Community pharmacy supply of emergency contraception. Collaboration is vital.
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Contraceptives, Postcoital↗
Biomedical subjects
G Ward
Publications and source records attributed to G Ward.
Inactivation of lignin peroxidase during oxidation of the highly reactive substrate ferulic acid.
Ferulic acid (4-hydroxy-3-methoxycinnamic acid) (FA) was found to be a highly reactive substrate for lignin peroxidase (LIP), exhibiting a k(cat) of 41.7 s(-1). Despite the high reactivity, two modes of inactivation prevailed during the oxidation of FA. The first, H(2)O(2)-dependent inactivation, was evidenced by incomplete substrate oxidation and accumulation of LIP compound III (LIPIII), even at relatively low H(2)O(2) concentrations. This was attributed to the high turnover rate along with the inability of FA to revert LIPIII to the native state, as evidenced by pre-steady-state kinetics. H(2)O(2)-dependent inactivation could be avoided by inclusion of veratryl alcohol (VA), which efficiently reverts LIPIII to the native state. However, VA also mediated FA oxidation, and significantly decreased the reaction rate, which is unlike for previously reported VA-mediated reactions. The second mechanism of LIP inactivation was attributed to binding of phenoxy radicals or oxidation products to the enzyme and its extent directly correlated with the amount of FA consumed. This inactivation could be considerably suppressed by inclusion of gelatin. Therefore, during the oxidation of highly reactive phenolics, different kinds of protectors are required for efficient oxidation and maintaining LIP activity over time. This is of importance when considering emerging biotechnological applications for LIP.
Journal Article↗
Initial steps of ferulic acid polymerization by lignin peroxidase.
The major products of the initial steps of ferulic acid polymerization by lignin peroxidase included three dehydrodimers resulting from beta-5' and beta-beta'coupling and two trimers resulting from the addition of ferulic acid moieties to decarboxylated derivatives of beta-O-4'- and beta-5'-coupled dehydrodimers. This is the first time that trimers have been identified from peroxidase-catalyzed oxidation of ferulic acid, and their formation appears to be favored by decarboxylation of dehydrodimer intermediates. After initial oxidation, the coupling reactions appear to be determined by the chemistry of ferulic acid phenoxy radicals, regardless of the enzyme and of whether the reaction is performed in vitro or in vivo. This claim is supported by our finding that horseradish peroxidase provides a similar product profile. Furthermore, two of the dehydrodimers were the two products obtained from laccase-catalyzed oxidation (Tatsumi, K. S., Freyer, A., Minard, R. D., and Bollag, J.-M. (1994) Environ. Sci. Technol. 28, 210-215), and the most abundant dehydrodimer is the most prominent in grass cell walls (Ralph, J., Quideau, S., Grabber, J. H., and Hatfield, R. D. (1994) J. Chem. Soc. Perkin Trans. 1, 3485-3498). Our results also indicate that the dehydrodimers and trimers are further oxidized by lignin peroxidase, suggesting that they are only intermediates in the polymerization of ferulic acid. The extent of polymerization appears to be dependent on the ionization potential of formed intermediates, H(2)O(2) concentration, and, probably, enzyme stability.
Chromatography, Gel↗
Therapeutic effects of cysteine protease inhibition in allergic lung inflammation: inhibition of allergen-specific T lymphocyte migration.
OBJECTIVE AND DESIGN: We have evaluated the effects of the broad-spectrum cysteine protease inhibitor E64 on allergic lung inflammation in the mouse ovalbumin model of human asthma. We have also characterised membrane-associated cathepsin enzyme activity on a range of cell types. MATERIALS: Balb/C mice, E64 and CA074, various cell lines. TREATMENT: E64 was administered by subcutaneous minipump into ovalbumin-sensitised mice prior to intranasal ovalbumin challenge. The effect of E64 on ovalbumin-induced inflammation in vivo and ovalbumin-specific T cell proliferation in vitro and ex vivo was examined. Membrane-associated cathepsin activity on various cell types was measured. RESULTS: E64 treatment (0.36-0.48 mg/day) led to a significant reduction in eosinophil numbers and lung weights in the mouse model. Histological examination of lungs confirmed the anti-inflammatory effect. E64 greatly reduced ovalbumin-specific T cell numbers in the lymph nodes draining the lung following intranasal challenge whilst an accumulation of these T cells was found in the 'priming' lymph nodes. An analysis of various cells involved in lymphocyte priming and migration revealed that monocytes, dendritic cells and endothelial cells express high levels of membrane-associated cathepsin B activity. CONCLUSIONS: Since E64 is not cell permeable and does not inhibit antigen-induced T cell proliferation in vitro or in vivo, the data indicate that membrane-associated cysteine proteases, possibly cathepsin B, may regulate T lymphocyte migration in vivo.
