Hydroxyurea in psoriasis.
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Dermatologic Agents↗
Biomedical subjects
N Reynolds
Publications and source records attributed to N Reynolds.
Calman and the new deal--compromising doctor training and patient care.
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Health Care Reform↗
Hospital pharmacy. A special dispensation.
A pilot scheme allowing hospital inpatients to take responsibility for administering their own drugs has been well received by patients and nurses. Requesting patients to bring in the drugs they are on at the time of admission has resulted in savings for the hospital. On admission, patients are issued with drugs for the whole of their expected hospital stay, and for two weeks after discharge. This has cut delays at the time of discharge.
Drug Prescriptions↗
Cdm1, the smallest subunit of DNA polymerase d in the fission yeast Schizosaccharomyces pombe, is non-essential for growth and division.
Highly purified DNA polymerase delta from the fission yeast Schizosaccharomyces pombe is a complex of at least four distinct subunits. Genes encoding three of these (pol3+/cdc6+, cdc1+ and cdc27+) have been characterised previously. Here we describe the isolation and characterisation of cdm1+, the gene encoding the smallest (22kDa) subunit of the Pol delta complex. Over-expression of cdm1+, which encodes a 160 amino-acid protein with no significant sequence similarity to proteins in current databases, is able to rescue cells carrying temperature-sensitive mutations in either pol3+/cdc6+, cdc1+ or cdc27+. Cells deleted for cdm1+ are viable, indicating that cdm1+ is non-essential for mitotic growth, and are no more sensitive to a variety of DNA replication inhibitors and DNA damaging agents than are wild-type cells. In addition, over-expression of cdm1+ suppresses the temperature-sensitive cdc24-M38 mutant suggesting that cdc24+ may also have a role in DNA polymerase delta function.
Amino Acid Sequence↗
Manganese requirement and toxicity in patients on home parenteral nutrition.
Two patients who were receiving home parenteral nutrition complained of vague neurological symptoms of such severity that they underwent full clinical appraisal. The only positive finding was that plasma manganese concentrations were greater than twice the upper 95% confidence interval of normal (7-27|nmol/l). In the light of this result all nine patients receiving home parenteral nutrition underwent evaluation for possible manganese toxicity. One other patient had serum manganese concentrations exceeding twice the upper limit (127|nmol/l). The three patients with elevated serum Mn had evidence of manganese deposition in the brain on magnetic resonance imaging scanning. In contrast two patients with normal plasma results had negative scans. Patient susceptibility appears very variable. We suggest that current amounts of trace elements provided in nutrition solutions may be a potential source of nutrient activity. The fine tuning of supply and demand may be difficult on account of a limited range of commercially available trace element solutions.
Basal Ganglia↗
Effects of flooding amino acids on incorporation of labeled amino acids into human muscle protein.
We investigated the effects of the nature of the flooding amino acid on the rate of incorporation of tracer leucine into human skeletal muscle sampled by biopsy. Twenty-three healthy young men (24.5 +/- 5. 0 yr, 76.2 +/- 8.3 kg) were studied in groups of four or five. First, the effects of flooding with phenylalanine, threonine, or arginine (all at 0.05 g/kg body wt) on the incorporation of tracer [13C]leucine were studied. Then the effects of flooding with labeled [13C]glycine [0.1 g/kg body wt, 20 atoms percent excess (APE)] and [13C]serine (0.05 g/kg body wt, 15 APE) on the incorporation of simultaneously infused [13C]leucine were investigated. When a large dose of phenylalanine or threonine was administered, incorporation of the tracer leucine was significantly increased (from 0.036 to 0. 067 %/h and 0.037 to 0.070 %/h, respectively; each P < 0.01). However, when arginine, glycine, or serine was administered as a flooding dose, no stimulation of tracer leucine incorporation could be observed. These results, together with those previously obtained, suggest that large doses of individual essential, but not nonessential, amino acids are able to stimulate incorporation of constantly infused tracer amino acids into human muscle protein.
