physiology: the whole is more than the sum of its parts.
In this article we examine the role of basic medical physiology in medical school education. We discuss the historical background, courses in this subject, and methods of teaching it. We conclude that the teaching of medical physiology should emphasize the study of organ systems and of the intact body. The techniques should emphasize meticulous observation, the posing of hypotheses, and the subsequent testing of the hypotheses, i.e., the use of the method used successfully in research. Students should learn the power of the experimental approach and to appreciate the immense variability possible in responses in complex organisms. They should also learn that principles of statistical probability applied logically can detect important differences in data that may be obscured by this variability. They should learn that there are no rigid answers when studying an individual and that they must continue to learn throughout their lives.
Animals↗
Meperidine-induced taste alteration.
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Adult↗
Medical complications of pregnancy.
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Adult↗
Evolution of beta-lactamase inhibitors.
After the introduction of penicillin G into therapeutics, bacteria became increasingly resistant to this penicillin and subsequent beta-lactam antibiotics. The major cause of this resistance is beta-lactamase, an enzyme produced by the bacterium, that destroys the antibiotic before it reaches its target within the bacterial cell. One of the ways to combat this resistance has been the use of beta-lactamase inhibitors, which protect the antibiotic by inactivating the destructive enzyme before the antibiotic reaches the infection site. At present, at least two beta-lactamase inhibitors are in clinical use, clavulanic acid and sulbactam, that are effective against most beta-lactamases, although relatively inactive against class I beta-lactamases, the cephalosporinases. Newly developed beta-lactamase inhibitors, however, especially BRL-42715, show some promise against these enzymes.
Anti-Bacterial Agents↗
Use of site-directed mutagenesis to identify valine-573 in the S'1 binding site of rat neutral endopeptidase 24.11 (enkephalinase).
On the basis of the identity of a segment of the amino acid sequence within the active site of the bacterial enzyme thermolysin and the mammalian enzyme neutral endopeptidase 24.11, the possible involvement of valine-573 of neutral endopeptidase 24.11 in substrate binding was investigated. Valine-573 was changed to leucine and to alanine by site-directed mutagenesis. The effect of these mutations on inhibitor binding and substrate catalysis was examined with a series of compounds containing variable P'1 residues. With a small P'1 residue such as alanine, both mutant enzymes exhibited kinetic properties essentially the same as the wild-type enzyme. However, with larger P'1 residues such as phenylalanine, tyrosine, and leucine, the Val573Leu mutant showed a 24-100-fold decrease in inhibitor affinity. Similarly substrates containing bulky P'1 residues showed a 10-40-fold decrease in Vmax with little change in Km. In contrast, the Val573Ala mutant showed only modest changes in terms of inhibitor binding or substrate turnover. These results support the proposed role of valine-573 as a part of the hydrophobic binding pocket, S'1 binding subsite, of neutral endopeptidase 24.11.
Amino Acid Sequence↗
Fine-needle aspiration biopsy diagnosis of endodermal sinus tumor: histologic and ultrastructural correlations.
Fine-needle aspiration biopsies from five patients with endodermal sinus tumors (ESTs) were reviewed, and the findings were correlated with histologic and ultrastructural appearances. In the aspiration smears, two types of tumor cells were seen, forming clusters of variable sizes. Type A cells had distinct cell borders, and their cytoplasm contained only occasional vacuoles. Type B cells had ill-defined cell borders and formed syncytial clusters; their cytoplasm was characterized by large numbers of rounded vacuoles. The background contained patches of mucoid material and macrophages with foamy cytoplasm. Eosinophilic hyaline cytoplasmic bodies and irregular deposits of intercellular basement membrane-like material were recognized easily in aspiration smears. These features correlated well with histologic and ultrastructural appearances. The significance of these findings in the fine-needle aspiration biopsy diagnosis of EST and its distinction from other germ-cell and non-germ-cell tumors is discussed.
Adult↗
High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association.
One hundred seventy-two patients with advanced breast cancer were randomized to receive oral standard-dose megestrol acetate (MA), 160 mg/d or high-dose MA, 800 mg/d. All but two patients had one prior trial of tamoxifen therapy for either metastatic disease (74%) or as adjuvant treatment (26%). Pretreatment characteristics were similar for both arms. High-dose MA resulted in a superior complete plus partial response rate (27% v 10%, P = .005), time to treatment failure (median, 8.0 v 3.2 months, P = .019), and survival (median, 22.4 v 16.5 months, P = .04) when compared with standard-dose therapy. These differences remained significant after adjustment for other covariates. Thirty-four patients were given high-dose MA after failure of standard-dose MA treatment, and none responded. Weight gain was the most distressing side effect, with 13% of standard-dose and 43% of high-dose patients gaining more than 20 lbs. Four major cardiovascular events occurred in patients receiving high-dose treatment and one in patients given standard doses. Other toxicity was modest. High-dose MA may represent a significant improvement in secondary endocrine therapy for advanced breast cancer patients refractory to initial endocrine treatment, but its use on a regular basis should be reserved until these results are confirmed by other clinical trials.
Adult↗
Phase II study of fluorouracil and recombinant interferon alfa-2a in previously untreated advanced colorectal carcinoma.
We conducted a phase II clinical trial of fluorouracil (5FU) and recombinant interferon alfa-2a (rIFN alpha-2a) in 52 previously untreated patients with bidimensionally measurable metastatic colorectal cancer. During week 1, 5FU was administered as a continuous intravenous infusion, 750 mg/m2/d for 5 consecutive days. Intravenous bolus administration of 5FU 750 mg/m2 was given weekly for 7 weeks starting on day 12. rIFN alpha-2a (Roferon; Hoffman-LaRoche, Nutley, NJ), 9 x 10(6) U, was administered subcutaneously three times weekly during weeks 1 to 8. Patients were evaluated for response on week 9. Of 52 patients enrolled in the study, 51 were assessable for toxicity, and 45 were assessable for response. Fifteen patients experienced partial response, and one patient achieved a clinical complete response for an overall response rate of 35% (95% confidence interval [CI], 22%, 50%). Median duration of response is 7.5 months (range, 4 to 11 months). Seventy percent of patients entered on the study are alive with a median follow-up duration of 7 months. Twenty-five percent of patients developed grade 4 toxicity, and 82% developed grade 3 toxicity. One drug-related death in the presence of sepsis was reported, and two treatment-related seizures occurred. Our experience with this schedule produced a lower response rate with greater toxicity than previously reported. Current randomized trials comparing this schedule of 5FU with rIFN alpha-2a to 5FU plus folinic acid (leucovorin) or single-agent 5FU may determine its role in the treatment of advanced colorectal carcinomas.
Colorectal Neoplasms↗
The role of the community psychiatric nurse.
The community psychiatric nurse is an essential element in a comprehensive mental health service. At present each nurse is expected to be a trained counsellor and psychotherapist, a skilled behaviour therapist and an expert assessor of clinical status. This superhuman role is unrealistic; a more appropriate one is outlined.
Behavior Therapy↗
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↗
The clinical pharmacology of paroxetine in healthy subjects.
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Administration, Oral↗