Allergens↗
Task-switching costs, Stroop-costs, and executive control: a correlational study.
Three correlational studies investigated the relationship between the time costs associated with Stroop stimuli (Stroop-costs) with the time costs associated with task-switching (switch-costs) obtained from colour-word stimuli and digit stimuli. In all studies, large and significant positive correlations were found between different measures of switch-costs. However, only small (and sometimes non-significant) correlations were obtained between the different measures of Stroop-costs and between measures of Stroop-costs and measures of switch-costs. The results are taken as evidence for the existence of some common or shared specialized mechanisms involved in task-switching, which are different from those used to overcome Stroop interference.
Adolescent↗
Thyroid stimulating hormone secretion is a dynamic process.
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Aged↗
Treatment for displaced intracapsular fracture of the proximal femur. A prospective, randomised trial in patients aged 65 to 79 years.
We performed a prospective, randomised trial comparing three treatments for displaced intracapsular fractures of the hip in 280 patients aged 65 to 79 years. The mean patient survival was significantly higher in the group undergoing reduction and internal fixation (79 months) compared with that with a cemented Thompson hemiarthroplasty or a cemented Monk bipolar hemiarthroplasty (61 months and 68 months, respectively). After three years, 32 of 93 patients (34.4%) who had undergone fixation had local complications, necessitating further intervention in 28 (30%). There were no significant differences in the functional outcome in survivors, who were reviewed annually to five years. Either reduction and internal fixation or cemented hemiarthroplasty may be offered as alternative treatments for a displaced intracapsular fracture in a mobile and mentally competent patient under the age of 80 years. The choice of procedure by the patient and the surgeon should be determined by the realisation that the use of internal fixation is associated with a 30% risk of failure requiring further surgery. If this is accepted, however, hemiarthroplasty is avoided, which, in our study has a significantly shorter mean survival time. The use of a bipolar prosthesis has no significant advantage.
Aged↗
Prostaglandin D synthase does not produce prostate-specific antigen cross-reactivity in renal cell carcinoma.
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Carcinoma, Renal Cell↗
Thymic stress in artificially reared and maternally reared rat pups.
It is well documented that the hypothalamic-pituitary-adrenal (HPA) axis influences immunological responses to stress. Maternal factors have been shown to be necessary for appropriate modulation of the HPA axis in the developing rat. The purpose of this study was to determine whether artificially reared (AR) infant rat pups (a procedure whereby infant rats are gastrostomized and reared independently of maternal factors) have an altered function of the HPA axis in terms of thymocyte apoptosis (programmed cell death) and other indices of thymic stress. AR and maternally reared (MR) Long-Evans rat pups were randomized to control, fasted, stressed, and fasted+stressed treatment groups, as well as an unhandled, MR naive group that served as a baseline control. AR rat pups were significantly heavier than MR (p<0.001). AR rat pups had significantly lighter thymuses than did the MR pups (p<0.001) and fasted pups had significantly lighter thymuses than unfasted pups, regardless of whether they were in the AR or MR condition (p<0.005). AR pups had significantly lower thymic cell numbers and a greater percent of necrotic cells than did MR pups. There were no significant effects of rearing condition on the percent of apoptotic thymocytes. The thymocyte alterations observed in this study between the two rearing conditions suggest that AR reduces thymic weight and cell numbers, which may have consequences for the development of adult cellular immunity.
Animals↗
Growth over 10 years following a 1-year trial of growth hormone therapy.
The growth of short children with chronic renal failure (CRF) and renal transplants was assessed over 10 years following entry into a 1-year trial of recombinant human growth hormone (rhGH) therapy. Patients were divided into three groups: 6 prepubertal patients with CRF (group 1), mean (range) age at start of trial 7.7 (5.0-10.4) years; 6 prepubertal patients with renal transplants (group 2), age 11.9 (9.5-14.6) years; and 6 pubertal patients with renal transplants (group 3), age 15.6 (14.1-18.3) years. In group 1, the mean (range) height standard deviation score (Ht SDS) increased from -2.9 (-3.7 to -2.2) to -1.9 (-2.9 to -0.5) over 4.0 (0.3-9.1) years of rhGH (P=0.04), and was -1.6 (-2.9 to -0.4) after 10 years of follow-up (NS). In group 2 Ht SDS increased from -3.3 (-4.5 to -1.9) to -2.9 (-5.4 to -0.5) over 2.7 (1.0-6.0) years and was -3.0 (-6.3 to -0.1) at final height (NS). In group 3 Ht SDS increased from -3.4 (-4.3 to -2.6) to -3.0 (-3.4 to -2.2) over 1.4 (0.2-2.3) years (NS) and was -2.5 (-3.0 to -1.9) at final height (P=0.03 from stopping rhGH to final height). Final height was attained in 13 patients, in whom Ht SDS increased from -3.2 (-4.3 to -1.9) to -2.6 (-3.9 to -0.5) on rhGH (P=0.004) and to -2.2 (-4.4 to -0.1) after stopping treatment (P=0.04). Four patients died, 2 have chronic hepatitis C, and 1 has had surgery for parathyroid adenomata. In conclusion, the majority of patients had an improvement in Ht SDS while on rhGH, which was maintained after stopping treatment.