Adult↗
The fission yeast Cdc1 protein, a homologue of the small subunit of DNA polymerase delta, binds to Pol3 and Cdc27.
cdc1+ is required for cell cycle progression in Schizosaccharomyces pombe. Cells carrying temperature-sensitive cdc1 mutants undergo cell cycle arrest when shifted to the restrictive temperature, becoming highly elongated. Here we describe the cloning and sequencing of cdc1+, which is shown to encode a 462 residue protein that displays significant sequence similarity to the small subunit of mammalian DNA polymerase delta. cdc1+ interacts genetically with pol3+, which encodes the large subunit of DNA polymerase delta in fission yeast, and the Cdc1 protein binds to Pol3 in vitro, strongly suggesting that Cdc1 is likely to be the small subunit of Pol delta. In addition, we show that cdc1+ overexpression is sufficient to rescue cells carrying temperature-sensitive cdc27 alleles and that the Cdc1 and Cdc27 proteins interact in vivo and in vitro. Deletion of either cdc1+ or cdc27+ results in cell cycle arrest with the arrested cells having a single nucleus with 2C DNA content. No evidence was obtained for a cut phenotype, indicating that neither cdc1+ nor cdc27+ is required for checkpoint function. cdc1 mutant cells are supersensitive to the DNA synthesis inhibitor hydroxyurea and to the DNA damaging agent MMS, display increased frequency of mini-chromosome loss and have an extended S phase.
Alleles↗
Post-exercise gastric emptying of carbohydrate solutions determined using the 13C acetate breath test.
In an attempt to measure gastric emptying of carbohydrate solutions after exercise, we used the 13C acetate breath test to differentiate the gastric emptying of three approximately isoenergetic carbohydrate solutions (i.e. glucose, glucose polymer and sucrose) from each other and from water. On four separate occasions, six post-absorptive subjects walked on an inclined treadmill at 70% maximum oxygen uptake for 1 h and were then given 330 ml of one of the solutions in which 150 mg of sodium 1-[13C] acetate had been dissolved. Breath samples were collected at regular (2-30 min) intervals over the next 3.5 h for analysis of expired 13CO2 by isotope ratio mass spectrometry. When water was given, all subjects reached peak breath enrichment after 30 min, and had a mean (SE) gastric emptying time of 33.2 (1.6) min. Peak breath enrichment occurred later for sucrose and glucose polymer at 54.3 (3.1) min and 59.0 (2.1) min respectively (P < 0.01), and for glucose this was even later, at 62.3 (1.0) min (P < 0.05). Calculated gastric emptying times for sucrose and glucose polymer were almost identical [66.5 (2.5) and 69.8 (2.9) min respectively], whereas that for glucose was significantly slower [76.8 (3.2) min; P < 0.02], probably reflecting the effects of increased osmolality. The gastric emptying of all carbohydrates were significantly longer than for water (P < 0.01). These results show that in the post-exercise state the 13C acetate breath test can be used to differentiate the gastric emptying rates of water and carbohydrate solutions of different properties.
Acetates↗
Nutrition support teams: an integral part of developing a gastroenterology service.
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Dietary Services↗
Assessment and referral patterns of patients admitted after deliberate self-poisoning.
The assessment and referral patterns of adult patients after deliberate self-poisoning in Dundee were examined. Questionnaires were completed by the admitting physicians and assessing psychiatrists over a 3 month period. Demographic data concerning the patients and the nature of self-harm were similar to previous studies. Initial referral rate was 95% but dropped to between 70% and 81% after the post receiving round. Up to 2 hours/day could be required for assessment and 75% of the cases required some form of psychiatric follow-up. Although both groups of doctors considered that the majority of patients required or would benefit from psychiatric referral, there was poor agreement when patients were independently categorised into high or low suicide risk (kappa = 0.04). Agreement was also low regarding whether referral was essential or not (kappa = 0.06). Although junior medical staff can play an important role in screening of patients, the psychiatric service, including trained nurses, may be best placed to provide a full assessment, where required.
Adult↗
Nurses' beliefs and attitudes toward visiting in adult critical care settings.
OBJECTIVE: To assess the beliefs and attitudes of critical care nurses about the effects of visiting on patients, staff and family. DESIGN: Both interviews and questionnaires were used to gather data on nurses' attitudes and beliefs about visiting and open visiting according to the format of Ajzen and Fishbein's Theory of Reasoned Action. SETTING: Five Utah intensive care units and three Ohio intensive care units. SAMPLE: Critical care nurses in Utah (N = 29) and Ohio (N = 41) were interviewed to assess their beliefs about the effects of visiting on patients, families, nurses and nursing care delivery. RESULTS: Nurses believed the consequence of visiting was more positive for the patient from a psychological perspective than from a physiological perspective but that the effects might differ depending on the patient, the visitor and the circumstances. They believed that visiting had negative consequences for families, because they became exhausted, and that visiting was disruptive for nursing care delivery. Their attitudes about effects of visiting on nursing staff were consistently more negative than were attitudes about the effects on the patient and the family. CONCLUSION: To provide an optimal situation for visiting, its negative consequences must be minimized and nurses' attitudes and beliefs about visiting must be assessed and addressed.