Adolescent↗
Sepsis: the critical role of iron.
Sepsis is a global problem which is exacerbated by increasing bacterial resistance to antibiotics. However, mechanisms of natural resistance can be extremely effective, and need to be exploited, but the availability of iron is critical for controlling bacterial growth. The diagnosis of sepsis and possible strategies for limiting iron availability are discussed.
Animals↗
A recency-based account of the primacy effect in free recall.
Seven experiments investigated the role of rehearsal in free recall to determine whether accounts of recency effects based on the ratio rule could be extended to provide an account of primacy effects based on the number, distribution, and recency of the rehearsals of the study items. Primacy items were rehearsed more often and further toward the end of the list than middle items, particularly with a slow presentation rate (Experiment 1) and with high-frequency words (Experiment 2). Recency, but not primacy, was reduced by a filled delay (Experiment 3), although significant recency survived a filled retention interval when a fixed-rehearsal strategy was used (Experiment 4). Experimenter-presented schedules of rehearsals resulted in similar serial position curves to those observed with participant-generated rehearsals (Experiment 5) and were used to confirm the main findings in Experiments 6 and 7.
Adolescent↗
Meningioma of the parapharyngeal space: case report.
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Female↗
Distamycin A selectively inhibits Acanthamoeba RNA synthesis and differentiation.
The effects of distamycin A on Acanthamoeba transcription, growth and differentiation were determined. Distamycin A inhibits transcription both in vitro and in vivo and can displace from DNA the transcription activator TATA binding protein promoter binding factor (TPBF). Inhibition in vivo is surprisingly selective for large rRNA precursors, 5S rRNA, profilin, S-adenosylmethionine synthetase, and extendin. Transcription from the TATA binding protein (TBP), TPBF, protein disulfide isomerase, tubulin and RNA polymerase II large subunit genes is only slightly inhibited. Moreover the rate of 5S rRNA transcription eventually recovers and exceeds that of untreated cells, while profilin transcription remains inhibited. Distamycin A inhibition is accompanied by a complex pattern of alterations to steady state levels of mRNAs. Actin, profilin and S-adenosylmethionine synthetase mRNAs are degraded, whereas mRNA encoding TBP is increased slightly in abundance. Transcription inhibition is accompanied by cessation of growth and severe morphological changes to Acanthamoeba, which are consistent with loss of production of mRNA encoding cytoskeletal proteins. Distamycin A also prevents starvation-induced differentiation of Acanthamoeba, in part due to complete prevention of cellulose production and cell wall formation.
Acanthamoeba↗
Development of DNA vaccines for foot-and-mouth disease, evaluation of vaccines encoding replicating and non-replicating nucleic acids in swine.
We have developed naked DNA vaccine candidates for foot-and-mouth disease (FMD), an important disease of domestic animals. The virus that causes this disease, FMDV, is a member of the picornavirus family, which includes many important human pathogens, such as poliovirus, hepatitis A virus, and rhinovirus. Picornaviruses are characterized by a small (7-9000 nucleotide) RNA genome that encodes capsid proteins, processing proteinases, and enzymes required for RNA replication. We have developed two different types of DNA vaccines for FMD. The first DNA vaccine, pP12X3C, encodes the viral capsid gene (P1) and the processing proteinase (3C). Cells transfected with this DNA produce processed viral antigen, and animals inoculated with this DNA using a gene gun produced detectable antiviral immune responses. Mouse inoculations with this plasmid, and with a derivative containing a mutation in the 3C proteinase, indicated that capsid assembly was essential for induction of neutralizing antibody responses. The second DNA vaccine candidate, pWRMHX, encodes the entire FMDV genome, including the RNA-dependent RNA polymerase, permitting the plasmid-encoded viral genomes to undergo amplification in susceptible cells. pWRMHX encodes a mutation at the cell binding site, preventing the replicated genomes from causing disease. Swine inoculated with this vaccine candidate produce viral particles lacking the cell binding site, and neutralizing antibodies that recognize the virus. Comparison of the immune responses elicited by pP12X3C and pWRMHX in swine indicate that the plasmid encoding the replicating genome stimulated a stronger immune response, and swine inoculated with pWRMHX by the intramuscular, intradermal, or gene gun routes were partially protected from a highly virulent FMD challenge.