Adult↗
Effects of changes in the mitochondrial genome on the performance of baking yeasts.
Modifications to the mitochondria in baking yeasts affect their performance in dough-raising tests significantly. Conversion of a respiratory-competent baking strain, sensitive to glucose repression, to the petite mutant, yielded a strain which was released from this effect, as shown by the increased development of the cytochrome c peak in the cytochrome spectrum, and which showed a comparably improved dough-raising performance, approaching the levels found for a respiratory-competent strain which was fully derepressed. Replacement of the mitochondria of one strain by those from another, in some cases, improved the performance of the recipient strain, especially if the latter was sensitive to glucose repression. In addition, reduction of glucose repression in single-spore clones derived from the composite strains, as determined by the increased size of the cytochrome c peak, usually segregated 2:2 both for this character and for improved dough-raising capability as well.
Genes, Fungal↗
Genetic manipulation of non-conventional yeasts by conventional and non-conventional methods.
In recent years, yeasts other than those belonging to the species Saccharomyces cerevisiae and Schizosaccharomyces pombe have become increasingly important in industrial processes. Species such as Pichia stipitis, Hansenula polymorpha, Zygosaccharomyces rouxii, Saccharomyces exiguus, Torulaspora delbrueckii, Yarrowia lipolytica and others whose perfect stage is known, can be manipulated genetically by classical methods, but those belonging to the genera Candida (C. utilis, C. tropicalis, C. bombicola, C. zeylanoides, C. boidinii, etc.), Brettanomyces, Cryptococcus, Rhodotorula, and others of the different form genera, cannot be treated in this way. Some, such as Schwanniomyces and Debaryomyces spp., which have a perfect stage, are still difficult to manipulate by conventional means. Genetic manipulation of these yeasts can be approached from two points of view; the first involving improvement of strains by cross-breeding within one species, and the second, the introduction of desirable genes from unrelated species and even from plants or animals. Two techniques are available for construction of industrially-useful strains from these yeasts: protoplast fusion and transformation with chimaeric plasmids containing the gene(s) it is desired to introduce into the recipient strain. The methods for the latter procedure are well known but can be laborious and time-consuming, especially if it is desired to introduce genes from plant or animal sources for production of enzymes, hormones, vaccines and similar products. Protoplast fusion is a simple technique which can be utilized in most laboratories and used for construction of improved yeast strains for brewing, baking, ethanol production and wine-making, either by the fusion of desirable strains of the same species which do not sporulate, or by introduction of genes from non-Saccharomyces species. Methods for fusion of species from different genera and isolation of the desired hybrids have been improved considerably in recent years. We have developed a method for isolation of strains carrying the desired genes by fusing a non-Saccharomyces species with an auxotrophic strain of Saccharomyces cerevisiae and selecting hybrids having the desired characteristics on appropriate media, after which the genes are transferred to the industrial strain by rare-mating, repeated protoplast fusion, or classical mating as required. The advantages and limitations of the method are under investigation.
Genetic Engineering↗
Applications of attenuated total reflection in the infrared analysis of carbohydrates and biological whole cell samples in aqueous solution.
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Candida↗
In vitro studies of a new synthetic thrombin inhibitor.
(2R, 4R)4-methyl-1-[N alpha-(3-methyl-1,2,3,4-tetrahydro-8-quinoline- sulfonyl)-L-arginyl]-2-piperidine carboxylic acid monohydrate (MCI-9038) was found to be a potent synthetic inhibitor of thrombin. In concentrations as low as 1 microM, the thrombin time, prothrombin time, and partial thromboplastin time were more than doubled. The venom (Bothrops atrox) time was similarly prolonged. The drug also inhibited the thrombin-induced activation of factors VIII and XIII. While MCI-9038 in concentrations of 10(-4) M had no effect on platelet aggregation induced by collagen, ADP, epinephrine, and arachidonate, nanomolar concentrations inhibited thrombin-induced platelet aggregation and the release of platelet ADP. The drug also significantly inhibited the adhesion of thrombin-treated platelets to cultured bovine aortic endothelial cells. We conclude that MCI-9038 is an extremely potent inhibitor of the effects of thrombin on platelets and clotting factors.
Arginine↗
Mechanism and characteristics of platelet activation by haematin.