Animals↗
Insulin secretion in growth hormone-deficient adults: effects of 24 months' therapy and five days' acute withdrawal of recombinant human growth hormone.
Beta-cell function in growth hormone (GH)-deficient (GHD) adults is poorly documented. Beta-cell function was therefore studied in 10 GHD adults (age, 40+/-3 years; weight, 79.3+/-4.8 kg; body mass index [BMI], 27.5+/-1.3 kg x m(-2)) before and after 6- and 24-month recombinant human GH (rhGH) therapy (0.24 IU x kg(-1) x wk(-1)) compared with 10 age-, sex-, weight-, and BMI-matched control subjects. With rhGH therapy, fat-free mass (FFM) increased (48.2+/-4.9, 52.5+/-4.8, and 59+/-6.8 kg, respectively) and fat mass (FM) decreased (33.8%+/-2.8%, 28.0%+/-3.0%, and 29.4%+/-2.5%, respectively), as did serum cholesterol. Oral glucose tolerance initially deteriorated at 6 months, but improved toward the control value by 24 months. Fasting insulin (FI) increased significantly, as did the acute insulin response to oral glucose (deltaAIR(OGTT)/deltaG) at 30 minutes (FI: pretreatment 9.8+/-0.8, 6 months, 14.0+/-1.8, 24 months 12.5+/-1.6 v control 11.4+/-1.9 mU x L(-1); deltaAIR(OGTT)/deltaG: pretreatment 201+/-24, 6 months 356+/-41, 24 months 382+/-86 v control 280+/-47 mU x mmol(-1)). However, the acute insulin response to intravenous (IV) glucose (AIR(G)) and IV glucagon at euglycemia and hyperglycemia did not change with rhGH therapy and were similar to the control group values. Importantly, the expected reciprocal relationships (as observed for the control group) between the various insulin secretory parameters and insulin sensitivity (SI) either were not present or were statistically weak in GHD subjects, despite the 35% decrease in SI by 24 months of rhGH therapy. In particular, over time, there was an attenuation of insulin secretion with respect to the ongoing insulin resistance with rhGH therapy, particularly for AIR(G) at 24 months. After 5 days of rhGH withdrawal, insulin secretion decreased and SI improved in GHD subjects. It is concluded that the current long-term rhGH treatment regimens appear to impact on insulin secretion such that the normal relationships between insulin secretion and SI are altered despite the favorable impact on body composition and serum lipid profiles.
Adult↗
Two tests of instance-based and abstract rule-based accounts of invariant learning.
Two manipulations are argued to distinguish between instance-based and abstract rule-based accounts of invariant learning. Three experiments examined the effects of manipulating the type of invariant feature in the learning set, and the type of training schedules prior to test. In line with traditional research, selection bias at test was present when the invariant was the consistent inclusion of a stimulus item in the learning set. However, the degree of bias was identical when the invariant was the consistent exclusion of the stimulus item. In addition, negative transfer of training was observed when subjects were trained on one learning set and then shifted training to the opposite learning set, but no positive transfer of training was observed when subjects were trained on one learning set and then continued training using the same learning set. These results are argued to be evidence for instance-based accounts of invariant learning.
Adult↗
Construction and evaluation of an attenuated vaccine for foot-and-mouth disease: difficulty adapting the leader proteinase-deleted strategy to the serotype O1 virus.
Over the last few years we have utilized a system to genetically engineer foot-and-mouth disease virus (FMDV) to produce live-attenuated vaccine candidates. These candidates have been generated in the genetic background of a tissue culture-adapted strain of serotype A12 virus. Based on this A12 system, we created a virus lacking the sequence encoding the leader (L) proteinase (Piccone et al., 1995), and demonstrated that this leaderless virus, A12-LLV2 was avirulent in bovine and swine, and could be used as an attenuated vaccine (Mason et al., 1997; Chinsangaram et al., 1998). The current study shows that a similar leader-deleted chimeric virus containing the genome of the type A12 virus with a substituted type O1 capsid coding region from a bovine-virulent virus can be constructed, and that the virus has low, but detectable virulence in swine. A second chimera specifying a tissue culture-adapted type O1 capsid lacking the RGD cell binding site, was avirulent in swine, but was not sufficiently immunogenic to provide protection from challenge. These results are described with respect to mechanisms of attenuation and antigen formation in live-attenuated virus-inoculated animals.
Amino Acid Substitution↗