The mechanism as well as some characteristics of haematin-induced human platelet aggregation were investigated. Haematin-induced platelet aggregation required the presence of devalent cations; Mg2+, and to a lesser extent, Co2+, were just as effective as Ca2+ in supporting the aggregation. Mono- and trivalent cations were ineffective. Verapamil inhibited the aggregation. The aggregation was accompanied by thromboxane formation which could be abolished by aspirin. The release of adenine nucleotides was only slightly inhibited by aspirin. The rate of aggregation and the ultrastructure of the aggregated platelets were comparable between control and aspirin-treated samples. It is concluded therefore that haematin-induced aggregation is not dependent on platelet prosta-glandin synthesis. Haematin induced binding of fibrinogen to platelets, and failed to aggregate thrombasthenic platelets. These findings indicate that haematin may induce platelet aggregation by promoting influx of divalent cations in association with increased fibrinogen binding and release of adenine nucleotides.
Adenosine Triphosphate↗
Fibrinolytic activity after administration of diflunisal and aspirin. A double-blind, randomized, placebo-controlled clinical trial.
A double-blind, randomized, placebo-controlled clinical trial was conducted to determine whether fibrinolysis was increased by the chronic administration of aspirin or diflunisal. Healthy male and female volunteers were randomized to receive either aspirin (1,300 mg every 12 h; 10 subjects), diflunisal (1,000 mg initially, then 500 mg every 12 h; 10 subjects), or placebo (10 subjects) for 8 days. Fibrinolytic activity was examined with the clot lysis assay, using native whole blood, platelet-rich plasma, and platelet-poor plasma, and with the kaolin-activated euglobulin lysis test. In addition, measurements were made of fibrinogen, fibrin/fibrinogen degradation products, plasminogen, and the thrombin time. Clot lysis was greater in whole blood and platelet-rich plasma than in platelet-poor plasma, and increased lysis was observed in specimens obtained in the afternoon as compared to those obtained in the morning. Fibrinolytic activity in the afternoon samples was significantly enhanced by both aspirin and diflunisal at the start of the trial (p less than 0.05), but by the afternoon of day 8, only aspirin showed some enhancement. Fibrinolytic activity, as measured by the euglobulin lysis time, actually declined in all study groups during the course of drug administration. No significant changes were recorded in any of the other assayed hemostatic parameters. We conclude that aspirin and diflunisal exert a modest, nonsustained enhancing effect on fibrinolysis in normal subjects.
Adult↗
The inactivation of hemostatic factors by hematin.
Prolonged clotting times and reduced levels of clotting factors have been reported in hematin-treated patients. This effect persists for up to 5 hr after hematin infusion, associated with plasma levels ranging from 0.01 to 0.04 mg/ml. Therefore we performed in vitro studies to investigate the effects of hematin on fibrinogen, thrombin, factor VIII:C, and plasmin. Hematin in a final concentration of 0.01 mg/ml inhibited the clotting of bovine fibrinogen (1.3 to 2.6 mg/ml) by bovine thrombin (0.12 U/ml) and inhibited the hydrolysis of a synthetic substrate by human thrombin. However, if the hematin was first mixed with albumin (25 mg/ml), fourfold higher concentrations were required to prolong the thrombin clotting time. Hematin, 0.035 mg/ml, reduced VIII:C activity from 0.88 to 0.40 U/ml as measured by two-stage assay. Hematin (0.05 mg/ml) also inhibited the activation of VIII:C by thrombin (0.04 U/ml): baseline activity, 0.84 U/ml; thrombin-activated, 2.94 U/ml; with hematin added, 1.33 U/ml. Hematin also inhibited clot lysis. The inclusion of hematin (0.03 mg/ml) in the diluting buffer reduced the lysis of whole blood clots from 86% +/- 5 to 23% +/- 5 (p less than 0.001, mean +/- S.D. of four determinations) and decreased the lysis of 125I-fibrin clots induced by plasmin (0.02 CTA U/ml) from 100% to 27%. In concentrations as low as 0.09 microgram/ml, hematin inhibited the hydrolysis of a synthetic substrate by plasmin. Hematin was mixed with fibrinogen, albumin, or thrombin, and the mixtures applied to Sephadex G-200 columns. Adherence of the hematin to Sephadex was prevented by either prerinsing the column with albumin or using borate buffer at pH 9.2. Hematin co-eluted with each protein applied to the column and, in the case of fibrinogen, altered its electrophoretic mobility and markedly prolonged the thrombin clotting time of the eluted fibrinogen. We conclude that hematin binds to a variety of hemostatic proteins, inhibiting their biologic activity.
Animals↗